Theoretical study on the interaction of pregabalin and olanzapine with DNA

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ZibaHooshiarSodagar

2016-12-01

Full Text Available This paper aims is to study the interaction of two drugs including pregabalin and olanzapine with DNA. For this purpose, density functional theory calculations and docking were used. The structure of pregabalin and olanzapine using B3Lyp theory level and the basis set 6-311 G(d,p was optimized. Highest occupied molecular orbital (HOMO and lowest unoccupied molecular orbital (LUMO calculated for each drugs. The obtained results showed that olanzapine is more reactive than pregabalin. Docking of drugs with DNA was performed and the results showed that binding affinity of olanzapine is higher than pregabalin. Also, the graphical results revealed that olanzapine interact with DNA via 5-terminal major groove of DNA, whereas pregabalin interact with DNA via 3- termind major groove.

Olanzapine-Induced Neuroleptic Malignant Syndrome

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Seyedhamze Hosseini

2017-05-01

Full Text Available Neuroleptic malignant syndrome (NMS is a rare but life-threatening idiosyncratic side effect resulting from neuroleptic drugs. NMS mainly occurs in patients treated with high-potency typical antipsychotics, but rarely caused by atypical antipsychotics. Although NMS is less common with atypical antipsychotic, but it seems that its incidence is rising due to increased administration of such drugs. We present the case of a 27-year-old man with a history of paranoid schizophrenia that showed signs consistent with NMS that occurred after treatment with olanzapine. The patient was adherent to treatment. He had decreased level of consciousness, muscle rigidity, diaphoresis, fever, drooling, urinary incontinence, and high blood pressure. This patient illustrates that NMS can occur due to treatment with atypical antipsychotic drugs like olanzapine, particularly in the presence of risk factors. This phenomenon is often unrecognized, underdiagnosed, or not treated properly. Physicians should be aware that NMS with extrapyramidal syndrome could occur with olanzapine at steady state doses without recent dosage adjustments or titration. It is essential that adequate and safe dose of medication is chosen and the patient is monitored by the signs and symptoms of this lethal syndrome.

COMPARATIVE STUDY OF OLANZAPINE AND QUETIAPINE IN PSYCHOTIC DISORDERS

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Bithorai Basumatary

2018-01-01

Full Text Available BACKGROUND Psychotic disorders are a group of chronic debilitating psychiatric illness characterised by loss in touch with reality and disorders of thought, behaviour, appearance and speech. The second generation atypical antipsychotic olanzapine has been reported to be the commonly prescribed antipsychotic. However, olanzapine can cause adverse effects like weight gain, hyperglycaemia, diabetes, dyslipidaemia and metabolic syndrome. Quetiapine, another second generation antipsychotic has good efficacy and has become well established in the treatment of schizophrenia and manic episodes. There are reports on adverse effects of hyperglycaemia and diabetes with quetiapine, but these are comparatively lesser than olanzapine. The aim of the study is to compare the efficacy of olanzapine and quetiapine in patients with psychotic disorders. MATERIALS AND METHODS It was an unicentric, open label, prospective and comparative clinical study. Subjects (n=80 who were diagnosed with psychotic disorder were randomly assigned to receive olanzapine (group 1 or quetiapine (group 2. The efficacy of the two drugs was assessed on the basis Brief Psychiatric Rating Scale (BPRS scores at baseline, 1 week and 6 weeks. UKU scale (Udvalg Kliniske Undersogelser and laboratory investigations were used to assess the safety profile. RESULTS The two study groups had comparable sociodemographic profile. Both the groups showed significant reduction in psychotic symptoms as compared from baseline to 1 week and 6 weeks (p<0.001. The intergroup comparison of the efficacy of the two groups did not show any statistically significant results. There was statistically insignificant differences in the occurrence of adverse effects in both the groups. Sedation (50% in both the groups was the most common adverse effect in both the groups. The use of concomitant medications was comparable in both the groups. Benzodiazepines (56.3% in the olanzapine group and 51.9% in the quetiapine group

Olanzapine treatment for tics in an adult woman with severe tourette syndrome.

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Hwang, Wen-Juh

2012-12-01

Olanzapine had been reported to be effective in the control of tics in a few adult female patients who had a short follow-up period. The author reports the successful outcome of long-term olanzapine treatment in an adult woman with severe Tourette syndrome. A 33-year-old woman who had severe motor and vocal tics (Modified Rush Videotape Rating Scale: 17/20) showed an excellent response to olanzapine 10 mg/day within 2 months. Her tic symptoms were well controlled with gradual reduction of her dose of olanzapine to 2.5 mg/day during the following 8 years. She was symptom-free without medications in the past 2 years. In addition, she had a normal menstrual cycle and became pregnant during the period of olanzapine treatment. Olanzapine may be the drug of first choice for treating severe Tourette syndrome in pubescent female adolescents and young women who wish to have children.

Intramuscular Olanzapine – a UK case series of early cases

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Taylor Mark

2007-04-01

Full Text Available Abstract Background Clinical trials assessing efficacy and safety of Intramuscular (IM Olanzapine in acute schizophrenia and acute mania have previously been undertaken in studies required for drug registration in patients who were required to give informed consent. These patients may have less severe forms of psychosis than patients treated in routine practice. Data derived from naturalistic practice following the launch of IM olanzapine may be helpful for clinicians in assessing efficacy and safety of IM olanzapine. The PANSS-EC scale used in the clinical studies may represent a tool that could be used in routine clinical practice. Case presentation We report on an early unselected case series of 7 patients who received IM olanzapine in routine clinical practice settings in the UK. In this case series, olanzapine IM was generally effective, and no adverse events were reported. Adjunctive benzodiazepines were given concomitantly in 1 of the 7 subjects. This is relevant as concomitant benzodiazepines are not recommended for a minimum of 1 hour post IM olanzapine administration. PANSS-EC data was collected in 2 of the 7 subjects. Conclusion Although patients had greater severity of psychosis than clinical trial patients there were no unexpected findings. In addition the PANSS-EC scale is a scale that may be useful in assessing the efficacy of IM antipsychotics in routine clinical practice.

Thrombocytopenia associated with olanzapine: A case report and review of literature

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Swapnajeet Sahoo

2016-01-01

Full Text Available There is limited literature on olanzapine-associated thrombocytopenia. In this report, we present a case of a 32-year-old female, suffering from persistent delusional disorder who had thrombocytopenia (46,000/mm3 with the use of olanzapine 25 mg/day, 6 weeks after starting medication. Blood film did not reveal any evidence of any dysplastic cells, disturbance in the count of other cell lines, and autoimmune workup including antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were found to be negative. Given no other etiology, olanzapine was gradually tapered, and platelet counts were monitored. Reduction in the dose of olanzapine led to an improvement in platelet counts which reached the normal range after complete stoppage of olanzapine. In view of continued psychotic symptoms, she was started on clozapine and which was gradually increased to 200 mg/day with biweekly monitoring of total platelet counts before each increment in the dose of clozapine. Thrombocytopenia did not recur with use of clozapine. With clozapine, her psychosis improved by nearly 60%. A review of literature revealed only eight case reports supporting the association of olanzapine and thrombocytopenia.

Olanzapine versus typical neuroleptics for schizophrenia: evaluation of social and economic costs

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Giorgio Mariani

2006-06-01

Full Text Available An important number of publications is reporting results from health outcomes studies comparing atypical antipsychotics (AA with typical neuroleptics (TN over 1 year of observation. Our study has prolonged the period observation of the economical and social outcomes to 4 years: 31 patients with schizophrenia were observed retrospectively during two years of TN treatment and then followed during 2 more years of olanzapine treatment after naturalistic switch. The results show a general reduction of health care interventions (territory and hospital during the olanzapine treatment period. Global costs during olanzapine treatment were lower than during TN treatment (10506 euros with TN vs 6193 euros with olanzapine over 2 years. The social outcome, measured through the registration of the number of working days in the two periods of the study (retrospective with TN and prospective with olanzapine, was better during olanzapine treatment, probably due to increased patient compliance to the rehabilitative activities offered by the Department of Mental Health. In our experience, olanzapine appeared to dominate TN treatment, as its higher acquisition costs were offset by the reduction of territorial and nosocomial health care interventions over two years of observation, and associated with higher involvement in rehabilitative and social activities.

Effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine for agitation associated with schizophrenia

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Katagiri H

2018-04-01

Full Text Available Hideaki Katagiri,1 Masanori Taketsuna,2 Shinpei Kondo,3 Kenta Kajimoto,4 Etsuko Aoi,5 Yuka Tanji1 1Bio-Medicines, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2Statistical Sciences, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Post Marketing Study Management, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 4Scientific Communications, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 5Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan Objective: To assess the effectiveness and safety of oral olanzapine treatment transitioned from rapid-acting intramuscular olanzapine (RAIM in patients with acute agitation associated with schizophrenia in a real-world clinical setting. Methods: The postmarketing surveillance study with a 3-day observational period after the last RAIM administration was conducted (original study. Following this, an extended study was added for patients who received oral olanzapine after RAIM administration during the original study period, in order to additionally observe them for 7 days after initial RAIM administration. Effectiveness and safety from initial RAIM administration were evaluated using the Positive and Negative Syndrome Scale-Excited Component score and treatment-emergent adverse events (TEAEs, respectively. Results: The effectiveness and safety analysis set included a total of 521 and 522 patients, respectively. A majority of patients received 10 mg of RAIM (475/522 patients, 91.0%. The mean ± SD total Positive and Negative Syndrome Scale-Excited Component score was 23.6±6.2 (n=318 at baseline (before initial RAIM administration, 17.4±6.8 (n=280 at 2 hours after initial administration, 16.2±6.8 (n=246 2 days after final administration, 14.9±6.2 (n=248 3 days after final administration, 13.8±5.9 (n=242 4 days after final administration, 13.2±5.8 (n=221 7 days after initial

Effect of olanzapine treatment on INR of a patient receiving warfarin therapy

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Derya Arslan

2016-06-01

Full Text Available Olanzapine is an atypical antipsychotic drug, commonly used in the management of psychotic symptoms in patients with schizoprenia and bipolar affective disorder. Deep venous thrombosis is a manifestation of venous thromboembolism. It is very well known that use of antipsychotic drugs increase the risk of thrombosis in a patient with schizophrenia. It has been reported in many studies the effects of olanzapine on thrombosis but there isn't any report about the effect of olanzapine on international normalized ratio (INR. in the medical literature. In this paper, a patient with schizophrenia and also family history of deep venous thrombosis who emerged deep venous thrombosis after being started on olanzapine treatment and effect of olanzapine treatment on INR has been reported. [Cukurova Med J 2016; 41(2.000: 370-373

Emphysematous pancreatitis predisposed by Olanzapine

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Sukhen Samanta

2014-01-01

Full Text Available A 32-year-old male presented to our intensive care unit with severe abdominal pain and was diagnosed as acute pancreatitis after 2 months of olanzapine therapy for bipolar disorder. His serum lipase was 900 u/L, serum triglyceride 560 mg/dL, and blood sugar, fasting and postprandial were 230 and 478 mg/dL, respectively on admission. Contrast enhanced computed tomography (CECT of abdomen was suggestive of acute pancreatitis. Repeat CECT showed gas inside pancreas and collection in peripancreatic area and patient underwent percutaneous drainage and antibiotics irrigation through the drain into pancreas. We describe the rare case of emphysematous pancreatitis due to development of diabetes, hypertriglyceridemia and immunosuppression predisposed by short duration olanzapine therapy.

Pharmaceutical studies on and clinical application of olanzapine suppositories prepared as a hospital preparation

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Matsumoto, Kazuaki; Kimura, Satoru; Takahashi, Kenichi; Yokoyama, Yuta; Miyazawa, Masayuki; Kushibiki, Satoko; Katamachi, Morio; Kizu, Junko

2016-01-01

Background A new formulation of olanzapine available for terminally ill patients is needed. Rectal administration using suppositories is an alternative for patients for whom administration via the oral route is not feasible. In the present study, we prepared olanzapine suppositories, and confirmed using pharmaceutical tests. Furthermore, we demonstrated the efficacy and safety of olanzapine suppositories in terminally ill patients. Methods We prepared olanzapine suppositories using bases cons...

The promotion of olanzapine in primary care: an examination of internal industry documents.

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Spielmans, Glen I

2009-07-01

Media reports have discussed how olanzapine was marketed off-label for dementia and subsyndromal bipolar disorder. Much of this marketing occurred in primary care settings. However, these reports have provided few details. In legal proceedings, Lilly disclosed internal documents that detail the strategies utilized to market olanzapine. The current paper addresses the marketing of olanzapine in detail based upon a review of these documents. All 358 documents released by Lilly are publicly available online. Documents were utilized for this review if they were relevant to the marketing of olanzapine in primary care settings in the United States. It was found that olanzapine was marketed off-label in primary care settings for relatively mild symptoms that were framed as bipolar disorder and schizophrenia. A key strategy in this campaign was the use of hypothetical patient profiles in detailing visits, most of which clearly failed to meet diagnostic criteria for any recognized mental disorder. Evidence emerged that olanzapine was also marketed off-label as a treatment for dementia.

Olanzapine affects locomotor activity and meal size in male rats

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van der Zwaal, Esther M.; Luijendijk, Mieneke C. M.; Evers, Simon S.; la Fleur, Susanne E.; Adan, Roger A. H.

2010-01-01

Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect. To investigate how olanzapine affects different aspects of energy balance, we used male rats to determine effects on meal patterns, food preference, locomotor activity

Olanzapine affects locomotor activity and meal size in male rats

NARCIS (Netherlands)

van der Zwaal, Esther M.; Luijendijk, Mieneke C. M.; Evers, Simon S.; la Fleur, Susanne E.; Adan, Roger A. H.

2010-01-01

Olanzapine is an antipsychotic drug that frequently induces weight gain accompanied by increased fat deposition as a side effect To investigate how olanzapine affects different aspects of energy balance we used male rats to determine effects on meal patterns food preference locomotor activity and

Delirium Associated with Olanzapine Therapy in an Elderly Male with Bipolar Affective Disorder

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Sharma, Ravi C.; Aggarwal, Ashish

2010-01-01

Atypical antipsychotic medications are commonly used to treat symptoms of delirium. Olanzapine has been successfully used in the treatment of delirium. However, there have been few case reports of delirium associated with olanzapine. We hereby report a case of delirium associated with olanzapine therapy. Possible risk factors and underlying pathogenesis is discussed.

Olanzapine and sibutramine have opposing effects on the motivation for palatable food.

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van der Zwaal, Esther M; Janhunen, Sanna K; Luijendijk, Mieneke C M; Baclesanu, Roxana; Vanderschuren, Louk J M J; Adan, Roger A H; La Fleur, Susanne E

2012-04-01

Both olanzapine and sibutramine target serotonergic and noradrenergic neurotransmission and influence body weight, but in opposite ways. The second-generation antipsychotic olanzapine, an antagonist at serotonergic and noradrenergic receptors, frequently induces weight gain as a side-effect, whereas sibutramine, a noradrenaline/serotonin reuptake inhibitor, is known as a weight-reducing agent. To investigate whether altered motivation for palatable food influences the effect of these drugs on body weight, we determined their effects on responding for sucrose pellets under a progressive ratio schedule of reinforcement in rats. We found that a low dose of olanzapine selectively increased responding to sucrose, without affecting free-feeding intake of sucrose. In contrast, sibutramine dose-dependently reduced responding to sucrose and similarly reduced free-feeding intake. Furthermore, coadministration of a dose of sibutramine that failed to affect responding to sucrose when administered alone prevented the increase in motivation by the effective dose of olanzapine. These data show that increased motivation for palatable food is likely to be a significant contributor to olanzapine-induced weight gain. Moreover, the ability of sibutramine to reduce this motivation for palatable food may play an important role in the efficacy of sibutramine as an add-on treatment to counteract olanzapine-induced weight gain.

A Comparative Study between Olanzapine and Risperidone in the Management of Schizophrenia

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Saeed Shoja Shafti

2014-01-01

Full Text Available Introduction. Since a variety of comparisons between risperidone and olanzapine have resulted in diverse outcomes, so safety and efficacy of them were compared again in a new trial. Method. Sixty female schizophrenic patients entered into one of the assigned groups for random allocation to olanzapine or risperidone (n=30 in each group in a double-blind, 12-week clinical trial. Scale for Assessment of Positive Symptoms (SAPS and Scale for Assessment of Negative Symptoms (SANS were used as the primary outcome measures. Clinical Global Impressions-Severity Scale (CGI-S, Schedule for Assessment of Insight (SAI, and finally Simpson Angus Scale (SAS as well were employed as secondary scales. Results. While both of olanzapine and risperidone were significantly effective for improvement of positive symptoms (P<0.0001, as regards negative symptoms, it was so only by means of olanzapine (P<0.0003. CGI-S and SAI, as well, were significantly improved in both of the groups. SAS increment was significant only in the risperidone group (P<0.02. Conclusion. While both of olanzapine and risperidone were equally effective for improvement of positive symptoms and insight, olanzapine showed superior efficacy with respect to negative symptoms, along with lesser extrapyramidal side effects, in comparison with risperidone.

5-Lipoxygenase-Activating Protein as a Modulator of Olanzapine-Induced Lipid Accumulation in Adipocyte

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Svetlana Dzitoyeva

2013-01-01

Full Text Available Experiments were performed in 3T3-L1 preadipocytes differentiated in vitro into adipocytes. Cells were treated with olanzapine and a 5-lipoxygenase (5-LOX activating protein (FLAP inhibitor MK-886. Lipid content was measured using an Oil Red O assay; 5-LOX and FLAP mRNA content was measured using quantitative real-time PCR; the corresponding protein contents were measured using quantitative Western blot assay. Olanzapine did not affect the cell content of 5-LOX mRNA and protein; it decreased FLAP mRNA and protein content at day five but not 24 hours after olanzapine addition. In the absence of MK-886, low concentrations of olanzapine increased lipid content only slightly, whereas a 56% increase was induced by 50 μM olanzapine. A 5-day cotreatment with 10 μM MK-886 potentiated the lipid increasing action of low concentrations of olanzapine. In contrast, in the presence of 50 μM olanzapine nanomolar and low micromolar concentrations of MK-886 reduced lipid content. These data suggest that FLAP system in adipocytes is affected by olanzapine and that it may modify how these cells respond to the second-generation antipsychotic drugs (SGADs. Clinical studies could evaluate whether the FLAP/5-LOX system could play a role in setting a variable individual susceptibility to the metabolic side effects of SGADs.

Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

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Ascher-Svanum H

2014-06-01

Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

Orally disintegrating olanzapine and potential differences in treatment-emergent weight gain

NARCIS (Netherlands)

Karagianis, Jamie; Hoffmann, Vicki Poole; Arranz, Belen; Treuer, Tamás; Maguire, Gerald A.; de Haan, Lieuwe; Chawla, Bharat

2008-01-01

Several papers and communications have reported possible weight reduction or less weight gain when patients start or switch to orally disintegrating olanzapine, as contrasted with standard oral olanzapine tablets. In this paper, the current literature is reviewed and hypothesized mechanisms of

An unusual case of hypothermia associated with therapeutic doses of olanzapine: a case report

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Ratnayake Shiroma L

2011-05-01

Full Text Available Abstract Introduction We report a case of a 42-year-old man who had symptomatic hypothermia as a result of taking olanzapine for paranoid schizophrenia. According to published data, only a few cases of hypothermia associated with olanzapine have been reported since its introduction into clinical use. Case presentation A 42-year-old Sri Lankan man with schizophrenia who was being treated with a therapeutic dose of olanzapine presented with reduced level of consciousness. He had a core temperature of 32°C and was bradycardic. At the time of admission, the electrocardiogram showed sinus bradycardia with J waves. He did not have any risk factors for developing hypothermia except the use of olanzapine. There was improvement in his clinical condition with reversal of electrocardiogram changes following gradual rewarming and the omission of olanzapine. Conclusion Hypothermia induced by antipsychotic medications is not uncommon, but olanzapine-induced hypothermia is rare and occurrence has been reported during initiation or increasing the dose. But here the patient developed hypothermia without dose adjustment.

Olanzapine causes hypothermia, inactivity, a deranged feeding pattern and weight gain in female Wistar rats

NARCIS (Netherlands)

Evers, S. S.; Calcagnoli, F.; van Dijk, G.; Scheurink, A. J. W.

2010-01-01

Olanzapine is an a-typical antipsychotic drug antagonizing predominantly 5-HT and dopamine but also histamine muscarin and a adrenergic receptors In humans Olanzapine induces weight gain and increases the risk of type 2 diabetes The underlying mechanisms of Olanzapine-induced weight gain are unclear

Olanzapine and sibutramine have opposing effects on the motivation for palatable food

NARCIS (Netherlands)

van der Zwaal, Esther M.; Janhunen, Sanna K.; Luijendijk, Mieneke C. M.; Baclesanu, Roxana; Vanderschuren, Louk J. M. J.; Adan, Roger A. H.; la Fleur, Susanne E.

2012-01-01

Both olanzapine and sibutramine target serotonergic and noradrenergic neurotransmission and influence body weight, but in opposite ways. The second-generation antipsychotic olanzapine, an antagonist at serotonergic and noradrenergic receptors, frequently induces weight gain as a side-effect, whereas

Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties

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Montgomery W

2012-02-01

Full Text Available William Montgomery1, Tamas Treuer2, Jamie Karagianis3, Haya Ascher-Svanum4, Gavan Harrison51Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 2Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 5Asia-Pacific Medical Communications, Eli Lilly and Company, Sydney, AustraliaAbstract: Orally disintegrating olanzapine (ODO is a rapid-dissolving formulation of olanzapine which disintegrates in saliva almost immediately, developed as a convenient and adherence-enhancing alternative to the standard olanzapine-coated tablet (SOT. Clinical studies, which form the basis of this review, have shown ODO and SOT to have similar efficacy and tolerability profiles. However, ODO appears to have a number of advantages over SOT in terms of adherence, patient preference, and reduction in nursing burden. Overall, the existing clinical data suggests that compared to SOT, ODO is not only well-suited for difficult-to-treat, agitated, and/or nonadherent patients but, due to its potential ability to improve adherence and greater patient preference, may also be an appropriate formulation for the majority of patients for which olanzapine is the antipsychotic of choice.Keywords: orodispersible formulation, orally disintegrating, olanzapine, atypical antipsychotics, patient adherence, preference, schizophrenia, bipolar disorder

Olanzapine is effective for refractory chemotherapy-induced nausea and vomiting irrespective of chemotherapy emetogenicity.

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Vig, Sierra; Seibert, Laurel; Green, Myke R

2014-01-01

The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08). The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

Metabolic syndrome and drug discontinuation in schizophrenia: a randomized trial comparing aripiprazole olanzapine and haloperidol.

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Parabiaghi, A; Tettamanti, M; D'Avanzo, B; Barbato, A

2016-01-01

To determine whether the prescription of aripiprazole, compared with olanzapine and haloperidol, was associated with a lower frequency of metabolic syndrome (MS) and treatment discontinuation at 1 year. Patients were randomly assigned to be treated open-label and according to usual clinical practice with either aripiprazole, olanzapine, or haloperidol and followed up for 1 year. Three hundred out-patients with persistent schizophrenia were recruited in 35 mental health services. The intention-to-treat (ITT) analysis found no significant differences in the rate of MS between aripiprazole (37%), olanzapine (47%), and haloperidol (42%). Treatment discontinuation for any cause was higher for aripiprazole (52%) than for olanzapine (33%; OR, 0.41; P = 0.004), or haloperidol (37%; OR, 0.51; P = 0.030). No significant difference was found between olanzapine and haloperidol. Time to discontinuation for any cause was longer for olanzapine than for aripiprazole (HR, 0.55; P haloperidol and aripiprazole, or between olanzapine and haloperidol. The prescription of aripiprazole did not significantly reduce the rates of MS, but its treatment retention was worse. Aripiprazole cannot be considered the safest and most effective drug for maintenance treatment of schizophrenia in routine care, although it may have a place in antipsychotic therapy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Effect of Ranitidine on Olanzapine-Induced Weight Gain

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Fatemeh Ranjbar

2013-01-01

Full Text Available Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6 kg at baseline. Thirty-three subjects (63.5% had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend’s slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with IRCT.ir 201009112181N5.

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Comparative Study From Sudan

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Alaa A.M. Osman

2018-05-01

Full Text Available Purpose: Chemotherapy-induced nausea and vomiting (CINV is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA–containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC. NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings. Patients and Methods: The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications and nausea control (no nausea, which were assessed in the acute (0 to 24 hours, delayed (24 to 120 hours, and overall (0 to 120 hours phases. Results: The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients. CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001. The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients. Conclusion: An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar

Alterations to melanocortinergic, GABAergic and cannabinoid neurotransmission associated with olanzapine-induced weight gain.

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Katrina Weston-Green

Full Text Available BACKGROUND/AIM: Second generation antipsychotics (SGAs are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapine-induced obesity. METHODOLOGY/RESULTS: Levels of pro-opiomelanocortin (POMC, neuropeptide Y (NPY and glutamic acid decarboxylase (GAD(65, enzyme for GABA synthesis mRNA expression, and cannabinoid CB1 receptor (CB1R binding density (using [(3H]SR-141716A were examined in the arcuate nucleus (Arc and dorsal vagal complex (DVC of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (3×/day, 14-days. Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD(65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. CONCLUSIONS: Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly by altering POMC transmission. Metabolic dysfunction can be modelled in the female rat using low, clinically-comparable olanzapine doses when administered in-line with the half-life of the drug.

Memantine enhances the effect of olanzapine in patients with schizophrenia: A randomized, placebo-controlled study

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Ahmad Fakhri

2016-12-01

Full Text Available Glutamate dysregulation may be involved in the neuropathology of schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a partial uncompetitive NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to olanzapine in patients with schizophrenia. In this double-blind, placebo-controlled studies, patients with schizophrenia according to DSM-IV clinical criteria were selected. Patients were randomly assigned to receive either memantine (week 1:10 mg/day; weeks 2-6:20 mg/day plus olanzapine (15-20 mg/day or olanzapine plus placebo. At baseline, no statistically significant difference regarding the mean total PANSS scores between treatment groups was found. Results showed that memantine significantly improved the positive and negative PANSS score in patients maintained on olanzapine after six weeks compared to olanzapine alone (P<0.001. Furthermore, female patients showed significantly better response than males, especially in positive PANSS score. No significant changes in extrapyramidal symptoms were observed.These findings indicate that olanzapine efficacy might be augmented with memantine. Furthermore, this effect is more remarkable in female patients with schizophrenia.

Olanzapine-induced weight gain: lessons learned from developing rat models

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van der Zwaal, E.M.

2011-01-01

Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying mechanisms. Therefore, this thesis describes the development of a number of rat models that were designed to determine the effects of olanzapine on different aspects of energy balance. In both short- a...

Olanzapine-associated hypothermia: a case report of a rare event

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Manuel Monti

2018-02-01

Full Text Available Hypothermia, a potentially fatal condition, is defined as a drop of the body temperature below 35°C. The most common cause of severe hypothermia is the environmental exposure to low-temperatures. Other causes include septicemia, diabetic ketoacidosis, trauma, acute spinal cord injury, prolonged cardiac arrest and hypothyroidism. The hypothermia is an infrequent, but previously documented, adverse effect of antipsychotic medications. A 83-year-old Italian woman was transported to the Emergency Room with a reduced level of consciousness, Glasgow coma scale 7. She was bradycardic (heart rate 42 bpm, 80/150 mmHg blood pressure and respiratory rate 26/min. Her physical examination was significant for an anal temperature of 31°C. Blood exam and chest X-ray were unremarkable. In her clinical history, she was suffering from generalized anxiety disorder for the last 2 years and was prescribed olanzapine 7.5 mg daily. In recent days, the patient experienced a cognitive impairment with heat intolerance and had been reduced the dose of olanzapine 5 mg daily. On the basis of the clinical findings, the patient’s body temperature and blood exam, the diagnosis of olanzapine-associated hypothermia was made. The patient was gradually rewarmed with blankets and warm saline infusion and the olanzapine therapy was discontinued. She gradually regained consciousness after 18 h and, after 1 day, the patient’s body temperature increased up to 37.8°C with an improvement of the neurological conditions. We reported about the case of a patient treated with stable doses of olanzapine for a long period of time that developed hypothermia, a potentially fatal complication. This case shows that it is important to consider every change in the patient behavior, e.g., the poor resistance to heat present in our patient, that should exhibit warning sign of hypothermia.

Eosinophilic myocarditis during treatment with olanzapine

DEFF Research Database (Denmark)

Vang, Torkel; Rosenzweig, Mary; Bruhn, Christina Hedegaard

2016-01-01

-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current...

Olanzapine induced biochemical and histopathological changes after its chronic administration in rats

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Rehmat Shah

2016-11-01

Full Text Available Objective: Olanzapine is a second generation antipsychotic acting mainly as a dopamine D2 and serotonine 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various other psychiatric illnesses. Even though olanzapine is widely used in psychiatry, its effects on the architecture of pancreas, liver and kidneys are little known. The histology of pancreas especially has never been studied. For these reasons, the current study was designed to elucidate the toxic effects of chronic administration of olanzapine on pancreas, liver and kidneys and the enzymes released by these tissues in an escalating dose manner. Methods: Fourteen male rats were divided into two groups equally, the olanzapine group and the controls. Olanzapine was administered in a dose of 5 mg/kg/d for the first eight weeks, 10 mg/kg/d for next four weeks and 15 mg/kg/d through the last two week period of 14 weeks experiment. The controls received acidified saline only. Both the groups received restricted diet (20 g/12 h. The body weight and level of random blood sugar (RBS were measured on a weekly basis. The levels of lipase, amylase, alanine transaminase (ALT and aspartate transaminase (AST were determined terminally. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Results: Significant loss in body weight, change in the level of random blood sugar (∗∗P  0.05. The pancreas has shown derangement of beta cells and fibrotic growth. A mild to moderate focal increase in glomerular cellularity, cellular proliferation and glomerular capsules with negligible basement membranes were observed in the kidneys. No changes were observed in the architecture of the liver. Conclusion: The findings of this study indicated that the incidence of adverse effects associated with olanzapine could be prevented/alleviated/delayed by allowing restricted diet.

Acute camptocormia induced by olanzapine: a case report

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Boyer Stéphane

2010-06-01

Full Text Available Abstract Introduction Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder. Case presentation A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L. Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later. Conclusions Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug

Efficacy of olanzapine long-acting injection in patients with acutely exacerbated schizophrenia: an insight from effect size comparison with historical oral data

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Detke Holland C

2012-05-01

Full Text Available Abstract Background To treat acute schizophrenia, a long-acting injectable antipsychotic needs a rapid onset of action and therapeutic profile similar to that of oral agents. The present post-hoc analyses compared results from a randomized, double-blind, placebo-controlled trial of olanzapine long-acting injection (LAI for acute schizophrenia with those observed in similarly designed trials of oral olanzapine. Methods Six-week results from the olanzapine LAI study (N = 404 were compared with those of 3 oral studies (study 1: olanzapine vs. haloperidol vs. placebo [N = 335]; study 2: olanzapine vs. haloperidol vs. low-dose olanzapine [N = 431]; study 3: olanzapine vs. placebo vs. low-dose olanzapine [N = 152]. All patients had baseline Brief Psychiatric Rating Scale (BPRS scores ≥24 (0–6 scale. Six-week effect sizes were calculated. Efficacy onset, pharmacokinetics, discontinuations, weight gain, and extrapyramidal symptoms were also assessed. Results At 6 weeks, mean BPRS scores decreased by 14 to 15 points for olanzapine LAI (405 mg/4 weeks, 210 or 300 mg/2 weeks, by 8 to 16 for oral olanzapine (10 ± 2.5 or 15 ± 2.5 mg/day, and by 12 to 13 for haloperidol (15 ± 5 mg/day. For those same dose groups, effect sizes vs. placebo for the BPRS were 0.7 to 0.8 for olanzapine LAI, 0.5 to 0.7 for oral olanzapine, and 0.6 for haloperidol. The first statistically significant separation from placebo on the BPRS occurred at 3 days for the olanzapine LAI groups and at 1 week for oral olanzapine and haloperidol (15 ± 5 mg/day in oral study 1 although as late as week 6 for the 10-mg/day olanzapine dose in oral study 3. Olanzapine concentrations were similar across studies. Weight gain ≥7% of baseline occurred in up to 35% of olanzapine LAI and oral patients versus up to 12% of haloperidol and placebo patients. Extrapyramidal symptoms were lowest in the olanzapine LAI groups and significantly greater

Olanzapine-Induced Mania in Bipolar Spectrum Disorder:A Case Report

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Mehrdad Eftekhar

2006-07-01

Full Text Available Objective: To report the case of a 46-year old male with major depressive disorder, who represented manic symptoms, when olanzapine was added to his treatment. Method: A 46-year old female, with a diagnosis of treatment resistant depression was referred to the authors. He had past history of depression for more than 20 years. The symptoms were present nearly every day since 1981, without any distinct period of remission, nor any noticeable fluctuation. His irritability had been disruptive to his family all these years. His doctor had prescribed maprotiline 25 mg/day, and lorazepam, 2mg/day, in addition to fluoxetine for the last 5 months. He is also a father of two children with methylphenidateresistant and sodium valproate-responsive attention-deficit hyperactivity disorder. Considering the antidepressant effects of olanzapine and its positive effects on irritability, the authors added olanzapine, to the patient’s previous medications. Results: After one week, he showed new problems such as talkativeness and beginning to smoke for the first time in his life, elevated mood, grandiosity about his intelligence and abilities, talkativeness, and shopping sprees. The score on the mania rating scale was 14. Fluoxetine was discontinued and sodium valproate, were prescribed. It took around 2 months to completely control the manic symptoms. Conclusions: In the patients with depression who show bipolar spectrum disorder features, adding mood stabilizers may be preferred to the drugs as olanzapine which could induce mania.

A comparative study of olanzapine versus asenapine in acute treatment of manic episode: A 3-week prospective study

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Ajeet Sidana

2014-01-01

Full Text Available Introduction: Treatment of bipolar disorders has evolved over the years from conventional mood stabilizers to second-generation antipsychotics. Among the atypical antipsychotics, few have been approved by Food and Drug Administration as treatment of bipolar disorders. Aim: To study the efficacy and tolerability of olanzapine and asenapine in the acute treatment of bipolar disorder-manic episode in a 3-week randomized prospective study. Materials and Methods: A 3-week randomized, prospective, comparative, flexible doses of olanzapine (5-30 mg/day and asenapine (10-20 mg/day for acute treatment of bipolar disorder-current manic episode with or without psychotic symptoms in hospitalized patients. Results: The end-point reduction in mean score of Young Mania rating scale in the olanzapine group was 15.82 in comparison to 6.88 in the asenapine group. Mean score on clinical global impression for bipolar disorder and positive and negative syndrome scale was significantly less in the olanzapine group at the end of the study. 81.81% patients in olanzapine group and 17.60% patients in asenapine group had clinical response. There was significant average weight gain in the olanzapine group - 1.9 kg in comparison to 0.87 kg in asenapine group. Conclusion: The clinical response with olanzapine is significantly higher than the asenapine in the treatment of bipolar disorder-manic episode with or without psychotic symptoms. However, there is significant weight gain in olanzapine-treated patients.

Differential weight restoration on olanzapine versus fluoxetine in identical twins with anorexia nervosa.

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Duvvuri, Vikas; Cromley, Taya; Klabunde, Megan; Boutelle, Kerri; Kaye, Walter H

2012-03-01

No studies have compared the response to selective serotonin reuptake inhibitors and atypical antipsychotics in anorexia nervosa. This case study examines such a comparison. This report describes a case of 12-year-old identical twins with anorexia nervosa, one of whom was treated with olanzapine and the other with fluoxetine, while undergoing family therapy. Twin A treated with fluoxetine went from 75 to 84.4% ideal body weight, while Twin B treated with olanzapine went from 72 to 99.9% ideal body weight over the course of 9 months. This case supports the need for adequately powered, controlled clinical trials to test the efficacy of olanzapine in adolescents presenting with anorexia nervosa. Copyright © 2011 Wiley Periodicals, Inc.

Naturalistic study of olanzapine in treatment-resistaant ...

African Journals Online (AJOL)

Naturalistic study of olanzapine in treatment-resistaant schizophrenia and acute mania, depression and obsessional disorder. ... Whereas the Fiji government provides all aspects of mental health care services free of charge to its citizens, many schizophrenics have failed to respond to classical antipsychotic drugs.

Batch and flow-injection methods for the spectrophotometric determination of olanzapine

Energy Technology Data Exchange (ETDEWEB)

Jasinska, A.; Nalewajko, E

2004-04-22

An indirect batch spectrophotometric and direct flow-injection (FI) visible spectrophotometric methods have been developed for the determination of the novel anti-psychotic drug olanzapine (OLA). The batch method is based on the oxidation of olanzapine by a known excess of potassium hexacyanoferrate(III) in the presence of the mixture of sulphuric and phosphoric acids (1:1 (v/v)). The absorbance of unreacted oxidant is measured at 425 nm. The absorbance decreases linearly with increasing concentration of the assayed drug. The FI method with detection at 540 nm is based on the direct oxidation of olanzapine one of two oxidants, cerium(IV) sulphate or potassium hexacyanoferrate(III) in acidic medium. The calibration graph were linear over the range of 2.5-40 {mu}g ml{sup -1} in the batch method and 0.05-300 and 0.5-250 {mu}g ml{sup -1} in the FI methods, used cerium (IV) sulphate and potassium hexacyanoferrate (III) respectively. Both FI methods gave similar results in terms of precision and accuracy. The relative standard deviation (R.S.D.), was <1%. The accuracy, obtained from recovery experiments, was 97.9-99.4%. The batch method gave slightly higher R.S.D. values (up to 2.3%) and lower values of accuracy (the recovery was between 96.5 and 96.6%). The methods developed were applied to the determination of olanzapine in a pharmaceutical product.

Double-blind, placebo-controlled study of dialectical behavior therapy plus olanzapine for borderline personality disorder.

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Soler, Joaquim; Pascual, Juan Carlos; Campins, Josefa; Barrachina, Judith; Puigdemont, Dolors; Alvarez, Enrique; Pérez, Victor

2005-06-01

The aim of this study was to determine the efficacy and safety of dialectical behavior therapy plus olanzapine compared with dialectical behavior therapy plus placebo in patients with borderline personality disorder. Sixty patients with borderline personality disorder were included in a 12-week, double-blind, placebo-controlled study. All patients received dialectical behavior therapy and were randomly assigned to receive either olanzapine or placebo following a 1-month baseline period. Seventy percent of the patients completed the 4-month trial. Combined treatment showed an overall improvement in most symptoms studied in both groups. Olanzapine was associated with a statistically significant improvement over placebo in depression, anxiety, and impulsivity/aggressive behavior. The mean dose of olanzapine was 8.83 mg/day. A combined psychotherapeutic plus pharmacological approach appears to lower dropout rates and constitutes an effective treatment for borderline personality disorder.

Naturalistic study of olanzapine in treatment-resistaant ...

African Journals Online (AJOL)

Background: Whereas the Fiji government provides all aspects of mental health care services free of charge to its citizens, many schizophrenics have failed to respond to classical antipsychotic drugs. Objective: To assess the efficacy and safety of olanzapine among various patients with severe psychiatric disorders.

Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: a double-blind, placebo-controlled trial.

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Narula, Preeta Kaur; Rehan, H S; Unni, K E S; Gupta, Neeraj

2010-05-01

Olanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters. In this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12 weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects. Topiramate resulted in a weight loss of 1.27+/-2.28 kg (pweight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Effect of Olanzapine on Clinical and Polysomnography Profiles in Patients with Schizophrenia

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Mohammad Zia Ul Haq Katshu

2018-01-01

Full Text Available Acute and short-term administration of olanzapine has a favorable effect on sleep in schizophrenia patients. This study aimed to clarify the effect of olanzapine on polysomnographic profiles of schizophrenia patients during the acute phase of illness after controlling for previous drug exposure. Twenty-five drug-naïve or drug-free schizophrenia patients were assessed at baseline and after six weeks of olanzapine treatment on Brief Psychiatric Rating Scale (BPRS, Positive and Negative Syndrome Scale (PANSS, and Udvalg for Kliniske Undersogelser (UKU side-effect rating scale and a whole-night polysomnography; fifteen patients completed the study. There was a significant reduction in all psychopathological variables with maximum reduction in PANSS total, BPRS total, and PANSS positive scores. A significant increase in total sleep time (TST, sleep efficiency (SE, nonrapid eye movement (NREM stage 1 duration, stage 3 duration, stage 4 duration, and stage 4 percentage of TST, number of rapid eye movement (REM periods, REM duration, and REM percentage of TST was observed. REM latency at baseline inversely predicted the reduction in BPRS total and PANSS total and positive scores. In summary, short-term treatment with olanzapine produced significant improvement in clinical and polysomnography profiles of patients with schizophrenia with shorter REM latency predicting a good clinical response.

Attenuating effect of reboxetine on appetite and weight gain in olanzapine-treated schizophrenia patients: a double-blind placebo-controlled study.

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Poyurovsky, Michael; Fuchs, Camil; Pashinian, Artashez; Levi, Aya; Faragian, Sarit; Maayan, Rachel; Gil-Ad, Irit

2007-06-01

Search for safe and effective strategies to diminish weight gain associated with second generation antipsychotics (SGAs) is imperative. In the present study, we sought to replicate our preliminary findings, which indicated that coadministration of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. Fifty-nine patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in this randomized double-blind study. Reboxetine (4 mg/day; 31 patients) or placebo (29 patients) was coadministered with olanzapine (10 mg/day) for 6 weeks. Analysis was by intention-to-treat. Nine patients in each group prematurely discontinued the trial. Olanzapine/reboxetine-treated patients showed a significantly lower increase in body weight (mean = 3.31 kg, SD = 2.73) than their olanzapine/placebo-treated counterparts (mean = 4.91 kg, SD = 2.45). Significantly fewer olanzapine/reboxetine-treated patients gained at least 7% of their initial weight, the cutoff for clinically significant weight gain (6 [19.4%] of 31 patients vs 13 [46.4%] of 28 patients). Seven (22.6%) olanzapine/reboxetine-treated patients compared to only one patient (3.6%) in the olanzapine/placebo group revealed no weight change or even modest weight loss. Appetite increase was significantly lower in the olanzapine/reboxetine than olanzapine/placebo group and was correlated with attenuation of weight gain. Reboxetine addition was safe and well tolerated. The results confirm that coadministration of reboxetine promotes a clinically meaningful attenuation of olanzapine-induced weight gain in schizophrenia patients. If substantiated in long-term studies, along with behavioral management and diet counseling, reboxetine may have a clinical utility in controlling SGA-induced weight gain.

Olanzapine-induced ischemic colitis

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Esteban Sáez-González

Full Text Available Background: Ischemic colitis (IC is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. Case report: We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Discussion: Antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

An In Vitro Analysis of Disintegration Times of Different Formulations of Olanzapine Orodispersible Tablet: A Preliminary Report

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Hobbs, David; Karagianis, Jamie; Treuer, Tamas; Raskin, Joel

2013-01-01

Background Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Objectives Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab® was included as a non-olanzapine ODT comparator. Research Design and Methods Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vit...

Long-term administration of olanzapine induces adiposity and increases hepatic fatty acid desaturation protein in female C57BL/6J mice

Science.gov (United States)

Hou, Po-Hsun; Chang, Geng-Ruei; Chen, Chin-Pin; Lin, Yen-Ling; Chao, I-Shuan; Shen, Ting-Ting; Mao, Frank Chiahung

2018-01-01

Objective(s): Weight gain and metabolic disturbances such as dyslipidemia, are frequent side effects of second-generation antipsychotics, including olanzapine. This study examined the metabolic effects of chronic olanzapine exposure. In addition, we investigated the hepatic fatty acid effects of olanzapine in female C57BL/6J mice fed a normal diet. Materials and Methods: Female C57BL/6J mice orally received olanzapine or normal saline for 7 weeks. The effects of long-term olanzapine exposure on body weight changes, food efficiency, blood glucose, triglyceride (TG), insulin, and leptin levels were observed. Hepatic TG and abdominal fat mass were investigated, and fat cell morphology was analyzed through histopathological methods. The levels of protein markers of fatty acid regulation in the liver, namely fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), were measured. Results: Olanzapine treatment increased the food intake of the mice as well as their body weight. Biochemical analyses showed that olanzapine increased blood TG, insulin, leptin, and hepatic TG. The olanzapine group exhibited increased abdominal fat mass and fat cell enlargement in abdominal fat tissue. Western blotting of the mouse liver revealed significantly higher (1.6-fold) levels of SCD-1 in the olanzapine group relative to the control group; by contrast, FAS levels in the two groups did not differ significantly. Conclusion: Enhanced lipogenesis triggered by increased hepatic SCD-1 activity might be a probable peripheral mechanism of olanzapine-induced dyslipidemia. Some adverse metabolic effects of olanzapine may be related to the disturbance of lipid homeostasis in the liver. PMID:29922430

Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases

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Stefaniak Victoria J

2010-06-01

Full Text Available Abstract Background An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI. During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI. Methods Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors. Results Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients. Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness. However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified. Conclusions Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post

Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study.

Science.gov (United States)

Novick, D; Gonzalez-Pinto, A; Haro, J M; Bertsch, J; Reed, C; Perrin, E; Tohen, M

2009-07-01

The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments. EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with the treatment of mania. Severity of mania and depression were assessed at baseline and 6 weeks using the YMRS and the 5-item version of the HAMD, respectively. 621 patients were analysed (n=107 valproate, n=514 olanzapine). Both groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with greater mean improvements in the olanzapine compared with the valproate group. Olanzapine was associated with more weight gain and less gastrointestinal difficulties than valproate. The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy seems to be more effective than valproate monotherapy in the treatment of acute mania.

Schizophrenia relapse after stopping olanzapine treatment during pregnancy: a case report

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Ifteni P

2014-10-01

Full Text Available Petru Ifteni,1,2 Marius A Moga,1 Victoria Burtea,1,2 Christoph U Correll3,4 1Faculty of Medicine, Transilvania University, Brasov, Romania; 2Psychiatry and Neurology Hospital, Brasov, Romania; 3Department of Psychiatry, The Zucker Hillside Hospital, North Shore-Long Island Jewish (LIJ Health System, New York, NY, USA; 4Hofstra North Shore-LIJ School of Medicine, New York, NY, USA Abstract: Women with schizophrenia have a high risk for symptom exacerbation or relapse during pregnancy and thereafter. Relapses are more frequent when antipsychotics are discontinued. This paper describes the case of a 28-year old woman with schizophrenia who continued treatment with olanzapine during the first trimester. Olanzapine, a second-generation antipsychotic, was administered at a therapeutic dose from week 1 of gestation until week 13 when she reported the pregnancy to her psychiatrist. Despite the psychiatrist’s recommendation to continue treatment, the patient stopped olanzapine at 20 weeks. She was hospitalized at week 36 for a schizophrenia relapse and was transferred to the obstetrics department where she gave birth by Cesarean section to a normal child. This case is important, illustrating the perils of unplanned pregnancy during antipsychotic treatment and abrupt discontinuation. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother in terms of symptom exacerbation and relapse if antipsychotic treatment is discontinued, and the potential risk to the fetus regarding possible teratogenic effects of continued antipsychotic treatment. Keywords: relapse, pregnancy, schizophrenia, olanzapine

Symptom response and side-effects of olanzapine and risperidone in young adults with recent onset schizophrenia

NARCIS (Netherlands)

van Bruggen, Johanna; Tijssen, Jans; Dingemans, Petrus; Gersons, Berthold; Linszen, Donald

2003-01-01

The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia. Actively symptomatic patients n=44) randomly, received olanzapine 15 mg (median dose) or risperidone 4 mg (median dose). Symptom response and side-effects were measured

Assessment of strategies for switching patients from olanzapine to risperidone: A randomized, open-label, rater-blinded study

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Berry Sally A

2008-06-01

Full Text Available Abstract Background In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone. Methods In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation: (i abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued. Results The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (± standard deviation (SD baseline Positive and Negative Syndrome Scale (PANSS total score of 75.6 ± 11.5. All-cause treatment discontinuation was lowest (12% in the group with the slowest olanzapine dose reduction (gradual 2 and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1. The relative risk of early discontinuation was 0.77 (confidence interval 0.61–0.99 for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at

RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.

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Christopher J Lynch

Full Text Available Second generation antipsychotics (SGAs, like olanzapine, exhibit acute metabolic side effects leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. Understanding how SGAs affect the skeletal muscle transcriptome could elucidate approaches for mitigating these side effects. Male Sprague-Dawley rats were infused intravenously with vehicle or olanzapine for 24h using a dose leading to a mild hyperglycemia. RNA-Seq was performed on gastrocnemius muscle, followed by alignment of the data with the Rat Genome Assembly 5.0. Olanzapine altered expression of 1347 out of 26407 genes. Genes encoding skeletal muscle fiber-type specific sarcomeric, ion channel, glycolytic, O2- and Ca2+-handling, TCA cycle, vascularization and lipid oxidation proteins and pathways, along with NADH shuttles and LDH isoforms were affected. Bioinformatics analyses indicate that olanzapine decreased the expression of slower and more oxidative fiber type genes (e.g., type 1, while up regulating those for the most glycolytic and least metabolically flexible, fast twitch fiber type, IIb. Protein turnover genes, necessary to bring about transition, were also up regulated. Potential upstream regulators were also identified. Olanzapine appears to be rapidly affecting the muscle transcriptome to bring about a change to a fast-glycolytic fiber type. Such fiber types are more susceptible than slow muscle to atrophy, and such transitions are observed in chronic metabolic diseases. Thus these effects could contribute to the altered body composition and metabolic disease olanzapine causes. A potential interventional strategy is implicated because aerobic exercise, in contrast to resistance exercise, can oppose such slow to fast fiber transitions.

Metabolic effects of Olanzapine versus Iloperidone: A 24 weeks ...

African Journals Online (AJOL)

Arun Kumar Agnihotri

The present study is aimed to comparatively evaluate the metabolic profile of olanzapine and iloperidone in cases of ... delusional disorders, acute and transient psychotic ... Data regarding age, sex, socio-economic status, family history, and.

Ziprasidone as an adjuvant for clozapine- or olanzapine-associated medical morbidity in chronic schizophrenia

Science.gov (United States)

Henderson, David C.; Fan, Xiaoduo; Copeland, Paul M.; Sharma, Bikash; Borba, Christina P.; Forstbauer, Sharon I.; Miley, Kate; Boxill, Ryan; Freudenreich, Oliver; Cather, Corey; Evins, A. Eden; Goff, Donald C.

2015-01-01

Objective This study sought to examine the effect of ziprasidone on olanzapine or clozapine associated medical morbidity such as insulin resistance, diabetes mellitus and impaired fasting glucose, obesity and hyperlipidemia in patients with schizophrenia or schizoaffective disorder. Method This was a six-week, open label trial of ziprasidone 160 mg/day added to a stable dose of olanzapine or clozapine in twenty-one schizophrenia or schizoaffective patients with diabetes mellitus, impaired fasting glucose, or insulin resistance. Results Ten olanzapine-treated subjects and eleven clozapine-treated subjects were enrolled in the study. There were no significant differences between the two groups at baseline for age, gender, education, ethnicity, BMI, cholesterol levels, or fasting glucose. At week six, there were no significant changes in weight, BMI, cholesterol levels, or fasting glucose. There was no significant difference in psychotic, negative or depressive symptoms. QTc significantly increased at week 2 but not at week 6. Conclusions The addition of 160 mg/day of ziprasidone was well tolerate but did not produce significant improvement in fasting glucose, insulin resistance, hyperlipidemia or lead to weight loss in olanzapine- or clozapine-treated subjects with schizophrenia or schizoaffective disorder. PMID:19283774

Safety and effectiveness of olanzapine in monotherapy: a multivariate analysis of a naturalistic study.

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Ciudad, Antonio; Gutiérrez, Miguel; Cañas, Fernando; Gibert, Juan; Gascón, Josep; Carrasco, José-Luis; Bobes, Julio; Gómez, Juan-Carlos; Alvarez, Enrique

2005-07-01

This study investigated safety and effectiveness of olanzapine in monotherapy compared with conventional antipsychotics in treatment of acute inpatients with schizophrenia. This was a prospective, comparative, nonrandomized, open-label, multisite, observational study of Spanish inpatients with an acute episode of schizophrenia. Data included safety assessments with an extrapyramidal symptoms (EPS) questionnaire and the report of spontaneous adverse events, plus clinical assessments with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate methodology was used to more adequately determine which factors can influence safety and effectiveness of olanzapine in monotherapy. 339 patients treated with olanzapine in monotherapy (OGm) and 385 patients treated with conventional antipsychotics (CG) were included in the analysis. Treatment-emergent EPS were significantly higher in the CG (pOGm (p=0.005). Logistic regression analyses revealed that the only variable significantly correlated with treatment-emergent EPS and clinical response was treatment strategy, with patients in OGm having 1.5 times the probability of obtaining a clinical response and patients in CG having 5 times the risk of developing EPS. In this naturalistic study olanzapine in monotherapy was better-tolerated and at least as effective as conventional antipsychotics.

Microtitrimetric determination of a drug content of pharmaceuticals containing olanzapine in non-aqueous medium

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KANAKAPURA BASAVAIAH

2009-05-01

Full Text Available Two simple, rapid, reliable and cost-effective methods based on titrimetry in non-aqueous medium are described for the determination of olanzapine in pharmaceuticals. In these methods, the drug dissolved in the glacial acetic acid was titrated with the acetous perchloric acid with visual and potentiometric end point detection, crystal violet being used as the indicator for visual titration. The methods are applicable over 1-15 mg range of olanzapine. The procedures were applied to determine olanzapine in pharmaceutical products and the results were found to be in a good agreement with those obtained by the reference method. Associated pharmaceutical materials did not interfere. The precision results, expressed by inter-day and intra-day relative standard deviation values, were satisfactory, higher than 2%. The accuracy was satisfactory as well. The methods proved to be suitable for the analysis of olanzapine in bulk drug and in tablets. The accuracy and reliability of the methods were further ascertained by recovery studies via a standard addition technique with percent recoveries in the range 97.51-103.7% with a standard deviation of less than 2%.

Determination of olanzapine in whole blood using simple protein precipitation and liquid chromatography-tandem mass spectrometry

DEFF Research Database (Denmark)

Nielsen, Marie Katrine Klose; Johansen, Sys Stybe

2009-01-01

A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation......, and stability. The absolute recovery obtained was 103% for olanzapine and 68% for IS. An LOQ of 0.005 mg/kg olanzapine in whole blood was achieved. Inter- and intraday precision were less than 11% within concentrations from 0.01 to 0.50 mg/kg, and the accuracy ranged from 85 to 115%. The method was subsequently...

MALDI-MS analysis and theoretical evaluation of olanzapine as a UV laser desorption ionization (LDI) matrix.

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Musharraf, Syed Ghulam; Ameer, Mariam; Ali, Arslan

2017-01-05

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) being soft ionization technique, has become a method of choice for high-throughput analysis of proteins and peptides. In this study, we have explored the potential of atypical anti-psychotic drug olanzapine (OLZ) as a matrix for MALDI-MS analysis of peptides aided with the theoretical studies. Seven small peptides were employed as target analytes to check performance of olanzapine and compared with conventional MALDI matrix α-cyano-4-hydroxycinnamic acid (HCCA). All peptides were successfully detected when olanzapine was used as a matrix. Moreover, peptides angiotensin Ι and angiotensin ΙΙ were detected with better S/N ratio and resolution with this method as compared to their analysis by HCCA. Computational studies were performed to determine the thermochemical properties of olanzapine in order to further evaluate its similarity to MALDI matrices which were found in good agreement with the data of existing MALDI matrices. Copyright © 2016. Published by Elsevier B.V.

Long-term weight loss observed with olanzapine orally disintegrating tablets in overweight patients with chronic schizophrenia. A 1 year open-label, prospective trial.

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Chawla, Bharat; Luxton-Andrew, Heather

2008-04-01

To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04). This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months. 2008 John Wiley & Sons, Ltd.

Differential weight restoration on olanzapine versus fluoxetine in identical twins with anorexia nervosa

OpenAIRE

Duvvuri, V; Cromley, T; Klabunde, M; Boutelle, K; Kaye, WH

2012-01-01

Objective: No studies have compared the response to selective serotonin reuptake inhibitors and atypical antipsychotics in anorexia nervosa. This case study examines such a comparison. Method: This report describes a case of 12-year-old identical twins with anorexia nervosa, one of whom was treated with olanzapine and the other with fluoxetine, while undergoing family therapy. Results: Twin A treated with fluoxetine went from 75 to 84.4% ideal body weight, while Twin B treated with olanzapine...

Pharmaco-epidemiological description of the population of the Marche Region (central Italy treated with the antipsychotic drug olanzapine

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Fiorenzo Mignini

2013-03-01

Full Text Available BACKGROUND. In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA promulgated a cautionary note. MATERIALS AND METHODS. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group. RESULTS. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note. CONCLUSIONS. Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review

DEFF Research Database (Denmark)

Ennis, Zandra Nymand; Damkier, Per

2015-01-01

/22 (5.1%) and 100/5 (5.0%), respectively. Relative risk estimates and 95% confidence intervals were 1.0 (0.7-1.4) (olanzapine), 1.0 (0.6-1.7) (quetiapine), 1.5 (0.9-2.2) (risperidone) and 1.4 (0.5-3.1) (aripiprazole). First-trimester exposure to olanzapine is not associated with an increased risk...

A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain.

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McElroy, Susan L; Winstanley, Erin; Mori, Nicole; Martens, Brian; McCoy, Jessica; Moeller, Dianna; Guerdjikova, Anna I; Keck, Paul E

2012-04-01

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

Determination of olanzapine and N-desmethyl-olanzapine in plasma using a reversed-phase HPLC coupled with coulochemical detection: correlation of olanzapine or N-desmethyl-olanzapine concentration with metabolic parameters.

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Mong-Liang Lu

Full Text Available Olanzapine (OLZ is one of the most prescribed atypical antipsychotic drugs but its use is associated with unfavorable metabolic abnormalities. N-desmethyl-olanzapine (DMO, one of the OLZ metabolites by CYP1A2, has been reported to have a normalizing action on metabolic abnormalities, but this remains unclear. Our aim was to explore the correlation between the concentrations of OLZ or DMO with various metabolic parameters in schizophrenic patients.The chromatographic analysis was carried out with a solvent delivery system coupled to a Coulochem III coulometric detector to determine OLZ and DMO simultaneously in OLZ-treated patients. The correlation between the concentration of OLZ or DMO and the metabolic parameters was analyzed by the Spearman rank order correlation method (r s.The established analytical method met proper standards for accuracy and reliability and the lower limitation of quantification for each injection of DMO or OLZ was 0.02 ng. The method was successfully used for the analysis of samples from nonsmoking patients (n = 48 treated with OLZ in the dosage range of 5-20 mg per day. There was no correlation between OLZ concentrations and tested metabolic parameters. DMO concentrations were negatively correlated with glucose (r s = -0.45 and DMO concentrations normalized by doses were also negatively correlated with insulin levels (r s = -0.39; however, there was a marginally positive correlation between DMO and homocysteine levels (r s = +0.38.The observed negative correlations between levels of DMO and glucose or insulin suggest a metabolic normalization role for DMO regardless of its positive correlation with a known cardiovascular risk factor, homocysteine. Additional studies of the mechanisms underlying DMO's metabolic effects are warranted.

An in vitro analysis of disintegration times of different formulations of olanzapine orodispersible tablet: a preliminary report.

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Hobbs, David; Karagianis, Jamie; Treuer, Tamas; Raskin, Joel

2013-12-01

Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab(®) was included as a non-olanzapine ODT comparator. Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vitro for formulation composition, manufacturing method, disintegration and dissolution characteristics, and formulation differences in comparison with freeze dried Zydis(®) ODT. Automated dissolution test equipment captured ODT dissolution rates by measuring real-time release of active ingredient. A high-speed video camera was used to capture tablet disintegration times in warm simulated saliva. The main outcome measure was the disintegration and dissolution characteristics of the ODT formulations. The ODT manufacturing method was associated with time to disintegrate; the fastest were freeze dried tablets, followed by soft compressed tablets and then hard/dense tablets. Olanzapine Zydis(®) was the only ODT that completely disintegrated in less than 4 s for all strengths (5, 10, 15, and 20 mg), followed by 5-mg Prolanz FAST(®) (12 s) and then risperidone ODT 4 mg (40 s). Reasons for slow dissolution of the olanzapine generics may include low product potency, excipient binding, excipient solubility, active ingredient particle size and incomplete disintegration. Differences in the formulation and manufacturing process of olanzapine ODTs appear to have a strong influence on the disintegration time of the active compound; differences that may potentially impact their use in clinical practice.

Olanzapine and haloperidol for the treatment of acute symptoms of mental disorders induced by amphetamine-type stimulants: A randomized controlled trial.

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Xue, Xiaobin; Song, Yun; Yu, Xiaojie; Fan, Qiang; Tang, Jiyou; Chen, Xu

2018-02-01

This study aimed to compare olanzapine and haloperidol efficacies in the treatment of acute psychiatric symptoms due to amphetamine-type stimulants (ATSs). The Zelen II design method was used; 124 patients with acute mental disorders due to amphetamine were randomly divided into olanzapine group (n = 63) and haloperidol group (n = 61). Then, a 4-week open-label medical therapy was performed. Clinical Global Impression Scale Item 2 was employed to evaluate the onset time; meanwhile, Brief Psychiatric Rating Scale (BPRS) was used at baseline and at posttreatment weeks 1, 2, and 4. Moreover, adverse reactions during the treatment were recorded. Onset time in the olanzapine group was significantly earlier than in the haloperidol group; BPRS scores in the olanzapine group were significantly lower than haloperidol group values at 1 and 2 weeks of treatment. The overall effective rates had no statistically significant difference. Short-term olanzapine and haloperidol treatments had equivalent efficacies in the treatment of acute symptoms of mental disorders due to ATSs; however, olanzapine administration resulted in relatively earlier disease onset, with less adverse reactions.

Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses

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Ciudad A

2013-11-01

Full Text Available Antonio Ciudad,1 Ernie Anand,2 Lovisa Berggren,3 Marta Casillas,4 Alexander Schacht,3 Elena Perrin5 1Department of Clinical Research and Development, Eli Lilly & Co, Madrid, Spain; 2Neuroscience Medical Affairs – EU, Lilly Research Centre, Windlesham, Surrey, UK; 3Global Statistical Sciences, Eli Lilly & Co, Bad Homburg, Germany; 4European Scientific Communications, Eli Lilly & Co, Madrid, Spain; 5Medical Department, Eli Lilly & Co, Suresnes, Paris, France Background: A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI from either oral olanzapine (OLZ or other antipsychotics (non-OLZ. Methods: Post hoc analyses were done based on two randomized studies (one short-term, one long-term conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8-week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. Results: These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ from the long-term study. Kaplan–Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209 or long-term study (P=0.448. Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198 or long-term (57.1% versus 47.8% respectively; P=0.238 studies. In the short-term study, no

Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism

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Stickelmeyer Mary

2010-06-01

Full Text Available Abstract Background Olanzapine long-acting injection (LAI is a salt-based depot antipsychotic combining olanzapine and pamoic acid. The slow intramuscular dissolution of this practically insoluble salt produces an extended release of olanzapine lasting up to 4 weeks. However, in a small number of injections ( Methods Healthcare providers involved in the PDSS cases were queried for clinical information around the events. Plasma samples from patients experiencing PDSS were collected when possible (12/30 cases and olanzapine concentrations compared with the known pharmacokinetic profile for olanzapine LAI. Product batches and used vials from the PDSS cases were evaluated for compliance with established manufacturing standards and/or possible user error. Because this depot formulation depends upon slow dissolution at the intramuscular injection site, in-vitro experiments were conducted to assess solubility of olanzapine pamoate in various media. Results Injection administrators reported no unusual occurrences during the injection. No anomalies were found with the product batches or the remaining suspension in the used vials. Olanzapine concentrations during PDSS events were higher than the expected 5-73 ng/mL range, with concentrations exceeding 100 ng/mL and in some cases reaching >600 ng/mL during the first hours after injection but then returning to the expected therapeutic range within 24 to 72 hours. Solubility and dissolution rate of olanzapine pamoate were also found to be substantially greater in plasma than in other media such as those approximating the environment in muscle tissue. Conclusions Manufacturing irregularities, improper drug reconstitution, and inappropriate dosing were ruled out as possible causes of PDSS. In-vitro solubility and in-vivo pharmacokinetic investigations suggest that PDSS is related to exposure of the injected product to a substantial volume of blood. This exposure is most likely the result of unintended partial

An efficacy analysis of olanzapine treatment data in schizophrenia patients with catatonic signs and symptoms.

Science.gov (United States)

Martényi, F; Metcalfe, S; Schausberger, B; Dossenbach, M R

2001-01-01

Thirty-five patients suffering from schizophrenia, as diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were preselected from 7 clinical trials according to a priori criteria of catatonic signs and symptoms based on 3 Positive and Negative Syndrome Scale (PANSS) items: scores for PANSS item 19 (mannerism and posturing) and either item 4 (excitement) or item 21 (motor retardation) had to exceed or equal 4 at baseline. This particular patient population represents a severely psychotic sample: mean +/- SD PANSS total scores at baseline were 129.26 +/- 19.76. After I week of olanzapine treatment, mean PANSS total score was decreased significantly (-13.14; p < .001), as was mean PANSS total score after 6 weeks of olanzapine treatment (-45.16; p < .001); additionally, the positive subscale, negative subscale, and mood scores improved significantly. A significant improvement in the catatonic signs and symptoms composite score was also observed at week 6 (-4.96; p < .001). The mean +/- SD daily dose of olanzapine was 18.00 +/- 2.89 mg after 6 weeks of treatment. The present data analysis suggests the efficacy of olanzapine in the treatment of severely ill schizophrenic patients with nonspecified catatonic signs and symptoms.

Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: A comparison of efficacy, safety, and side effects.

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Boettger, Soenke; Jenewein, Josef; Breitbart, William

2015-08-01

The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium. The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed. The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%). Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report

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Okazaki K

2017-11-01

Full Text Available Kosuke Okazaki, Kazuhiko Yamamuro, Toshifumi Kishimoto Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Japan Aims: Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases.Methods: We treated a case of olanzapine-induced weight gain in a 41-year-old man with schizophrenia by switching his medication from olanzapine to asenapine.Results: The weight gain improved after switching the medication, from 80.3 to 75.0 kg, a weight loss of 6.6%, and there was no significant worsening of psychological symptoms or other adverse effects.Conclusions: Asenapine might be effective for treating patients with schizophrenia who experience olanzapine-induced weight gain. Keywords: olanzapine, weight gain, schizophrenia, asenapine

Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

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Ann E Maloney

2010-11-01

Full Text Available Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS disorders and pediatric bipolar disorder (pedBP, are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine

Reboxetine Enhances the Olanzapine-Induced Antipsychotic-Like Effect, Cortical Dopamine Outflow and NMDA Receptor-Mediated Transmission

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Marcus, Monica M; Jardemark, Kent; Malmerfelt, Anna; Björkholm, Carl; Svensson, Torgny H

2010-01-01

Preclinical data have shown that addition of the selective norepinephrine transporter (NET) inhibitor reboxetine increases the antipsychotic-like effect of the D2/3 antagonist raclopride and, in parallel, enhances cortical dopamine output. Subsequent clinical results suggested that adding reboxetine to stable treatments with various antipsychotic drugs (APDs) may improve positive, negative and depressive symptoms in schizophrenia. In this study, we investigated in rats the effects of adding reboxetine to the second-generation APD olanzapine on: (i) antipsychotic efficacy, using the conditioned avoidance response (CAR) test, (ii) extrapyramidal side effect (EPS) liability, using a catalepsy test, (iii) dopamine efflux in the medial prefrontal cortex and the nucleus accumbens, using in vivo microdialysis in freely moving animals and (iv) cortical N-methyl--aspartate (NMDA) receptor-mediated transmission, using intracellular electrophysiological recording in vitro. Reboxetine (6 mg/kg) enhanced the suppression of CAR induced by a suboptimal dose (1.25 mg/kg), but not an optimal (2.5 mg/kg) dose of olanzapine without any concomitant catalepsy. Addition of reboxetine to the low dose of olanzapine also markedly increased cortical dopamine outflow and facilitated prefrontal NMDA receptor-mediated transmission. Our data suggest that adjunctive treatment with a NET inhibitor may enhance the therapeutic effect of low-dose olanzapine in schizophrenia without increasing EPS liability and add an antidepressant action, thus in principle allowing for a dose reduction of olanzapine with a concomitant reduction of dose-related side effects, such as EPS and weight gain. PMID:20463659

Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia.

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Blasi, Giuseppe; Popolizio, Teresa; Taurisano, Paolo; Caforio, Grazia; Romano, Raffaella; Di Giorgio, Annabella; Sambataro, Fabio; Rubino, Valeria; Latorre, Valeria; Lo Bianco, Luciana; Fazio, Leonardo; Nardini, Marcello; Weinberger, Daniel R; Bertolino, Alessandro

2009-07-15

Earlier imaging studies in schizophrenia have reported abnormal amygdala and prefrontal cortex activity during emotion processing. We investigated with functional magnetic resonance imaging (fMRI) during emotion processing changes in activity of the amygdala and of prefrontal cortex in patients with schizophrenia during 8 weeks of olanzapine treatment. Twelve previously drug-free/naive patients with schizophrenia were treated with olanzapine for 8 weeks and underwent two fMRI scans after 4 and 8 weeks of treatment during implicit and explicit emotional processing. Twelve healthy subjects were also scanned twice to control for potential repetition effects. Results showed a diagnosis by time interaction in left amygdala and a diagnosis by time by task interaction in right ventrolateral prefrontal cortex. In particular, activity in left amygdala was greater in patients than in controls at the first scan during both explicit and implicit processing, while it was lower in patients at the second relative to the first scan. Furthermore, during implicit processing, right ventrolateral prefrontal cortex activity was lower in patients than controls at the first scan, while it was greater in patients at the second relative to the first scan. These results suggest that longitudinal treatment with olanzapine may be associated with specific changes in activity of the amygdala and prefrontal cortex during emotional processing in schizophrenia.

Metabolic effects of Olanzapine versus Iloperidone: A 24 weeks ...

African Journals Online (AJOL)

Atypical antipsychotics have become the mainstay of therapy for psychosis. Though extrapyramidal side effects have been reduced with atypical antipsychotics, yet there are increased concerns over metabolic effects. The present study is aimed to comparatively evaluate the metabolic profile of olanzapine and iloperidone ...

Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis.

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Praharaj, Samir Kumar; Jana, Amlan Kusum; Goyal, Nishant; Sinha, Vinod Kumar

2011-03-01

Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n= 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P= 0.00002, I(2) = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m(-2) lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Intramuscular Olanzapine in the Management of Behavioral and Psychological Symptoms in Hospitalized Older Adults: A Retrospective Descriptive Study

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Silvia Duong

2015-01-01

Full Text Available Background. While behavioral and psychological symptoms are frequent in hospitalized older adults with dementia or delirium, data supporting the off-label use of intramuscular atypical antipsychotics remain scarce. We examined the use of short-acting intramuscular (IM olanzapine in hospitalized older adults to manage behavioral and psychological symptoms. Methods. A retrospective observational study of inpatients 65 years or older with at least one order for olanzapine IM during admission in urban Ontario Canada was conducted. Patient demographics, prescriptions for olanzapine IM, reason for administration, perceived effectiveness, adverse events, concurrently prescribed psychotropics, comorbidities, and patient discharge destination were recorded. Results. Among 82 patients aged 65–96 years (mean ± SD 79.3 ± 7.7 85 cases were identified. Cognitive impairment or dementia affected 63.5% and 50.6% had comorbidities. Olanzapine IM was ordered 102 times and 34 patients (41% received at least one dose. The intended efficacy was achieved in 79.4% of 78 cases of 124 doses given (62.9%. Fourteen (41% patients who received doses experienced adverse events, with sedation and hypotension being the most common. Conclusions. Olanzapine IM appears effective in hospitalized older adults but is associated with potential adverse events. Structured monitoring and documentation are needed to ensure safe use in this high-risk population.

Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy.

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Sato, Junya; Kashiwaba, Masahiro; Komatsu, Hideaki; Ishida, Kazushige; Nihei, Satoru; Kudo, Kenzo

2016-05-01

Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated. Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Drug–drug conditioning between citalopram and haloperidol or olanzapine in a conditioned avoidance response model: implications for polypharmacy in schizophrenia

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Sparkman, Nathan L.; Li, Ming

2016-01-01

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. Following acquisition of the avoidance response, rats were then randomly assigned to receive vehicle, citalopram (10.0 mg/kg, intraperitoneally), haloperidol (0.05 mg/kg, subcutaneously), olanzapine (1.0 mg/kg, subcutaneously), combined haloperidol with citalopram, or combined olanzapine with citalopram treatment for seven avoidance test sessions. In comparison with antipsychotic treatment alone, combined treatment with citalopram potentiated the antiavoidance effect of olanzapine or haloperidol (to a lesser extent) during the seven drug-test sessions. In addition, repeated pairing of citalopram with haloperidol or olanzapine caused citalopram to show a newly acquired avoidance-disruptive effect. This effect was context specific because citalopram paired with haloperidol or olanzapine outside the avoidance testing context (i.e. home cages) did not show such an effect. These findings indicate that concurrent antidepressant and antipsychotic treatments may engender a DDC process that follows the general Pavlovian associative conditioning principles. They also indicate that adjunctive citalopram treatment may enhance the antipsychotic efficacy of haloperidol and olanzapine in the

Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

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James A. Bourgeois

2014-01-01

Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

Comparison of olanzapine and risperidone in the EMBLEM Study: translation of randomized controlled trial findings into clinical practice.

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Novick, Diego; Reed, Catherine; Haro, Josep Maria; Gonzalez-Pinto, Ana; Perrin, Elena; Aguado, Jaume; Tohen, Mauricio

2010-09-01

Data from the EMBLEM Study, a 2-year, prospective, observational study of health outcomes associated with acute treatment of patients experiencing a manic/mixed episode of bipolar disorder, was used to compare the effectiveness of olanzapine monotherapy versus risperidone monotherapy, and to investigate whether the treatment effects were similar to those reported in a 3-week, randomized controlled trial assessing the same treatments. Symptom severity measures included the Young Mania Rating Scale (YMRS), the 5-item Hamilton Depression Rating Scale, and the Clinical Global Impression-Bipolar Disorder Scale. A total of 245 EMBLEM inpatients were analyzed with YMRS >or=20: olanzapine (n=209), risperidone (n=36). Both the treatment groups had similar improvements in YMRS from baseline to 6 weeks, but there was a significantly greater improvement in 5-item Hamilton Depression Rating Scale in the olanzapine group. There was a similar improvement in Clinical Global Impression-Bipolar Disorder Scale in both the groups and the occurrence of treatment-emergent adverse events and weight gain did not differ between the treatment groups. The EMBLEM results partly support those of the randomized controlled trial, which suggests olanzapine and risperidone have similar improvements in mania but that olanzapine monotherapy may be more effective than risperidone monotherapy in the treatment of depressive symptoms associated with mania. Limitations include differences in study design, patient population, and length of follow-up.

Intramuscular olanzapine versus intramuscular aripiprazole for the treatment of agitation in patients with schizophrenia: A pragmatic double-blind randomized trial.

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Kittipeerachon, Mantana; Chaichan, Warawat

2016-10-01

To evaluate and compare the effectiveness and adverse effects of intramuscular (IM) olanzapine and IM aripiprazole for the treatment of agitated patients with schizophrenia in clinical practice. A 24-hour randomized double-blind study carried out at a psychiatric hospital in Thailand enrolled adult patients (18-65years old) with schizophrenia experiencing agitation. Patients received one dose of IM olanzapine or IM aripiprazole followed by routine oral psychotropic medications. Efficacy was primarily measured using the Excited Component of the Positive and Negative Syndrome Scale (PANSS-EC). A total of 80 patients with a PANSS-EC score range of 22-35 entered the study, of whom 13% had a medical comorbidity and 40% a history of active substance abuse. The 40 patients receiving IM olanzapine showed greater improvement than the 40 patients receiving IM aripiprazole in PANSS-EC scores at 2h after the injection (p=0.002) but not at 24h. The two treatments were well tolerated. Patients receiving IM olanzapine experienced greater somnolence than those receiving IM aripiprazole. There were no clinically relevant changes in vital signs in either group. The results indicate that IM olanzapine and aripiprazole are similarly effective and well tolerated in the real-world treatment of agitation associated with schizophrenia over the first 24h. However, in the early hours, IM olanzapine may produce more sedation and reductions in agitation. Copyright © 2016 Elsevier B.V. All rights reserved.

Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific Alterations of NMDA Receptor Subunits

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Liu, Xiao; Li, Jitao; Guo, Chunmei; Wang, Hongli; Sun, Yaxin; Wang, Han; Su, Yun-Ai; Li, Keqing; Si, Tianmei

2018-01-01

Cognitive dysfunction constitutes an essential component in schizophrenia for its early presence in the pathophysiology of the disease and close relatedness to life quality of patients. To develop effective treatment of cognitive deficits, it is important to understand their neurobiological causes and to identify potential therapeutic targets. In this study, adopting repeated MK-801 treatment as an animal model of schizophrenia, we investigated whether antipsychotic drugs, olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how the reversal processes recruited proteins involved in glutamate neurotransmission in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose chronic MK-801 treatment impaired object-in-context recognition memory and reversal learning in the Morris water maze, leaving reference memory relatively unaffected, and that these cognitive deficits can be partially reversed by olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801 treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA) receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK-801-induced cognitive deficits may be associated with region-specific changes in NMDA receptor subunits and the reversal of specific NMDA receptor subunits may underlie the cognition-enhancing effects of olanzapine. PMID:29375333

Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties

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Zhao J

2014-02-01

Full Text Available Jingping Zhao,1 Jianjun Ou,1 Haibo Xue,2 Li Liu,2 William Montgomery,3 Tamas Treuer4 1Mental Health Institute of The Second Xiangya Hospital, Hunan Province Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Lilly Suzhou Pharmaceutical Co, Ltd, Jiangsu, People's Republic of China; 3Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 4Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary Abstract: The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People's Republic of China, Hong Kong, and Taiwan and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. Keywords: orally disintegrating, olanzapine, Chinese, schizophrenia, patients

Olanzapine-induced weight gain: lessons learned from developing rat models

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van der Zwaal, E.M.

2011-01-01

Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying

Natural oils as skin permeation enhancers for transdermal delivery of olanzapine: in vitro and in vivo evaluation.

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Aggarwal, Geeta; Dhawan, Sanju; HariKumar, S L

2012-03-01

The feasibility of development of transdermal delivery system of olanzapine utilizing natural oils as permeation enhancers was investigated. Penetration enhancing potential of corn (maize) oil, groundnut oil and jojoba oil on in vitro permeation of olanzapine across rat skin was studied. The magnitude of flux enhancement factor with corn oil, groundnut oil and jojoba oil was 7.06, 5.31 and 1.9 respectively at 5mg/ml concentration in solvent system. On the basis of in vitro permeation studies, eudragit based matrix type transdermal patches of olanzapine were fabricated using optimized concentrations of natural oils as permeation enhancers. All transdermal patches were found to be uniform with respect to physical characteristics. The interaction studies carried out by comparing the results of ultraviolet, HPLC and FTIR analyses for the pure drug, polymers and mixture of drug and polymers indicated no chemical interaction between the drug and excipients. Corn oil containing unsaturated fatty acids was found to be promising natural permeation enhancer for transdermal delivery of olanzapine with greatest cumulative amount of drug permeated (1010.68 μg/cm²/h) up to 24 h and caused no skin irritation. The fabricated transdermal patches were found to be stable. The pharmacokinetic characteristics of the final optimized matrix patch (T2) were determined after transdermal application to rabbits. The calculated relative bioavailability of TDDS was 113.6 % as compared to oral administration of olanzapine. The therapeutic effectiveness of optimized transdermal system was confirmed by tranquillizing activity in rotarod and grip mice model.

Matrix-assisted laser-desorption/ionization mass spectrometric imaging of olanzapine in a single hair using esculetin as a matrix.

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Wang, Hang; Wang, Ying; Wang, Ge; Hong, Lizhi

2017-07-15

Matrix-assisted laser desorption/ionization-mass spectrometric imaging (MALDI-MSI) for the analysis of intact hair is a powerful tool for monitoring changes in drug consumption. The embedding of a low drug concentration in the hydrophobic hair matrix makes it difficult to extract and detect, and requires an improved method to increase detection sensitivity. In this study, an MSI method using MALDI-Fourier transform ion cyclotron resonance was developed for direct identification and imaging of olanzapine in hair samples using the positive ion mode. Following decontamination, scalp hair samples from an olanzapine user were scraped from the proximal to the distal end three times, and 5mm hair sections were fixed onto an Indium-Tin-Oxide (ITO)-coated microscopic glass slide. Esculetin (6,7-dihydroxy-2H-chromen-2-one) was used as a new hydrophobic matrix to increase the affinity, extraction and ionization efficiency of olanzapine in the hair samples. The spatial distribution of olanzapine was observed using five single hairs from the same drug user. This matrix improves the affinity of olanzapine in hair for molecular imaging with mass spectrometry. This method may provide a detection power for olanzapine to the nanogram level per 5mm hair. Time course changes in the MSI results were also compared with quantitative HPLC-MS/MS for each 5mm segment of single hair shafts selected from the MALDI target. MALDI imaging intensities in single hairs showed good semi-quantitative correlation with the results from conventional HPLC-MS/MS. MALDI-MSI is suitable for monitoring drug intake with a high time resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

How can lipid nanocarriers improve transdermal delivery of olanzapine?

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Iqbal, Nimra; Vitorino, Carla; Taylor, Kevin M G

2017-06-01

The development of a transdermal nanocarrier drug delivery system with potential for the treatment of psychiatric disorders, such as schizophrenia and bipolar disorder, is described. Lipid nanocarriers (LN), encompassing various solid:liquid lipid compositions were formulated and assessed as potential nanosystems for transdermal delivery of olanzapine. A previously optimized method of hot high pressure homogenization (HPH) was adopted for the production of the LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Precirol  ® was selected as the solid lipid for progression of studies. SLN exhibited the best performance for transdermal delivery of olanzapine, based on in vitro release and permeation studies, coupled with results from physicochemical characterization of several solid:liquid lipid formulations. Stability tests, performed to give an indication of long-term storage behavior of the formulations, were in good agreement with previous studies for the best choice of solid:liquid lipid ratio. Overall, these findings highlight the SLN-based formulation as promising for the further inclusion in and production of transdermal patches, representing an innovative therapeutic approach.

Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

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Ye W

2012-01-01

Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

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Zhang, Chen; Li, Ming

2011-01-01

Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

Olanzapine-induced neuroleptic malignant syndrome in a patient with bipolar affective disorder: Does quetiapine holds the solution?

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Praveen Tripathi

2013-01-01

Full Text Available Neuroleptic Malignant Syndrome (NMS is a rare, severe and life threatening condition induced by antipsychotic medications. It is commonly encountered with the use of first generation antipsychotics, however cases of NMS have been reported with the use of second generation antipsychotics like Olanzapine, Risperidone, Paliperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine and Clozapine, though the incidence of such reports is rare. Due to decreased use of first generation antipsychotics, NMS is reported less frequently now a days. In this case report- we highlight the management issues of a patient suffering from bipolar affective disorder, who had developed NMS following intramuscular injection of haloperidol, which was withdrawn and olanzapine was given later on. The patient had again developed NMS with olanzapine. Finally the patient was managed with modified electroconvulsive therapy and discharged on Lithium carbonate and Quetiapine.

Olanzapine-Induced Diabetic Ketoacidosis and Neuroleptic Malignant Syndrome with Rhabdomyolysis: A Case Report

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Young Kyoung Sa

2013-03-01

Full Text Available Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS. However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA. In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

Population pharmacokinetics analysis of olanzapine for Chinese psychotic patients based on clinical therapeutic drug monitoring data with assistance of meta-analysis.

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Yin, Anyue; Shang, Dewei; Wen, Yuguan; Li, Liang; Zhou, Tianyan; Lu, Wei

2016-08-01

The aim of this study was to build an eligible population pharmacokinetic (PK) model for olanzapine in Chinese psychotic patients based on therapeutic drug monitoring (TDM) data, with assistance of meta-analysis, to facilitate individualized therapy. Population PK analysis for olanzapine was performed using NONMEM software (version 7.3.0). TDM data were collected from Guangzhou Brain Hospital (China). Because of the limitations of TDM data, model-based meta-analysis was performed to construct a structural model to assist the modeling of TDM data as prior estimates. After analyzing related covariates, a simulation was performed to predict concentrations for different types of patients under common dose regimens. A two-compartment model with first-order absorption and elimination was developed for olanzapine oral tablets, based on 23 articles with 390 data points. The model was then applied to the TDM data. Gender and smoking habits were found to be significant covariates that influence the clearance of olanzapine. To achieve a blood concentration of 20 ng/mL (the lower boundary of the recommended therapeutic range), simulation results indicated that the dose regimen of olanzapine should be 5 mg BID (twice a day), ≥ 5 mg QD (every day) plus 10 mg QN (every night), or >10 mg BID for female nonsmokers, male nonsmokers and male smokers, respectively. The population PK model, built using meta-analysis, could facilitate the modeling of TDM data collected from Chinese psychotic patients. The factors that significantly influence olanzapine disposition were determined and the final model could be used for individualized treatment.

Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

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Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

2011-05-01

Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study

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Novick, D; Gonzalez-Pinto, A; Haro, J M

2009-01-01

OBJECTIVES: The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments. METHODS: EMBLEM (European Mania in Bipolar Evaluation......: The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy seems to be more effective than valproate monotherapy in the treatment of acute mania....

The metabolic effects of olanzapine and topiramate in rats and humans

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Evers, S.S.; van Dijk, G.; van Vliet, A.; Scheurink, A.J.W.

In humans the anti-psychotic Olanzapine (OLZ) has negative side effects on metabolism: it causes weight gain and increases the risk of developing type 2 Diabetes. The anti-convulsant Topiramate (TPM) has the opposite effects: it reduces body weight and improves insulin sensitivity. Because of this,

Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis.

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Zipursky, Robert B; Christensen, Bruce K; Daskalakis, Zafiris; Epstein, Irvin; Roy, Paul; Furimsky, Ivana; Sanger, Todd; Kapur, Shitij

2005-07-01

Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy. Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment. At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6). These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.

A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.

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Kotler, Moshe; Dilbaz, Nesrin; Rosa, Fernanda; Paterakis, Periklis; Milanova, Vihra; Smulevich, Anatoly B; Lahaye, Marjolein; Schreiner, Andreas

2016-01-01

The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients. Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.

Effectiveness of olanzapine monotherapy and olanzapine combination treatment in the long term following acute mania--results of a two year observational study in bipolar disorder (EMBLEM).

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Gonzalez-Pinto, Ana; Vieta, Eduard; Reed, Catherine; Novick, Diego; Barraco, Alessandra; Aguado, Jaume; Haro, Josep Maria

2011-06-01

This study compared the 2-year outcomes of patients with a manic/mixed episode of bipolar disorder taking olanzapine monotherapy or olanzapine in combination with other agents. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of clinical and functional outcomes of bipolar patients with an index manic/mixed episode. The study consisted of two phases: acute (12 weeks) and maintenance (follow-up over 2 years). The longitudinal outcome measure was the Clinical Global Impression-Bipolar Disorder scale. Cox regression models compared outcomes of both therapy groups using intention-to-treat and switching medication analysis. Treatment-emergent adverse events were also assessed. 1076 patients were included in this analysis. 29% took olanzapine as monotherapy (n = 313) and 71% as combination (n = 763) at 12-weeks post-baseline (end of study acute phase). After adjusting for patient characteristics using switching medication analysis, only relapse rates differed (p = 0.01) in favour of monotherapy-treated patients. There was no significant difference in rates of improvement, remission, and recovery. Patients treated with combination therapy reported more tremor (OR 2.37, 95%CI 1.44-3.89) and polyuria (OR 3.08, 95%CI 1.45-6.54) treatment-emergent events than monotherapy, although weight change was greater in the monotherapy group. Unknown confounding and potential selection bias may differentially impact treatment outcomes. EMBLEM patients benefitted from the selected therapy to a similar extent. Differences in patient characteristics between those prescribed monotherapy and combination therapy appear to be clinically relevant in the treatment decision. Physicians must balance the benefits and risks when determining appropriate treatment for individual patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Predictors of continuation with olanzapine during the 1-year naturalistic treatment of patients with schizophrenia in Japan

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Ye W

2011-12-01

Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Yuka Tanji3, Jennifer A Flynn3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People’s Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan KK, Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Treatment continuation is considered an important measure of antipsychotic effectiveness in schizophrenia, reflecting the medication’s efficacy, safety, and tolerability from both patients’ and clinicians’ perspectives. This study identified characteristics of patients with schizophrenia who continue olanzapine therapy for a 1-year period in Japan.Methods: In a large (N = 1850, prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Baseline characteristics were compared using t-tests and chi-square tests. Stepwise logistic regression was used to identify independent baseline predictors of treatment continuation.Results: Most patients (68.2% continued with olanzapine therapy for the full 1-year study period, with an average duration of 265.5 ± 119.4 days. At baseline, patients who continued were significantly more likely to be male, older, and inpatients; have longer illness duration, higher negative and cognitive symptoms, better health-related quality of life, and prior anticholinergic use. Continuers were significantly less likely to engage in social activities, live independently, work for pay, or have prior antidepressant use. Continuers showed significantly greater early (3-month improvement in global symptom severity. Logistic regression found that continuation was significantly predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.Conclusions: In this large naturalistic study in Japan, most patients with schizophrenia stayed on olanzapine therapy for

The use of olanzapine in Huntington disease accompanied by psychotic symptoms

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Cafer Alhan

2014-06-01

Full Text Available Huntington's disease is an autosomal dominant neurodegenerative disease. The disease begins between the ages of 30-50, including motor symptoms, psychiatric symptoms and is characterized by progressive dementia. Common psychiatric disorders of Huntington’s disease include mood and anxiety disorders, behavior and personality changes. Psychosis is relatively rare. Here, a patient is present, who has Huntington’s disease, which is associated with psychotic symptoms. 61-year-old male patient who were followed for Huntington disease for 25 years was admitted for complaints of thinking of poisoning and refuse to eat something. Patient was started on olanzapine at dose of 5 mg/day. In follow up psychotic symptoms disappeared. Emerging psychotic symptoms in Huntington disease is created a need for antipsychotic treatment. Atypical antipsychotic agents should be preferred in the treatment and as in the case olanzapine may be used as a treatment option should be kept in mind to control both involuntary movements and psychotic symptoms in Huntington's disease with psychotic features. J Clin Exp Invest 2014; 5 (2: 326-328

A patient treated with olanzapine developing diabetes de novo : proposal for hyperglycaemia screening

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Duiverman, M. L.; Cohen, D.; van Oven, W.; Nieboer, P.

2007-01-01

We report a patient with schizophrenia who developed diabetes mellitus during treatment with olanzapine. The case confirms the pattern of atypical antipsychotic-related diabetic emergencies: rapid onset in relatively young patients, often with severe glucose derangements and serious complications.

Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1

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Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila

2015-01-01

have previously found that the atypical antipsychotics clozapine and olanzapine inhibited G protein activation and, surprisingly, induced both internalization and lysosomal degradation of 5-HT7 receptors. Here, we aimed to determine the mechanism of clozapine- and olanzapine-mediated degradation of 5......-HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine...... of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1....

Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

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Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

2013-03-01

This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

Comparison of the effect of Olanzapine and Sertraline on patients suffering from personality disorder, receiving methadone maintenance therapy

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mozhgan Jariani

2009-03-01

Full Text Available Background: Borderline Personality disorder is a disabling disease affecting 2% of general population. Various drugs have been suggested for treatment of borderline Personality disorder. If a drug could alleviate a wide range of symptoms, it would be more suitable. In these disorders drug addiction is very common. This fact makes the symptoms complicated and the treatment more difficult. This study is designed to evaluate the effect of Olanzapine and Sertraline in patients suffering from personality disorders who are on methadone maintenance therapy. Materials and Methods: This clinical trial study was carried out on 120 male and female cases chosen for methadone maintenance therapy through interview by a psychiatrist based on DSM-IV-TR diagnostic criteria for BPD. Afterwards they were randomly divided into two groups. These groups separately received Olanzapine (5-10 mg daily and Sertraline (50-100 mg daily therapy. The SCL-90 questionnaire was filled out by the participants before treatment and at the 4th, 8th and 12th weeks of the treatment. Results: According to this clinical trial, Olanzapine and Sertraline were effective in ameliorating symptoms of depression, anxiety and aggression, reducing sensitivity in interpersonal relationship and alleviating obsessive symptoms, pessimistic behaviors and somatization disorders in patients with personality disorders on methadone maintenance therapy. Conclusion: As results of this study stated that Olanzapine and Sertraline are definitely effective in alleviating symptoms of patients with personality disorder, prescribing theses drugs are highly recommended for these patients. .

Evaluation of striatal dopamine transporter density using ({sup 123}I)-{beta}-CIT SPECT in schizophrenic patients treated with olanzapine: pilot study

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Kim, Chul Eung; Moon, Hey Won; Choe, Won Sick; Kim, Chang Ho; Chi, Dae Yoon [Inha Univ., Incheon (Korea, Republic of)

2002-08-01

This pilot study was performed to understand the pharmacological effect of olanzapine, an atypical antipsychotic agent, on dopamine transporter in schizophrenic patients. Six patients (3 male, 3 female) with schizophrenia, who had not taken any psychotropic drugs for at least four weeks, were studied. Nuclear imaging using ({sup 123}I)-{beta}-CIT SPECT was obtained before and after 4-week treatment with olanzapine. Analysis of ROI on the striatum, caudate nucleus, and putamen was performed. Post-treatment uptake was significantly increased in all the ROIs compared with pre-treatment uptake. This preliminary study with the small number of schizophrenic patients suggested an increase in uptake of dopamine transporter in the striatum, caudate nucleus, and putamen after 4-week treatment with olanzapine, which warrants a large-scaled controlled study to confirm the current findings.

A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

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Vance L Albaugh

Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical antipsychotics.ClinicalTrials.gov NCT00741026.

Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

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Ball, M Patricia; Warren, Kimberly R; Feldman, Stephanie; McMahon, Robert P; Kelly, Deanna L; Buchanan, Robert W

2011-04-01

In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

A Case Report of Mania and Psychosis Five Months after Traumatic Brain Injury Successfully Treated Using Olanzapine

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Giordano F. Cittolin-Santos

2017-01-01

Full Text Available Background. There are few published pharmacologic trials for the treatment of acute mania following traumatic brain injury (TBI. To our knowledge, we present the first case report of an individual being treated and stabilized with olanzapine monotherapy for this condition. Case Presentation. We describe the case of a 53-year-old African American male admitted to an inpatient psychiatric hospital with one month of behavioral changes including irritability, decreased need for sleep, hyperverbal speech, hypergraphia, and paranoia five months after TBI. Using Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5 criteria, he was diagnosed with bipolar disorder due to traumatic brain injury, with manic features. He was serially evaluated with clinical rating scales to measure symptom severity. The Young Mania Rating Scale (YMRS score upon admission was 31, and the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS score was initially 9. After eight days of milieu treatment and gradual titration of olanzapine to 15 mg nightly, his symptoms completely abated, with YMRS and CRDPSS scores at zero on the day of discharge. Conclusion. Olanzapine was effective and well tolerated for the treatment of mania following TBI.

Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: An open-label, randomized controlled trial.

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Huang, Charles Lung-Cheng; Hwang, Tzung-Jeng; Chen, Yi-Hsing; Huang, Guan-Hua; Hsieh, Ming H; Chen, Hsiu-Hsi; Hwu, Hai-Gwo

2015-05-01

To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p haloperidol + lorazepam: -9.9, p Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277). Copyright © 2015. Published by Elsevier B.V.

Postinjection delirium/sedation syndrome in patients with schizophrenia receiving olanzapine long-acting injection: results from a large observational study.

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Meyers, Kristin J; Upadhyaya, Himanshu P; Landry, John L; Chhabra-Khanna, Rashna; Falk, Deborah M; Seetharama Rao, Balasubramanya; Jones, Meghan E

2017-07-01

Postinjection delirium/sedation syndrome (PDSS) has been reported uncommonly during treatment with olanzapine long-acting injection (LAI), a sustained-release formulation of olanzapine. The primary aim of the study was to estimate the incidence per injection and per patient of PDSS events in adult patients with schizophrenia who were receiving olanzapine LAI in real-world clinical practice. Secondary aims were to further characterise the clinical presentation of PDSS events, to identify potential risk factors associated with PDSS events and to characterise hospitalisations at baseline and post-baseline. A prospective observational study of adult patients with schizophrenia receiving olanzapine LAI from 24 countries. Data were collected on patient characteristics, olanzapine LAI treatment and any adverse events (AEs). All AEs were reviewed and adjudicated for PDSS using predetermined criteria. There were 46 confirmed PDSS events (0.044% of the 103 505 injections) in 45 patients (1.17% of the 3858 patients). Based on 45 confirmed events with time-to-onset information, 91.1% ( n =41) occurred within 1 h of injection. Time-to-recovery from the event was within 72 h for 95.6% of patients (range 6 h to 11 days). Risk factors for PDSS (per-injection) included high dose (odds ratio (OR) high/low =3.95; P =0.006) and male gender (OR female/male =0.42; P =0.017). Results of this study confirm previously reported PDSS rates, time to onset and recovery, and the severity of PDSS events, and suggest that higher doses and male gender are potential risk factors associated with PDSS. All authors are full-time employees and hold stock/stock options in Eli Lilly, which funded this study. This post-authorisation safety study (PASS) was proposed by Eli Lilly when submitting the original marketing authorisation application for olanzapine LAI in 2007. The protocol and final study report for this European Union regulatory commitment are publicly accessible via the European Network of

Effect of olanzapine combined with modified electroconvulsive therapy on cytokines, sTNFRs and neural electrophysiological characteristics in patients with schizophrenia

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Wei Cheng

2016-12-01

Full Text Available Objective: To analyze the effect of olanzapine combined with modified electroconvulsive therapy on cytokines, sTNFRs and neural electrophysiological characteristics in patients with schizophrenia. Methods: Patients with schizophrenia treated in our hospital between March 2013 and March 2016 were selected and randomly divided into two groups, the observation group received olanzapine combined with modified electroconvulsive therapy, and the control group received olanzapine therapy. After 6 weeks of treatment, serum levels of soluble tumor necrosis factor receptor (sTNFR, acute phase reaction proteins and brain function indexes as well as the neural electrophysiological characteristics were compared between the two groups. Results: After 6 weeks of treatment, serum sTNFRs, CRP, CER and AAG content of observation group were lower than those of control group while TRF content was higher than that of control group; serum brain function indexes NGF and BDNF content were higher than those of control group while GFAP, S100B, NSE and Hcy content were lower than those of control group; nerve electrophysiology indexes P300, LPP and ERN amplitude were higher than those of control group while LPP amplitude was lower than that of control group. Conclusions: Olanzapine combined with modified electroconvulsive therapy can optimize the condition of schizophrenia, reduce the abnormal degree of nerve electrophysiology and help to improve treatment outcome.

Sammenligning af sertindols og olanzapins effekt på kognition

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Nielsen, René Ernst

Der er gennem de senere år kommet tiltagende fokus, både nationalt og internationalt, på de kognitive deficits der ses hos patienter med skizofreni. Det er kendt at den farmakologiske behandling har indflydelse på kognition funktion, men det er endnu ikke fyldestgørende klarlagt hvorledes de enke...... enkelte atypiske antipsykotika påvirker kognitiv funktion. Der vil blive beskrevet studiedesign for SEROLA studiet, som sammenligner sertindol og olanzapin med kognition, målt med CANTAB, som primært outcome....

Association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use

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Ikram, H.; Ahmed, T.M.; Hayat, A.; Ullah, Q.I.; Nawaz, A.

2017-01-01

Objective: To determine the association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use. Study Design: Case control study. Place and Duration of Study: Chemical pathology department Army Medical College Rawalpindi, from Nov 2014 to Oct 2015. Material and Methods: The study was carried out on 240 subjects, 120 cases and 120 controls. For the purpose of the study cases were divided into four groups A, B, C and D according to the duration of drug use. Group A patients included those who the last the drug olanzapine for the last three months. Group B patients included those who were using the drug olanzapine for the last six months. Group C and D included those who were using the drug for last 1 year and more than one year (2-5 years) respectively. By employing non probability convenience sampling technique the data was collected from patients having the diagnosis of psychosis as per DSM IV modified criteria through a proforma and fasting blood samples were drawn. These samples were tested for fasting serum lipid profile and fasting plasma glucose. The data obtained were analyzed using SPSS version 21. For quantitative data Mean and SD were calculated. For qualitative data frequency and percentages were calculated. Qualitative data was compared using chi square test whereas quantitative data was compared using independent sample t-test. Results: There was statistically no significant difference in fasting plasma glucose between group A and B and their controls whereas in group C and D these levels were significantly high as compared to controls. Triglyceride levels were significantly higher and HDL cholesterol levels were significantly lower in all four groups as compared to controls. Comparison of qualitative data which included waist circumference and blood pressure showed statistically no significant rise for group A whereas waist circumference showed insignificant rise and blood pressure showed statistically

Delirium with anticholinergic symptoms after a combination of paliperidone and olanzapine pamoate in a patient known to smoke cannabis: an unfortunate coincidence.

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Kokalj, Anja; Rijavec, Nikolina; Tavčar, Rok

2016-06-22

We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone. 2016 BMJ Publishing Group Ltd.

Severe ischemic colitis following olanzapine use: a Case Report

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Samuel Raimundo Fernandes

Full Text Available Ischemic colitis is the most common subtype of intestinal ischemia usually resulting from vasospasm, vessel occlusion or mesenteric hypoperfusion. Neuroleptics have seldom been linked to ischemic colitis by blocking peripheral anticholinergic and antiserotonergic receptors inducing severe gastrointestinal paresis. We report a young patient with severe ischemic colitis requiring surgery due to necrosis of the bowel. After exclusion of other potential causes, olanzapine was admitted as the cause of ischemia. Clinicians should be aware of how to recognize and treat the potentially life-threatening effects of neuroleptics.

A Study to Assess the Therapeutic Effect of Enalapril on Olanzapine Induced Metabolic Syndrome in Wistar Rats.

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Arivazhahan, Avinash; Bairy, Laxminarayana Kurady; Nayak, Veena; Kunder, Sushil Kiran

2017-02-01

Metabolic Syndrome (MS) is a complex of risk factors for the development of cardiovascular complications and Type 2 Diabetes Mellitus (DM). Pharmacological management of the condition is complex, as multiple drug groups have to be used, as the syndrome itself is multi faceted. Angiotensin Converting Enzyme Inhibitors (ACEIs) are chiefly used to manage the hypertensive component of the syndrome. However, recent studies have shown that these drugs may have a role in the non hypertensive aspects of the syndrome as well. To evaluate the therapeutic effect of enalapril on total body weight, random blood glucose and serum lipid profile in a rodent model of olanzapine induced MS. Three different dosages (1 mg/kg/day, 10 mg/kg/day and 20 mg/kg/day) of oral enalapril were administered (for three weeks) in albino wistar rats, which received prior intra peritoneal olanzapine (for three weeks), and compared against control (normal saline) and standard (olanzapine only and enalapril only) groups. Parameters like total body weight, random blood glucose and serum lipid profile were measured at baseline, at three weeks and at six weeks. Enalapril at 20 mg/kg/day was found to be effective in reversing the weight gain, hyperglycaemia and hypercholesterolaemia, without any changes in triglycerides, High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 10 mg/kg/day of enalapril prevented any further rise in body weight, blood glucose, total cholesterol and serum triglycerides, after olanzapine was stopped. 1 mg/kg/day of enalapril was ineffective. High dose of enalapril may be considered as a component of therapeutic regimens to combat weight gain, hyperglycaemia and dyslipidaemia seen in MS, in addition to its antihypertensive utility. Further rodent and clinical studies may be required to ascertain the same.

Safety and effectiveness of rapid-acting intramuscular olanzapine for agitation associated with schizophrenia – Japan postmarketing surveillance study

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Katagiri H

2018-01-01

Full Text Available Hideaki Katagiri,1 Masanori Taketsuna,2 Shinpei Kondo,3 Kenta Kajimoto,4 Etsuko Aoi,5 Yuka Tanji1 1Bio Medicine, 2Statistical Sciences, 3Post Marketing Study Management, 4Scientific Communications, Medicines Development Unit Japan, 5Global Patient Safety Japan, Quality and Patient Safety, Eli Lilly Japan K.K., Kobe, Japan Objective: The objective of this study was to evaluate the safety and effectiveness of rapid-acting intramuscular (IM olanzapine in the treatment of acute agitation associated with schizophrenia in real-world clinical settings in Japan.Methods: In this multicenter, postmarketing surveillance (PMS study, patients with acute agitation associated with schizophrenia were treated with IM olanzapine daily in a daily clinical setting. The observational period ranged from 1 to 7 days, including the day of initial administration. Safety was assessed by reporting treatment-emergent adverse events (TEAEs and adverse drug reactions (ADRs. The Positive and Negative Syndrome Scale – Excited Component (PANSS-EC score was used to evaluate effectiveness at baseline and at 2 hours (after each administration, 2 days, and 3 days (end of the observational period from the last administration of the IM olanzapine injection.Results: The safety analysis set included 999 patients, and the initial dose of 10 mg was administered to 955 patients. TEAEs were reported in 28 patients (36 events, the most common of which were dyslalia (5 patients, akathisia and somno­lence (4 patients each, hepatic function abnormal (3 patients, and constipation and dehydration (2 patients each. One serious adverse event of akathisia occurred during the observation period. The PANSS-EC score (mean ± standard deviation was 23.3±6.4 (n=625 at baseline, 16.9±7.0 (n=522 at 2 hours after initial injection, and 14.9±6.5 (n=650 at the last observation carried forward.Conclusion: The results of this Japanese PMS study demonstrated that IM olanzapine is safe and has a

Treatment with olanzapine is associated with modulation of the default mode network in patients with Schizophrenia.

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Sambataro, Fabio; Blasi, Giuseppe; Fazio, Leonardo; Caforio, Grazia; Taurisano, Paolo; Romano, Raffaella; Di Giorgio, Annabella; Gelao, Barbara; Lo Bianco, Luciana; Papazacharias, Apostolos; Popolizio, Teresa; Nardini, Marcello; Bertolino, Alessandro

2010-03-01

Earlier studies have shown widespread alterations of functional connectivity of various brain networks in schizophrenia, including the default mode network (DMN). The DMN has also an important role in the performance of cognitive tasks. Furthermore, treatment with second-generation antipsychotic drugs may ameliorate to some degree working memory (WM) deficits and related brain activity. The aim of this study was to evaluate the effects of treatment with olanzapine monotherapy on functional connectivity among brain regions of the DMN during WM. Seventeen patients underwent an 8-week prospective study and completed two functional magnetic resonance imaging (fMRI) scans at 4 and 8 weeks of treatment during the performance of the N-back WM task. To control for potential repetition effects, 19 healthy controls also underwent two fMRI scans at a similar time interval. We used spatial group-independent component analysis (ICA) to analyze fMRI data. Relative to controls, patients with schizophrenia had reduced connectivity strength within the DMN in posterior cingulate, whereas it was greater in precuneus and inferior parietal lobule. Treatment with olanzapine was associated with increases in DMN connectivity with ventromedial prefrontal cortex, but not in posterior regions of DMN. These results suggest that treatment with olanzapine is associated with the modulation of DMN connectivity in schizophrenia. In addition, our findings suggest critical functional differences in the regions of DMN.

Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

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Song, Jae Chun; Seo, Mi Kyoung; Park, Sung Woo; Lee, Jung Goo; Kim, Young Hoon

2016-01-01

Objective We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice. Methods MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus. Results MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p801 in mice via the stimulating effects of neurogenesis. PMID:27489382

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol : Results of the EIRE Study.

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Bobes, Julio; Rejas, J; Garcia-Garcia, M; Rico-Villademoros, F; García-Portilla, M P; Madrigal, M; Hernández, G

2002-09-01

The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia - Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions. Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser - Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ 2 ) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used. 636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ 2 : p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ 2 : p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ 2 : p < 0.05). Olanzapine, quetiapine

Evaluation of the efficacy and safety of olanzapine as an adjunctive treatment for anorexia nervosa in adolescent females: a randomized, double-blind, placebo-controlled trial

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Moher David

2008-01-01

Full Text Available Abstract Background Anorexia Nervosa (AN is a serious, debilitating condition that causes significant physical, emotional, and functional impairment. The condition is characterized by destructive weight loss behaviours and a refusal to maintain body weight at or above a minimally normal weight for age and height. AN often develops in adolescence and is a predominantly female disorder. Treatment for AN typically involves medical, nutritional and psychological interventions. Pharmacotherapy is also often used; however, the literature on the effectiveness of these drugs in a pediatric population is very limited. Olanzapine, which is an 'atypical' antipsychotic, is becoming more widespread in the treatment of AN. Olanzapine is hypothesized to facilitate weight gain, while decreasing levels of agitation and decreasing resistance to treatment in young women with AN. This randomized, double-blind placebo-controlled trial seeks to examine the effectiveness and safety of olanzapine in female youth with AN. Methods/Design Adolescent females between the ages of 12 and 17 diagnosed with AN (either restricting or binge/purge type or Eating Disorder Not Otherwise Specified with a Body Mass Index of less than or equal to 17.5, will be offered inclusion in the study. Patients will be randomly assigned to receive either olanzapine or placebo. Patients assigned to receive olanzapine will start at a low dose of 1.25 mg/day for three days, followed by 2.5 mg/day for four days, 5 mg/day for one week, then 7.5 mg/day (the target dose chosen for 10 weeks. After 10 weeks at 7.5 mg the medication will be tapered and discontinued over a period of two weeks. The effectiveness of olanzapine versus placebo will be determined by investigating the change from baseline on measures of eating attitudes and behaviors, depression and anxiety, and change in Body Mass Index at week 12, and after a follow-up period at week 40. It is anticipated that 67 participants will be recruited

Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

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Løberg Else-Marie

2011-08-01

Full Text Available Abstract Background Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs. The Bergen Psychosis Project (BPP is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis. Methods Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale - Depression factor (PANSS-D and the Calgary Depression Scale for Schizophrenia (CDSS. Results A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p Conclusions There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis. Trial Registration ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529

Orally disintegrating and oral standard olanzapine tablets similarly elevate the homeostasis model assessment of insulin resistance index and plasma triglyceride levels in 12 healthy men: a randomized crossover study.

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Vidarsdottir, Solrun; Vlug, Pauline; Roelfsema, Ferdinand; Frölich, Marijke; Pijl, Hanno

2010-09-01

Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637. © Copyright

Treatment-completion rates with olanzapine long-acting injection versus risperidone long-acting injection in a 12-month, open-label treatment of schizophrenia: indirect, exploratory comparisons

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Ascher-Svanum H

2012-05-01

Full Text Available Haya Ascher-Svanum1, William S Montgomery2, David P McDonnell3, Kristina A Coleman4, Peter D Feldman11Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly Australia Pty Ltd, West Ryde, New South Wales, Australia; 3Eli Lilly and Company, Cork, Ireland; 4OptumInsight, Lilyfield, New South Wales, AustraliaBackground: Little is known about the comparative effectiveness of atypical antipsychotics in long-acting injection formulation. Due to the absence of head-to-head studies comparing olanzapine long-acting injection and risperidone long-acting injection, this study was intended to make exploratory, indirect, cross-study comparisons between the long-acting formulations of these two atypical antipsychotics in their effectiveness in treating patients with schizophrenia.Methods: Indirect, cross-study comparisons between olanzapine long-acting injection and risperidone long-acting injection used 12-month treatment-completion rates, because discontinuation of an antipsychotic for any cause is a recognized proxy measure of the medication's effectiveness in treating schizophrenia. Following a systematic review of the literature, two indirect comparisons were conducted using open-label, single-cohort studies in which subjects were stabilized on an antipsychotic medication before depot initiation. The first analysis compared olanzapine long-acting injection (one study with pooled data from nine identified risperidone long-acting injection studies. The second analysis was a “sensitivity analysis,” using only the most similar studies, one for olanzapine long-acting injection and one for risperidone long-acting injection, which shared near-identical study designs and involved study cohorts with near-identical patient characteristics. Pearson Chi-square tests assessed group differences on treatment-completion rates.Results: Comparison of olanzapine long-acting injection data (931 patients with the pooled data from the nine

Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia

NARCIS (Netherlands)

Lavalaye, J.; Linszen, D. H.; Booij, J.; Reneman, L.; Gersons, B. P.; van Royen, E. A.

1999-01-01

A crucial characteristic of antipsychotic medication is the occupancy of the dopamine (DA) D2 receptor. We assessed striatal DA D2 receptor occupancy by olanzapine and risperidone in 36 young patients [31 males, 5 females; mean age 21.1 years (16-28)] with first episode schizophrenia, using

Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone

OpenAIRE

Baldaçara,Leonardo; Sanches,Marsal; Cordeiro,Daniel Cruz; Jackowski,Andrea Parolin

2011-01-01

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or halop...

Highly sensitive voltammetric sensor based on immobilization of bisphosphoramidate-derivative and quantum dots onto multi-walled carbon nanotubes modified gold electrode for the electrocatalytic determination of olanzapine

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Mohammadi-Behzad, Leila [Department of Analytical Chemistry, Faculty of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Gholivand, Mohammad Bagher, E-mail: mbgholivand@yahoo.com [Department of Analytical Chemistry, Faculty of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Shamsipur, Mojtaba [Department of Analytical Chemistry, Faculty of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Gholivand, Khodayar [Department of Chemistry, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Barati, Ali [Department of Analytical Chemistry, Faculty of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Gholami, Akram [Department of Chemistry, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

2016-03-01

In the present paper, a new bisphosphoramidate derivative compound, 1, 4-bis(N-methyl)-benzene-bis(N-phenyl, N-benzoylphosphoramidate) (BMBPBP), was synthesized and used as a mediator for the electrocatalytic oxidation of olanzapine. The electro-oxidation of olanzapine at the surface of the BMBPBP/CdS-quantum dots/multi-walled carbon nanotubes (BMBPBP/CdS-QDs/MWCNTs) modified gold electrode was studied using cyclic voltammetry, chronoamperometry and electrochemical impedance spectroscopy. This sensor showed an excellent electrocatalytic oxidation activity toward olanzapine at less positive potential, pronounced current response, and good sensitivity. The diffusion coefficient and kinetic parameters (such as electron transfer coefficient and the heterogeneous rate constant) were determined for olanzapine oxidation, using the electrochemical approaches. Surface morphology and electrochemical properties of the prepared modified electrode were investigated by scanning electron microscopy (SEM), cyclic voltammetry and electrochemical impedance spectroscopy techniques. The hydrodynamic amperometry at rotating modified electrode at constant potential versus reference electrode was used for detection of olanzapine. Under optimized conditions, the calibration plot was linear in the concentration range of 20 nM to 100 μM and detection limit was found to be 6 nM. The proposed method was successfully applied to the determination of olanzapine in pharmaceuticals and human serum samples. - Highlights: • A highly sensitive sensor for OLZ determination was developed. • The sensor constructed based on immobilization of BMBPBP on CdS-QDs/MWCNTs Au electrode • The morphology of the modified electrode was examined by SEM. • The prepared sensor shows stable electrochemical behavior at a wide pH range. • The proposed sensor is used for trace determination of OLZ in real samples.

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

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Elsworth, John D; Morrow, Bret A; Hajszan, Tibor; Leranth, Csaba; Roth, Robert H

2011-01-01

Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine. PMID:21677652

Gabapentin adjunctive to risperidone or olanzapine in partially responsive schizophrenia: an open-label pilot study

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Adel Gabriel

2010-10-01

Full Text Available Adel GabrielDepartments of Psychiatry and Community Health Sciences, University of Calgary, Alberta, CanadaBackground: There is a great need in the treatment of schizophrenia for a drug, or drug ­combinations, to improve clinical response with fewer serious side effects. The objective of this study was to explore the therapeutic effects and tolerability of the anticonvulsant gabapentin as an adjunctive in the treatment of patients with partially responsive schizophrenia.Methods: Ten consenting patients with a confirmed Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision diagnosis of schizophrenia were identified. All patients failed at least one 12-week treatment trial with risperidone or olanzapine. Gabapentin was added to ongoing antipsychotic treatment with olanzapine or risperidone for eight weeks. The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS. Other scales included the Calgary Depression Scale (CDSS and the Abnormal Involuntary Movement Scale (AIMS. Repeated-measures multivariate analysis of variance was utilized to examine changes in outcome measures over time with adjunctive treatment with gabapentin.Results: There was a significant drop in the PANSS and CDSS scores at endpoint (week 8. There were no significant differences between the two treatment groups with regard to changes in all outcome measures or in AIMS score. The adjunctive treatments were well tolerated and side effects were transient.Conclusion: Gabapentin could be used successfully as an adjunct to novel antipsychotics in partially responsive schizophrenia. However, large controlled studies are needed to examine the effectiveness of gabapentin in psychotic disorders.Keywords: schizophrenia, refractory, adjunctive treatment, gabapentin, risperidone, olanzapine

The Study of the Effectiveness of Olanzapine as a Maintenance Treatment in Opioid Dependents, a Randomized Clinical Trial

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Azarekhsh Mokri

2009-08-01

Full Text Available Introduction: In this research, researchers want to study the effectiveness of Olanzapine on reduction of substance abuse relapse among people who are dependent to opioid material, merely. Method: A randomized clinical trial was designed. The population was opioid dependence subjects (only men that were diagnosed based on DSM-IV TR criteria, and referred to national center of addiction studies clinic. Detoxification was done by using of Clonidine, Clonazepam, Disiklomin, and NSAIDS within7 through 10 days. In second stage, the Patients who were referred to the clinic those men who had satisfied criterions selected. Demographic forms, testimonial certificate, Addiction Severity Index, Beck Depression Questionnaire, Zung Self report anxiety test administered among selected sample. Sample divided to two groups (placebo and Olanzapine the research last for 8 weeks. Results: the results showed that addiction severity reduced in both groups, but there was not significant difference in reduction of addiction severity between two groups. There was significant difference in depression and anxiety among mean scores of base line and follow up in both groups but there was not significant difference between two groups in follow up measures. Conclusion: Altogether, the results did not confirm the effectiveness of Olanzapine on maintenance treatment of opioid dependence.

Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

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Anand E

2016-10-01

Full Text Available Ernie Anand,1 Lovisa Berggren,2 John Landry,3 Ágoston Tóth,4 Holland C Detke5 1Neuroscience Medical Affairs, Eli Lilly & Company Ltd, Windlesham, UK; 2Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany; 3Global Statistical Sciences, Eli Lilly Canada Inc., Toronto, ON, Canada; 4Neuroscience, Lilly Hungary, Budapest, Hungary; 5Psychiatry and Pain Disorders, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Background: The objective of the present analysis is to determine the impact of the 3-hour observation period for olanzapine long-acting injection (LAI on patient satisfaction and well-being by comparing data collected before and after its implementation. Methods: This is a post hoc analysis of patients treated with olanzapine LAI in 1 a 6-month fixed-dose randomized controlled trial and/or 2 a 6-year open-label safety study. This analysis was limited to patients with schizophrenia who were treated with olanzapine LAI consistent with the approved indication and dosing recommendations of the European Union Summary of Product Characteristics (N=966. Of the 966 patients, the analysis further focused only on those patients who received both 1 at least one injection before the implementation of the 3-hour observation period and 2 at least one injection after implementation of the 3-hour observation period (N=487. Patient satisfaction was assessed with the three-item Patient Satisfaction with Medication Questionnaire-Modified. Responses were averaged across all postbaseline visits occurring before (ie, without the implementation of the 3-hour observation period and across all postbaseline visits occurring after (ie, with the implementation of the 3-hour observation period. In addition, the rate of postinjection delirium/sedation syndrome events was calculated. Results: There was no meaningful change after implementation of the 3-hour observation period in satisfaction (before: mean [SD] =4.0 [1.02] and

Adjunctive Use of Olanzapine in the Treatment of Avoidant Restrictive Food Intake Disorder in Children and Adolescents in an Eating Disorders Program.

Science.gov (United States)

Brewerton, Timothy D; D'Agostino, Meredith

2017-12-01

There is little information about the pharmacological treatment of avoidant and restrictive food intake disorder (ARFID), a challenging feeding disorder associated with marked impairment and developmental arrest. This brief clinical report seeks to fill this gap. A retrospective chart review of nine patients with ARFID treated in an eating disorder (ED) program (residential, partial hospital, and intensive outpatient levels of care) with adjunctive olanzapine was undertaken. The mean initial and final olanzapine doses were 0.9 + 0.63 mg/day and 2.8 + 1.47 mg/day, respectively. There was a statistically significant difference in weight gain pre- versus post-olanzapine treatment (3.3 ± 7.3 lbs vs. 13.1 ± 7.9 lbs [2.99 ± 6.62 lb SI vs. 11.88 ± 7.17 lb SI], paired t-test (p ARFID patients. Future randomized, placebo-controlled studies in ARFID are warranted.

Development of a modified electrode with amine-functionalized TiO{sub 2}/multi-walled carbon nanotubes nanocomposite for electrochemical sensing of the atypical neuroleptic drug olanzapine

Energy Technology Data Exchange (ETDEWEB)

Arvand, Majid, E-mail: arvand@guilan.ac.ir; Palizkar, Bahareh

2013-12-01

In this work, using of amine-functionalized TiO{sub 2}/multi-walled carbon nanotubes (NH{sub 2}-TiO{sub 2}-MWCNTs) nanocomposite for modification of glassy carbon electrode (GCE) was investigated. The nanocomposite was characterized by Fourier transformed infrared spectroscopy, transmission electron microscopy and scanning electron microscopy. The efficiency of modified electrode for electrocatalytic the oxidation of olanzapine was studied by cyclic voltammetry, square wave voltammetry and chronoamperometry. The electrochemical measurements were carried out in phosphate-buffered solution (PBS, pH 5.0). The NH{sub 2}-TiO{sub 2}-MWCNTs/GCE provided high surface area and more sensitive performance. The charge transfer coefficient (α) and the apparent charge transfer rate constant (k{sub s}) were calculated to be equal to 0.42 and 0.173 s{sup −1}, respectively. The square wave voltammetry exhibited two linear dynamic ranges and a detection limit of 0.09 μM of olanzapine. In addition, the modified electrode was employed for the determination of olanzapine in pharmaceutical and human blood serum samples in order to illustrate the applicability of proposed method. - Highlights: • A simple and rapid sensor for determination of olanzapine in tablet and serum was prepared. • The amine-functionalized TiO{sub 2}-MWCNTs/GCE showed an obvious increase in surface area. • The presence of NH{sub 2}-TiO{sub 2} nanoparticles showed good ability to distinguish the response of olanzapine.

Combination use of atomoxetine hydrochloride and olanzapine in the treatment of attention-deficit/hyperactivity disorder with comorbid disruptive behavior disorder in children and adolescents 10-18 years of age.

Science.gov (United States)

Holzer, Barry; Lopes, Vasco; Lehman, Robert

2013-08-01

The aim of this study was to assess the use of atomoxetine and olanzapine in combination to treat attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behaviors in children and adolescents 10-18 years of age. Eleven subjects ages 10-18 received open-label atomoxetine and olanzapine for a 10 week treatment period. Patients were assessed at baseline, 2 weeks, 4 weeks, 6 weeks, and 10 weeks (posttreatment). ADHD improvement was measured through the ADHD Rating Scale (ADHD-RS) (Investigator and Parent ratings). Aggression was measured through the Modified Overt Aggression Scale (MOAS). The combined use of atomoxetine and olanzapine resulted in statistically significant improvement in ADHD symptoms and overt aggression from baseline to posttreatment. As evidenced by a 33% reduction in symptoms on the ADHD-RS-I and the MOAS, 73% of patients were considered responders to ADHD treatment, whereas 55% responded to treatment for aggression. Both medications were generally well tolerated. Olanzapine treatment was associated with significant weight gain. Patients gained, on average, 3.9 kg. throughout the treatment period. These data provide initial evidence that combination use of atomoxetine and olanzapine for the treatment of ADHD and comorbid disruptive behaviors was effective in reducing ADHD symptoms and aggressive behavior in a 10 week treatment period.

Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

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Gobbi G

2014-05-01

Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

In vivo effects of olanzapine on striatal dopamine D[sub 2]/D[sub 3] receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

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Dresel, S.; Rossmueller, B.; Hahn, K.; Tatsch, K. (Department of Nuclear Medicine, University of Munich (Germany)); Mager, T.; Meisenzahl, E.; Moeller, H.J. (Department of Psychiatry, University of Munich (Germany))

1999-08-01

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D[sub 2]/D[sub 3] receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [[sup 123]I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [[sup 123]I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrance of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [[sup 123]I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D[sub 2]/D[sub 3] receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D[sub 2]/D[sub 3] receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D[sub 2]/D[sub 3] receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D[sub 2]/D[sub 3] availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings

In vivo effects of olanzapine on striatal dopamine D{sub 2}/D{sub 3} receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

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Dresel, S.; Rossmueller, B.; Hahn, K.; Tatsch, K. [Department of Nuclear Medicine, University of Munich (Germany); Mager, T.; Meisenzahl, E.; Moeller, H.J. [Department of Psychiatry, University of Munich (Germany)

1999-08-01

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D{sub 2}/D{sub 3} receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [{sup 123}I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [{sup 123}I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrance of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [{sup 123}I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D{sub 2}/D{sub 3} receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D{sub 2}/D{sub 3} receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D{sub 2}/D{sub 3} receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D{sub 2}/D{sub 3} availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings

The effect of betahistine, a histamine H1 receptor agonist/H3 antagonist, on olanzapine-induced weight gain in first-episode schizophrenia patients.

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Poyurovsky, Michael; Pashinian, Artashes; Levi, Aya; Weizman, Ronit; Weizman, Abraham

2005-03-01

Histamine antagonism has been implicated in antipsychotic drug-induced weight gain. Betahistine, a histamine enhancer with H1 agonistic/H3 antagonistic properties (48 mg t.i.d.), was coadministered with olanzapine (10 mg/day) in three first-episode schizophrenia patients for 6 weeks. Body weight was measured at baseline and weekly thereafter. Clinical rating scales were completed at baseline and at week 6. All participants gained weight (mean weight gain 3.1+/-0.9 kg) and a similar pattern of weight gain was observed: an increase during the first 2 weeks and no additional weight gain (two patients) or minor weight loss (one patient) from weeks 3 to 6. None gained 7% of baseline weight, which is the cut-off for clinically significant weight gain. Betahistine was safe and well tolerated and did not interfere with the antipsychotic effect of olanzapine. Our findings justify a placebo-controlled evaluation of the putative weight-attenuating effect of betahistine in olanzapine-induced weight gain.

Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia

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Watson Susan B

2011-02-01

Full Text Available Abstract Background In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI in schizophrenia (Kane et al., 2010, apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes. Methods Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140, "medium" (405 mg/4 weeks; N = 318, or "high" (300 mg/2 weeks; N = 141 dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data, or the Cochran-Armitage test (categorical data. Results Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose, mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02], high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose, fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose. Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p Conclusions Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When

Olanzapine has better efficacy compared to risperidone for treatment of negative symptoms in schizophrenia

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P N Suresh Kumar

2016-01-01

Conclusions: Both treatments were well-tolerated and efficacious. Greater reductions in severity of the illness and negative symptoms were seen with olanzapine consistently through 1 year. The frequency and severity of extrapyramidal symptoms were negligible and similar in the two treatment groups. Weight gain, hyperlipidemia, and hyperglycemia were comparable in both groups. Risperidone produced significant hyperprolactinemia.

Converging evidence for the association of functional genetic variation in the serotonin receptor 2a gene with prefrontal function and olanzapine treatment.

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Blasi, Giuseppe; De Virgilio, Caterina; Papazacharias, Apostolos; Taurisano, Paolo; Gelao, Barbara; Fazio, Leonardo; Ursini, Gianluca; Sinibaldi, Lorenzo; Andriola, Ileana; Masellis, Rita; Romano, Raffaella; Rampino, Antonio; Di Giorgio, Annabella; Lo Bianco, Luciana; Caforio, Grazia; Piva, Francesco; Popolizio, Teresa; Bellantuono, Cesario; Todarello, Orlando; Kleinman, Joel E; Gadaleta, Gemma; Weinberger, Daniel R; Bertolino, Alessandro

2013-09-01

Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (HTR2A rs6314, C>T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects. To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine. In silico predictions, in vitro, and case-control investigations. Academic and clinical facilities. The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. EXPOSURES Patients received olanzapine monotherapy for 8 weeks. In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia. Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on HTR2A expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level-dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment. Our results suggest that HTR2A rs6314 affects 5-HT2AR expression and

Efficacy of olanzapine in symptom relief and quality of life in gastric cancer patients receiving chemotherapy

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Novin Nikbakhsh

2016-01-01

Full Text Available Background: Considering the incidence and prevalence rates of gastric cancer in Mazandaran Province of Iran, this research was performed to evaluate the efficacy and safety of olanzapine in symptom relief and quality of life (QOL improvement of gastric patients receiving chemotherapy. Materials and Methods: This clinical trial was conducted on thirty new cases of gastric cancer patients whose treatment protocol was planned on chemotherapy and were allocated into two groups by simple random sampling. Intervention group (15 patients received olanzapine tablets (2.5–10 mg/day a day before the beginning of chemotherapy; in the 1st day of chemotherapy to 8 weeks after chemotherapy, besides the routine treatment regimens. The control group received only the routine treatment regimens. The patients were followed for 8 weeks after intervention. All of the patients were assessed with Hospital Anxiety and Depression Scale (HADS and WHO-QOL-BREF questionnaires; further, Rhodes index was used to evaluate nausea and vomiting (N/V status. Results: All the recruited patients continued the allocated interventions (no lost to follow-up. N/V decreased in the case group, but the difference was not statistically significant (P = 0.438. The patients' appetite and body mass index increased (P = 0.006. Anxiety and depression subscales of HADS had significant differences between the two groups (P 0.05. No significant increase was observed in fasting and 2-h postprandial blood glucose and lipid profile (P > 0.05. Conclusion: Olanzapine can be considered as an effective drug to increase appetite and decrease anxiety and depression in patients with gastric cancer.

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

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Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

2003-01-01

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment ( 12 weeks) are lacking. Our results suggest that none of the atypical

Evaluation of antidepressant like property of amisulpride per se and its comparison with fluoxetine and olanzapine using forced swimming test in albino mice.

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Pawar, Ganesh R; Agrawal, Rajendra P; Phadnis, Pradeep; Paliwal, Abhay; Vyas, Savita; Solanki, Pooja

2009-01-01

Amisulpride, an atypical antipsychotic was evaluated for antidepressant like activity in forced swimming test in Swiss albino mice. The effect of amisulpride was compared with that of fluoxetine, the standard antidepressant and olanzapine, another atypical antipsychotic claimed to have antidepressant like activity. Both acute and chronic studies were carried out. In both the studies, animals were divided into four groups (n = 8 each) and subjected to oral drug interventions as follows -- Group 1- control (distilled water, 1 mL/kg); Group 2- fluoxetine in a dose of 10 mg/kg 23.5, 5 and 1 h before the test; Group 3-amisulpride in a dose of 70 mg/kg 23.5, 5 and 1 h before the test; Group 4- olanzapine in a dose of 2 mg/kg 23.5, 5 and 1 h before the study. In the chronic study, the treatment was given daily for 28 days with last dose being given 2 h prior to the test. A time sampling method was used to score the behavioral activity in each group. Results of both the studies indicated that animals given amisulpride displayed significant improvement in swimming behavior (p Fluoxetine also showed significant difference in activity as compared to amisulpride and olanzapine (p swimming phases in albino mice (p > 0.05). We conclude that amisulpride per se has an antidepressant like activity comparable to that of olanzapine though the activity was significantly less than that of fluoxetine.

Tolerability and efficacy of paliperidone ER compared to olanzapine in the treatment of schizophrenia: A randomized, double-blind, multicentric trial

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Sandip Shah

2011-01-01

Full Text Available Background: Paliperidone is an active metabolite of risperidone and actss through a combination of central dopamine Type 2 (D2 and serotonin Type 2 (5HT2A receptor antagonism. Aim: The present randomized, double-blind, multicentric trial was designed to determine the safety and efficacy of paliperidone extended release (ER compared to olanzapine in the treatment of acute schizophrenia. Materials and Methods: A total of 214 patients with diagnosis of schizophrenia were randomized to paliperidone ER (n=109 and olanzapine (n=106 treatment groups. Totally 206 patients were evaluated for efficacy parameters using Positive and negative syndrome scale (PANSS score and Clinical Global Impression-severity of illness (CGI-S and Clinical Global Impression-improvement of illness (CGI-I scales. Safety was assessed by treatment-emergent adverse events and movement disorders. Results: All patients showed significant reduction in PANSS scores at the end of treatment. However, the results were comparable and there was no significant difference at the end of the trial between paliperidone ER group and olanzapine group. Both the treatment groups showed decrease in the severity of illness and improvement in symptomatology. The most common adverse events reported in paliperidone ER versus olanzapine group were Extra Pyramidal Syndrome (EPS (13.7% vs. 15.6%, headache (12.7% vs. 8.9%, increased appetite (8.8% vs. 10.0% and drowsiness (4.9% vs. 303%. There was no clinically relevant difference in change from baseline to the end of the trial in abnormal involuntary movement scale (AIMS and barnes akathisia rating scale (BARS total scores between both the groups. Conclusion: Paliperidone ER is effective in controlling schizophrenic symptoms as well as exhibits comparable tolerability profile. Thus, paliperidone ER has the potential to be a useful new treatment option for patients with schizophrenia.

Expression changes of serotonin receptor gene subtype 5HT3a in peripheral blood mononuclear cells from schizophrenic patients treated with haloperidol and Olanzapin.

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Shariati, Gholam Reza; Ahangari, Ghasem; Hossein-nezhad, Arash; Asadi, Seyed Mohammad; Pooyafard, Farzaneh; Ahmadkhaniha, Hamid Reza

2009-09-01

Serotonin receptors are involved in pathophysiology of schizophrenia and may mediate other neurotransmitter effects. We investigated serotonin receptors gene expression in peripheral blood mononuclear cells (PBMC) of naïve schizophrenic patients, before and after treatment. Also serotonin receptor gene expression was compared in two treatment groups including Haloperidol and Olanzapine. The PBMC was separated from whole blood by Ficoll-hypaque. The total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using primer pairs specific for 5HT(3a) serotonin receptor mRNA and beta-actin as internal control. The results showed the presence of subtype of serotonin receptor in lymphocytes. Serotonin gene expression showed significant changes in Olanzapine treatment group which correlated with Clinical Global Impression (CGI) score improvement. In conclusion, the present study has shown that human PBMC express serotonin receptors 5HT(3a). Moreover, clinical symptom improvement of Olanzapin may be demonstrated by a change in serotonin receptor gene expression.

Risperidone, quetiapine, and olanzapine adjunctive treatments in major depression with psychotic features: a comparative study

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Gabriel A

2013-04-01

Full Text Available A Gabriel Departments of Psychiatry and Community Health Sciences, University of Calgary, Calgary, AB, Canada Objectives: The purpose of this study was to compare the effectiveness of novel antipsychotics in the treatment of psychotic depression. Method: Consecutive patients who were admitted (n = 51 with a confirmed diagnosis of major depression with psychotic features (delusions or hallucinations or both participated in this open-label, naturalistic study. All patients were treated with selective serotonin reuptake inhibitors (SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs (citalopram or venlafaxine extended release [XR], and atypical antipsychotic agents were added, as tolerated, during the first week of initiating the citalopram or venlafaxine. There were patients (n = 16 who received risperidone, who received quetiapine (n = 20, and who received olanzapine (n = 15, as an adjunctive treatment to either citalopram or venlafaxine for at least 8 weeks. Outcome measures included the Clinical Global Impression-Severity subscale (CGI-S, as the primary outcome measure, as well as the Hamilton Rating Scale for Depression-21 item (HAM-D21 and the Brief Psychiatric Rating Scale (BPRS. Tolerance to treatments and weight changes were monitored over the period of the trial. Results: All patients completed the trial with no drop outs. At 8 weeks, there was a statistically significant (P 0.01 in the olanzapine group. Conclusion: Quetiapine, risperidone, and olanzapine, given as adjunctive treatment with SSRIS or SNRIs can significantly and equally improve depressive and psychotic symptoms, in the short-term treatment of major depression with psychotic features. The author recommends that large controlled trials be conducted to examine the differences in long-term efficacy and tolerance between the atypical antipsychotic agents, in the treatment of major depression with or without psychotic features. Keywords: depression, novels

IVIVC from Long Acting Olanzapine Microspheres

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Susan D'Souza

2014-01-01

Full Text Available In this study, four PLGA microsphere formulations of Olanzapine were characterized on the basis of their in vitro behavior at 37°C, using a dialysis based method, with the goal of obtaining an IVIVC. In vivo profiles were determined by deconvolution (Nelson-Wagner method and using fractional AUC. The in vitro and in vivo release profiles exhibited the same rank order of drug release. Further, in vivo profiles obtained with both approaches were nearly superimposable, suggesting that fractional AUC could be used as an alternative to the Nelson-Wagner method. A comparison of drug release profiles for the four formulations revealed that the in vitro profile lagged slightly behind in vivo release, but the results were not statistically significant (P0.96 between in vitro release and in vivo measurements confirmed the excellent relationship between in vitro drug release and the amount of drug absorbed in vivo. The results of this study suggest that proper selection of an in vitro method will greatly aid in establishing a Level A IVIVC for long acting injectables.

Effect of Environmental Cues on Behavioral Efficacy of Haloperidol, Olanzapine and Clozapine in Rats

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Sun, Tao; Liu, Xinfeng; Li, Ming

2014-01-01

Previous studies have reported that context can powerfully modulate the inhibitory effect of an antipsychotic drug on phencyclidine (PCP)-induced hyperlocomotion (a behavioral test used to evaluate putative antipsychotic drugs). The present study investigated the experimental conditions under which environmental stimuli exert their influence through associative conditioning processes. Experiment 1 examined the extent to which prior antipsychotic treatment in the home cages affected a drug’s ability to inhibit PCP-induced hyperlocomotion in a novel motor activity test apparatus. Five days of repeated haloperidol (0.05 mg/kg, sc) and olanzapine (2.0 mg/kg, sc) treatment in the home cages still potentiated their inhibition of PCP-induced hyperlocomotion (i.e. sensitization) assessed in a new environment, whereas the clozapine (10.0 mg/kg, sc) treatment enhanced the development of clozapine tolerance, indicating a lack of environmental modulation of antipsychotic efficacy. Experiment 2 assessed the impact of different numbers of antipsychotic administrations in either the home environment or test environment (e.g. 4, 2 or 0) on a drug’s ability to inhibit PCP-induced hyperlocomotion. Repeated administration of clozapine (5.0 mg/kg, sc) or olanzapine (1.0 mg/kg, sc) for 4 consecutive days, regardless of where these treatments occurred, caused a similar level of inhibition on PCP-induced hyperlocomotion. However, 4-day haloperidol (0.03 mg/kg, sc) treatment in the test apparatus caused a significant higher inhibition than 4-day home cage treatment. Thus, more exposures to the test environment under the influence of haloperidol (but not clozapine or olanzapine) cause a stronger inhibition than fewer exposures, indicating a strong environmental modulation. Collectively, these findings suggest that prior antipsychotic treatment in one environment could alter later antipsychotic-like response assessed in a different environment under certain test conditions. Therefore

Oral haloperidol or olanzapine intake produces distinct and region-specific increase in cannabinoid receptor levels that is prevented by high fat diet.

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Delis, Foteini; Rosko, Lauren; Shroff, Aditya; Leonard, Kenneth E; Thanos, Panayotis K

2017-10-03

Clinical studies show higher levels of cannabinoid CB1 receptors (CB1R) in the brain of schizophrenic patients while preclinical studies report a significant functional interaction between dopamine D2 receptors and CB1Rs as well as an upregulation of CB1Rs after antipsychotic treatment. These findings prompted us to study the effects of chronic oral intake of a first and a second generation antipsychotic, haloperidol and olanzapine, on the levels and distribution of CB1Rs in the rat brain. Rats consumed either regular chow or high-fat food and drank water, haloperidol drinking solution (1.5mg/kg), or olanzapine drinking solution (10mg/kg) for four weeks. Motor and cognitive functions were tested at the end of treatment week 3 and upon drug discontinuation. Two days after drug discontinuation, rats were euthanized and brains were processed for in vitro receptor autoradiography. In chow-fed animals, haloperidol and olanzapine increased CB1R levels in the basal ganglia and the hippocampus, in a similar, but not identical pattern. In addition, olanzapine had unique effects in CB1R upregulation in higher order cognitive areas, in the secondary somatosensory cortex, in the visual and auditory cortices and the geniculate nuclei, as well as in the hypothalamus. High fat food consumption prevented antipsychotic-induced increase in CB1R levels in all regions examined, with one exception, the globus pallidus, in which they were higher in haloperidol-treated rats. The results point towards the hypothesis that increased CB1R levels could be a confounding effect of antipsychotic medication in schizophrenia that is circumveneted by high fat feeding. Copyright © 2017 Elsevier Inc. All rights reserved.

A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers

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Evers, Simon S; van Vliet, André; van Vugt, Barbara; Scheurink, Antonius; van Dijk, Gertjan

2016-01-01

Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side

A COMPARATIVE STUDY OF ORAL OLANZAPINE AND ORAL HALOPERIDOL ON GLUCOSE TOLERANCE LEVELS IN PATIENTS WITH SCHIZOPHRENIA

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G N S Sangeetha Lakshmi

2015-08-01

Full Text Available Background: Schizophrenia is a mental disorder characterized by persistent defects in the perception, thinking or the expression of reality. The term “schizophrenia” translates roughly as “shattered mind,” and comes from the Greek (schizo, “to split” or “to divide” and (phrēn, “mind”. Material and Methods: The study was designed to be a prospective control study. Schizophrenic patients taking Olanzapine and Haloperidol were selected and follow up at three weeks and six weeks was done. Results: In this prospective control study, Olanzapine and Haloperidol were associated with an increase in Blood Glucose Levels. The mean changes in Glucose remained within clinically normal range in this six week study. Conclusion: Antipsychotic treatmemt leads to the development of Diabetes mellitus in a significant 10.1% of patients within 6 weeks. Given the serious implications for morbidity and mortality attributable to diabetes mellitus, clinicians need to be aware of these risk factors when treating patients with chronic schizophrenia

Central administration of an orexin receptor 1 antagonist prevents the stimulatory effect of Olanzapine on endogenous glucose production

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Girault, Elodie M.; Foppen, Ewout; Ackermans, Mariëtte T.; Fliers, Eric; Kalsbeek, Andries

2013-01-01

Atypical antipsychotic drugs such as Olanzapine (Olan) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. It has been shown that peripheral injections of Olan activate neurons in

Ziprasidone versus olanzapine, risperidone or quetiapine in patients with chronic schizophrenia: a 12-week open-label, multicentre clinical trial

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Lublin, Henrik; Haug, Hans-Joachim; Koponen, Hannu

2009-01-01

The efficacy, safety and tolerability of ziprasidone versus the comparators olanzapine, risperidone or quetiapine were investigated in adult patients with chronic schizophrenia, schizoaffective and schizophreniform disorders, with lack of efficacy or intolerance to their previous antipsychotic tr...

Sertindole, in contrast to clozapine and olanzapine, does not disrupt water maze performance after acute or chronic treatment

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Didriksen, Michael; Kreilgaard, Mads; Arnt, Jørn

2006-01-01

Cognitive deficits in schizophrenia are associated with poor functional outcome, and may be further aggravated by treatment with antipsychotics. In the present study the acute and chronic (3 weeks of treatment) effects of clozapine, olanzapine, and sertindole on performance in the Morris water ma...

Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study

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Novick, D; Gonzalez-Pinto, A; Haro, J M

2009-01-01

OBJECTIVES: The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments. METHODS: EMBLEM (European Mania in Bipolar Evaluation of Medi...

Change in level of productivity in the treatment of schizophrenia with olanzapine or other antipsychotics

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Osuntokun Olawale

2011-05-01

Full Text Available Abstract Background When treating schizophrenia, improving patients' productivity level is a major goal considering schizophrenia is a leading cause of functional disability. Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia. However, little has been done to systematically investigate productivity levels in schizophrenia. We set out to better understand the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications. We also assessed the links between productivity level and other clinical outcomes. Methods This post hoc analysis used data from 6 randomized, double-blind clinical trials of patients with schizophrenia or schizoaffective disorder, with each trial being of approximately 6 months duration. Change in productivity level was compared between olanzapine-treated patients (HGBG, n = 172; HGHJ, n = 277; HGJB, n = 171; HGLB, n = 281; HGGN, n = 159; HGDH, n = 131 and patients treated with other antipsychotic medications (separately vs. haloperidol [HGGN, n = 97; HGDH, n = 132], risperidone [HGBG, n = 167; HGGN, n = 158], quetiapine [HGJB, n = 175], ziprasidone [HGHJ, n = 271] and aripiprazole [HGLB, n = 285]. Productivity was defined as functional activities/work including working for pay, studying, housekeeping and volunteer work. Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75% to 100% of the time. Results Chronically ill patients treated with olanzapine (OLZ experienced significantly greater improvement in productivity when compared to patients treated with risperidone (RISP (OLZ = 0.22 ± 1.19, RISP = -0.03 ± 1.17, p = 0.033 or ziprasidone (ZIP (OLZ = 0.50 ± 1.38, ZIP = 0.25 ± 1.27, p = 0.026, but did not significantly differ from the quetiapine, aripiprazole or haloperidol treatment groups. Among

Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

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M. Suzuki

2014-01-01

Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

Melatonin for Reducing Weight Gain Following Administration of Atypical Antipsychotic Olanzapine for Adolescents with Bipolar Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

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Mostafavi, Seyed-Ali; Solhi, Mahmoud; Mohammadi, Mohammad-Reza; Akhondzadeh, Shahin

2017-06-01

We aimed to evaluate melatonin effectiveness in weight gain reduction following olanzapine use for 11-17-year-old bipolar disorder patients. Seventy-seven adolescent outpatients, subsequent to their initial diagnosis of bipolar I disorder by a psychiatrist, entered this study. After assessing inclusion and exclusion criteria, 48 patients consented to participate. Twenty-four patients were allocated to receive olanzapine, lithium carbonate, and melatonin, and 24 patients were allocated to receive olanzapine, lithium carbonate, and placebo by simple randomization. The Young Mania Rating Scale (YMRS) was performed at baseline. Before treatment and after 6 and 12 weeks of treatment, weight, height, and body mass index (BMI) were measured. Analysis of variance (ANOVA) with repeated measure and t-test were used to analyze data. Nineteen patients in each group finished the study and their data were entered for analysis. Mean rise in BMI in the melatonin group compared with placebo (2.45 vs. 3.25 respectively) was marginally significant (t = 1.936; df = 36; p = 0.061). ANOVA with repeated measure also showed a marginally significant difference (F = 3.74; df = 1; p = 0.061) between groups and across time in regard to BMI. Mean body weight rise in the melatonin group compared with the placebo group (5.8 kg vs. 8.2 kg respectively) was marginally significant (t = 1.923; df = 28; p = 0.065). ANOVA with repeated measure also showed a marginally significant difference (F = 3.73; df = 1.1; p = 0.056) between groups and across time for body weight. Coadministration of melatonin with olanzapine and lithium carbonate in adolescents with bipolar disorder could reduce the sharp weight gain side effect of these drugs to near significance.

Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects

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Girault, Elodie M.; Guigas, Bruno; Alkemade, Anneke; Foppen, Ewout; Ackermans, Mariëtte T.; la Fleur, Susanne E.; Fliers, Eric; Kalsbeek, Andries

2014-01-01

Atypical antipsychotic drugs such as olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these metabolic side-effects are unknown at the moment. In this study, we investigated the metabolic changes induced by a chronic

Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects

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Girault, Elodie M; Guigas, Bruno; Alkemade, Anneke; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, A.

Atypical antipsychotic drugs such as olanzapine induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these metabolic side-effects are unknown at the moment. In this study, we investigated the metabolic changes induced by a chronic

Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial

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Grootens, K.P.; Veelen, N.M. van; Peuskens, J.; Sabbe, B.G.C.; Thys, E.; Buitelaar, J.K.; Verkes, R.J.; Kahn, R.S.

2011-01-01

INTRODUCTION: Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia. METHODS: The study was an

Ziprasidone Vs Olanzapine in Recent-Onset Schizophrenia and Schizoaffective Disorder : Results of an 8-Week Double-Blind Randomized Controlled Trial

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Grootens, K. P.; van Veelen, N. M. J.; Peuskens, J.; Sabbe, B. G. C.; Thys, E.; Buitelaar, J. K.; Verkes, R. J.; Kahn, R. S.

Introduction: Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia. Methods: The study was an

Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder

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Larsen, Julie R; Vedtofte, Louise; Jakobsen, Mathilde S L

2017-01-01

in Denmark. Of 214 eligible participants with a schizophrenia spectrum disorder, 103 were randomized to liraglutide or placebo. Participants received stable treatment with clozapine or olanzapine, were overweight or obese, and had prediabetes. Data were collected from May 1, 2013, through February 25, 2016...

Does participation in a weight control program also improve clinical and functional outcomes for Chinese patients with schizophrenia treated with olanzapine?

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Montgomery W

2014-07-01

Full Text Available William Montgomery,1 Tamas Treuer,2 Wenyu Ye,3 Hai Bo Xue,4 Sheng Hu Wu,4 Li Liu,4 Zbigniew Kadziola,5 Michael D Stensland,6 Haya Ascher-Svanum7 1Global Health Outcomes Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 2Neuroscience Research, Eli Lilly and Company, Budapest, Hungary; 3Global Statistical Sciences, Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People's Republic of China; 4Medical Department, Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People's Republic of China; 5Global Statistical Sciences, Eli Lilly GmbH, Vienna, Republic of Austria; 6Agile Outcomes Research, Inc., Rochester, MN, USA; 7Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA Objectives: This study examined whether participation in a weight control program (WCP by patients with schizophrenia treated with olanzapine was also associated with improvements in clinical and functional outcomes. Methods: A post-hoc analysis was conducted using data from the Chinese subgroup (n=330 of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia who initiated or switched to oral olanzapine. At study entry and monthly visits, participants were assessed with the Clinical Global Impression of Severity, and measures of patient insight, social activities, and work impairment. The primary comparison was between the 153 patients who participated in a WCP at study entry (n=93 or during the study (n=60 and the 177 patients who did not participate in a weight control program (non-WCP. Mixed Models for Repeated Measures with baseline covariates were used to compare outcomes over time. Kaplan–Meier survival analysis was used to assess time to response. Results: Participants had a mean age of 29.0 years and 29.3 years, and 51.0% and 57.6% were female for WCP and non-WCP groups, respectively. Average initiated daily dose for olanzapine was 9.5±5.4 mg. WCP participants gained less weight than non-participants (3.9 kg vs

A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

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Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki

2017-09-01

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Early response or nonresponse at week 2 and week 3 predict ultimate response or nonresponse in adolescents with schizophrenia treated with olanzapine

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Stentebjerg-Olesen, Marie; Ganocy, Stephen J; Findling, Robert L

2015-01-01

%; remission was defined cross-sectionally using Andreasen et al. (2005) criteria. By week 2 (n = 69) and 3 (n = 66), olanzapine-treated youth achieved 73.3 and 85.5 % of their overall BPRS-C score reduction at 6 weeks last observation carried forward. ER and ENR patients did not differ significantly regarding...... baseline demographic, illness and treatment variables. ER 2 (frequency = 68.1 %) and ER 3 (frequency = 65.2 %) significantly predicted UR and remission (p = 0.0044-p power. A ≥ 20 % BPRS-C reduction threshold for ER had best predictive validity (area under...... and ENR groups. Adolescents with schizophrenia experienced the majority of symptomatic improvement early during olanzapine treatment. ER predicted UR and remission, with ER3 having best predictive power. A ≥ 20 % improvement threshold for defining ER was confirmed as a robust outcome indicator....

Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: A prospective study of 113 patients with recent-onset schizophrenia or related disorders

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de Haan, Lieuwe; Beuk, Nico; Hoogenboom, Britt; Dingemans, Peter; Linszen, Don

2002-01-01

Objective: To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. Method: We conducted a prospective study of consecutively hospitalized

Comparative study of adverse effects of Olanzapine and Risperidone on blood suger, lipid and other side effects in psychotic disorders

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mitra safa

2008-10-01

Full Text Available Safa M1, Mohammadi MR2, Saki M3, Delfan B4, Tarrahi MJ5, Rouhandeh M6 1. Assistant Professor, Department of psychiatry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 2. GP, Khorramabad, Iran 3. Instructor, Department of Nursing, Faculty of Nursing and Midwifery, Lorestan University of Medical Sciences, Khorramabad, Iran 4. Associate Professor, Department of Pharmacology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran 5. Instructor, Department of Epidemiology, Faculty of Health, Lorestan University of Medical Sciences, Khorramabad, Iran 6. BSc in Nursing, Khorramabad, Iran Abstract Background: Chronic mental disorders are among the problems in psychiatrics. Atypical anti psychotic drugs are new effective medications to treat these disorders. Unfortunately these drugs lead to side effects such as increase in blood glocuse, weight gain and edema. This study aims to investigate adverse effects of Olanzapine and Rispridone on lipid level and blood glocuse and other complications in patients with psychotic disorders. Materials and methods: This clinical trial-double blinded study, patients with psychotic disorders were randomly categorized into two groups. Group one treated with Olanzapine and other with Rispridone. All the subjects were initially assessed for blood sugar and lipids, and in the case of normal, they were randomly assigned to two groups in a double- blinded method to be treated with Olanzapine or Risperidone. Blood sugar and lipids tests were performed for all subjects at the 1st week and 3 months after initiation of therapy. Other complications were assessed too, then the data were analyzed using SPSS software. Results: The results of the study indicated that the levels of cholesterol, triglycerides and blood suger rose significantly at the 1st week and third month after beginning the treatment. Increase of cholesterol and triglyceride in the Olanzapine and Risperidone

Negative effects of chronic oral chlorpromazine and olanzapine treatment on the performance of tasks designed to assess spatial learning and working memory in rats.

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Terry, A V; Warner, S E; Vandenhuerk, L; Pillai, A; Mahadik, S P; Zhang, G; Bartlett, M G

2008-10-28

Learning potential and memory capacity are factors that strongly predict the level of rehabilitation and the long-term functional outcome in patients with schizophrenia. Unfortunately, however, the effects of antipsychotic drugs (i.e. the primary treatments for schizophrenia) on these components of cognition are unclear, particularly when they are administered chronically (i.e. a standard clinical practice). In this rodent study we evaluated the effects of different time periods (ranging from 2 weeks to 6 months) of oral treatment with the first generation antipsychotic chlorpromazine (10.0 mg/kg/day), or the second generation antipsychotic olanzapine (10.0 mg/kg/day) on the repeated acquisition of a water maze task (i.e. a method of assessing spatial learning potential in a repeated testing format). We assessed locomotor function (in an open field) and employed a radial arm maze (RAM) task to assess antipsychotic effects (5.0 and 10.0 mg/kg/day doses) on spatial working memory during the treatment period between 15 days and 2 months. Finally, we conducted experiments using liquid chromatography/tandem mass spectrometry (LC-MS/MS) to evaluate the therapeutic relevance of our method of drug delivery (oral administration in drinking water). In the water maze experiments, both antipsychotics were associated with impairments in acquisition in the earlier test sessions that could eventually be overcome with repeated testing while olanzapine also impaired retention in probe trials. Both antipsychotics were also associated with impairments in delayed non-match-to-position trials in the RAM and some impairments of motor function (especially in the case of olanzapine) as indicated by slightly reduced swim speeds in the water maze and decreased activity in some components of the open field assessment. Finally, LC-MS/MS studies indicated that the method of antipsychotic administration generated clinically relevant plasma levels in the rat. These animal data indicate that

Reversal of olanzapine-induced weight gain in a patient with schizophrenia by switching to asenapine: a case report

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Okazaki, Kosuke; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2017-01-01

Kosuke Okazaki, Kazuhiko Yamamuro, Toshifumi Kishimoto Department of Psychiatry, Nara Medical University School of Medicine, Kashihara, Japan Aims: Antipsychotics are effective for treating schizophrenia, but atypical antipsychotics can cause several adverse side effects including weight gain, hyperprolactinemia, and extrapyramidal symptoms. Moreover, weight gain increases the risk of metabolic diseases.Methods: We treated a case of olanzapine-induced weight gain in a 41-year-old man with s...

Predictors and correlates for weight changes in patients co-treated with olanzapine and weight mitigating agents; a post-hoc analysis

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Heinloth Alexandra N

2009-03-01

Full Text Available Abstract Background This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions. Methods Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI ≥ 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68, sibutramine (n = 42, or amantadine (n = 48. Individual patients were analyzed for categorical weight loss ≥ 2 kg and weight gain ≥ 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale. Results Predictors/correlates of weight loss ≥ 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain ≥ 1 kg. Conclusion The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy. Trial Registration This analysis was not

Predictors and correlates for weight changes in patients co-treated with olanzapine and weight mitigating agents; a post-hoc analysis.

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Stauffer, Virginia L; Lipkovich, Ilya; Hoffmann, Vicki Poole; Heinloth, Alexandra N; McGregor, H Scott; Kinon, Bruce J

2009-03-28

This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions. Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI) > or = 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68), sibutramine (n = 42), or amantadine (n = 48). Individual patients were analyzed for categorical weight loss > or= 2 kg and weight gain > or = 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale. Predictors/correlates of weight loss > or = 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain > or = 1 kg. The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy. This analysis was not a clinical trial and did not involve any medical intervention.

Evaluation of health resources expenditure in two groups of psychotic patients treated with olanzapine and typical neuroleptics in a Italian Mental Health Department in Calabria Region

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Anna Caputo

2008-01-01

Full Text Available Numerous Italian and international trials have studied the global costs of treatment with olanzapine and typical neuroleptics. Our analysis confirms those results. In our study, treatment with olanzapine, as compared to typical neuroleptics, was associated with a greater reduction in emergency interventions (hospitalisations, with an increased use of rehabilitation services and with a small increase in the number of working days. The differences between the two groups for this variable were not great, while the differences in the assessment scores appeared important and statistically significant. The results of present study are relative to the practice of one Italian Mental Health Department and, for this reason, cannot be generalized. Anyway, they are another indication of increased efficiency of atypicals treatment over older neuroleptics in schizophrenia.

Olanzapine plus dialectical behavior therapy for women with high irritability who meet criteria for borderline personality disorder: a double-blind, placebo-controlled pilot study.

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Linehan, Marsha M; McDavid, Joshua D; Brown, Milton Z; Sayrs, Jennifer H R; Gallop, Robert J

2008-06-01

This double-blind study examined whether olanzapine augments the efficacy of dialectical behavior therapy (DBT) in reducing anger and hostility in borderline personality disorder patients. Twenty-four women with borderline personality disorder (DSM-IV criteria) and high levels of irritability and anger received 6 months of DBT. Subjects were randomly assigned to receive either low-dose olanzapine or placebo and were assessed with standardized measures in a double-blind manner. The study was conducted from September 2000 to December 2002. Intent-to-treat analyses indicated that both treatment conditions resulted in significant improvement in irritability, aggression, depression, and self-inflicted injury (p borderline personality disorder. Effect sizes were moderate to large, with the small sample size likely limiting the ability to detect significant results. Overall, there were large and consistent reductions in irritability, aggression, depression, and self-injury for both groups of subjects receiving DBT.

Prophylactic use of olanzapine and quetiapine from pregnancy to the postpartum period in women with bipolar disorder: a case series.

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Uguz, Faruk

2017-11-01

The management of bipolar disorder in pregnant and postpartum women is one of the most difficult issues in clinical practice. Data on the efficacy of mood stabilizers, except lithium and antipsychotics, in the maintenance treatment of bipolar disorders during pregnancy and postpartum period are very limited. This report presents results of prophylaxis with olanzapine and quetiapine with regard to affective episodes in pregnancy to the postpartum period.

Metformin plus sibutramine for olanzapine-associated weight gain and metabolic dysfunction in schizophrenia: a 12-week double-blind, placebo-controlled pilot study.

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Baptista, Trino; Uzcátegui, Euderruh; Rangel, Nairy; El Fakih, Yamily; Galeazzi, Tatiana; Beaulieu, Serge; de Baptista, Enma Araujo

2008-05-30

Metformin (850-1700 mg) plus sibutramine (10-20 mg, n=13) or placebo (n=15) was administered for 12 weeks in olanzapine-treated chronic schizophrenia patients. Weight loss was similar in both groups: -2.8+/-3.2 kg vs. -1.4+/-2.6 kg. Except for preventing a triglyceride increase, the drug combination lacked efficacy for metabolic control in this clinical population.

The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys

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Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M

2005-01-01

exposed to oral haloperidol, olanzapine or sham for a 17-27 month period. The resulting plasma drug levels were comparable to those seen in subjects with schizophrenia treated with these medications. After the exposure, we observed an 8-11% reduction in mean fresh brain weights as well as left cerebrum...

Impact of race on efficacy and safety during treatment with olanzapine in schizophrenia, schizophreniform or schizoaffective disorder

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Hoffmann Vicki

2010-11-01

Full Text Available Abstract Background To examine potential differences in efficacy and safety of treatment with olanzapine in patients with schizophrenia of white and black descent. Methods A post-hoc, pooled analysis of 6 randomized, double-blind trials in the treatment of schizophrenia, schizophreniform disorder, or schizoaffective disorder compared white (N = 605 and black (N = 375 patients treated with olanzapine (5 to 20 mg/day for 24 to 28 weeks. Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS total score; and positive, negative, and general psychopathology scores; and the Clinical Global Impression of Severity (CGI-S scores at 6 months. Safety measures included differences in the frequencies of adverse events along with measures of extrapyramidal symptoms, weight, glucose, and lipid changes over time. Results 51% of black patients and 45% of white patients experienced early study discontinuation (P = .133. Of those who discontinued, significantly more white patients experienced psychiatric worsening (P = .002 while significantly more black patients discontinued for reasons other than efficacy or tolerability (P = .014. Discontinuation for intolerability was not different between groups (P = .320. For the estimated change in PANSS total score over 6 months, there was no significant difference in efficacy between white and black patients (P = .928, nor on the estimated PANSS positive (P = .435, negative (P = .756 or general psychopathology (P = .165 scores. Overall, there was no significant difference in the change in CGI-S score between groups from baseline to endpoint (P = .979. Weight change was not significantly different in white and black patients over 6 months (P = .127. However, mean weight change was significantly greater in black versus white patients at Weeks 12 and 20 only (P = .028 and P = .026, respectively. Additionally, a significantly greater percentage of black patients experienced clinically significant

Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study [Corrigendum

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Wani RA

2015-03-01

Full Text Available Wani RA, Dar MA, Chandel RK, et al Title of paper should have been “Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a randomized, open-label study”.  Read the original paper 

A single-dose, randomized, two-way crossover study comparing two olanzapine tablet products in healthy adult male volunteers under fasting conditions.

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Elshafeey, Ahmed H; Elsherbiny, Mohamed A; Fathallah, Mohsen M

2009-03-01

Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The aim of this study was to assess the bioequivalence of 2 commercial 10-mg tablet formulations of olanzapine by statistical analysis of the pharmacokinetic parameters C(max), AUC from 0 to 72 hours after dosing (AUC(0-72)), and AUC(0-infinity) as required by the Egyptian health authority for the marketing of a generic product. This bioequivalence study was carried out in healthy male volunteers using a single-dose, randomized, 2-way crossover design under fasting conditions. Statistical analysis of the pharmacokinetic parameters C(max), AUC(0-72), and AUC(0-infinity) was conducted to determine bioequivalence (after log-transformation of data using analysis of variance and 90% CIs) and to gain marketing approval in Egypt. The formulations were considered to be bioequivalent if the log-transformed ratios of the 3 pharmacokinetic parameters were within the predetermined bioequivalence range (ie, 80%-125%), as established by the US Food and Drug Administration (FDA). Both the test product (Trademark: Integrol((R)) [Global Napi Pharmaceuticals, Cairo, Egypt]) and the reference product (Trademark: Zyprexa((R)) [Eli Lilly and Company, Basingstoke, Hampshire, United Kingdom]) were administered as 10-mg tablets with 240 mL of water after an overnight fast on 2 treatment days, separated by a 2-week washout period. After dosing, serial blood samples were collected for 72 hours. Plasma samples were analyzed using a sensitive, reproducible, and accurate liquid chromatography-tandem mass spectrometry method capable of quantitating olanzapine in the range of 0.167 to 16.7 ng/mL, with a lower limit of quantitation of 0.167 ng/mL. Adverse events were reported by the volunteers as instructed or observed by the resident physician, and were recorded, tabulated, and evaluated. Twenty-four healthy adult male volunteers participated in this study. Their mean (SD) age was 24.7 (6.2) years (range, 19

Early evaluation of patient risk for substantial weight gain during olanzapine treatment for schizophrenia, schizophreniform, or schizoaffective disorder

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Hardy Thomas A

2008-09-01

Full Text Available Abstract Background To make well informed treatment decisions for their patients, clinicians need credible information about potential risk for substantial weight gain. We therefore conducted a post-hoc analysis of clinical trial data, examining early weight gain as a predictor of later substantial weight gain. Methods Data from 669 (Study 1 and 102 (Study 2 olanzapine-treated patients diagnosed with schizophrenia, schizophreniform, or schizoaffective disorder were analyzed to identify and validate weight gain cut-offs at Weeks 1–4 that were predictive of substantial weight gain (defined as an increase of ≥ 5, 7, 10 kg or 7% of baseline weight after approximately 30 weeks of treatment. Baseline characteristics alone, baseline characteristics plus weight change from baseline to Weeks 1, 2, 3 or 4, and weight change from baseline to Weeks 1, 2, 3, or 4 alone were evaluated as predictors of substantial weight gain. Similar analyses were performed to determine BMI increase cut-offs at Weeks 1–4 of treatment that were predictive of substantial increase in BMI (1, 2 or 3 kg/m2 increase from baseline. Results At Weeks 1 and 2, predictions based on early weight gain plus baseline characteristics were more robust than those based on early weight gain alone. However, by Weeks 3 and 4, there was little difference between the operating characteristics associated with these two sets of predictors. The positive predictive values ranged from 30.1% to 73.5%, while the negative predictive values ranged from 58.1% to 89.0%. Predictions based on early BMI increase plus baseline characteristics were not uniformly more robust at any time compared to those based on early BMI increase alone. The positive predictive values ranged from 38.3% to 83.5%, while negative predictive values ranged from 42.1% to 84.7%. For analyses of both early weight gain and early BMI increase, results for the validation dataset were similar to those observed in the primary dataset

Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

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Ye W

2014-05-01

Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: The aims of this analysis were to identify factors associated with early response (at 4 weeks to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China.Methods: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330. Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine.Results: One hundred and thirty patients (40% achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97, fewer years since first diagnosis (OR 0.94, CI 0.90–0.98, a greater number of social activities (OR 1.22, CI 1.05–1.40, participation in a weight control program (OR 1.81, CI 1.04–3.15, and high adherence

MK-801-induced deficits in social recognition in rats: reversal by aripiprazole, but not olanzapine, risperidone, or cannabidiol.

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Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Kikuchi, Tetsuro; Stott, Colin; Riedel, Gernot

2015-12-01

Deficiencies in social activities are hallmarks of numerous brain disorders. With respect to schizophrenia, social withdrawal belongs to the category of negative symptoms and is associated with deficits in the cognitive domain. Here, we used the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801) for induction of social withdrawal in rats and assessed the efficacy of several atypical antipsychotics with different pharmacological profiles as putative treatment. In addition, we reasoned that the marijuana constituent cannabidiol (CBD) may provide benefit or could be proposed as an adjunct treatment in combination with antipsychotics. Hooded Lister rats were tested in the three-chamber version for social interaction, with an initial novelty phase, followed after 3 min by a short-term recognition memory phase. No drug treatment affected sociability. However, distinct effects on social recognition were revealed. MK-801 reduced social recognition memory at all doses (>0.03 mg/kg). Predosing with aripiprazole dose-dependently (2 or 10 mg/kg) prevented the memory decline, but doses of 0.1 mg/kg risperidone or 1 mg/kg olanzapine did not. Intriguingly, CBD impaired social recognition memory (12 and 30 mg/kg) but did not rescue the MK-801-induced deficits. When CBD was combined with protective doses of aripiprazole (CBD-aripiprazole at 12 :  or 5 : 2 mg/kg) the benefit of the antipsychotic was lost. At the same time, activity-related changes in behaviour were excluded as underlying reasons for these pharmacological effects. Collectively, the combined activity of aripiprazole on dopamine D2 and serotonin 5HT1A receptors appears to provide a significant advantage over risperidone and olanzapine with respect to the rescue of cognitive deficits reminiscent of schizophrenia. The differential pharmacological properties of CBD, which are seemingly beneficial in human patients, did not back-translate and rescue the MK-801-induced social memory deficit.

Comparison of clinical outcomes with orodispersible versus standard oral olanzapine tablets in nonadherent patients with schizophrenia or bipolar disorder.

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Novick, Diego; Montgomery, William; Treuer, Tamas; Koyanagi, Ai; Aguado, Jaume; Kraemer, Susanne; Haro, Josep Maria

2017-01-01

Medication nonadherence is common in the treatment of patients with severe mental illness and is a frequent cause of relapse. Different formulations have been developed in an effort to improve medication adherence. The aim of this study was to explore whether there are differential clinical outcomes between two different formulations of olanzapine (orodispersible tablets [ODTs] vs standard oral tablets [SOT]) for the treatment of nonadherent patients with schizophrenia or bipolar disorder. Data for this analysis were from an observational study conducted in Europe (N=903). Adult schizophrenia and bipolar disorder patients in outpatient settings who initiated or changed to either olanzapine ODT or SOT according to physician decision within the last 45 days were eligible for enrollment. The follow-up period was 1 year. Of the 903 participants, 266 nonadherent patients (Medication Adherence Rating Scale score 0-4 at baseline) were included in the analysis. Clinical outcomes of interest were: 1) hospitalization and 2) relapse identified by the participating psychiatrist or hospitalization. An adjusted logistic regression model was fitted. Patients taking ODT had more severe illness at baseline ( P <0.001) as assessed with the Clinical Global Impression with mean (standard deviation [SD]) scores of ODT 4.63 (1.03) and SOT 4 (1.16). In the regression models adjusted for potential confounders, patients taking ODT had significantly lower odds for hospitalization (odds ratio =0.355; 95% confidence interval =0.13-0.974) and relapse or hospitalization (odds ratio =0.368; 95% confidence interval =0.183-0.739), respectively. Nonadherent patients with schizophrenia or bipolar disorder treated with the orodispersible formulation were less likely to be hospitalized or suffer relapse compared to those patients taking the standard oral coated tablets.

Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine Metabolismo calórico, leptina e parâmetros bioquímicos se alteram em ratos submetidos à administração crônica de olanzapina

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Alexandra I. Zugno

2012-06-01

Full Text Available OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control; Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric; and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle, and Groups 2, 3, and 4 (liver. Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.OBJETIVOS: A olanzapina, uma droga antipsicótica atípica com afinidade por locais de ligação de dopamina, serotonina e histamina, parece se associar a um ganho de peso e a alterações metabólicas consideráveis. O objetivo desse estudo foi avaliar o ganho de peso e as alterações metabólicas em ratos tratados com olanzapina numa dieta hipercalórica. MÉTODOS: Usamos 40 ratos divididos em 4 grupos: Grupo 1, condições padrão de alimento e água (controle; Grupo 2, dieta padrão mais olanzapina; Grupo 3, dieta hipercalórica; e Grupo 4, olanzapina mais dieta hipercalórica. Olanzapina foi administrada por gavagem a uma dose de 3 mg/kg por 9 semanas. RESULTADOS: Não houve alterações significativas nos níveis de colesterol

DRD2/AKT1 interaction on D2 c-AMP independent signaling, attentional processing, and response to olanzapine treatment in schizophrenia.

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Blasi, Giuseppe; Napolitano, Francesco; Ursini, Gianluca; Taurisano, Paolo; Romano, Raffaella; Caforio, Grazia; Fazio, Leonardo; Gelao, Barbara; Di Giorgio, Annabella; Iacovelli, Luisa; Sinibaldi, Lorenzo; Popolizio, Teresa; Usiello, Alessandro; Bertolino, Alessandro

2011-01-18

The D2/AKT1/GSK-3β signaling pathway has been involved in the downstream intracellular effects of dopamine, in the pathophysiology of cognitive deficits and related brain activity in schizophrenia, as well as in response to treatment with antipsychotics. Polymorphisms in the D2 (DRD2 rs1076560) and AKT1 (AKT1 rs1130233) genes have been associated with their respective protein expression and with higher-order cognition and brain function, including attention. Given the strong potential for their relationship, we investigated the interaction of these polymorphisms on multiple molecular and in vivo phenotypes associated with this signaling pathway. We measured AKT1 and GSK-3β proteins and phosphorylation in human peripheral blood mononuclear cells, functional MRI cingulate response during attentional control, behavioral accuracy during sustained attention, and response to 8 wk of treatment with olanzapine in a total of 190 healthy subjects and 66 patients with schizophrenia. In healthy subjects, we found that the interaction between the T allele of DRD2 rs1076560 and the A allele of AKT1 rs1130233 was associated with reduced AKT1 protein levels and reduced phosphorylation of GSK-3β, as well as with altered cingulate response and reduced behavioral accuracy during attentional processing. On the other hand, interaction of these two alleles was associated with greater improvement of Positive and Negative Syndrome Scale scores in patients with schizophrenia after treatment with olanzapine. The present results indicate that these functional polymorphisms are epistatically associated with multiple phenotypes of relevance to schizophrenia. Our results also lend support to further investigation of this downstream molecular pathway in the etiology and treatment of this disorder.

Anthropometric parameters as indicators of metabolic derangements in schizophrenia patients stabilized on olanzapine in an Indian rural population

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Jayanta Kumar Rout

2012-01-01

Full Text Available Context: For any given body mass, Asian Indians have higher central obesity than Europeans. A periodic measurement of body mass index (BMI and waist hip ratio (WHR is practically more feasible than other parameters of metabolic syndrome by repeated blood collection. However, few studies are available on the relative importance of BMI and WHR as markers of dyslipidemia and insulin resistance in schizophrenia patients stabilized on second generation antipsychotics in Indian population. Aim: We conducted the present study on such patients to examine whether BMI or WHR can better predict dyslipidemia and insulin resistance in these patients in a rural area. Settings and Design: The study was a hospital based case control study under rural settings on 38 schizophrenia patients stabilized on olanzapine and 30 matched controls. Materials and Methods: Fasting concentrations of blood glucose, lipid parameters and serum insulin were assessed. Data for Homeostatic model for assessment of insulin resistance (HOMA-IR, BMI, and WHR were obtained to assess the insulin resistance, overall body fat distribution and abdominal fat dispensation respectively. Statistical analysis used: ′t′ test was performed to assay any difference in corresponding mean values between cases and controls. Dependence of HOMA-IR on key parameters was assessed by analysis of co-variance (ANCOVA study. Results: Cases exhibited significantly higher values for HOMA-IR, serum triglyceride and low density lipoprotein cholesterol (LDLc with a significantly lower high density lipoprotein cholesterol (HDLc level. ANCOVA study reflected that irrespective of age and sex, HOMA-IR was dependent on serum triglyceride level and WHR (F=8.3 and 5.7 respectively, P<0.05, but not on BMI (F<0.001, P=0.997. Conclusions: Central obesity could be more closely associated with the pathogenesis of prediabetic state in our case group. So, WHR is a better anthropometric parameter than BMI for an early

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats.

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Ratajczak, P; Kus, K; Gołembiowska, K; Noworyta-Sokołowska, K; Woźniak, A; Zaprutko, T; Nowakowska, E

2016-09-01

The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance.

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Remington, Gary J; Teo, Celine; Wilson, Virginia; Chintoh, Araba; Guenette, Melanie; Ahsan, Zohra; Giacca, Adria; Hahn, Margaret K

2015-11-01

Antipsychotics (APs) are linked to diabetes, even without weight gain. Whether anti-diabetic drugs are efficacious in reversing the direct effects of APs on glucose pathways is largely undetermined. We tested two metformin (Met) doses to prevent impairments seen following a dose of olanzapine (Ola) (3 mg/kg); glucokinetics were measured using the hyperinsulinemic-euglycemic clamp (HIEC). Met (150 mg/kg; n=13, or 400 mg/kg; n=11) or vehicle (Veh) (n=11) was administered through gavage preceding an overnight fast, followed by a second dose prior to the HIEC. Eleven additional animals were gavaged with Veh and received a Veh injection during the HIEC (Veh/Veh); all others received Ola. Basal glucose was similar across treatment groups. The Met 400 group had significantly greater glucose appearance (Ra) in the basal period (i.e., before Ola, or hyperinsulinemia) vs other groups. During hyperinsulinemia, glucose infusion rate (GINF) to maintain euglycemia (reflective of whole-body insulin sensitivity) was higher in Veh/Veh vs other groups. Met 150/Ola animals demonstrated increased GINF relative to Veh/Ola during early time points of the HIEC. Glucose utilization during hyperinsulinemia, relative to basal conditions, was significantly higher in Veh/Veh vs other groups. The change in hepatic glucose production (HGP) from basal to hyperinsulinemia demonstrated significantly greater decreases in Veh/Veh and Met 150/Ola groups vs Veh/Ola. Given the increase in basal Ra with Met 400, we measured serum lactate (substrate for HGP), finding increased levels in Met 400 vs Veh and Met 150. In conclusion, Met attenuates hepatic insulin resistance observed with acute Ola administration, but fails to improve peripheral insulin resistance. Use of supra-therapeutic doses of Met may mask metabolic benefits by increasing lactate. © 2015 Society for Endocrinology.

Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder: A Randomized Clinical Trial.

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Larsen, Julie R; Vedtofte, Louise; Jakobsen, Mathilde S L; Jespersen, Hans R; Jakobsen, Michelle I; Svensson, Camilla K; Koyuncu, Kamuran; Schjerning, Ole; Oturai, Peter S; Kjaer, Andreas; Nielsen, Jimmi; Holst, Jens J; Ekstrøm, Claus T; Correll, Christoph U; Vilsbøll, Tina; Fink-Jensen, Anders

2017-07-01

Compared with the general population, patients with schizophrenia have a 2- to 3-fold higher mortality rate primarily caused by cardiovascular disease. Previous interventions designed to counteract antipsychotic-induced weight gain and cardiometabolic disturbances reported limited effects. To determine the effects of the glucagon-like peptide-1 receptor agonist liraglutide added to clozapine or olanzapine treatment of schizophrenia spectrum disorders. This randomized clinical double-blind trial enrolled participants at 2 clinical sites in Denmark. Of 214 eligible participants with a schizophrenia spectrum disorder, 103 were randomized to liraglutide or placebo. Participants received stable treatment with clozapine or olanzapine, were overweight or obese, and had prediabetes. Data were collected from May 1, 2013, through February 25, 2016. Treatment for 16 weeks with once-daily subcutaneous injection of liraglutide or placebo. Trial drug therapy was titrated during the first 2 weeks of the study. The primary end point was change in glucose tolerance estimated by a 75-g oral glucose tolerance test result. Secondary end points included change in body weight and cardiometabolic parameters. Of the 103 patients undergoing randomization (60 men [58.3%] and 43 women [41.7%]), 97 were included in the efficacy analysis, with a mean (SD) age of 42.5 (10.5) years and mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 33.8 (5.9). The liraglutide and placebo groups had comparable characteristics (mean [SD] age, 42.1 [10.7] vs 43.0 [10.5] years; 30 men in each group; mean [SD] body mass index, 33.7 [5.1] vs 33.9 [6.6]). A total of 96 randomized participants (93.2%) completed the trial. Glucose tolerance improved in the liraglutide group compared with the placebo group (P < .001). Altogether, 30 liraglutide-treated participants (63.8%) developed normal glucose tolerance compared with 8 placebo-treated participants (16.0%) (P�

Dose reduction of risperidone and olanzapine can improve cognitive function and negative symptoms in stable schizophrenic patients: A single-blinded, 52-week, randomized controlled study.

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Zhou, Yanling; Li, Guannan; Li, Dan; Cui, Hongmei; Ning, Yuping

2018-05-01

The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all pNegative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all pnegative symptoms in patients with stabilized schizophrenia.

Mesoporous hydroxyapatite as a carrier of olanzapine for long-acting antidepression treatment in rats with induced depression.

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Shyong, Yan-Jye; Wang, Mao-Hsien; Kuo, Li-Wei; Su, Chang-Fu; Kuo, Wei-Ting; Chang, Kuo-Chi; Lin, Feng-Huei

2017-06-10

An antidepressant carrier, mesoporous hydroxyapatite olanzapine (mesoHAP-OLZ), was designed to maintain 3weeks of constant medication release. The carrier was intramuscularly (IM) injected, where cellular activity played a role in achieving the goal of constant release. The efficiency of the treatment was evaluated from 3 perspectives in in vivo studies: locomotor activities, biomarkers, and learning and memory ability. MesoHAP-OLZ can increase the locomotor activity in rats with induced depression determined by open field test (OFT) and forced swim test (FST). Serotonin (5-HT), one of the most important biomarker in depression can also be increased by mesoHAP-OLZ, leading to increased hippocampus activity as measured by functional magnetic resonance imaging (fMRI). MesoHAP-OLZ can also improve learning and memory ability in rats with induced depression during Morris water maze (MWM) test. Our findings further show that mesoHAP-OLZ can provide long-term drug release with a single IM injection, helping to solve the problem of non-adherent medication intake that often occurs in antidepressant therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Quality by Design in the development of hydrophilic interaction liquid chromatography method with gradient elution for the analysis of olanzapine.

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Tumpa, Anja; Stajić, Ana; Jančić-Stojanović, Biljana; Medenica, Mirjana

2017-02-05

This paper deals with the development of hydrophilic interaction liquid chromatography (HILIC) method with gradient elution, in accordance with Analytical Quality by Design (AQbD) methodology, for the first time. The method is developed for olanzapine and its seven related substances. Following step by step AQbD methodology, firstly as critical process parameters (CPPs) temperature, starting content of aqueous phase and duration of linear gradient are recognized, and as critical quality attributes (CQAs) separation criterion S of critical pairs of substances are investigated. Rechtschaffen design is used for the creation of models that describe the dependence between CPPs and CQAs. The design space that is obtained at the end is used for choosing the optimal conditions (set point). The method is fully validated at the end to verify the adequacy of the chosen optimal conditions and applied to real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of federal and state off-label marketing investigations on drug prescribing: The case of olanzapine.

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Wang, Bo; Studdert, David M; Sarpatwari, Ameet; Franklin, Jessica M; Landon, Joan; Kesselheim, Aaron S

2017-01-01

In the past decade, the federal government has frequently investigated and prosecuted pharmaceutical manufacturers for illegal promotion of drugs for indications not approved by the Food and Drug Administration (FDA) ("off-label" uses). State governments can choose to coordinate with the federal investigation, or pursue their own independent state investigations. One of the largest-ever off-label prosecutions relates to the atypical antipsychotic drug olanzapine (Zyprexa). In a series of settlements between 2008 and 2010, Eli Lilly paid $1.4 billion to the federal government and over $290 million to state governments. We examined the effect of these settlements on off-label prescribing of this medication, taking advantage of geographical differences in states' involvement in the investigations and the timing of the settlements. However, we did not find a reduction in off-label prescribing; rather, there were no prescribing changes among states that joined the federal investigation, those that pursued independent state investigations, and states that pursued no investigations at all. Since the settlements of state investigations of off-label prescribing do not appear to significantly impact prescribing rates, policymakers should consider alternate ways of reducing the prevalence of non-evidence-based off-label use to complement their ongoing investigations.

LC–MS/MS assay for olanzapine in human plasma and its application to a bioequivalence study

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Dinesh S. Patel

2012-10-01

Full Text Available This paper describes a selective and sensitive assay for the determination of olanzapine (OLZ in human plasma based on liquid chromatography–tandem mass spectrometry (LC–MS/MS. The analyte and quetiapine as internal standard (IS were extracted from 200 μL plasma via solid phase extraction on Waters Oasis HLB cartridges. Chromatographic separation was achieved on an ACE 5C18-300 column (100 mm×4.6 mm, 5 μm under isocratic conditions in a run time of 3.5 min. Mass spectrometric detection involved electrospray ionization in the positive ion mode followed by multiple reaction monitoring (MRM of the transitions at m/z 313/256 for OLZ and m/z 384/253 for the IS. The assay was linear in the range 0.10–40.0 ng/mL with a lower limit of quantitation and limit of detection of 0.10 and 0.012 ng/mL, respectively. Intra- and inter-day precision (as coefficient of variation and relative recovery were 90%, respectively. The method was successfully applied to a bioequivalence study of 5 and 10 mg OLZ disintegrating tablets in 40 healthy Indian males with reproducibility by incurred sample reanalysis in the range −7.43 to 8.07%.

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine.

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Zhang, Chen; Li, Ming

2012-02-01

Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL or OLZ for 5 consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated HAL or OLZ treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with HAL or OLZ did not show a stronger inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may develop an association with unconditional drug effects through a Pavlovian conditioning process. They may also serve as occasion setters to modulate the expression of sensitized responses. As antipsychotic sensitization mimics the clinical

Hypomania after augmenting venlafaxine and olanzapine with sarcosine in a patient with schizophrenia: a case study

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Strzelecki D

2015-02-01

Full Text Available Dominik Strzelecki, Justyna Szyburska, Magdalena Kotlicka-Antczak, Olga KałużyńskaDepartment of Affective and Psychotic Disorders, Medical University of Lódz, Central Clinical Hospital, Lódz, PolandAbstract: Glutamate is the main excitatory neurotransmitter in the central nervous system. Dysfunction of the glutamatergic system plays an important and well-established role in the pathogenesis of schizophrenia. Agents with glutamatergic properties such as N-methyl-D-aspartate receptor coagonists (ie, glycine, D-cycloserine and glycine transporter type 1 inhibitors (eg, sarcosine, bitopertin are investigated in schizophrenia with special focus on negative and cognitive symptomatology. In this article, we describe a case of a 34-year-old woman with diagnosis of schizophrenia with persistent moderate negative and cognitive symptoms, a participant of the Polish Sarcosine Study (PULSAR treated with olanzapine (25 mg per day and venlafaxine (75 mg per day. During ten weeks of sarcosine administration (2 g per day the patient’s activity and mood improved, but in the following 2 weeks, the patient reported decreased need for sleep, elevated mood, libido and general activity. We diagnosed drug-induced hypomania and recommended decreasing the daily dose of venlafaxine to 37.5 mg per day, which resulted in normalization of mood and activity in about 1 week. After this change, activity and mood remained stable and better than before adding sarcosine, and subsequent depressive symptoms were not noted. We describe here the second case report where sarcosine induced important affect changes when added to antidepressive and antipsychotic treatment, which supports the hypothesis of clinically important glutamate–serotonin interaction.Keywords: MNDA receptor, glutamatergic system, serotoninergic system

Probing of possible olanzapine binding site on human serum albumin: Combination of spectroscopic methods and molecular dynamics simulation

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Shahlaei, Mohsen; Rahimi, Behnoosh; Ashrafi-Kooshk, Mohammad Reza; Sadrjavadi, Komail; Khodarahmi, Reza

2015-01-01

Human serum albumin (HSA)-drug binding affinity is one of the major factors that determine the pharmacokinetics, halftime and bioavailability of drugs in various tissues. In the present study, the interaction of olanzapine (OLZ), a thienobenzodiazepine drug, administered for the treatment of schizophrenia and bipolar disorder, with HSA has been studied using spectroscopic methods such as ultraviolet absorbance, fluorescence and FTIR combined with computational procedures. Analyzing of the Stern–Volmer quenching data showed only one primary binding site on HSA with a binding constant of 4.12×10 4 M −1 at 298 K. Thermodynamic analyses showed enthalpy change (ΔH°) and entropy change (ΔS°) were 28.03±3.42 kJ mol −1 and −25.52±11.52 J mol −1 K −1 , respectively. Molecular docking results suggested the hydrophobic residues such as Val 216 , Leu 327 , Ala 350 and polar residues such as Glu 354 play an important role in the drug binding. Decrement in α-helix content of the protein upon OLZ binding was also confirmed by evidences provided by molecular dynamics simulation as well as FTIR spectroscopy. - Highlights: • Leu 327 , Ala 350 as well as hydrophilic residues of HSA play an important role in the binding reaction. • The drug has only one primary binding site on HSA with a binding constant of 4.12×10 4 M −1 at 298 K. • The drug binds near to site I

Probing of possible olanzapine binding site on human serum albumin: Combination of spectroscopic methods and molecular dynamics simulation

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Shahlaei, Mohsen, E-mail: mohsenshahlaei@yahoo.com [Nano drug delivery research Center, Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Rahimi, Behnoosh [Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Student research committee, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Ashrafi-Kooshk, Mohammad Reza [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Sadrjavadi, Komail [Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Khodarahmi, Reza, E-mail: rkhodarahmi@mbrc.ac.ir [Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of)

2015-02-15

Human serum albumin (HSA)-drug binding affinity is one of the major factors that determine the pharmacokinetics, halftime and bioavailability of drugs in various tissues. In the present study, the interaction of olanzapine (OLZ), a thienobenzodiazepine drug, administered for the treatment of schizophrenia and bipolar disorder, with HSA has been studied using spectroscopic methods such as ultraviolet absorbance, fluorescence and FTIR combined with computational procedures. Analyzing of the Stern–Volmer quenching data showed only one primary binding site on HSA with a binding constant of 4.12×10{sup 4} M{sup −1} at 298 K. Thermodynamic analyses showed enthalpy change (ΔH°) and entropy change (ΔS°) were 28.03±3.42 kJ mol{sup −1} and −25.52±11.52 J mol{sup −1} K{sup −1}, respectively. Molecular docking results suggested the hydrophobic residues such as Val{sub 216}, Leu{sub 327}, Ala{sub 350} and polar residues such as Glu{sub 354} play an important role in the drug binding. Decrement in α-helix content of the protein upon OLZ binding was also confirmed by evidences provided by molecular dynamics simulation as well as FTIR spectroscopy. - Highlights: • Leu{sub 327}, Ala{sub 350} as well as hydrophilic residues of HSA play an important role in the binding reaction. • The drug has only one primary binding site on HSA with a binding constant of 4.12×10{sup 4} M{sup −1} at 298 K. • The drug binds near to site I.

Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

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Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

2016-05-01

Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

Costi del trattamento con oloprazina nelle fasi iniziali della schizofrenia

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Domenico Berardi

2002-06-01

Full Text Available Objective: In Italy, use of olanzapine in the public sector was limited by law to patients that had failed treatment with conventional antipsychotics, due to the higher purchase price of the drug. This restriction prevented first-episode patients and patients early in the course of their illness from being treated with olanzapine. The present study investigates economic consequences of this policy. Design: The present study retrospectively outlines treatment costs of patients switched to olanzapine during the early stages of schizophrenia as compared to the costs of patients switched during a later stage of the illness. Setting: The study was conducted within Italian Community Mental Health Services. Patients: The cost of pharmacological and non-pharmacological treatment was retrospectively calculated in 25 out-patients with schizophrenia and related disorders over a one-year span. Thirteen patients were switched to olanzapine in the early stage of their illness, prior to drug approval under a compassionate use regimen. Twelve patients started olanzapine under the restriction in a later stage of illness following failed treatment with a conventional antipsychotic. Results: While total treatment costs between the two groups was similar, cost distribution was different. Early Switch patients had higher drug costs and higher rehabilitation costs, while Late Switch patients had higher hospitalisation costs. Conclusions: Small patient numbers and design limitations prevent conclusions being drawn regarding the ultimate impact on outcome and total treatment cost of restriction of olanzapine to second-line use. Despite this, our findings demonstrate that within the context of the Italian CMHS, patients treated with olanzapine while still in the early stages of schizophrenia do not necessarily cost more overall compared to patients who receive olanzapine after failing treatment with a conventional antipsychotic.

Influenza del trattamento della schizofrenia con neurolettici tipici o olanzapina sui costi sanitari e sugli outcomes lavorativi

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Angelomarco Barioglio

2005-06-01

Full Text Available The aim of the present study was to evaluate the global treatment cost of schizophrenia with olanzapine or typical neuroleptics, according to Local Health Care Unit point of view. This analysis was performed through naturalistic observation of a cohort of schizophrenic patients referring to Ascoli Piceno ASL Department of Mental Health during 4 years (2001-2004. During year 2003, investigators have identified a cohort of patients who were undergoing treatment switch from typical neuroleptics to olanzapine. These patients, after the switch, are observed prospectively for the next 2 years and retrospectively for the last 2 years of treament. This method allow us to collect data about 4 years of treatment: 2 years of typical neuroleptic treatment followed by 2 years of olanzapine treatment. The present work is presenting the analysis of the first 3 years of observation. The results of our analysis are demonstrating that olanzapine treatment, through a better patient-physician alliance and with rehabilitative activities, allow lower total medical costs for the treatment of schizophrenia than typical neuroleptics. The higher acquisition cost of olanzapine versus typical neuroleptics was compensated by less hospitalizations and territorial medical interventions. During olanzapine treatment patients followed more rehabilitative activities (+71,26%, p <0,0001 and increased their working activities (+39,13%, p< 0,001.

Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

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Onaolapo, Olakunle James; Ademakinwa, Olayemi Quyyom; Olalekan, Temitayo Opeyemi; Onaolapo, Adejoke Yetunde

2017-09-01

We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

Schizophrenia symptoms and functioning in patients receiving long-term treatment with olanzapine long-acting injection formulation: a pooled analysis

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Peuskens Joseph

2012-08-01

Full Text Available Abstract Background This analysis of pooled data evaluates treatment outcomes of patients with schizophrenia receiving maintenance treatment with olanzapine long-acting injection (OLAI by means of a categorical approach addressing the symptomatic and functional status of patients at different times. Methods Patients were grouped into 5 categories at baseline, 6 months, and 12 months. Shifts between categories were assessed for individual patients and factors associated with improvement were analyzed. 1182 patients from 3 clinical trials were included in the current analysis. Results At baseline, 434 (36.8% patients had minimal Positive and Negative Syndrome Scale (PANSS symptoms but seriously impaired Heinrich Carpenter’s Quality of Life Scale (QLS functioning; 303 (25.6% had moderate to severe symptoms and seriously impaired function; 208 (17.6% had mild to moderate symptoms but good functioning, and 162 (13.7% had minimal symptoms and good functioning. Baseline category was significantly associated with Clinical Global Impression – Severity (CGI-S, extrapyramidal symptoms, working status, age, and number of previous episodes. The majority of all patients starting OLAI treatment maintained or improved (62% at 6 months and 52% at 12 months their symptom and functioning levels on OLAI maintenance treatment. Less than 8% of the patients showed worsening of symptoms or functioning. An improvement in category was associated with high PANSS positive and low CGI-S scores at baseline. Conclusions We present evidence that a composite assessment of schizophrenic patients including symptom severity and functioning is helpful in the evaluation of maintenance treatment outcomes. This approach could also be useful for the assessment of treatment options in clinical practice. The trials from which data are reported here were registered on clinicaltrials.gov as NCT00088491, NCT00088465, and NCT00320489.

METHODS ELABORATION ON DETECTION OF SOME ATYPICAL NEUROLYTIC AGENTS FOR CHEMICAL AND TOXICOLOGICAL ANALYSIS

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I. P. Remezova

2014-01-01

Full Text Available It is necessary to elaborate methods of atypical neuroleptic agents detection as individual substances and in different combinations as well for diagnosis of poisoning by some of them: clozapine, risperidone, sertindole, olanzapine, aripiprazole. The purpose of this work is methods elaboration of detection of clozapine, risperidone, sertindole, olanzapine, aripiprazole, haloperidol, oxazepam, carbamazapine using TLC, HPLC and UV spectrophotometry methods. During this work we used tablet forms of clozapine, risperidone, sertindole, olanzapine, aripiprazole. It is possible to use solution systems like ethanol-water-25% ammonia solution (8:1:1, toluolacetone-ethanol-25% ammonia solution (45:45:7.5:2.5, dioxan-chloroform-acetone-25% ammonia solution (47.5:45:5:2.5 for preliminary examination of atypical neuroleptic agents under study in combination with typical neuroleptics and tranquilizers with undirected analysis (general screening. System of solvents ethyl-acetate-chloroform-25% ammonia solution (85:10:5 is recommended to use for individual screening of risperidone, sertindole, olanzapine, haloperidol, benzol-ethanol-25% ammonia solution (50:10:0.5 system to use for clozapine, sertindole, olanzapine. Ethanol-25% ammonia solution (100:1.5 system is reasonable to use for chromatographic clearance of extracts from biological substances under study. We recommend using HPLC method and UV spectrophotometry for carrying out of a principal examination of clozapine, risperidone, sertindole, olanzapine and aripiprazole in case one of the substances under study is determined in the object.

Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of the European Medicines Agency/European Medicines Agency Adverse Drug Reactions' Database.

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Chiappini, Stefania; Schifano, Fabrizio

2018-02-01

A recent years' increase in both prescribing and availability of second-generation antipsychotics (SGAs) has been observed. According to the literature, typically made up by case studies/series, quetiapine seems to be the most commonly misused SGA, with both intranasal and intravenous intake modalities having been described. Another SGA that has been anecdotally reported to be misused is olanzapine. For these molecules, both a previous history of drug misuse and being an inmate have been described as factors associated with misuse. Hence, while providing here an updated literature review of the topic, we aimed at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as reported to the European Medicines Agency's EudraVigilance (EV) database; this was carried out in comparison with the reference drug olanzapine. All spontaneous, European Medicines Agency database reports relating to both quetiapine (2005-2016) and olanzapine (2004-2016) misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive analysis was performed. From the EV database, 18,112 (8.64% of 209,571) and 4178 (7.58% of 55,100) adverse drug reaction reports of misuse/abuse/dependence/withdrawal were associated with quetiapine and olanzapine, respectively. The resulting proportional reporting ratio values suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse drug reactions were more frequently reported for quetiapine (1.07, 1.01, and 5.25, respectively) in comparison with olanzapine. Despite data collection limitations, present EV data may suggest that, at least in comparison with olanzapine, quetiapine misuse may be a cause for concern.

Interruzione del trattamento nei pazienti con schizofrenia che ricevono olanzapina o aripiprazolo: metanalisi degli studi clinici controllati

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Benedetta Santarlasci

2005-03-01

Full Text Available BACKGROUND: In schizophrenia the drop-out rate can be used as proxy of effectiveness. The drop-out evaluation is also important considering the relevant economic impact for NHS of an antipsychotic therapy discontinuation in terms of patient hospitalization and other related healthcare resources consumption. OBJECTIVE: To analyze the differences in the rates of drop-out from clinical trials between olanzapine and aripiprazole. METHODS: Literature search was based on MEDLINE, on Iowa-IDIS and Drugdex databases (1966-Dec 2004. Analysis included 12 randomized controlled trials (3.778 patients, 8 for olanzapine (2.559 patients and 4 for aripiprazole (1.219 patients. RCT inclusion criteria were: a Patients affected by schizophrenia; b Randomized assignment to olanzapine or aripiprazole treatment group; c Number of patients included in the treatment group higher than 100; d Drop-out frequency evaluation between 4th and 26th weeks of follow-up. RESULTS: The rate of treatment discontinuation was greater for aripiprazole than for olanzapine (42,2% vs. 31,6% respectively. The comparison between drop-out percentages is statistically significant (p<0,001. CONCLUSIONS: The incidence of drop-outs was better controlled in the olanzapine group of studies than in the aripiprazole group of studies.

A randomized, double-blind, placebo-controlled proof of concept study to evaluate samidorphan in the prevention of olanzapine-induced weight gain in healthy volunteers.

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Silverman, Bernard L; Martin, William; Memisoglu, Asli; DiPetrillo, Lauren; Correll, Christoph U; Kane, John M

2017-11-17

Antipsychotic medications are associated with weight gain and adverse metabolic effects that complicate the treatment and management of schizophrenia. Olanzapine (OLZ) in particular is associated with significant weight gain and adverse metabolic effects. The present Phase 1, proof of concept, multicenter, randomized, double-blind, placebo-controlled study investigated the safety and effect on weight of a combination of OLZ (10mg) and the opioid modulator samidorphan (SAM; 5mg) in comparison to OLZ alone in healthy, male normal weight volunteers. Altogether, 106 male subjects with stable body weight and BMI 18-25kg/m 2 were randomized to OLZ alone, OLZ+SAM, SAM alone, or placebo in a 2:2:1:1 ratio. The primary efficacy endpoint, mean (SD) body weight change from baseline to last assessment in the 3-week treatment period, was significantly less for OLZ+SAM vs. OLZ alone subjects [+2.2 (1.4) kg vs. +3.1 (1.9) kg; respectively; p=0.02]. In contrast, there was no significant difference in weight from baseline for either SAM or placebo [+0.1 (1.0) kg and +0.8 (1.4) kg, respectively]; p=0.09. Overall, OLZ+SAM compared to OLZ alone had similar safety and tolerability. In addition, less nausea was observed in subjects given OLZ+SAM compared to SAM alone. Thus, OLZ+SAM may offer effective treatment of schizophrenia with less weight gain and metabolic risk. Additional research exploring additional doses over longer durations in psychiatric populations is warranted. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal naturalistic approach.

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Castro-Fornieles, Josefina; Parellada, Mara; Soutullo, César A; Baeza, Immaculada; Gonzalez-Pinto, Ana; Graell, Montserrat; Paya, Beatriz; Moreno, Dolores; de la Serna, Elena; Arango, Celso

2008-08-01

The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months. Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months. Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.

Olanzapine Injection

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... It works by changing the activity of certain natural substances in the brain. ... signs of infection excessive sweating muscle stiffness confusion fast or ... the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study.

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Joseph F Hayes

2016-08-01

Full Text Available There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148, valproate (n = 1670, olanzapine (n = 1477, or quetiapine (n = 1376 as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43. Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001. Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012 and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003, compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007 and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013 were also reduced relative

Livello di dipendenza dai Servizi Territoriali e costi relativi al trattamento della schizofrenia

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Giorgio D’Allio

2005-12-01

Full Text Available The present study was designed to evaluate the level of dependence from Mental Health Care Department, in Casale Monferrato, of three groups of psychotic patients treated with olanzapine (31, risperidone (30 or typical neuroleptics (31. The observation was retrospective, lasting one year (2003-2004, and collected data relative to health care resources as specialist visits, home interventions operated by nurses or physicians, drug administration, rehabilitation, psychotherapy, hospitalizations. The data collected allowed to evidentiate substantial differences among olanzapine and risperidone treated patients, usually younger, versus typical treated patients, usually older and more chronic. In general, atypical treated patients, evidentiate a reduction of home nurse intervention in respect to typical treated patients while olanzapine shows a trend in hospitalization and specialist visits reduction versus risperidone. Total health care costs are not significantly different among the three groups but evidentiate interventions more oriented to rehabilitation in the group treated with olanzapine while risperidone treated patients needed a major number of hospitalizations. Typical treated patients requested, instead, an high number of home intervention due to their chronic conditions and cognitive imparement.

Cost effectiveness of long-acting risperidone injection versus alternative antipsychotic agents in patients with schizophrenia in the USA.

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Edwards, Natalie C; Locklear, Julie C; Rupnow, Marcia F T; Diamond, Ronald J

2005-01-01

The availability of long-acting risperidone injection may increase adherence and lead to improved clinical and economic outcomes for individuals with schizophrenia. The objective of this study was to assess the cost effectiveness of long-acting risperidone, oral risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and haloperidol depot in patients with schizophrenia over 1 year from a healthcare system perspective. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were utilized to populate a decision analytical model comparing the seven treatment alternatives. The model captured rates of patient compliance, the rates, frequency and duration of relapse, incidence of adverse events, and healthcare resource utilization and associated costs. Primary outcomes were expressed in terms of percentage of patients relapsing per year, number of relapse days per year (number and duration of relapses per patient per year), and total direct 2003 medical cost per patient per year. On the basis of model projections, the proportions of patients experiencing a relapse requiring hospitalization in 1 year were 66% for haloperidol depot, 41% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 26% for long-acting risperidone, whereas the proportions of patients with an exacerbation not requiring hospitalization were 60% for haloperidol depot, 37% for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 24% for long-acting risperidone. The mean number of days of relapse requiring hospitalization per patient per year were 28 for haloperidol depot, 18 for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, and 11 for long-acting risperidone, whereas the mean number of days of exacerbation not requiring hospitalization were eight for haloperidol depot, five for oral risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole

A Canadian naturalistic study of a community-based cohort treated for bipolar disorder

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Chandresena Ranjith

2010-03-01

Full Text Available Abstract Background Bipolar illness is associated with significant psychosocial morbidity and health resource utilization. Second generation antipsychotics, used alone or in combination with mood stabilizers are effective in treating acute mania in community settings. This study was designed to compare the change in clinical parameters and resource utilization at one month in a group of patients who required treatment intervention for exacerbation of mania. The clinical response at one year was also evaluated. Methods 496 patients were enrolled at 75 psychiatric practices across Canada. The Olanzapine cohort (n = 287 included patients who had olanzapine added to their medication regimen or the dose of olanzapine increased. The Other cohort (n = 209 had a medication other than olanzapine added or the dose adjusted. Changes from baseline in the Young Mania Rating Scale (YMRS, Montgomery Asberg Depression Rating Scale, Beck Anxiety Inventory and SF-12 Health Survey were compared at one month using ANCOVA. Categorical variables at one month for health resource utilization, employment status, abuse/dependency, and the number of suicide attempts were compared using Fisher's Exact test. Patients were followed for one year and a subgroup was evaluated. Results At one month, patients in the Olanzapine cohort recorded a mean reduction in the YMRS of 11.5, significantly greater than the mean reduction in the Other cohort of 9.7 (ANCOVA P = 0.002. The Olanzapine cohort was significantly improved compared to the Other cohort on the scales for depression and anxiety and did not experience the deterioration in physical functioning seen in the Other cohort. No significant differences were detected in health-related quality-of-life measures, employment status, drug abuse/dependency, number of suicide attempts, mental functioning, emergency room visits or inpatient psychiatric hospitalizations. In a subgroup treated for 12 months with a single second generation

Development of a stability-indicating UPLC method for determining olanzapine and its associated degradation products present in active pharmaceutical ingredients and pharmaceutical dosage forms.

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Krishnaiah, Ch; Vishnu Murthy, M; Kumar, Ramesh; Mukkanti, K

2011-03-25

A simple, sensitive and reproducible ultra performance liquid chromatography (UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of olanzapine (OLN) in API and pharmaceutical dosage forms. The method is applicable to the quantification of related substances and assays of drug substances. Chromatographic separation was achieved on Acquity UPLC BEH 100-mm, 2.1-mm, and 1.7-μm C-18 columns, and the gradient eluted within a short runtime, i.e., within 10.0 min. The eluted compounds were monitored at 250 nm, the flow rate was 0.3 mL/min, and the column oven temperature was maintained at 27°C. The resolution of OLN and eight (potential, bi-products and degradation) impurities was greater than 2.0 for all pairs of components. The high correlation coefficient (r(2)>0.9991) values indicated clear correlations between the investigated compound concentrations and their peak areas within the test ranges. The repeatability and intermediate precision, expressed by the RSD, were less than 2.4%. The accuracy and validity of the method were further ascertained by performing recovery studies via a spike method. The accuracy of the method expressed as relative error was satisfactory. No interference was observed from concomitant substances normally added to the tablets. The drug was subjected to the International Conference on Harmonization (ICH)-prescribed hydrolytic, oxidative, photolytic and thermal stress conditions. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. Copyright © 2010 Elsevier B.V. All rights reserved.

In vivo pharmacological evaluations of novel olanzapine analogues in rats: a potential new avenue for the treatment of schizophrenia.

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Somayeh Jafari

Full Text Available Olanzapine (Olz is one of the most effective antipsychotic drugs commonly used for treating schizophrenia. Unfortunately, Olz administration is associated with severe weight gain and metabolic disturbances. Both patients and clinicians are highly interested in the development of new antipsychotics which are as effective as atypical antipsychotics but which have a lower propensity to induce metabolic side effects. In the present study, we examined two new derivatives of Olz; OlzEt (2-ethyl-4-(4'-methylpiperazin-1'-yl-10Hbenzo[b]thieno[2,3-e][1,4]diazepine, and OlzHomo (2-ethyl-4-(4'-methyl-1',4'-diazepan-1'-yl-10H-benzo[b]thieno[2,3-e] [1,4]diazepine, for their tendency to induce weight gain in rats. Weight gain and metabolic changes were measured in female Sprague Dawley rats. Animals were treated orally with Olz, OlzEt, OlzHomo (3 or 6 mg/kg/day, or vehicle (n = 8, three times daily at eight-hour intervals for 5 weeks. Furthermore, a phencyclidine (PCP-treated rat model was used to examine the prevention of PCP-induced hyperlocomotor activity relevant for schizophrenia therapy. Male Sprague Dawley rats were pre-treated with a single dose (3 mg/kg/day of Olz, OlzEt, OlzHomo, or vehicle (n = 12, for 2 weeks. Locomotor activity was recorded following a subcutaneous injection with either saline or PCP (10 mg/kg. Olz was found to induce weight gain, hyperphagia, visceral fat accumulation, and metabolic changes associated with reduced histamatergic H1 receptor density in the hypothalamus of treated rats. In contrast, OlzEt and OlzHomo presented promising antipsychotic effects, which did not induce weight gain or fat deposition in the treated animals. Behavioural analysis showed OlzEt to attenuate PCP-induced hyperactivity to a level similar to that of Olz; however, OlzHomo showed a lower propensity to inhibit these stereotyped behaviours. Our data suggest that the therapeutic effectiveness of OlzHomo may be delivered at a higher dose than

Medication and physical activity and physical fitness in severe mental illness.

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Perez-Cruzado, David; Cuesta-Vargas, Antonio; Vera-Garcia, Elisa; Mayoral-Cleries, Fermín

2018-05-23

Anti-psychotic medication has emerged as the primary medical treatment for people with severe mental illness, despite the great risks involved in the use of this medication. In addition, this population suffers from problems of obesity, sedentary lifestyle and poor physical fitness, which is aggravated by the use of this type of medication. The objective of this study is to explore the influence of the most commonly used antipsychotics in this population (Olanzapine and Risperidone) on physical activity and the physical fitness of people with severe mental illness. Sixty-two people between 26 and 61 years of age with severe mental illness were assessed. All participants were evaluated with a battery of 11 physical tests to assess their physical fitness and with the IPAQ-short version questionnaire to determine their level of physical activity. The doses of Risperidone and Olanzapine were also evaluated in all participants. Significant differences were found for physical activity, with higher levels reported in those patients with severe mental illness who did not take any of these medications. Regarding physical fitness, significant differences were only found for the consumption of Risperidone, with better physical fitness levels seen in patients who did not consume this medication; on the other hand, for the consumption of Olanzapine, differences were found in muscular strength, balance and aerobic condition with better values in non-Olanzapine consumers compared with Olanzapine consumers. Copyright © 2018 Elsevier B.V. All rights reserved.

Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.

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Sacristán, J A; Gómez, J C; Montejo, A L; Vieta, E; Gregor, K J

2000-05-01

The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001). The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

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Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

Tranquilização rápida para pacientes agitados nos serviços de emergência psiquiátrica: um ensaio clínico randomisado de olanzapina, ziprasidona, haloperidol mais prometazina, haloperidol mais midazolam e haloperidol em monoterapia

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Baldaçara, Leonardo; Sanches, Marsal; Cordeiro, Daniel Cruz; Jackowski, Andrea Parolin

2011-01-01

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or halop...

Efficacy and Safety of Citalopram Compared to Atypical Antipsychotics on Agitation in Nursing Home Residents With Alzheimer Dementia.

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Viscogliosi, Giovanni; Chiriac, Iulia Maria; Ettorre, Evaristo

2017-09-01

To assess efficacy and safety of citalopram compared to quetiapine and olanzapine for the treatment of agitation in patients with Alzheimer disease (AD). Longitudinal, 6-month study. Nursing home (NH). 75 NH residents with AD and agitation, randomized to citalopram (n = 25), quetiapine (n = 25), or olanzapine (n = 25). Changes in Neuropsychiatric Inventory (NPI) agitation subscale score and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC) were used to assess treatment efficacy. Participants were surveilled for adverse health outcomes. Citalopram treatment (30±5.8 mg/d) resulted in similar 6-month efficacy compared to both quetiapine (94.0±40.4 mg/d) and olanzapine (5.2±1.6 mg/d), lower occurrence of falls than olanzapine [odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.68-0.97, P = .012], lower incidence of orthostatic hypotension than both quetiapine (OR = 0.80, 95% CI = 0.66-0.95, P = .032) and olanzapine (OR = 0.75, 95% CI = 0.69-0.91, P = .02), and less all-cause hospitalizations than both quetiapine (OR = 0.92, 95% CI = 0.88-0.95, P = .016) and olanzapine (OR = 0.78, 95% CI = 0.64-0.92, P = .004), after multiple adjustment for potentially confounding variables. No differences were observed for cognitive and functional decline, QTc prolongation, and infections. Citalopram resulted in similar efficacy and less adverse outcomes when compared to 2 atypical antipsychotics for treatment of agitation in NH residents with AD. Replication of these findings and assessment of long-term efficacy and safety of citalopram for treatment of neuropsychiatric symptoms in dementia are needed. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of the free volume sizes and shapes determined from crystallographic and PALS data

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Tydda Maciej

2015-12-01

Full Text Available Two different classes of molecular crystals were investigated. The first group was benzenediols, which are characterized by the same chemical composition but a different organization of their crystallographic structures; all of the compounds from this group have only one kind of free volumes. The second class was represented by olanzapine, which has more complex chemical composition and two kinds of free volumes in the structure. The o-Ps lifetime values determined from positron annihilation lifetime spectroscopy (PALS measurements agree quite well with those calculated for sizes found from crystallographic data for benzenediols (agreement within 10% of the lifetime values. For olanzapine, a good agreement is observed in the case of cuboidal free volumes, while for the other kind of void, the agreement is less satisfactory. Positronium diffusion coefficient determined from o-Ps redistribution in olanzapine agrees with these found for polymers.

The effects of typical and atypical antipsychotics on the electrical activity of the brain in a rat model

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Oytun Erbaş

2013-09-01

Full Text Available Objective: Antipsychotic drugs are known to have strongeffect on the bioelectric activity in the brain. However,some studies addressing the changes on electroencephalography(EEG caused by typical and atypical antipsychoticdrugs are conflicting. We aimed to compare the effectsof typical and atypical antipsychotics on the electricalactivity in the brain via EEG recordings in a rat model.Methods: Thirty-two Sprague Dawley adult male ratswere used in the study. The rats were divided into fivegroups, randomly (n=7, for each group. The first groupwas used as control group and administered 1 ml/kg salineintraperitoneally (IP. Haloperidol (1 mg/kg (group 2,chlorpromazine (5 mg/kg (group 3, olanzapine (1 mg/kg(group 4, ziprasidone (1 mg/ kg (group 5 were injectedIP for five consecutive days. Then, EEG recordings ofeach group were taken for 30 minutes.Results: The percentages of delta and theta waves inhaloperidol, chlorpromazine, olanzapine and ziprasidonegroups were found to have a highly significant differencecompared with the saline administration group (p<0.001.The theta waves in the olanzapine and ziprasidonegroups were increased compared with haloperidol andchlorpromazine groups (p<0.05.Conclusion: The typical and atypical antipsychotic drugsmay be risk factor for EEG abnormalities. This studyshows that antipsychotic drugs should be used with caution.J Clin Exp Invest 2013; 4 (3: 279-284Key words: Haloperidol, chlorpromazine, olanzapine,ziprasidone, EEG, rat

Risperidone-induced enuresis in two children with autistic disorder.

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Hergüner, Sabri; Mukaddes, Nahit Motavalli

2007-08-01

Risperidone appears to be effective in treating behavioral problems in children with autistic disorder. Although increased appetite, weight gain, and sedation are among the most common side effects, risperidone-induced enuresis is rarely reported. We will present two cases with risperidone-induced enuresis, and discuss our findings in the context of current literature. Two children aged 11 and 10 years, diagnosed with autism and mental retardation, have developed new-onset diurnal and nocturnal enuresis respectively on their first and second weeks of risperidone monotherapy (1.5 and 1 mg/day). They did not experience sedation, and their medical history and workup were unremarkable. As enuresis did not resolve spontaneously, we decided to substitute risperidone with olanzapine. Enuresis ceased rapidly after discontinuation of risperidone with no emergence when patients were treated with olanzapine 5 mg/day for a period of 6 months and 1 year, respectively. Although the pathophysiology of antipsychotic-induced enuresis remains unclear, a number of mechanisms including alpha(1)-adrenergic blockade, dopamine blockade, and antimuscarinic effects has been proposed. Olanzapine has lower alpha(1)-adrenergic and dopaminergic blockade properties, thus changing risperidone to olanzapine may be an alternative modality in risperidone-induced enuresis when antipsychotic treatment is crucial. Clinicians should be more vigilant about screening for this side effect, especially in younger population with developmental disabilities.

Amisulpride versus other atypical antipsychotics for schizophrenia

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Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50

Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

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Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

2015-01-01

limited experimental information exists about the effects of α1-adrenergic receptor activity of antipsychotic drugs in pro-arrhythmic models, we have decided to investigate this. In this study we show that four antipsychotic drugs all have high affinity for α1-adrenergic receptor (sertindole>risperidone>haloperidol......>olanzapine) and all block IKr (sertindole>haloperidol>risperidone>olanzapine). In canine Purkinje fibres, α1-adrenergic stimulation prolonged action potential duration; however, the stimulation does not cause afterdepolarizations, even in the presence of dofetilide-induced delayed repolarization. We showed...

Control of Nausea and Vomiting in Patients Receiving Anthracycline/Cyclophosphamide Chemotherapy for Breast Cancer.

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Nawa-Nishigaki, Minako; Kobayashi, Ryo; Suzuki, Akio; Hirose, Chiemi; Matsuoka, Rie; Mori, Ryutaro; Futamura, Manabu; Sugiyama, Tadashi; Yoshida, Kazuhiro; Itoh, Yoshinori

2018-02-01

Chemotherapy-induced nausea and vomiting (CINV) is one of most distressing adverse events during cancer chemotherapy. In breast cancer patients receiving anthracycline and cyclophosphamide (AC) chemotherapy, CINV is poorly controlled. The prevalence of guideline-consistent antiemetic medication and control of CINV were investigated retrospectively in breast cancer patients receiving the first cycle of AC chemotherapy. Risks for CINV were analyzed by the multivariate logistic regression analysis. The effect of olanzapine added to the standard antiemetic medication on the incidence of CINV was subsequently evaluated in separate patients who received the first cycle of AC chemotherapy. Although the guideline-consistent antiemetic medication was performed in all subjects, the control rate of nausea (32%), but not vomiting (78%) was low. Risk analysis indicated that age younger than 55-year-old was a significant factor that reduces the control of both nausea and vomiting. Olanzapine (5 mg/day for 5 days), when added to the standard three-drug antiemetic medication, significantly improved the control of nausea and complete response. CINV was poorly controlled in breast cancer patients receiving AC chemotherapy, in which age younger than 55-year-old was a significant risk for both nausea and vomiting. Olanzapine was effective for improvement of the control of CINV associated with AC chemotherapy. Therefore, care should be taken to prevent CINV in young patients receiving AC chemotherapy by adding olanzapine to the standard three-drug antiemetic medication. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Antipsychotic polypharmacy in clozapine resistant schizophrenia: a randomized controlled trial of tapering antipsychotic co-treatment

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Jari Tiihonen

2012-01-01

Full Text Available There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N = 15 who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.

Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment

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Rayees Ahmad Wani

2015-01-01

Full Text Available Background: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. Materials and Methods: Fifty patients (32 males and 18 females diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females was taken for comparison. Results were interpreted using American Diabetic Association criteria. Results: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. Conclusion: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

L’impatto farmacoeconomico del trattamento della schizofrenia con antipsicotici tipici ed atipici: l’esperienza di un DSM della Regione Sicilia

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Tommaso Federico

2005-12-01

Full Text Available Il presente lavoro è stato realizzato con il patrocinio del Dipartimento Ispettorato Regionale Sanitario dell.Assessorato per la Sanità della Regione Sicilia, nella persona del Dirigente Generale Dott. Saverio Ciriminna BACKGROUND: The comparatively high acquisition costs of the new antipsychotic drugs have induced the mental health community to look closely at their potential benefits. OBJECTIVE: To compare the clinical and economic outcomes associated with olanzapine, risperidone and typical neuroleptics treatment for schizophrenia. METHODS:Amulticenter, observational, two-years long, retrospective and prospective study was conducted with 229 psychotic patients (in charge by psychiatric Centers of Regione Sicilia - Italy. Clinical outcomes were assessed using changes in CGI (Clinical Global Impression and PANSS (Positive and Negative Syndrome Scale scores. The economic data collection included pharmacological and non-pharmacological resources consumption (hospitalizations, medical/nurse visits, etc.. The economic evaluation was conducted in the perspective of the Local Psychiatric Services. RESULTS: The results in terms of clinical performance indicated an advantage (statistically significant in the olanzapine group of patients. The pharmacological costs were significantly lower (p0,05. Treatment with olanzapine was associated with a lower non-pharmacological resources consumption and showed a general reduction (p<0,05 vs. risperidone of total treatment costs between 1st and 2nd year of observation. CONCLUSIONS:Within the context of the local health care Services, olanzapine appears to be the “dominant” therapeutic option compared with risperidone and typical neuroleptics. Treatment with risperidone appears to be “cost-neutral” compared with typical neuroleptics.

Self-harm, Unintentional Injury, and Suicide in Bipolar Disorder During Maintenance Mood Stabilizer Treatment: A UK Population-Based Electronic Health Records Study.

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Hayes, Joseph F; Pitman, Alexandra; Marston, Louise; Walters, Kate; Geddes, John R; King, Michael; Osborn, David P J

2016-06-01

Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium's potential antisuicidal properties through reduction in impulsive aggression. To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate. This investigation was a propensity score (PS)-adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment. The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide. Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine

Transfusion practice in Helsinki University Central Hospital: an analysis of diagnosis-related groups (DRG).

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Syrjälä, M T; Kytöniemi, I; Mikkolainen, K; Ranimo, J; Lauharanta, J

2001-12-01

Transfusion data combined with data automatically recorded in hospital databases provides an outstanding tool for blood utilization reporting. When the reporting is performed with an online analytical processing (OLAP) tool, real time reporting can be provided to blood subscribers. When this data is combined with a common patient classification system, Diagnosis-Related Groups (DRG), it is possible to produce statistical results, that are similar in different institutions and may provide a means for international transfusion bench-marking and cost comparison. We use a DRG classification to describe the transfusion practice in Helsinki University Central Hospital. The key indicators include the percentage of transfused patients, the number of transfused units and costs in different DRG groups, as well as transfusion rates per DRG weighted treatment episodes. Ninety-three per cent of all transfusions could be classified into different DRGs. The largest blood-using DRG group was acute adult leukaemia (DRG 473), which accounted for 10.4% of all transfusion costs. The 13 largest blood consuming DRGs accounted for half the total costs in 1998. Currently, there is a lack of an internationally accepted standardized way to report institutional or national transfusion practices. DRG-based transfusion reporting might serve as a means for transfusion benchmarking and thus aid studies of variations in transfusion practice.

A comprehensive protocol to evaluate the use of blood and its components in Latin America and the Caribbean

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Ana E. del Pozo

2015-06-01

Full Text Available Blood transfusion safety is a critical part of appropriate health care. Considering the limited information available on the use of blood and its components in Latin America and the Caribbean, the Grupo Cooperativo iberoamericano de Medicina Transfusional (Ibero-American Cooperative Group for Transfusion Medicine; GCIAMT, through its Research and International Affairs committees, carried out a project to develop a protocol that would facilitate the evaluation of blood usage at the country, jurisdiction, and institutional levels in varied country contexts. Experts in blood safety from the Pan American Health Organization (Washington, DC, United States, the University of São Paulo (São Paulo, Brazil, the Hemocentro of São Paulo (São Paulo, Brazil, and GCIAMT designed a 2-step comprehensive blood-use evaluation protocol: step 1 collects data from blood requests, and step 2, from medical charts. At a minimum, 1 000 analyzed requests are necessary; as such, study periods vary depending on the number of transfusion requests issued. An Internet-based application, the Modular Research System-Study Management System (MRS-SMS, houses the data and produces reports on how hospitals request blood, how blood is issued, who requires blood and blood components, and as an added benefit, how many blood units are wasted and what the real demand for blood is.

Second-generation antipsychotic use in children and adolescents: a six-month prospective cohort study in drug-naïve patients.

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Arango, Celso; Giráldez, Miriam; Merchán-Naranjo, Jessica; Baeza, Inmaculada; Castro-Fornieles, Josefina; Alda, Jose-Angel; Martínez-Cantarero, Carmen; Moreno, Carmen; de Andrés, Pilar; Cuerda, Cristina; de la Serna, Elena; Correll, Christoph U; Fraguas, David; Parellada, Mara

2014-11-01

To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths. This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group. From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be "at risk of adverse health outcome" increased during the 6 months from 8.9% to 29.2% for risperidone (p < .0001), 6.8% to 38.1% for olanzapine (p < .0001), and 6.3% to 4.0% for quetiapine (p = .91). Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns. Copyright © 2014 American Academy of Child and Adolescent

Asenapine effects on individual Young Mania Rating Scale items in bipolar disorder patients with acute manic or mixed episodes: a pooled analysis

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Cazorla P

2013-03-01

Full Text Available Pilar Cazorla, Jun Zhao, Mary Mackle, Armin Szegedi Merck, Rahway, NJ, USA Background: An exploratory post hoc analysis was conducted to evaluate the potential differential effects over time of asenapine and olanzapine compared with placebo on the eleven individual items comprising the Young Mania Rating Scale (YMRS in patients with manic or mixed episodes in bipolar I disorder. Methods: Data were pooled from two 3-week randomized, controlled trials in which the eleven individual items comprising the YMRS were measured over 21 days. An analysis of covariance model adjusted by baseline value was used to test for differences in changes from baseline in YMRS scores between groups. Results: Each of the eleven individual YMRS item scores was significantly reduced compared with placebo at day 21. After 2 days of treatment, asenapine and olanzapine were superior to placebo for six of the YMRS items: disruptive/aggressive behavior, content, irritability, elevated mood, sleep, and speech. Conclusion: Reduction in manic symptoms over 21 days was associated with a broad-based improvement across all symptom domains with no subset of symptoms predominating. Keywords: asenapine, Young Mania Rating Scale, bipolar disorder, YMRS, antipsychotic, olanzapine

Correlation between plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia.

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Kaneda, Yasuhiro; Kawamura, Ichiro; Ohmori, Tetsuro

2005-01-01

The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.

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Angelopoulos, Elias; Theleritis, Christos; Economou, Marina; Georgatou, Korina; Papageorgiou, Charalambos C; Tsaltas, Eleftheria

2017-07-01

In the recent study by Verhoeven and Egger, 2015 and the recent letter to the editor by Boot et al. 2015 an emphasis is given to the best possible pharmacological treatment of 22q11-2 Deletion-Syndrome related psychoses. We would like to present the case of a 23-year old Cypriot patient with 22q11.2 deletion syndrome who fulfilled criteria for treatment resistant schizophrenia (TRS). He was sequentially treated with aripiprazole, risperidone, olanzapine, haloperidol and a combination treatment with olanzapine and haloperidol. Clozapine was the only antipsychotic medication that has improved his condition. © Georg Thieme Verlag KG Stuttgart · New York.

Cost-Utility Analysis of Depot Atypical Antipsychotics for Chronic Schizophrenia in Croatia.

Science.gov (United States)

Jukic, Vlado; Jakovljevic, Miro; Filipcic, Igor; Herceg, Miroslav; Silic, Ante; Tomljanovic, Tatjana; Zilbershtein, Roman; Jensen, Rasmus C D; Hemels, Michiel E H; Einarson, Thomas R

As a nation with a developing economy, Croatia is faced with making choices between pharmaceutical products, including depot injectable antipsychotics. We conducted a pharmacoeconomic analysis to determine the cost-effectiveness of atypical depots in Croatia. A 1-year decision-analytic framework modeled drug use. We determined the average direct cost to the Croatian Institute for Health Insurance of using depot formulations of paliperidone palmitate long-acting injectable (PP-LAI), risperidone LAI (RIS-LAI), or olanzapine LAI (OLZ-LAI). An expert panel plus literature-derived clinical rates populated the core model, along with costs adjusted to 2012 by using the Croatian consumer price index. Clinical outcomes included quality-adjusted life-years, hospitalization rates, emergency room treatment rates, and relapse days. Robustness of results was examined with one-way sensitivity analyses on important inputs; overall, all inputs were varied over 10,000 simulations in a Monte Carlo analysis. Costs (quality-adjusted life-years) per patient were €5061 (0.817) for PP-LAI, €5168 (0.807) for RIS-LAI, and €6410 (0.812) for OLZ-LAI. PP-LAI had the fewest relapse days, emergency room visits, and hospitalizations. Results were sensitive against RIS-LAI with respect to drug costs and adherence rates, but were generally robust overall, dominating OLZ-LAI in 77.3% and RIS-LAI in 56.8% of the simulations. PP-LAI dominated the other drugs because it had the lowest cost and best clinical outcomes. Compared with depots of olanzapine and risperidone and oral olanzapine, PP-LAI was the cost-effective atypical LAI for treating chronic schizophrenia in Croatia. Using depot paliperidone in place of either olanzapine or risperidone would reduce the overall costs of caring for these patients. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

DISRUPTION OF CONDITIONED REWARD ASSOCIATION BY TYPICAL AND ATYPICAL ANTIPSYCHOTICS

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Danna, C.L.; Elmer, G.I.

2013-01-01

Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100 μg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3–30 μg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward

Il trattamento dei disturbi psicotici con olanzapina, risperidone e neurolettici tipici: una valutazione comparativa di costo/efficacia in una realtà psichiatrica locale

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Egidio Filippelli

2005-09-01

Full Text Available BACKGROUND: Several clinical trials demonstrated that atypical antipsychotics are more effective but also more expensive (as drug cost compared with the typical neuroleptics by treating psychotic disorders. The present study aimed to evaluate this result using an observational approach which better reflects the real clinical practice. OBJECTIVE: To evaluate clinical effectiveness (including work and social functioning and overall direct costs in a group of patients affected by psychotic disorders (schizophrenia and bipolar and treated with typical and atypical (olanzapine and risperidone antipsychotics. METHODS: With a multicentre observational design - two years long - 89 patients (in charge by Psychiatric Centers of Regione Campania - Italy were assessed using CGI (Clinical Global Impression and GAF (Global Assessment of Functioning scales. Moreover economic data were collected with reference to pharmacological and non-pharmacological (hospitalization, medical/nurse visits, etc. resources consumption. The pharmacoeconomic analysis were conducted choosing the perspective of the local Psychiatric Services for costs attribution. RESULTS: Considering the treatment outcomes, the use of the atypical drugs provided better performances with reference to the patients quality of life. The results in terms of work and social functioning indicated an advantage in the olanzapine group of patients. Overall direct costs of treatment (drugs and healthcare resources didn’t generate significant differences among the groups of therapy despite the pharmacological cost evidentiated an economic advantage (p<0,05 in the typical group due to the cheaper cost of these drugs. The use of olanzapine was associated to a lower number of hospitalizations and showed a general reduction (- 16% of total treatment costs between 1st and 2nd year of observation. CONCLUSIONS: The lack of side effects, the improvement in work and social functioning, associated to a more efficient

One-year risk of psychiatric hospitalization and associated treatment costs in bipolar disorder treated with atypical antipsychotics: a retrospective claims database analysis

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Pikalov Andrei

2011-01-01

Full Text Available Abstract Background This study compared 1-year risk of psychiatric hospitalization and treatment costs in commercially insured patients with bipolar disorder, treated with aripiprazole, ziprasidone, olanzapine, quetiapine or risperidone. Methods This was a retrospective propensity score-matched cohort study using the Ingenix Lab/Rx integrated insurance claims dataset. Patients with bipolar disorder and 180 days of pre-index enrollment without antipsychotic exposure who received atypical antipsychotic agents were followed for up to 12 months following the initial antipsychotic prescription. The primary analysis used Cox proportional hazards regression to evaluate time-dependent risk of hospitalization, adjusting for age, sex and pre-index hospitalization. Generalized gamma regression compared post-index costs between treatment groups. Results Compared to aripiprazole, ziprasidone, olanzapine and quetiapine had higher risks for hospitalization (hazard ratio 1.96, 1.55 and 1.56, respectively; p Conclusions In commercially insured adults with bipolar disorder followed for 1 year after initiation of atypical antipsychotics, treatment with aripiprazole was associated with a lower risk of psychiatric hospitalization than ziprasidone, quetiapine, olanzapine and risperidone, although this did not reach significance with the latter. Aripiprazole was also associated with significantly lower total healthcare costs than quetiapine, but not the other comparators.

Serum prolactin, leptin, lipids and lipoproteins levels during antipsychotics treatment in Parkinson's disease and related psychosis.

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Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

2006-01-01

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (prelationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

Cost-effectiveness model of long-acting risperidone in schizophrenia in the US.

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Edwards, Natalie C; Rupnow, Marcia F T; Pashos, Chris L; Botteman, Marc F; Diamond, Ronald J

2005-01-01

Schizophrenia is a devastating and costly illness that affects 1% of the population in the US. Effective pharmacological therapies are available but suboptimal patient adherence to either acute or long-term therapeutic regimens reduces their effectiveness. The availability of a long-acting injection (LAI) formulation of risperidone may increase adherence and improve clinical and economic outcomes for people with schizophrenia. To assess the cost effectiveness of risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI over a 1-year time period in outpatients with schizophrenia who had previously suffered a relapse requiring hospitalisation. US healthcare system. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were used to populate a decision-analysis model comparing the four treatment alternatives. The model captured: rates of patient compliance; rates, frequency and duration of relapse; incidence of adverse events (bodyweight gain and extrapyramidal effects); and healthcare resource utilisation and associated costs. Primary outcomes were: the proportion of patients with relapse; the frequency of relapse per patient; the number of relapse days per patient; and total direct medical cost per patient per year. Costs are in year 2002 US dollars. Based on model projections, the proportions of patients experiencing a relapse requiring hospitalisation after 1 year of treatment were 66% for haloperidol decanoate LAI, 41% for oral risperidone and oral olanzapine and 26% for risperidone LAI, while the proportion of patients with a relapse not requiring hospitalisation were 60%, 37%, 37% and 24%, respectively. The mean number of days of relapse requiring hospitalisation per patient per year was 28 for haloperidol decanoate LAI, 18 for oral risperidone and oral olanzapine and 11 for risperidone LAI, while the mean number of days of relapse not requiring

A comparison of two novel antipsychotics in first episode non-affective psychosis: one-year outcome on symptoms, motor side effects and cognition.

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Malla, Ashok; Norman, Ross; Scholten, Derek; Townsend, Laurel; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2004-12-15

The main objective of this study was to compare 1-year outcome on symptoms, extrapyramidal side effects (EPS) , positive and negative symptoms, and domains of cognition in first episode psychosis (FEP) patients. Drug-naive FEP patients, who were similar on a number of characteristics likely to affect outcome, were treated with only one antipsychotic (risperidone or olanzapine) for at least 1 year and compared at baseline and after 1 year of treatment. Differences in outcome were assessed using an analysis of co-variance with change scores between initial assessment and after 1 year of treatment on levels of psychotic, disorganization and psychomotor poverty symptoms, EPS (parkinsonism, akathesia and dyskineisa) and domains of cognition as the dependent variable, respective baseline scores as covariates, and drug group as the independent variable. While patients in both groups showed substantial improvement, there were no significant differences in the magnitude of change in reality distortion, disorganization and psychomotor poverty symptoms. Trends in change in EPS favouring olanzapine and on some domains of cognition (processing speed and executive functions) favouring risperidone failed to reach statistical significance. The failure to confirm previous claims of greater improvement on either risperidone or olanzapine in patients with a first episode of psychosis may be the result of methodological bias introduced by unequal dosing between the two drugs or the use of chronically ill and treatment-refractory patients in previous studies.

Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

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Szkultecka-Dębek, Monika; Miernik, Katarzyna; Stelmachowski, Jarosław; Jakovljević, Miro; Jukić, Vlado; Aadamsoo, Kaire; Janno, Sven; Bitter, István; Tolna, Judit; Jarema, Marek; Jankovic, Slobodan; Pecenak, Jan; Vavrusova, Livia; Tavčar, Rok; Walczak, Jacek; Talbot, Darren; Augustyńska, Joanna

2016-09-01

The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries

[Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

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Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

2014-01-01

To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry

DEFF Research Database (Denmark)

Kiss, A; Bundzikova, J; Pirnik, Z

2010-01-01

rats were injected intraperitoneally with haloperidol (1 mg/kg), clozapine (30 mg/kg), olanzapine (30 mg/kg), risperidone (2mg/kg), and vehicle (5% chremophor) and were sacrificed 60 min later by a fixative. Fos, Fos/OXY, and Fos/AVP labelings were visualized by immunohistochemistry in the SON, 5...... accessory (ACS) cell groups, and 4 distinct PVN subdivisions using a computerized light microscope. Most apparent activation of single Fos, Fos/OXY, and Fos/AVP cells was induced by clozapine and olanzapine; effects of risperidone and haloperidol were substantially lower; no colocalizations were revealed...... of risperidone and haloperidol. Variabilities in Fos distribution in the PVN, SON, and ACS induced by antipsychotics may be helpful to understand more precisely the extent of their extra-forebrain actions with possible presumption of their functional impact and side effect consequences....

Cost Effectiveness of Paliperidone Long-Acting Injectable Versus Other Antipsychotics for the Maintenance Treatment of Schizophrenia in France.

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Druais, Sylvain; Doutriaux, Agathe; Cognet, Magali; Godet, Annabelle; Lançon, Christophe; Levy, Pierre; Samalin, Ludovic; Guillon, Pascal

2016-04-01

French clinical recommendations suggest prescribing long-acting injectable (LAI) antipsychotics to patients with a maintenance treatment indication in schizophrenia. Despite this, and due to their relatively high acquisition and administration costs, LAIs are still underused in clinical practice in France, thus highlighting the need for pharmacoeconomic evaluations. Our objective was to estimate the cost effectiveness of paliperidone LAI (or paliperidone palmitate), a once-monthly second-generation LAI antipsychotic, compared with the most common antipsychotic medications for the maintenance treatment of schizophrenia in France. A Markov model was developed to simulate the progression of a cohort of schizophrenic patients through four health states (stable treated, stable non-treated, relapse and death) and to consider up to three lines of treatment to account for changes in treatment management. Paliperidone LAI was compared with risperidone LAI, aripiprazole LAI, olanzapine LAI, haloperidol LAI (or haloperidol decanoate) and oral olanzapine. Costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over 5 years based on 3-month cycles with a discount rate of 4% and from a French health insurance perspective. Patients were considered to be stabilised after a schizophrenic episode and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on real-life French data to capture adherence effects. Safety and utility data were derived from international publications. Additionally, costs were retrieved from French health insurance databases and publications. Finally, expert opinion was used for validation purposes or in case of gaps in data. The robustness of results was assessed through deterministic and

Bipolar Medications and Weight Gain

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... mood stabilizer. The medication Symbyax combines the antidepressant fluoxetine and the antipsychotic olanzapine and is associated with ... in body weight and psychotropic drugs: A systematic synthesis of the literature. PLOS One. 2012;7:e36889. ...

Antipsychotic Medication in Children and Adolescents : A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

NARCIS (Netherlands)

Roke, Yvette; van Harten, Peter N.; Boot, Annemieke M.; Buitelaar, Jan K.

Objective: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. Method: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine,

Antipsychotic medication in children and adolescents: a descriptive review of the effects on prolactin level and associated side effects.

NARCIS (Netherlands)

Roke, Y.; Harten, P.N. van; Boot, A.M.; Buitelaar, J.K.

2009-01-01

OBJECTIVE: This review reports the incidence of hyperprolactinemia, its relationship with genotype, and prolactin-related side effects in children and adolescents treated with antipsychotics. METHOD: Data on prolactin levels were available for haloperidol, pimozide, risperidone, olanzapine,

Development and Validation of Reverse Phase High Performance ...

African Journals Online (AJOL)

Performance Chromatography Method for Determination of. Olanzapine in ... Lowest limit of quantification (LLOQ) was 1 ng/ml while inter-day and intra-day precision was < 12.5 and 5.1 % .... Chromatograms of blank plasma and drug free.

Patient perspectives on antipsychotic treatments and their association with clinical outcomes

Directory of Open Access Journals (Sweden)

Hong Liu-Seifert

2010-09-01

Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

[Informed Consent and the Approval by Ethics Committees of Studies Involving the Use of Atypical Antipsychotics in the Management of Delirium].

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Millán-González, Ricardo

2012-03-01

Delirium is an acute alteration of consciousness and cognition. Atypical antipsychotics (AA) have recently become a main part of its treatment. Studies in this population generate a series of ethical dilemmas concerning the voluntary participation of patients and their state of vulnerability since their mental faculties are, by definition, compromised. To assess whether studies with AA for the treatment of delirium obtained an approval by an ethics committee on human research (ECHR), if an informed consent (IC) was obtained, whether the IC was verbal or written, and who gave the approval to participate. Systematic review of Medline for studies of delirium where quetiapine and olanzapine were the main treatment, assessing the existence of an ECHR approval and implementation of an IC. 11 studies were identified (6 of quetiapine and 5 of olanzapine). 5 had an ECHR approval. Most studies examining the treatment of delirium with quetiapine or olanzapine were not subject to approval by an ECHR and most of them did not obtain an IC from the patient's legal guardian. It is essential that future studies of antipsychotics and other drugs for the treatment of delirium have the protocol approved by an ECHR and a written IC signed by the patient's legal representative, since by definition delirium is a condition that compromises superior mental processes. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

Science.gov (United States)

Zheng, Jolene; Vasselli, Joseph R; King, Jason F; King, Michael L; We, Wenqian; Fitzpatrick, Zachary; Johnson, William D; Finley, John W; Martin, Roy J; Keenan, Michael J; Enright, Frederic M; Greenway, Frank L

The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 μg/mL) increased the IFD (12.1 ± 0.1%, P < 0.02), which was blocked by betahistine (763 μg/mL, 39.3 ± 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

Efficacy of antipsychotic drugs against hostility in the European First-Episode Schizophrenia Trial (EUFEST)

NARCIS (Netherlands)

Volavka, Jan; Czobor, Pal; Derks, Eske M.; Bitter, Istvan; Libiger, Jan; Kahn, René S.; Fleischhacker, W. Wolfgang; Kahn, R. S.; Fleischhacker, W. W.; Boter, H.; Keet, I. P. M.; Brugman, C.; Davidson, M.; Dollfus, S.; Gaebel, W.; Galderisi, S.; Gheorghe, M.; Gonen, I.; Grobbee, D. E.; Hranov, L. G.; Hummer, M.; Libiger, J.; Králové, Hradec; Lindefors, N.; López-Ibor, J. J.; Nijssen, K.; Peuskens, J.; Prelipceanu, D.; Riecher-Rössler, A.; Rybakowski, J. K.; Sedvall, G.; von Wilmsdorff, M.

2011-01-01

To compare the effects of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on hostility in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. We used the data acquired in the European First-Episode Schizophrenia Trial, an open, randomized trial

A schizophrenic patient with cerebral infarctions after hemorrhagic shock

Directory of Open Access Journals (Sweden)

Youichi Yanagawa

2013-01-01

Full Text Available We herein report the fourth case of cerebral infarction, concomitant with hemorrhagic shock, in English literature. A 33-year-old male, who had been diagnosed with schizophrenia and given a prescription for Olanzapine, was discovered with multiple self-inflicted bleeding cuts on his wrist. On arrival, he was in hemorrhagic shock without verbal responsiveness, but his vital signs were normalized following infusion of Lactate Ringer′s solution. The neuroradiological studies revealed multiple cerebral ischemic lesions without any vascular abnormality. He was diagnosed with speech apraxia, motor aphasia, and dysgraphia, due to multiple cerebral infarctions. As there was no obvious causative factor with regard to the occurrence of cerebral infarction in the patient, the hypoperfusion due to hemorrhagic shock, and the thromboembolic tendency due to Olanzapine, might have acted together to lead to the patient′s cerebral ischemia.

Establishing the cut-off score for remission and severity-ranges on the Psychotic Depression Assessment Scale (PDAS)

DEFF Research Database (Denmark)

Østergaard, Søren D; Rothschild, Anthony J; Flint, Alastair J

2016-01-01

BACKGROUND: The Psychotic Depression Assessment Scale (PDAS) is a rating scale dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to establish the PDAS cut-off for remission of PD as well as PDAS score-ranges for mild, moderate, and severe PD...... on the PDAS and the severity-ranges for mild, moderate, and severe PD were defined using the Clinical Global Impression - Severity scale (CGI-S) as reference by means of pair-wise receiver operating characteristic (ROC) analyses. Subsequently, it was tested whether remission on the PDAS could separate...... the effects of Olanzapine+Sertraline vs. Olanzapine+Placebo through an intention-to-treat, mixed-effects logistic regression of the data from STOP-PD. RESULTS: According to the ROC analyses, the ideal cut-off for remission of PD was a PDAS total score moderate...

Measuring neuroleptic-induced akathisia by three-channel actometry.

Science.gov (United States)

Tuisku, K; Lauerma, H; Holi, M; Markkula, J; Rimon, R

1999-11-30

Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The actometers were attached to the ankles and waists of ten patients, suffering from NIA, and to ten matched healthy controls. Five of the patients were changed to olanzapine treatment, and these patients were re-examined during the no-NIA condition. NIA was associated with manyfold movement activity during controlled rest (sitting) but not with increased daily overall motor activity. Movement frequencies in NIA seemed to be pathognomonic. Actometry is promising for investigation and clinical assessment of NIA. Olanzapine proved to be an adequate treatment choice for NIA patients.

Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST)

NARCIS (Netherlands)

Pijnenborg, G. H. M.; Timmerman, M. E.; Derks, E. M.; Fleischhacker, W. W.; Kahn, R. S.; Aleman, A.

2015-01-01

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in

Differential effects of antipsychotic drugs on insight in first episode schizophrenia : Data from the European First-Episode Schizophrenia Trial (EUFEST)

NARCIS (Netherlands)

Pijnenborg, G. H. M.; Timmerman, Marieke; Derks, E.M.; Fleischhacker, W. W.; Kahn, R. S.; Aleman, A.

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in

Use of psychotropic drugs during pregnancy and breast-feeding

DEFF Research Database (Denmark)

Larsen, E R; Damkier, P; Pedersen, L H

2015-01-01

and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. CONCLUSION: It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how...

[Cost-effectiveness analysis of schizophrenic patient care settings: impact of an atypical antipsychotic under long-acting injection formulation].

Science.gov (United States)

Llorca, P M; Miadi-Fargier, H; Lançon, C; Jasso Mosqueda, G; Casadebaig, F; Philippe, A; Guillon, P; Mehnert, A; Omnès, L F; Chicoye, A; Durand-Zaleski, I

2005-01-01

pharmaceutical formulation of antipsychotics. Hospitalization and relapse risks are lower in compliant than in non-compliant patients. The main objective of this pharmacoeconomic analysis is to evaluate the impact in terms of medical benefits and costs of the following strategies: 1. Risperidone long-acting injection: first long-acting injectable atypical antipsychotic; 2. Haloperidol depot: long-acting injectable conventional neuroleptic; 3. Olanzapine: atypical antipsychotic available commercially in oral formulation. The target population defined for the study are young schizophrenic patients treated for at least 1 year and whose disorder has not been diagnosed for longer than 5 years. The time horizon is 2 years. A cost-effectiveness analysis is performed. The perspective adopted is the French Health System. The main hypothesis of the model is that an increase in compliance linked to the use of long-acting injectable formulation could lead to an increased efficacy and a modification of the cost-effectiveness ratio. A decision tree was built. Six periods of follow-up are identified with a duration of 4-months per period. The tree contains 3 principal arms, each one corresponding to a specific treatment: risperidone LA injection, haloperidol decanoate and olanzapine. For each arm, at the chance node, two health states are identified: either the patient responds favourably to the treatment or does not respond favourably and requires a switch to another drug treatment. After a period of response, the patient can either remain in the same state or experiences a clinical deterioration. If the patient presents a clinical deterioration, he can either go back to a positive response state after a period of intensive follow-up or remain in an insufficient response state; in this case, a change of antipsychotic treatment is necessary. In the model, a patient should receive four different treatments before a long-term hospitalization takes put in place. According to the market

Measuring treatment response in psychotic depression

DEFF Research Database (Denmark)

Østergaard, Søren D; Meyers, Barnett S; Flint, Alastair J

2014-01-01

). The response to the two regimens was compared using both a mixed effects model and effect size statistics on the total scores of three rating scales: the 17-item Hamilton Depression Rating Scale (HAM-D17), its 6-item melancholia subscale (HAM-D6), and the 11-item PDAS consisting of the HAM-D6 plus five items......BACKGROUND: There is no established psychometric instrument dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to investigate whether a new composite rating scale, the Psychotic Depression Assessment Scale (PDAS), covering both the psychotic...... and the depressive domains of PD, could detect differences in effect between two psychopharmacological treatment regimens. METHODS: We reanalyzed the data from the Study of Pharmacotherapy of Psychotic Depression (STOP-PD), which compared the effect of Olanzapine+Sertraline (n=129) versus Olanzapine+Placebo (n=130...

Recruitment of beta-arrestin2 to the dopamine D2 receptor: insights into anti-psychotic and anti-parkinsonian drug receptor signaling

DEFF Research Database (Denmark)

Klewe, Ib V; Nielsen, Søren M; Tarpø, Louise

2008-01-01

, SNPA all acted as partial agonists with decreasing efficacy in the BRET assay. In contrast, a wide selection of typical and atypical anti-psychotics was incapable of stimulating beta-arrestin2 recruitment to the D2 receptor. Moreover, we observed that haloperidol, sertindole, olanzapine, clozapine...

Volumetric changes in the Basal Ganglia after antipsychotic monotherapy

DEFF Research Database (Denmark)

Ebdrup, B H; Nørbak, H; Borgwardt, S

2013-01-01

studies. Results: We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs) have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged from 3-24 months...

Cognitive Function and Depression in Symptom Resolution in Schizophrenia Patients Treated with an Atypical Antipsychotic

Science.gov (United States)

Stip, Emmanuel; Mancini-Marie, Adham

2004-01-01

Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…

Author Details

African Journals Online (AJOL)

Randomized, interventional, prospective, comparative study to evaluate the antihypertensive efficacy and tolerability of ramipril versus telmisartan in stage 1 hypertensive patients with diabetes mellitus. Abstract PDF · Vol 11, No 2 (2016) - Articles Metabolic effects of Olanzapine versus Iloperidone: A 24 weeks randomized, ...

Second derivative spectrophotometric determination of ...

African Journals Online (AJOL)

Hemn

2013-11-13

Nov 13, 2013 ... olanzapine in pharmaceutical formulation.Int.J.ChemTech. Res.2(1):756-761. Stanisz B, Paszun S, Lesniak M (2009). Validation of UV derivative spectrophotometric method for determination of benazepril hydrochloride in tablets and evaluation of its stability.ActaPoloniaePharmaceutica-Drug Research.

Haloperidol versus second-generation antipsychotics in the long-term treatment of schizophrenia.

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Buoli, Massimiliano; Kahn, René S; Serati, Marta; Altamura, A Carlo; Cahn, Wiepke

2016-07-01

The purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed-up for 36 months. Two hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance. Patients treated with haloperidol discontinued more than the other groups (Breslow: risperidone p haloperidol group than in the olanzapine group (p haloperidol group than with olanzapine (p haloperidol. In addition, atypical antipsychotics seem to be more protective against recurrences than haloperidol. However, these results should be cautiously interpreted in the light of potential confounder factors such as duration of illness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Other Possible Clinical Applications of Drugs with 5HT2A effect in Liaison Psychiatry: Cases Report].

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Corredor, Catalina Ayala; Castillo, Carolina Solís

2012-03-01

In liaison psychiatry it is possible to get an integral view of patient's treatment and needs, paying special attention to pharmacological interactions and contraindications. Some particular cases motivated the description, report and review about other possible applications of 5HT2A and 5HT3 antagonist, particularly Mirtazapine and Olanzapine, in hyperalgesia syndrome, tinnitus and Progressive Multifocal Leukoencephalopathy by JC virus. Cases report. We describe 3 cases of patients in which Mirtazapine and Olanzapine were necessary not only to control psychiatric symptoms (affective / behavioral symptoms and insomnia) but to act as adjuvant therapy in axis III diseases. The use of any drug in psychiatry must take in to account the context of the patient, the presence of comorbidity, contraindications and pharmacological interactions so as to grant a positive outcome also promoting the multidisciplinary work between specialists. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Second-generation antipsychotic and diabetes mellitus in children and adolescents

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Carlo Ripoli

2017-12-01

Full Text Available Second generation antipsychotics (SGA are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before, clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety.

Atypical antipsychotics in the treatment of early-onset schizophrenia

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Hrdlicka M

2015-04-01

Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

Corrected QT changes during antipsychotic treatment of children and adolescents

DEFF Research Database (Denmark)

Jensen, Karsten Gjessing; Juul, Klaus; Fink-Jensen, Anders

2015-01-01

covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n...

Author Details

African Journals Online (AJOL)

Singh, Shivangna. Vol 11, No 2 (2016) - Articles Metabolic effects of Olanzapine versus Iloperidone: A 24 weeks randomized, prospective, interventional study. Abstract PDF. ISSN: 1694-0423. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL ...

Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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Kjell A Svensson

2012-05-01

Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration Adverse Event database: a systematic Bayesian signal detection analysis.

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Baker, Ross A; Pikalov, Andrei; Tran, Quynh-Van; Kremenets, Tatyana; Arani, Ramin B; Doraiswamy, P Murali

2009-01-01

Prior literature suggests that the risk of diabetes-related adverse events (DRAEs) differs between atypical antipsychotics. The present study evaluated the potential association between atypical antipsychotics or haloperidol and diabetes using data from the FDA AERS database. Analysis of AERS data was conducted for clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole or haloperidol with 24 DRAEs from the Medical Dictionary for Regulatory Activities using a Multi-item Gamma Poisson Shrinker (MGPS) data-mining algorithm. Using MGPS, adjusted reporting ratios (Empiric Bayes Geometric Mean or EBGM) and 90% confidence intervals (CIs; EB05-EB95) were calculated to estimate the degree of drug-event association relative to all drugs and events. Logistic regression odds ratios and 90% CIs (LR05-LR95) were calculated for diabetes mellitus events. All six atypicals had an EB05 >/= 2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2-10.0; 1306 cases); risperidone 3.8 (3.5-4.1; 447 cases); quetiapine 3.5 (3.2-3.9; 283 cases); clozapine 3.1 (2.9-3.3; 464 cases); ziprasidone 2.4 (2.0-2.9; 74 cases); aripiprazole 2.4 (1.9-2.9; 71 cases); haloperidol 2.0 (1.7-2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios. In the AERS database, lower associations with DRAEs were seen for haloperidol, aripiprazole and ziprasidone, and higher associations were seen for olanzapine, risperidone, clozapine and quetiapine. Our findings support differential risk of diabetes across atypical antipsychotics, reinforcing the need for metabolic monitoring of patients taking antipsychotics.

Positive modulation of glutamatergic receptors potentiates the suppressive effects of antipsychotics on conditioned avoidance responding in rats

DEFF Research Database (Denmark)

Olsen, Christina Kurre; Kreilgaard, Mads; Didriksen, Michael

2006-01-01

.c.), olanzapine (0.63 mg/kg, s.c.) and clozapine (1.3 mg/kg, s.c.) without causing additional motor disturbances. Thus, the adjunct enhancement of NMDA or AMPA receptor function observed clinically, appears reflected in the present rat CAR study. Consequently, our data lend further support to the potential use...

Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

DEFF Research Database (Denmark)

Pouzet, B; Mow, T; Kreilgaard, Mads

2003-01-01

compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

Double-Blind Maintenance Safety and Effectiveness Findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

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Findling, Robert L.; Johnson, Jacqueline L.; McClellan, Jon; Frazier, Jean A.; Vitiello, Benedetto; Hamer, Robert M.; Lieberman, Jeffrey A.; Ritz, Louise; McNamara, Nora K.; Lingler, Jacqui; Hlastala, Stefanie; Pierson, Leslie; Puglia, Madeline; Maloney, Ann E.; Kaufman, Emily Michael; Noyes, Nancy; Sikich, Linmarie

2010-01-01

Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders. Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication…

Self-limiting atypical antipsychotics-induced edema: Clinical cases and systematic review

OpenAIRE

Musa Usman Umar; Aminu Taura Abdullahi

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review.

Science.gov (United States)

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect.

Comparing the side effect profile of the Atypical Antipsychotics | Alao ...

African Journals Online (AJOL)

Postclozapine, l'Administration de la nourriture et de la Drogue (FDA) avait ratifié l'utilisation de quatre antipsychotique, atypique, risperidone, olanzapine quetiapine et ziprasidone tout neufs pour le traitement de schizophrénie. En conséquence de leur double récepteur obstruction fonctions, le sérotonine, et dopamine, ...

Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia

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Swartz Marvin

2006-02-01

Full Text Available Abstract Background There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia. Methods We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone or oral typical antipsychotics (low, medium, or high potency were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods. To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a only 1 medication episode for each patient, the one with which the patient was treated first, and (b all medication episodes, including those simultaneously initiated on more than 1 antipsychotic. Results Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days compared to typical antipsychotics (N = 534, 197.2 days; p Conclusion In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium

An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis.

Science.gov (United States)

Agid, Ofer; Arenovich, Tamara; Sajeev, Gautam; Zipursky, Robert B; Kapur, Shitij; Foussias, George; Remington, Gary

2011-11-01

Early, effective treatment in first-episode schizophrenia is advocated, although evidence based on a systematic approach over multiple antipsychotic trials is lacking. Employing a naturalistic design, we examined response rates over 3 circumscribed antipsychotic trials. Between June 2003 and December 2008, 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health, Toronto, Ontario, Canada, following an algorithm that moved them through 2 antipsychotic trials, followed by a trial with clozapine. For the first 2 trials, treatment consisted of risperidone followed by olanzapine, or vice versa; each trial consisted of 3 stages (low-, full-, or high-dose) lasting up to 4 weeks at each level and adjusted according to response/tolerability. Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 (much improved) or 1 (very much improved) and/or a Brief Psychiatric Rating Scale Thought Disorder subscale score ≤ 6. Data were analyzed retrospectively, and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003. In trial 1, 74.5% of individuals responded, with rates significantly higher for olanzapine (82.1%, 115/140) versus risperidone (66.3%, 69/104; P = .005). With trial 2, response rate dropped dramatically to 16.6% but again was significantly higher for olanzapine (25.7%, 9/35) compared to risperidone (4.0%, 1/25; P = .04). Response rate climbed above 70% once more, specifically 75.0% (21/28), in those individuals who agreed to a third trial with clozapine. Results confirm a high response rate (75%) to initial antipsychotic treatment in first-episode schizophrenia. A considerably lower response rate (algorithm. © Copyright 2011 Physicians Postgraduate Press, Inc.

Analyses of functional brain connectivity; Untersuchungen zur funktionellen Konnektivitaet des Gehirns

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Stephan, K.E.

2003-03-01

This dissertation includes two independent studies that investigate two complementary aspects of functional connectivity in the Macaque and the human brain. In the first study, a computational meta-analysis of published electrophysiological data on context-independent functional brain connectivity was conducted by means of three independent methods. The second study investigated the effects of the atypical antipsychotic substance olanzapine on the functional connectivity of the cerebellum during a simple motor task (self-paced finger tapping). Six schizophrenic patients and six control subjects matched for age and sex were investigated by functional magnetic resonance imaging (fMRI) twice. This study provided the first experimental data on the effects of atypical antipsychotic agents on functional brain connectivity and demonstrated pronounced olanzapine-dependent changes of functional couplings between cerebellum, thalamus, and prefrontal cortex. (orig.) [German] In der hier vorgelegten Arbeit werden zwei komplementaere Aspekte der funktionellen Konnektivitaet - im Gehirn des Makaken und Menschen anhand zweier separater Studien untersucht. In der ersten Studie wurde mittels dreier unabhaengiger Methoden eine Metaanalyse publizierter elektrophysiologischer Daten zur kontextunabhaengigen funktionellen Konnektivitaet des Makakenkortex durchgefuehrt. Diese Studie erbrachte damit zum ersten Mal den Nachweis einer funktionellen Small World-Netzwerkstruktur des Primatenkortex. In der zweiten Studie wurde der Effekt des atypischen Neuroleptikums Olanzapin auf die funktionelle Konnektivitaet des Zerebellums im Kontext einer einfachen motorischen Aufgabe (selbstgesteuertes Fingertrapping) untersucht. Sechs schizophrene Patienten, die Neuroleptika-naiv bzw. -entwoehnt waren, sowie sechs alters- und geschlechtsentprechende Kontrollprobanden wurden im Abstand von jeweils drei Wochen mit funktioneller Magnetresonanztomografie (fMRT) untersucht. Diese Studie lieferte die ersten

Self-limiting Atypical Antipsychotics-induced Edema: Clinical Cases and Systematic Review

Science.gov (United States)

Umar, Musa Usman; Abdullahi, Aminu Taura

2016-01-01

A number of atypical antipsychotics have been associated with peripheral edema. The exact cause is not known. We report two cases of olanzapine-induced edema and a brief review of atypical antipsychotic-induced edema, possible risk factors, etiology, and clinical features. The recommendation is given on different methods of managing this side effect. PMID:27335511

Identification of Splice Variants as Molecular Markers in Parkinson’s Disease

Science.gov (United States)

2006-09-01

compazine, beta blockers ; e. Drugs with significant muscarinic receptor antagonist activity: Cogentin, Akineton, Artane, Ditropan, Detrol, Elavil...f. Drugs known to improve dyskinesias: amantadine, dextromethorphan, beta - blockers , fluoxitene, clozapine, quetiapine, olanzapine, buspirone, other...disease based on the presence of a characteristic clinical history and neurological findings including at least 2 of the following: resting tremor

Nocturnal Anxiety in a Youth with Rapid-onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD).

Science.gov (United States)

Grudnikoff, Eugene; Foley, Carmel; Poole, Claudette; Theodosiadis, Eva

2013-08-01

Behavioral and psychiatric disorders are common in youth with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD). We outline a rational approach to psychiatric treatment of a patient with a complex medical condition. We report the course of symptoms in a teen with ROHHAD, the inpatient treatment, and review current evidence for use of psychopharmacologic agents in youth with sleep and anxiety disturbances. A 14-year-old female began rapidly gaining weight as a preschooler, developed hormonal imbalance, and mixed sleep apnea. Consultation was requested after a month of ROHHAD exacerbation, with severe anxiety, insomnia, and auditory hallucinations. Olanzapine and citalopram were helpful in controlling the symptoms. Following discharge, the patient gained weight and olanzapine was discontinued. Lorazepam was started in coordination with pulmonary service. Relevant pharmacologic considerations included risk of respiratory suppression, history of paradoxical reaction to hypnotics, hepatic isoenzyme interactions and side effects of antipsychotics. Core symptoms of ROHHAD may precipitate psychiatric disorders. A systematic evidence-based approach to psychopharmacology is necessary in the setting of psychiatric consultation.

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African Journals Online (AJOL)

Obadeji, A. Vol 9, No 2 (2011) - Articles Peripheral Oedema in a Patient taking Olanzapine (A Case Report) Abstract. ISSN: 0189-1774. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors · FAQ's · More about AJOL · AJOL's Partners · Terms and Conditions of Use · Contact AJOL ...

Aripiprazole versus other atypical antipsychotics for schizophrenia

Science.gov (United States)

Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; El-Sayeh, Hany George G; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of other second generation antipsychotics. Objectives To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side

Quetiapine versus other atypical antipsychotics for schizophrenia

Science.gov (United States)

Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; Srisurapanont, Manit; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (’atypical’) antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ. Objectives To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. Selection criteria We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone. A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear

Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid

Directory of Open Access Journals (Sweden)

Markus K. Larsson

2015-01-01

Full Text Available Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6, olanzapine (2 mg/kg, n = 6, and clozapine (20 mg/kg, n = 6 or saline ( n = 6 for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.

Testing of bioactive-nanovesicles on hepatotoxicity of atypical antipsychotics via digital holography.

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Ozturk Kirbay, Fatma; Geyik, Caner; Guler, Emine; Yesiltepe, Ozan; Gumus, Zinar Pinar; Odaci Demirkol, Dilek; Coskunol, Hakan; Timur, Suna

2017-04-01

Atypical antipsychotic drugs induce hepatic toxicity. Thus, it is of importance to eliminate the side effects of these drugs. Herein we describe the preparation of nanoemulsions with a dietary supplement; wheat germ oil (WGO), to ameliorate the liver damage induced by clozapine and olanzapine. THLE-2 cell line was used as a model to investigate the effects of these nanoemulsions on cell viability as well as antioxidative efficiency after antipsychotic insult. In this context, a conventional cell culture method; MTT was used along with a novel cellular imaging technique called digital holography (DH) to evaluate cell viability. Obtained data confirmed that both clozapine and olanzapine induced the liver damage in in vitro model and WGO nanoemulsions were found to be effective on cells and eliminate the cytotoxic effects of these drugs. Briefly, this study has some outputs as follows; it showed that different dietary supplements can be used in such formulations instead of their pristine forms to increase bioavailability. Also, DH was successfully applied for the monitoring of cell viability and it could be a promising approach as the reactive-free cytotoxicity test. Copyright © 2017 Elsevier B.V. All rights reserved.

naturalistic study of olanzapine in treatment-resistant schizophrenia

African Journals Online (AJOL)

hi-tech

2000-02-02

Feb 2, 2000 ... of some 800,000 mixed race people, of whom the indigenous race ... severity of mania, depression, anxiety and OCD; (ii) the Clinical. Global Impression ... schizophrenia (36 or 56.3%), Bipolar I disorder, manic phase (8 or ...

Metabolic Signature of Antipsychotics used in the Treatment of Autism

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2016-12-01

pediatric, adult, and geriatric patients with schizophrenia, bipolar disorder, major depression, post-traumatic stress disorder and autism [1, 2]. While most...Endocrine manifestations of eating disorders. J.Clin.Endocrinol.Metab 96, 333-343 60. Jin,H. et al. (2008) Impact of atypical antipsychotic therapy on...2010) Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis

Risperidone-induced reversible neutropenia.

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Kattalai Kailasam, Vasanth; Chima, Victoria; Nnamdi, Uchechukwu; Sharma, Kavita; Shah, Kairav

2017-01-01

This case report presents a 44-year-old man with a history of schizophrenia who developed neutropenia on risperidone therapy. The patient's laboratory reports showed a gradual decline of leukocytes and neutrophils after resolution and rechallenging. This was reversed with the discontinuation of risperidone and by switching to olanzapine. In this case report, we also discuss the updated evidence base for management of risperidone-induced neutropenia.

Antipsychotic use in children and adolescents: a 1-year follow-up study.

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Baeza, Inmaculada; de la Serna, Elena; Calvo-Escalona, Rosa; Morer, Astrid; Merchán-Naranjo, Jessica; Tapia, Cecilia; Martínez-Cantarero, Ma Carmen; Andrés, Patrícia; Alda, José A; Sánchez, Bernardo; Arango, Celso; Castro-Fornieles, Josefina

2014-10-01

The objective of this study was to analyze the initial treatment with antipsychotics (APs) and its changes during the first year of treatment in patients visited in specialized child and adolescent psychiatry departments. Participants were 265 patients, aged 4 to 17 years, who attended consecutively at 4 different centers and were naive of AP or quasi-naive (less than 30 days since the beginning of AP treatment). Type of AP, dosage, and concomitant medication were registered at baseline, 1, 3, 6, and 12 months after beginning the treatment with AP. At baseline, the patients' mean age was 14.4 (2.9) years, and 145 (54.7%) patients were males. Antipsychotics were more prescribed in the following: schizophrenia spectrum disorders (30.2%), disruptive behavior disorders (DBDs) (18.9%), bipolar disorders (14.3%), depressive disorders (12.8%), and eating disorders (11.7%). A total of 93.2% of the patients were on an off-label indication of AP. Risperidone was the AP most prescribed in all the assessments, but differences were observed in the type of AP according to diagnosis. Thus, risperidone was significantly most prescribed in patients with DBD and olanzapine was most prescribed in patients with eating disorders. Olanzapine and quetiapine were the second-generation APs (SGAs) most prescribed after risperidone, and haloperidol was the most prescribed first-generation AP. Up to 8.3% of patients during the follow-up were on AP polypharmacy. Almost 16% patients had a change in its AP treatment during the follow-up, and the main switch was from one SGA to another. Second-generation APs were the APs most prescribed in our sample and approximately 93% of the patients used AP off-label. Risperidone was the most common AP used above all in patients with DBD, whereas olanzapine was most prescribed in patients with eating disorders. Antipsychotic polypharmacy and switch rates were low during the follow-up.

Propensity score estimation to address calendar time-specific channeling in comparative effectiveness research of second generation antipsychotics.

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Stacie B Dusetzina

Full Text Available Channeling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies.To demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time.Florida Medicaid data from 2001-2006.Retrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk.Increased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81-3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77-3.04.Changes in channeling over time was evident for several covariates but had limited impact on cardiovascular risk

Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: a cost effectiveness study.

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Geitona, Maria; Kousoulakou, Hara; Ollandezos, Markos; Athanasakis, Kostas; Papanicolaou, Sotiria; Kyriopoulos, Ioannis

2008-08-28

To compare the costs and effects of paliperidone extended release (ER), a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone) over a 1-year time period. A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 f risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole) with a lower cost compared to the other therapies examined (euro 7,030 compared to euro 7,034 for olanzapine, euro 7,082 for risperidone, euro 8,321 for quetiapine, euro 7,713 for ziprasidone and euro 7,807 for aripiprazole). During the sensitivity analysis, a +/- 10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Treatment with paliperidone ER can lead to lower total cost and higher number of stable days in most of the

Costs and effects of paliperidone extended release compared with alternative oral antipsychotic agents in patients with schizophrenia in Greece: A cost effectiveness study

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Papanicolaou Sotiria

2008-08-01

Full Text Available Abstract Background To compare the costs and effects of paliperidone extended release (ER, a new pharmaceutical treatment for the management of schizophrenia, with the most frequently prescribed oral treatments in Greece (namely risperidone, olanzapine, quetiapine, aripiprazole and ziprasidone over a 1-year time period. Methods A decision tree was developed and tailored to the specific circumstances of the Greek healthcare system. Therapeutic effectiveness was defined as the annual number of stable days and the clinical data was collected from international clinical trials and published sources. The study population was patients who suffer from schizophrenia with acute exacerbation. During a consensus panel of 10 psychiatrists and 6 health economists, data were collected on the clinical practice and medical resource utilisation. Unit costs were derived from public sources and official reimbursement tariffs. For the comparators official retail prices were used. Since a price had not yet been granted for paliperidone ER at the time of the study, the conservative assumption of including the average of the highest targeted European prices was used, overestimating the price of paliperidone ER in Greece. The study was conducted from the perspective of the National Healthcare System. Results The data indicate that paliperidone ER might offer an increased number of stable days (272.5 compared to 272.2 for olanzapine, 265.5 f risperidone, 260.7 for quetiapine, 260.5 for ziprasidone and 258.6 for aripiprazole with a lower cost compared to the other therapies examined (€7,030 compared to €7,034 for olanzapine, €7,082 for risperidone, €8,321 for quetiapine, €7,713 for ziprasidone and €7,807 for aripiprazole. During the sensitivity analysis, a ± 10% change in the duration and frequency of relapses and the economic parameters did not lead to significant changes in the results. Conclusion Treatment with paliperidone ER can lead to lower total cost

Atypical antipsychotics as add-on treatment in late-life depression

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Cakir S

2016-09-01

Full Text Available Sibel Cakir,1 Zeynep Senkal2 1Department of Psychiatry, Mood Disorders, Geriatric Psychiatry Unit, Istanbul Medical School, Istanbul University, 2Department of Psychiatry, Marmara University, Istanbul, Turkey Background: Second-generation antipsychotics (SGAs have been used in the augmentation of treatment-resistant depression. However, little is known about their effectiveness, tolerability, and adverse events in the treatment of late-life depression, which were the aim of this study.Methods: The retrospective data of patients aged >65 years who had a major depressive episode with inadequate response to antidepressant treatment and had adjuvant SGA treatment were analyzed. The outcome measures were the number of the patients who continued to use SGAs in the fourth and twelfth weeks, adverse events, and changes in symptoms of depression. Results: Thirty-five patients were screened: 21 (60% had quetiapine, twelve (34.28% had aripiprazole, and two (5.71% had olanzapine adjuvant treatment. The mean age was 72.17±5.02 years, and 65.7% of the patients were women. The mean daily dose was 85.71±47.80 mg for quetiapine, 3.33±1.23 mg for aripiprazole, and 3.75±1.76 mg for olanzapine. The Geriatric Depression Scale scores of all patients were significantly decreased in the fourth week and were significant in the aripiprazole group (P=0.02. Of the 35 patients, 23 (65.7% patients discontinued the study within 12 weeks. The frequency of adverse events was similar in all SGAs, and the most common were sedation, dizziness, constipation, and orthostatic hypotension with quetiapine, and akathisia and headache because of aripiprazole. Conclusion: This study indicates that dropout ratio of patients with SGAs is high, and a subgroup of patients with late-life depression may benefit from SGAs. Effectiveness is significant in aripiprazole, and adverse events of SGAs were not serious but common in elderly patients. Keywords: treatment resistance, aripiprazole

Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

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Correll Christoph

2005-05-01

Full Text Available Abstract Background Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. Methods Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796 who were initiated during the study on olanzapine (N = 405, quetiapine (N = 115, or risperidone (N = 276. The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. Results During the 1-year period, only a third (35.7% of the patients were treated predominately with monotherapy (>300 days. Most patients (57.7% had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days. Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043 or quetiapine (p = .002. The number of monotherapy days was significantly greater for olanzapine than quetiapine (p Conclusion Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic

Second-generation antipsychotics for major depressive disorder and dysthymia.

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Komossa, Katja; Depping, Anna M; Gaudchau, Andrea; Kissling, Werner; Leucht, Stefan

2010-12-08

Major depressive disorder (MDD) is a common condition with a lifetime prevalence of 15% to 18%, which leads to considerable suffering and disability. Some antipsychotics have been reported to induce remission in major depression, when added to an antidepressant. To evaluate the effects of second-generation antipsychotic (SGA) drugs (alone or augmentation) compared with placebo or antidepressants for people with MDD or dysthymia. The Cochrane Depression, Anxiety and Neurosis Group's controlled trial registers (CCDANCTR-Studies and CCDANCTR-References) were searched up to 21 July 2010. The author team ran complementary searches on clinicaltrials.gov and contacted key authors and drug companies. We included all randomised, double-blind trials comparing oral SGA treatment (alone or augmentation) with other forms of pharmaceutical treatment or placebo in people with MDD or dysthymia. We extracted data independently. For dichotomous data we calculated the odds ratio (OR) and 95% confidence interval (CI) on an intention-to-treat basis, and for continuous data the mean difference (MD), based on a random-effects model. We presented each comparison separately; we did not perform a pooled data analysis. We included 28 trials with 8487 participants on five SGAs: amisulpride, aripiprazole, olanzapine, quetiapine and risperidone.Three studies (1092 participants) provided data on aripiprazole augmentation in MDD. All efficacy data (response n = 1092, three RCTs, OR 0.48; 95% CI 0.37 to 0.63), (MADRS n = 1077, three RCTs, MD -3.04; 95% CI -4.09 to -2) indicated a benefit for aripiprazole but  more side effects (weight gain, EPS) .Seven trials (1754 participants) reported data on olanzapine. Compared to placebo fewer people discontinued treatment due to inefficacy; compared to antidepressants there were no efficacy differences, olanzapine augmentation showed symptom reduction (MADRS n = 808, five RCTs, MD -2.84; 95% CI -5.48 to -0.20), but also more weight or prolactin increase

Toward an understanding of antipsychotic drug induced weight gain - use of a rodent model

OpenAIRE

Stefanidis, Aneta

2017-01-01

Antipsychotic drug therapy is a fundamental tool in the treatment of schizophrenia and other psychoses. Recent years have seen the development of new antipsychotic compounds with an improved acute adverse effect profile; however these are often associated with weight gain and increased risk of metabolic disturbances. Olanzapine, despite its considerable adverse impact on weight gain and associated pathologies, has been recognized as the most efficacious antipsychotic drug in the treatment of ...

Psychosis and Silent Celiac Disease in a Down Syndrome Adolescent: A Case Report

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Amparo Morant

2011-01-01

Full Text Available Celiac disease is an autoimmune systemic disorder. It presents gastrointestinal and nongastrointestinal manifestations as well as associated conditions. We report a 16-year-old Down syndrome girl who presented psychosis symptomatology, and she was diagnosed as having silent celiac disease. Olanzapine treatment and gluten-free diet were satisfactory. It is necessary to consider celiac disease in Down syndrome patients with psychiatric symptoms, mainly psychotic symptomatology.

Clozapine-induced severe eosinophilia: report of a case with good outcome

OpenAIRE

Marcelino,Carla R. B.; Dantas,Clarissa de R.

2013-01-01

INTRODUCTION: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. METHODS: Case report and literature review. RESULTS: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils b...

Simultaneous determination of amino acids and neurotransmitters in plasma samples from schizophrenic patients by hydrophilic interaction liquid chromatography with tandem mass spectrometry.

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Domingues, Diego Soares; Crevelin, Eduardo José; de Moraes, Luiz Alberto Beraldo; Cecilio Hallak, Jaime Eduardo; de Souza Crippa, José Alexandre; Costa Queiroz, Maria Eugênia

2015-03-01

A sensitive, reproducible, and rapid method was developed for the simultaneous determination of underivatized amino acids (aspartate, serine, glycine, alanine, methionine, leucine, tyrosine, and tryptophan) and neurotransmitters (glutamate and γ-aminobutyric acid) in plasma samples using hydrophilic interaction liquid chromatography coupled to triple quadrupole tandem mass spectrometry. The plasma concentrations of amino acids and neurotransmitters obtained from 35 schizophrenic patients in treatment with clozapine (27 patients) and olanzapine (eight patients) were compared with those obtained from 38 healthy volunteers to monitor the effectiveness of treatment. The chromatographic conditions separated ten target compounds within 3 min. This method presented linear ranges that varied from (lower limit of quantification: 9.7-13.3 nmol/mL) to (upper limit of quantification: 19.4-800 nmol/mL), intra- and interassay precision with coefficients of variation lower than 10%, and relative standard error values of the accuracy ranged from -2.1 to 9.9%. The proposed method appropriately determines amino acids and neurotransmitters in plasma from schizophrenic patients. Compared with the control group (healthy volunteers), the plasma levels of methionine in schizophrenic patients treated with olanzapine are statistically significantly higher. Moreover, schizophrenic patients treated with clozapine tend to have increased plasma levels of glutamate. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diet and exercise effects on aerobic fitness and body composition in seriously mentally ill adults.

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Giannopoulou, Ifigenia; Botonis, Petros; Kostara, Christina; Skouroliakou, Maria

2014-01-01

Low exercise capacity and high obesity levels are the main characteristics of people with serious mental illness (SMI). We conducted a pilot study on the effects of a 3-month exercise and dietary intervention on the aerobic capacity and body composition of obese adults with SMI taking Olanzapine, a second generation antipsychotic medication known to induce weight increments. Fifty adults with SMI (15 males and 35 females) followed a 3-month weight loss intervention programme based on exercise and diet. Pre- and post-intervention, a submaximal [Formula: see text]O2 exercise test was performed in order to assess [Formula: see text]O2max anthropometric and body composition measurements were also performed. All participants were obese (body mass index (BMI): 33.61 ± 0.91 kg/m(2)). Pre- and post-intervention, a submaximal [Formula: see text]O2 exercise test on the treadmill was performed in order to assess [Formula: see text]O2max anthropometric and body composition measurements were also performed. Significant reductions in body weight, BMI, body fat and waist circumference were found from pre to post (p exercise and diet improves the aerobic capacity and body composition of obese adults with SMI, despite the use of Olanzapine.

Impulsivity and novel object recognition test of rat model for vascular cognitive impairment after antipsychotics treatment

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Ronny T Wirasto

2016-12-01

Full Text Available ABSTRACT Vascular cognitive impairment (VCI is a common condition in which no standard treatment has been approved. VCI is often accompanied by behavioral problems which require psychiatric interventions. The common therapeutic agent used for the acute management is antipsychotic injections. Current findings showed that atypical antipsychotic possess better safety profile for treating behavioral problems related to VCI compared to typical antipsychotic. In this study, we induced VCI in Sprague Dawley rats between 6-8 weeks old using bilateral carotid communist artery occlusion technique. The subjects were divided into 4 treatment groups: sham, olanzapine, haloperidol, and risperidone groups. Subjects received intramuscular injections of subsequent drugs for 3 days post VCI induction. Impulsive behavior and object recognition were examined using cliff jumping test and novel object recognition test. The analyses results showed that impulsive behavior was lower in the olanzapine and haloperidol groups compared to sham group, although it was not statistically significant (p = 0.651. The results also showed that there were no significant differences in the time spent exploring old and novel objects in all groups (p = 0.945;0.637 respectively. In conclusion, antipsychotic injection might not be effective to control impulsive behavior post VCI induction.

Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

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Azekawa T

2011-11-01

Full Text Available Takaharu Azekawa, Shizuko Ohashi, Akira ItamiShioiri Mental Clinic, Yokosuka-shi, Kanagawa-ken, JapanBackground: Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting.Methods: Using a retrospective cohort study design, we screened all outpatients (n = 7936 who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703 diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic.Results: Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant.Conclusion: Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.Keywords: retrospective study, second-generation antipsychotics, effectiveness, treatment continuation, schizophrenia, aripiprazole

Linezolid induced black hairy tongue

OpenAIRE

Govindan Balaji; B Maharani; Velappan Ravichandran; Thiyagarajan Parthasarathi

2014-01-01

Black hairy tongue (BHT) also called as lingua villosa nigra, is a self limiting benign condition characterized by hypertrophy and elongation of filiform papillae of tongue with brown or black discoloration. Smoking, poor oral hygiene, xerostomia, using peroxide containing mouth washes, substance abuse and drugs (steroids, methyldopa, olanzapine, etc) are the predisposing factors. However its occurrence in relation to linezolid ingestion among south Indians has not been reported in PubMed dat...

A Case of Eating Disorder

OpenAIRE

Amitabh Saha; Neha Sharma

2016-01-01

This is a case of Eating Disorder, which is described in a teenage girl who presented with intractable vomiting, hydropneumothorax and pulmonary Koch′s. The patient′s initial presentation was markedpreoccupation with body shape and image, restrictive eating, which progressed to episodes of vomiting after every meal, and led to academic decline followed by amenorrhoea and deterioration of general medical condition. She was managed with nutritional restoration, ATT and Olanzapine with Fluoxetin...

Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics; Nuklearmedizinische Rezeptordiagnostik bei schizophrenen Patienten unter Therapie mit typischen und atypischen Neuroleptika

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Dresel, S.; Tatsch, K. [Klinik und Poliklinik fuer Nuklearmedizin der Ludwig-Maximilians-Univ. Muenchen (Germany); Meisenzahl, E. [Psychiatrische Klinik der Ludwig-Maximilians-Univ. Muenchen (Germany); Scherer, J. [Bezirkskrankenhaus Haar (Germany)

2002-09-01

Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [German] Die pharmakologische Therapie von Erkrankungen aus dem schizophrenen Formenkreis erfolgt durch typische und atypische Neuroleptika. Beide Gruppen unterscheiden sich klinsich im Wesentlichen durch die Eigenschaft, extrapyramidal

Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

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Moore R Andrew

2007-08-01

Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics

Predictors of type 2 diabetes in a nationally representative sample of adults with psychosis

OpenAIRE

Foley, Debra L; Mackinnon, Andrew; Morgan, Vera A; Watts, Gerald F; McGrath, John J; Castle, David J; Waterreus, Anna; Galletly, Cherrie A

2014-01-01

Antipsychotic drugs such as clozapine and olanzapine are associated with an increased risk for type 2 diabetes, but relatively little is known about the relationship between risk factors for type 2 diabetes established in the general population and type 2 diabetes in people with psychosis. We estimated the prevalence of established risk factors and their association with type 2 diabetes in a nationally representative sample of people with an ICD-10 psychosis (N=1642) who gave a fasting blood ...

Treatment of bipolar disorder: a complex treatment for a multi-faceted disorder

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Fresno David

2007-10-01

Full Text Available Abstract Background Manic-depression or bipolar disorder (BD is a multi-faceted illness with an inevitably complex treatment. Methods This article summarizes the current status of our knowledge and practice of its treatment. Results It is widely accepted that lithium is moderately useful during all phases of bipolar illness and it might possess a specific effectiveness on suicidal prevention. Both first and second generation antipsychotics are widely used and the FDA has approved olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole for the treatment of acute mania. These could also be useful in the treatment of bipolar depression, but only limited data exists so far to support the use of quetiapine monotherapy or the olanzapine-fluoxetine combination. Some, but not all, anticonvulsants possess a broad spectrum of effectiveness, including mixed dysphoric and rapid-cycling forms. Lamotrigine may be effective in the treatment of depression but not mania. Antidepressant use is controversial. Guidelines suggest their cautious use in combination with an antimanic agent, because they are supposed to induce switching to mania or hypomania, mixed episodes and rapid cycling. Conclusion The first-line psychosocial intervention in BD is psychoeducation, followed by cognitive-behavioral therapy. Other treatment options include Electroconvulsive therapy and transcranial magnetic stimulation. There is a gap between the evidence base, which comes mostly from monotherapy trials, and clinical practice, where complex treatment regimens are the rule.

A Case of Eating Disorder

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Amitabh Saha

2016-01-01

Full Text Available This is a case of Eating Disorder, which is described in a teenage girl who presented with intractable vomiting, hydropneumothorax and pulmonary Koch′s. The patient′s initial presentation was markedpreoccupation with body shape and image, restrictive eating, which progressed to episodes of vomiting after every meal, and led to academic decline followed by amenorrhoea and deterioration of general medical condition. She was managed with nutritional restoration, ATT and Olanzapine with Fluoxetine, to which she responded poorly.

Risperidone versus other atypical antipsychotics for schizophrenia

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Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with

Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

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Maher, Alicia R; Theodore, George

2012-06-01

Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including

Antipsychotic switching for people with schizophrenia who have neuroleptic-induced weight or metabolic problems.

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Mukundan, Anitha; Faulkner, Guy; Cohn, Tony; Remington, Gary

2010-12-08

Weight gain is common for people with schizophrenia and this has serious implications for a patient's health and well being. Switching strategies have been recommended as a management option. To determine the effects of antipsychotic medication switching as a strategy for reducing or preventing weight gain and metabolic problems in people with schizophrenia. We searched key databases and the Cochrane Schizophrenia Group's trials register (January 2005 and June 2007), reference sections within relevant papers and contacted the first author of each relevant study and other experts to collect further information. All clinical randomised controlled trials comparing switching of antipsychotic medication as an intervention for antipsychotic induced weight gain and metabolic problems with continuation of medication and/or other weight loss treatments (pharmacological and non pharmacological) in people with schizophrenia or schizophrenia-like illnesses. Studies were reliably selected, quality assessed and data extracted. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. The primary outcome measures were weight loss, metabolic syndrome, relapse and general mental state. We included four studies for the review with a total of 636 participants. All except one study had a duration of 26 weeks or less. There was a mean weight loss of 1.94 kg (2 RCT, n = 287, CI -3.9 to 0.08) when switched to aripiprazole or quetiapine from olanzapine. BMI also decreased when switched to quetiapine (1 RCT, n = 129, MD -0.52 CI -1.26 to 0.22) and aripiprazole (1 RCT, n = 173, RR 0.28 CI 0.13 to 0.57) from olanzapine.Fasting blood glucose showed a significant decrease when switched to aripiprazole or quetiapine from olanzapine. (2 RCT, MD -2.53 n = 280 CI -2.94 to -2.11). One RCT also showed a favourable lipid profile when switched to aripiprazole but these measures were reported as percentage

Blinded prospective evaluation of computer-based mechanistic schizophrenia disease model for predicting drug response.

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Hugo Geerts

Full Text Available The tremendous advances in understanding the neurobiological circuits involved in schizophrenia have not translated into more effective treatments. An alternative strategy is to use a recently published 'Quantitative Systems Pharmacology' computer-based mechanistic disease model of cortical/subcortical and striatal circuits based upon preclinical physiology, human pathology and pharmacology. The physiology of 27 relevant dopamine, serotonin, acetylcholine, norepinephrine, gamma-aminobutyric acid (GABA and glutamate-mediated targets is calibrated using retrospective clinical data on 24 different antipsychotics. The model was challenged to predict quantitatively the clinical outcome in a blinded fashion of two experimental antipsychotic drugs; JNJ37822681, a highly selective low-affinity dopamine D(2 antagonist and ocaperidone, a very high affinity dopamine D(2 antagonist, using only pharmacology and human positron emission tomography (PET imaging data. The model correctly predicted the lower performance of JNJ37822681 on the positive and negative syndrome scale (PANSS total score and the higher extra-pyramidal symptom (EPS liability compared to olanzapine and the relative performance of ocaperidone against olanzapine, but did not predict the absolute PANSS total score outcome and EPS liability for ocaperidone, possibly due to placebo responses and EPS assessment methods. Because of its virtual nature, this modeling approach can support central nervous system research and development by accounting for unique human drug properties, such as human metabolites, exposure, genotypes and off-target effects and can be a helpful tool for drug discovery and development.

Treatment of Post-Traumatic Stress Disorder Nightmares at a Veterans Affairs Medical Center

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Detweiler, Mark B.; Pagadala, Bhuvaneshwar; Candelario, Joseph; Boyle, Jennifer S.; Detweiler, Jonna G.; Lutgens, Brian W.

2016-01-01

The effectiveness of medications for PTSD in general has been well studied, but the effectiveness of medicatio.ns prescribed specifically for post-traumatic stress disorder (PTSD) nightmares is less well known. This retrospective chart review examined the efficacy of various medications used in actual treatment of PTSD nightmares at one Veteran Affairs Hospital. Records at the Salem, VA Veterans Affairs Medical Center (VAMC) were examined from 2009 to 2013 to check for the efficacy of actual treatments used in comparis.on with treatments suggested in three main review articles. The final sample consisted of 327 patients and 478 separate medication trials involving 21 individual medications plus 13 different medication combinations. The three most frequently utilized medications were prazosin (107 trials), risperidone (81 trials), and quetiapine (72 trials). Five medications had 20 or more trials with successful results (partial to full nightmare cessation) in >50% of trials: risperidone (77%, 1.0–6.0 mg), clonidine (63%, 0.1–2.0 mg), quetiapine (50%, 12.5–800.0 mg), mirtazapine (50%; 7.5–30.0 mg), and terazosin (64%, 50.0–300.0 mg). Notably, olanzapine (2.5–10.0) was successful (full remission) in all five prescription trials in five separate patients. Based on the clinical results, the use of risperidone, clonidine, terazosin, and olanzapine warrants additional investigation in clinically controlled trials as medications prescribed specifically for PTSD nightmares. PMID:27999253

Diurnal variation in Cotard's syndrome (copresent with Capgras delusion) following traumatic brain injury.

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Butler, P V

2000-08-01

The aim of this paper is to document regular nocturnal intensification of delusional nihilistic and persecutory ideas (Cotard delusion) linked with extreme depersonalisation and hypervivid dreaming. A 17-year-old man presented with Cotard and Capgras delusions after sustaining multiple cognitive impairments secondary to traumatic brain injury. Delusional ideation fully resolved within 14 days of commencement of olanzapine 5 mg daily. This patient's experience of perceptual abnormalities and impairments in meta-abilities related to self-monitoring and critical inferencing lends support to multicomponent sensory processing accounts of brain injury related, content-specific delusional syndromes.

Twenty-four months of antipsychotic treatment in children and adolescents with first psychotic episode: discontinuation and tolerability.

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Noguera, Ana; Ballesta, Patricia; Baeza, Immaculada; Arango, Celso; de la Serna, Elena; González-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Carmen; Otero, Soraya; Castro-Fornieles, Josefina

2013-08-01

The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects. The sample comprised 110 patients, aged 9 to 17 years, with a first psychotic episode. Pharmacological treatment, changes, reasons for discontinuation, and the UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale were registered at 6, 12, and 24 months of follow-up. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, were the most commonly used. The discontinuation rate was 44.5% at 6 months, 59.1% at 12 months, and 70.9% at 24 months. Discontinuation rates or reasons for discontinuation (adverse reaction, insufficient response, and other) did not differ significantly between antipsychotics. At 6 months, significant differences were found in body mass index increase and body mass index z score increase, which were higher with olanzapine, and in neurological effects, which were higher with risperidone; at 12 and 24 months, these differences were no longer significant. High maintenance rates were found in the clozapine group, although they had higher scores on the autonomic subscale of the UKU. A long follow-up period reveals high discontinuation rates similar to those observed in adults, particularly during the first year. No differences were found between antipsychotics. Differences in adverse effects were found at 6 months but not subsequently after changes in treatment. Clozapine had a high maintenance rate, and its tolerability was comparable to that of other antipsychotics.

Receptor imaging of schizophrenic patients under treatment with typical and atypical neuroleptics

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Dresel, S.; Tatsch, K.; Meisenzahl, E.; Scherer, J.

2002-01-01

Schizophrenic psychosis is typically treated by typical and atypical neuroleptics. Both groups of drugs differ with regard to induction of extrapyramidal side effects. The occupancy of postsynaptic dopaminergic D2 receptors is considered to be an essential aspect of their antipsychotic properties. The dopamine D2 receptor status can be assessed by means of [I-123]IBZM SPECT. Studies on the typical neuroleptic haloperidol revealed an exponential dose response relationship measured by IBZM. Extrapyramidal side effects were presented by all patients below a threshold of the specific binding of IBZM below 0.4 (with one exception, norm value: >0.95). Also under treatment with the atypical neuroleptic clozapine an exponential dose response relationship was found. However, none of these patients showed extrapyramidal side effects. Recently introduced, new atypical neuroleptics such as risperidone and olanzapine again presented with an exponential relationship between daily dose and IBZM binding. The curves of the latter were in between the curves of haloperidol and clozapine. Extrapyramidal side effects were documented in a less number of patients treated with risperidone as compared to haloperidol, for olanzapine only one patient revealed these findings in our own patient group. The pharmacological profile of atypical neuroleptics shows - in addition to their binding to dopamine receptors - also high affinities to the receptors of other neurotransmitter systems, particularly the serotonergic system. Therefore, the lower incidence of extrapyramidal side effects seen by atypical in comparison to typical neuroleptics is at least in part most likely due to a complex interaction on a variety of neurotransmitter systems. (orig.) [de

Efficacy, acceptability and tolerability of 8 atypical antipsychotics in Chinese patients with acute schizophrenia: A network meta-analysis.

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Bai, Zhihua; Wang, Guoqiang; Cai, Shangli; Ding, Xindi; Liu, Weiwei; Huang, Depei; Shen, Weidi; Zhang, Juncheng; Chen, Kui; Yang, Yuqing; Zhang, Lili; Zhao, Xiaochen; Ouyang, Qiong; Zhao, Jingping; Lu, Huafei; Hao, Wei

2017-07-01

We aimed to create hierarchies of the efficacy, acceptability and tolerability of eight atypical antipsychotics in the treatment of Chinese patients with acute schizophrenia. We systematically searched for RCT articles published between January 1st 2005 and December 31st 2014 in electronic databases (Medline, Pubmed, Embase, the Cochrane Library and ClinicalTrial.gov for studies in English and the China National Knowledge Infrastructure, Wan Fang, and VIP Information/Chinese Scientific Journals Database for studies in Chinese). The primary outcome was efficacy, as measured by the change of PANSS total score. Pairwise comparisons were performed using random-effects model by the Dersimonian-Laird method and network meta-analyses were performed in a Bayesian set. Sixty high-quality RCTs with 6418 participants were included. A pattern of superiority from olanzapine, paliperidone and amisulpride was seen in the primary outcome. Only paliperidone was found better than aripiprazole (odds ratio, 0.49 [95% credible intervals, 0.25 to 0.99]), ziprasidone (0.42 [0.21 to 0.85]) and quetiapine (0.36 [0.13 to 0.93]) in terms of all-cause discontinuation. The best and worst drugs in terms of weight gain, EPS and somnolence were aripiprazole and olanzapine, clozapine and amisulpride, aripiprazole and clozapine, respectively. The rank of efficacy did not change substantially in sensitivity analyses or in meta-regressions. Our findings provided the hierarchies of eight antipsychotics in efficacy, acceptability and tolerability. These findings are expected to help Chinese clinicians to select the appropriate antipsychotic drug for their patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

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Haeberle Anne

2012-09-01

Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.

A bibliometric study of scientific research conducted on second-generation antipsychotic drugs in Singapore.

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López-Muñoz, Francisco; Sim, Kang; Shen, Winston Wu; Huelves, Lorena; Moreno, Raquel; Molina, Juan de Dios; Rubio, Gabriel; Noriega, Concha; Pérez-Nieto, Miguel Ángel; Alamo, Cecilio

2014-01-01

A bibliometric study was carried out to ascertain the volume and impact of scientific literature published on second-generation antipsychotic drugs (SGAs) in Singapore from 1997 to 2011. A search of the EMBASE and MEDLINE databases was performed to identify articles originating from Singapore that included the descriptors 'atypic* antipsychotic*', 'second-generation antipsychotic*', 'clozapine', 'risperidone', 'olanzapine', 'ziprasidone', 'quetiapine', 'sertindole', 'aripiprazole', 'paliperidone', 'amisulpride', 'zotepine', 'asenapine', 'iloperidone', 'lurasidone', 'perospirone' and 'blonanserin' in the article titles. Certain bibliometric indicators of production and dispersion (e.g. Price's Law on the increase of scientific literature, and Bradford's Law) were applied, and the participation index of various countries was calculated. The bibliometric data was also correlated with some social and health data from Singapore, such as the total per capita expenditure on health and gross domestic expenditure on research and development. From 1997 to 2011, a total of 51 articles on SGAs in Singapore were published. Our results suggested non-fulfilment of Price's Law (r = 0.0648 after exponential adjustment vs. r = 0.2140 after linear adjustment). The most widely studied drugs were clozapine (21 articles), risperidone (16 articles) and olanzapine (8 articles). Division into Bradford zones yielded a nucleus occupied by the Journal of Clinical Psychopharmacology (6 articles) and the Singapore Medical Journal(4 articles). The analysed material was published in a total of 30 journals, with the majority from six journals. Four of these six journals have an impact factor greater than 2. Publications on SGAs in Singapore are still too few to confirm an exponential growth of scientific literature.

The impact of reference pricing and extension of generic substitution on the daily cost of antipsychotic medication in Finland.

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Koskinen, Hanna; Ahola, Elina; Saastamoinen, Leena K; Mikkola, Hennamari; Martikainen, Jaana E

2014-12-01

To assess the impact of reference pricing and extension of generic substitution on the daily cost of antipsychotic drugs in Finland during the first year after its launch. Furthermore, the additional impact of reference pricing on prior implemented generic substitution is assessed. A retrospective analysis was performed between 2006 and 2010. A segmented linear regression analysis of interrupted time series was used to estimate changes in the levels and trends in the cost of one day of treatment. Of the study drugs, clozapine belonged to generic substitution already at the start of the study period while olanzapine and quetiapine were included in generic substitution alongside with reference pricing in 2009. Risperidone was included in generic substitution in 2008, before reference pricing. A substantial decrease in the daily cost of all four antipsychotic substances was seen after one year of the implementation of reference pricing and the extension of generic substitution. The impact ranged from -29.9% to -66.3%, and it was most substantial on the daily cost of olanzapine. Also in the daily cost of risperidone a substantial decrease of -43.3% was observed. However, most of these savings, -32.6%, were generated by generic substitution which had been adopted prior. Reference pricing and the extension of generic substitution produced substantial savings on antipsychotic medication costs during the first year after its launch, but the intensity of the impact differed between active substances. Furthermore, our results suggest that the additional cost savings from reference pricing after prior implemented generic substitution, are comparatively low.

Weight change from 3-year observational data: findings from the worldwide schizophrenia outpatient health outcomes database.

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Bushe, Chris J; Slooff, Cees J; Haddad, Peter M; Karagianis, Jamie L

2012-06-01

Weight change data from randomized clinical trials are often of limited duration and trials do not always report a full range of clinically relevant categorical end points. We conducted a post hoc analysis of data from the observational Worldwide Schizophrenia Outpatient Health Outcomes database (2000-2005) on weight change in 4,626 patients completing 3 years of antipsychotic monotherapy with amisulpride, clozapine, olanzapine, quetiapine, risperidone, and oral and depot first-generation antipsychotics (FGAs). Reported outcomes included mean and categorical weight changes and the trajectories of different measures of weight change. Mean weight gain was lowest with amisulpride (1.8 kg; 95% CI, 0.2-3.3) and highest with olanzapine (4.2 kg; 95% CI, 3.9-4.5). Weight change for all antipsychotics was most rapid during the first 6 months; subsequent weight change was slower but did not plateau. All drugs showed considerable individual variation in weight change. The proportion losing ≥7% of their baseline bodyweight was highest with quetiapine (10%; 95% CI, 7%-16%) and lowest with depot FGAs (5%; 95% CI, 3%-10%). Between 7% and 15% of patients moved into an overweight or obese body mass index (kg/m2)category (≥25). The degree of weight gain varied between antipsychotics. All antipsychotics were associated with significant (≥7%) weight loss and gain from baseline. The mean rate of weight gain was maximal during the first 6 months but continued over 3 years without a plateau in this specific cohort. Patients should receive regular monitoring of weight throughout treatment. © Copyright 2012 Physicians Postgraduate Press, Inc.

Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

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Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P

2007-02-01

Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.

Atypical antipsychotics as augmentation therapy in anorexia nervosa.

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Enrica Marzola

Full Text Available Anorexia nervosa (AN is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings.

The role of sedation tests in identifying sedative drug effects in healthy volunteers and their power to dissociate sedative-related impairments from memory dysfunctions.

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Wezenberg, E; Sabbe, B G C; Hulstijn, W; Ruigt, G S F; Verkes, R J

2007-08-01

The study investigated whether four specified drugs would show similar patterns on tests considered to measure sedation. In addition, their drug-effect patterns on sedation and memory performance were compared to determine whether the sedative effects could be differentiated from the memory effects. Two double-blind, placebo-controlled, crossover studies, each with 16 healthy volunteers, were performed, one testing lorazepam (2.5 mg) and mirtazapine (15 mg) and the other olanzapine (10 mg) and haloperidol (2.5 mg). Subjective sedation was assessed by means of visual analogue scales (VAS) and objective sedation using a simple-reaction-time (SRT) task and a choice-reaction-time (CRT) task, code substitution (symbol digit substitution test (SDST)) and the peak velocity of saccadic eye movements (SEM). A verbal memory test (VMT) was administered to evaluate memory capacity. Apart from haloperidol, all drugs proved to impair performance on all five sedation indices. Contrary to the VAS, the objective measures yielded different response profiles. Two types of drug-effect patterns emerged: one for greater impairments in response speed (SRT, SEM) and one for greater impairments in information processing (CRT, SDST). Lorazepam and olanzapine impeded memory performance, whereas mirtazapine did not. With the use of standardized scores it proved possible to differentiate between the size of the effects of the drugs on the sedation and memory tests. To accurately assess the level and nature of sedation and to differentiate sedation from memory impairments different types of sedation measures are required. Besides studying the subjective effects, it is recommended to also test psychomotor responses and information processing speed.

Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

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Sahlberg, Marie; Holm, Ellen; Gislason, Gunnar H

2015-01-01

events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. METHODS AND RESULTS: We followed all treatment-naïve Danish citizens...... of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of levomepromazine (3.80, 95% CI 3.43 to 4.21) and haloperidol (1.85, 95% CI 1.67 to 2.05) and lower for treatment with flupentixol (0.54, 95% CI 0.45 to 0.66), ziprasidone (0.31, 95% CI 0...

Electroconvulsive therapy for lycanthropy and Cotard syndrome: a case report.

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Grover, Sandeep; Shah, Ruchita; Ghosh, Abhishek

2010-12-01

We present a case of psychotic depression presenting with lycanthropy (being converted to a pig) and Cotard syndrome simultaneously and treated with electroconvulsive therapy. A 37-year-old female patient developed psychotic depression after a stressor (a possibility of having a malignancy). As her depression worsened, she developed delusional belief of self being metamorphosed to a pig and her children also being metamorphosed into pig. In addition, she had the delusional belief that her own body and body of her children was rotting away. She was treated with electroconvulsive therapy along with venlafaxine and olanzapine, with which she improved completely.

A case report on very late onset mania

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Manjunadh Muraleedharan

2017-06-01

Full Text Available Diagnosing primary psychiatric disorder in elderly is a challenge considering the high prevalence of neurological and other medical diseases presenting with psychiatric manifestation. The first episode of mania occurring after the age of 80 years is extremely rare. We report a case of an 88-year-old married Hindu male educated up to fifth standard from rural background and lower socioeconomic status presenting with first episode mania, diagnosed using the tenth revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10 criteria. Secondary causes were ruled out and successfully treated with low dose olanzapine.

First Episode of Psychosis in a Middle-Aged Patient with a 14-Year History of Conversion Disorder

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Vaios Peritogiannis

2014-01-01

Full Text Available We present a case of a middle-aged male patient with a long history of conversion disorder and histrionic personality, who presented with newly onset psychotic symptoms while being engaged to treatment with a community mental health team in a primary care setting. The symptoms could not be attributed to an organic cause. After a short course of olanzapine treatment which caused adverse effects, the symptomatology responded well to low dose amisulpride. Conversion symptoms were stable throughout the psychotic episode. This case illustrates the complex interplay between disorders classified in different categories (somatoform versus psychotic disorders.

Schizophrenia relapse after stopping olanzapine treatment during pregnancy: a case report

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Ifteni, Petru; Moga, Marius A; Burtea, Victoria; Correll, Christoph U

2014-01-01

Petru Ifteni,1,2 Marius A Moga,1 Victoria Burtea,1,2 Christoph U Correll3,4 1Faculty of Medicine, Transilvania University, Brasov, Romania; 2Psychiatry and Neurology Hospital, Brasov, Romania; 3Department of Psychiatry, The Zucker Hillside Hospital, North Shore-Long Island Jewish (LIJ) Health System, New York, NY, USA; 4Hofstra North Shore-LIJ School of Medicine, New York, NY, USA Abstract: Women with schizophrenia have a high risk for symptom exacerbation or relapse during pregnan...

Effect of Clozapine vs Other Second-Generation Antipsychotics on Hospitalization and Seclusion: A Retrospective Mirror-Image Study in a Japanese Public Psychiatric Hospital.

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Misawa, Fuminari; Suzuki, Takefumi; Fujii, Yasuo

2017-12-01

Clozapine has been regarded as the gold standard for patients with treatment-resistant schizophrenia, but a recent network meta-analysis has questioned its relative superiority over other second-generation antipsychotics (SGAs) such as olanzapine and risperidone. We conducted a retrospective mirror-image study of clozapine vs other SGAs to evaluate real-world effectiveness of clozapine in terms of the duration of hospitalization and seclusion, both of which represent a critical outcome. We included all patients who initiated clozapine at the Yamanashi Prefectural KITA Hospital and had continued to take any SGA(s) other than clozapine for at least 1 year before the initiation of clozapine. We obtained data on hospitalization and seclusion during 1 year of SGA treatment (SGA phase) and 1 year after the treatment was switched to clozapine (clozapine phase). The study included 35 patients (21 men, 31 with schizophrenia, 4 with schizoaffective disorder) with the average ± SD age of 37.3 ± 11.1 years. The results indicated that total hospitalization days did not differ significantly between SGA and clozapine treatment. However, total duration of seclusion was significantly shorter in the clozapine phase than in the SGA phase. Furthermore, the number of patients who were secluded at least once was significantly smaller in the clozapine phase than in the SGA phase. The results were essentially unchanged when outlier patients were excluded and only when patients taking olanzapine and/or risperidone during the SGA phase were considered. Although the findings from this retrospective analysis need to be further tested in prospective trials, they endorse the relative effectiveness of clozapine over other SGAs in the real world.

N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H MRS) study.

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Szulc, Agata; Galińska, Beata; Tarasów, Eugeniusz; Kubas, Bozena; Dzienis, Wojciech; Konarzewska, Beata; Poplawska, Regina; Tomczak, Anna A; Czernikiewicz, Andrzej; Walecki, Jerzy

2007-05-01

NAA, marker of neurons integrity and viability, is one of the most important brain metabolites visible in 1H MRS. In most studies of schizophrenia, the decrease of NAA level was observed in the temporal, frontal lobes and in the thalamus. This finding was observed more often among chronic patients, what suggests the influence of disease duration or the effect of neuroleptic treatment. The aim of the present study was the comparison of NAA levels in brain of schizophrenic patients taking typical and atypical neuroleptics. We analyzed the NAA levels in selected brain areas in 58 schizophrenic patients and 21 healthy controls. 10 patients were treated with typical neuroleptics, 10 patients with clozapine, 17 received olanzapine and 21 - risperidone. 1H MRS was performed on a 1,5 MR scanner with PRESS sequence. Voxels of 2x2x2 cm were localized in the left frontal, left temporal lobe and left thalamus. There were no differences in NAA levels between patients on typical and atypical medications analyzed together and separately (olanzapine, clozapine and risperidone groups). We also did not find any differences between patients taking selected atypical neuroleptics and controls. The NAA level in the thalamus in the group of patients receiving typical antipsychotics was the lowest among all groups and differed significantly from healthy controls. The results of our study suggest that atypical neuroleptics may have favorable effect on NAA concentration in brain of schizophrenic patients. Decrease in NAA level in patients taking typical medication may be caused by the progression of the disease or by the direct action of these drugs.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Acute and long-term treatment of mixed states in bipolar disorder.

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Grunze, Heinz; Vieta, Eduard; Goodwin, Guy M; Bowden, Charles; Licht, Rasmus W; Azorin, Jean-Michel; Yatham, Lakshmi; Mosolov, Sergey; Möller, Hans-Jürgen; Kasper, Siegfried

2018-02-01

Although clinically highly relevant, the recognition and treatment of bipolar mixed states has played only an underpart in recent guidelines. This WFSBP guideline has been developed to supply a systematic overview of all scientific evidence pertaining to the acute and long-term treatment of bipolar mixed states in adults. Material used for these guidelines is based on a systematic literature search using various data bases. Their scientific rigour was categorised into six levels of evidence (A-F), and different grades of recommendation to ensure practicability were assigned. We examined data pertaining to the acute treatment of manic and depressive symptoms in bipolar mixed patients, as well as data pertaining to the prevention of mixed recurrences after an index episode of any type, or recurrence of any type after a mixed index episode. Manic symptoms in bipolar mixed states appeared responsive to treatment with several atypical antipsychotics, the best evidence resting with olanzapine. For depressive symptoms, addition of ziprasidone to treatment as usual may be beneficial; however, the evidence base is much more limited than for the treatment of manic symptoms. Besides olanzapine and quetiapine, valproate and lithium should also be considered for recurrence prevention. The concept of mixed states changed over time, and recently became much more comprehensive with the release of DSM-5. As a consequence, studies in bipolar mixed patients targeted slightly different bipolar subpopulations. In addition, trial designs in acute and maintenance treatment also advanced in recent years in response to regulatory demands. Current treatment recommendations are still based on limited evidence, and there is a clear demand for confirmative studies adopting the DSM-5 specifier with mixed features concept.

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists.

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Bošnjak, Snežana M; Gralla, Richard J; Schwartzberg, Lee

2017-05-01

Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK 1 RAs when combined with 5-HT 3 RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK 1 RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK 1 RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.

[Pharmacological Treatment for Adult Diagnosed With Schizophrenia With Agitation or Violent Behavior].

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Gómez-Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; Ávila, Mauricio J; Jaramillo González, Luis Eduardo; Vélez Fernández, Carolina; Vélez Traslaviña, Ángela; García Valencia, Jenny; Pinzón-Amado, Alexander

2014-01-01

To determine the most effective pharmacological intervention and to bring recommendations for decision-making in the management of adults with schizophrenia with violent behavior or agitation. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. It is recommended the use of parenteral drugs in all agitated patient who does not respond to the measures of persuasion. The drugs with better evidence on effectiveness (control of violent behavior) are haloperidol and benzodiazepines, administered jointly or individually. Olanzapine is also an option considering that should only be used in institutions where a psychiatrist is available 24hours. Ziprasidone can be considered as a second-line drug. The information about the side effects associated with these drugs is insufficient and has low quality. Violent behavior in adults with schizophrenia represents a risk for themselves and for those around them, so the opportune implementation of interventions aimed to calm the patient, in order to prevent potential negative outcomes is necessary. It is recommended to initiate these interventions with measures of verbal persuasion, and if these measures are not effective, appropriate use of parenteral drugs: haloperidol and benzodiazepines as first-line and olanzapine and ziprasidone as second choices. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Reviewing current and emerging antiemetics for chemotherapy-induced nausea and vomiting prophylaxis.

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Natale, James J

2015-01-01

This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

Challenges in managing a mother with a dual diagnosis of peripartum cardiomyopathy and paranoid schizophrenia - a case report.

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Weerasundera, Rajiv; Yogaratnam, Jegan

2013-01-01

Psychotic illness has a low incidence in the puerperal period. Peripartum cardiomyopathy as a complication of pregnancy is also rare. We report a case where the above two conditions occurred simultaneously in a patient and posed significant difficulties in the clinical management. She was diagnosed as having paranoid schizophrenia and peripartum cardiomyopathy. Many of the antipsychotics were contraindicated, and electroconvulsive therapy could not be administered due to the added risks involved with regard to anesthesia. She was therefore managed with clonazepam and olanzapine. This case highlights the challenges in a patient with a psychiatric illness presenting with comorbid physical illness. Copyright © 2013 Elsevier Inc. All rights reserved.

Edema associated with quetiapine

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Koleva, Hristina K.; Erickson, Mark A.; Vanderlip, Erik R.; Tansey, Janeta; Mac, Joseph; Fiedorowicz, Jess G.

2010-01-01

Background Edema associated with quetiapine has been described in only one case report to date and represents a potentially serious adverse reaction. Methods We present a case series of three patients who developed bilateral leg edema following initiation of quetiapine. Results One of these patients had a recurrence of edema with subsequent rechallenge. Another patient developed quetiapine-induced edema following a prior episode of olanzapine-induced edema. All the cases present a compelling temporal relationship between the drug challenge and the adverse event. Conclusions Prompt recognition and intervention with discontinuation of the offending agent is important for this potentially serious, seemingly idiosyncratic, vascular complication. PMID:19439156

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

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Mohammad, Othman; Osser, David N

2014-01-01

This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

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Razzouk, Denise; Kayo, Monica; Sousa, Aglaé; Gregorio, Guilherme; Cogo-Moreira, Hugo; Cardoso, Andrea Alves; Mari, Jair de Jesus

2015-01-01

Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce. To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil. A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated. 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs. Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle

Blonanserin Ameliorates Phencyclidine-Induced Visual-Recognition Memory Deficits: the Complex Mechanism of Blonanserin Action Involving D3-5-HT2A and D1-NMDA Receptors in the mPFC

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Hida, Hirotake; Mouri, Akihiro; Mori, Kentaro; Matsumoto, Yurie; Seki, Takeshi; Taniguchi, Masayuki; Yamada, Kiyofumi; Iwamoto, Kunihiro; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2015-01-01

Blonanserin differs from currently used serotonin 5-HT2A/dopamine-D2 receptor antagonists in that it exhibits higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effects of blonanserin on cognitive impairment in an animal model of schizophrenia. We also sought to elucidate the molecular mechanism underlying this involvement. Blonanserin, as well as olanzapine, significantly ameliorated phencyclidine (PCP)-induced impairment of visual-recognition memory, as demonstrated by the novel-object recognition test (NORT) and increased extracellular dopamine levels in the medial prefrontal cortex (mPFC). With blonanserin, both of these effects were antagonized by DOI (a serotonin 5-HT2A receptor agonist) and 7-OH-DPAT (a dopamine-D3 receptor agonist), whereas the effects of olanzapine were antagonized by DOI but not by 7-OH-DPAT. The ameliorating effect was also antagonized by SCH23390 (a dopamine-D1 receptor antagonist) and H-89 (a protein kinase A (PKA) inhibitor). Blonanserin significantly remediated the decrease in phosphorylation levels of PKA at Thr197 and of NR1 (an essential subunit of N-methyl-D-aspartate (NMDA) receptors) at Ser897 by PKA in the mPFC after a NORT training session in the PCP-administered mice. There were no differences in the levels of NR1 phosphorylated at Ser896 by PKC in any group. These results suggest that the ameliorating effect of blonanserin on PCP-induced cognitive impairment is associated with indirect functional stimulation of the dopamine-D1-PKA-NMDA receptor pathway following augmentation of dopaminergic neurotransmission due to inhibition of both dopamine-D3 and serotonin 5-HT2A receptors in the mPFC. PMID:25120077

Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats.

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Abdallah Ahnaou

Full Text Available Improvement of cognitive impairments represents a high medical need in the development of new antipsychotics. Aberrant EEG gamma oscillations and reductions in the P1/N1 complex peak amplitude of the auditory evoked potential (AEP are neurophysiological biomarkers for schizophrenia that indicate disruption in sensory information processing. Inhibition of phosphodiesterase (i.e. PDE10A and activation of metabotropic glutamate receptor (mGluR2 signaling are believed to provide antipsychotic efficacy in schizophrenia, but it is unclear whether this occurs with cognition-enhancing potential. The present study used the auditory paired click paradigm in passive awake Sprague Dawley rats to 1 model disruption of AEP waveforms and oscillations as observed in schizophrenia by peripheral administration of amphetamine and the N-methyl-D-aspartate (NMDA antagonist phencyclidine (PCP; 2 confirm the potential of the antipsychotics risperidone and olanzapine to attenuate these disruptions; 3 evaluate the potential of mGluR2 agonist LY404039 and PDE10 inhibitor PQ-10 to improve AEP deficits in both the amphetamine and PCP models. PCP and amphetamine disrupted auditory information processing to the first click, associated with suppression of the P1/N1 complex peak amplitude, and increased cortical gamma oscillations. Risperidone and olanzapine normalized PCP and amphetamine-induced abnormalities in AEP waveforms and aberrant gamma/alpha oscillations, respectively. LY404039 increased P1/N1 complex peak amplitudes and potently attenuated the disruptive effects of both PCP and amphetamine on AEPs amplitudes and oscillations. However, PQ-10 failed to show such effect in either models. These outcomes indicate that modulation of the mGluR2 results in effective restoration of abnormalities in AEP components in two widely used animal models of psychosis, whereas PDE10A inhibition does not.

The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography - tandem mass spectrometry.

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Patteet, Lisbeth; Maudens, Kristof E; Stove, Christophe P; Lambert, Willy E; Morrens, Manuel; Sabbe, Bernard; Neels, Hugo

2015-06-01

Therapeutic drug monitoring of antipsychotics is important in optimizing individual therapy. In psychiatric populations, classical venous blood sampling is experienced as frightening. Interest in alternative techniques, like dried blood spots (DBS), has consequently increased. A fast and easy to perform DBS method for quantification of 16 antipsychotics (amisulpride, aripiprazole, asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride, lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone, sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared using 25 μL of whole blood and extraction of complete spots was performed using methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was reconstituted in the mobile phase and 10 μL were injected on an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Separation using a C18 column and gradient elution with a flow rate of 0.5 mL/min resulted in a 6-min run-time. Ionization was performed in positive mode and a dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%). Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low concentration) and lurasidone (low concentration). Imprecision was only aberrant for lurasidone at low and medium concentration. All compounds were stable during 1 month at room temperature, 4 °C and -18 °C. Lurasidone was unstable when the extract was stored for 12 h on the autosampler. Absolute matrix effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median 98.8%). The DBS method was successfully applied on 25-μL capillary DBS from patients and proved to be a reliable alternative for quantification of all antipsychotics except for olanzapine and N-desmethylolanzapine. Copyright © 2014 John Wiley & Sons, Ltd.

An acute rat in vivo screening model to predict compounds that alter blood glucose and/or insulin regulation.

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Brott, David A; Diamond, Melody; Campbell, Pam; Zuvich, Andy; Cheatham, Letitia; Bentley, Patricia; Gorko, Mary Ann; Fikes, James; Saye, JoAnne

2013-01-01

Drug-induced glucose dysregulation and insulin resistance have been associated with weight gain and potential induction and/or exacerbation of diabetes mellitus in the clinic suggesting they may be safety biomarkers when developing antipsychotics. Glucose and insulin have also been suggested as potential efficacy biomarkers for some oncology compounds. The objective of this study was to qualify a medium throughput rat in vivo acute Intravenous Glucose Tolerance Test (IVGTT) for predicting compounds that will induce altered blood glucose and/or insulin levels. Acute and sub-chronic studies were performed to qualify an acute IVGTT model. Double cannulated male rats (Han-Wistar and Sprague-Dawley) were administered vehicle, olanzapine, aripiprazole or other compounds at t=-44min for acute studies and at time=-44min on the last day of dosing for sub-chronic studies, treated with dextrose (time=0min; i.v.) and blood collected using an automated Culex® system for glucose and insulin analysis (time=-45, -1, 2, 10, 15, 30, 45, 60, 75, 90, 120, 150 and 180min). Olanzapine significantly increased glucose and insulin area under the curve (AUC) values while aripiprazole AUC values were similar to control, in both acute and sub-chronic studies. All atypical antipsychotics evaluated were consistent with literature references of clinical weight gain. As efficacy biomarkers, insulin AUC but not glucose AUC values were increased with a compound known to have insulin growth factor-1 (IGF-1) activity, compared to control treatment. These studies qualified the medium throughput acute IVGTT model to more quickly screen compounds for 1) safety - the potential to elicit glucose dysregulation and/or insulin resistance and 2) efficacy - as a surrogate for compounds affecting the glucose and/or insulin regulatory pathways. These data demonstrate that the same in vivo rat model and assays can be used to predict both clinical safety and efficacy of compounds. © 2013.

The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR study (NCT00237913

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Pans Miranda

2008-12-01

Full Text Available Abstract Background The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC, which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]. Method This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone in patients with schizophrenia (DSM-IV-TR criteria. The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX. This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper. Results A total of 555 patients were randomised to receive aripiprazole (n = 284 or SOC (n = 271. Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC. Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p Conclusion The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.

Endocrine and Metabolic Adverse Effects of Psychotropic Drugs in Children and Adolescents

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Evrim Aktepe

2011-12-01

Full Text Available ABSTRACT Much as an increase in the use of psychotropic drugs is observed in children and adolescents over the last decade, the endocrine and metabolic side effects of these drugs can limit their use. Atypical antipsychotics can cause many side effects, which are not suitable for the developmental periods of children and adolescents, such as those related with thyroid, blood sugar, level of sex hormones, growth rate and bone metabolism. Children are under a more serious risk regarding the weight increasing effects of atypical antipsychotics and weight gain that is not proportionate with age is especially important due to the association between glucose or lipid abnormalities and cardiovascular mortality. Aripiprazole and ziprasidone are the least risky antipsychotic drugs when it comes to metabolic side affects. The antipsychotic drug that is associated with weight increase and diabetes in children and adolescents most is olanzapine. Even though there are no comparative long-term data concerning children, it is suggested by the currently available information that metabolic side effects including dyslipidemia and impaired glucose tolerance are at an alarming level when it comes to long-term treatment with antipsychotics. The most risky agents in terms of hyperglycemia and glucosuria development are olanzapine and clozapine. Use of risperidone and haloperidol should be undertaken with caution since it may bring about the risk of hyperprolactinemia. Among the antidepressants associated with weight loss and suppression of appetite are selective serotonin reuptake inhibitors, bupropion and venlafaxine. Thyroid functions can be affected by lithium, carbamazepine and valproate treatments. It is reported that the side effect most frequently associated with valproate is weight increase. The relationship between valproate treatment and the development of hyperandrogenism and polycystic ovary syndrome in young women should also be kept in mind. [TAF Prev

Diagnostic and therapeutic hardships with mixed affective state presenting as catatonia in a patient with intellectual disability

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Karthick Subramanian

2017-01-01

Full Text Available Mixed affective episodes can be misdiagnosed, especially in patients with intellectual disability (ID. We describe the case of an 18-year-old girl with mild ID, who presented with features of catatonia during the first mixed episode. These symptoms responded well to electroconvulsive therapy, following which clear affective symptoms emerged. Her affective episode did not respond adequately to olanzapine but improved significantly after the addition of sodium valproate. The difficulties of diagnosing affective episodes in persons with intellectual disabilities are discussed. This case suggests that mixed affective episodes should be considered in the differential diagnosis when poorly elaborated affective and psychotic symptoms are present in a patient with ID.

Effectiveness of maintenance therapy of lithium vs other mood stabilizers in monotherapy and in combinations

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Kessing, Lars Vedel; Bauer, Michael; Nolen, Willem A.

2018-01-01

Objectives: For the first time to present a systematic review of observational studies on the efficiency of lithium monotherapy in comparison with other maintenance mood stabilizers in monotherapy and in combination. Methods: As part of the International Society for Bipolar Disorders (ISBD) Task...... Force on Lithium Treatment, we undertook a systematic literature search of non-randomized controlled observational studies on (i) lithium monotherapy vs treatment with another maintenance mood stabilizer in monotherapy and (ii) lithium in combination with other mood stabilizers vs monotherapy. Results......: In eight out of nine identified studies including a total of lithium monotherapy was associated with improved outcome compared with another mood stabilizer in monotherapy, including valproate, lamotrigine, olanzapine, quetiapine, unspecified anticonvulsants, carbamazepine...

Effects of cigarette smoking on priapism induced by quetiapine: a case report

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Hosseini Seyed

2012-10-01

Full Text Available Abstract Priapism is defined as an unwanted, prolonged, and painful erection which is unrelated to sexual stimulation. Some case studies suggest that priapism is an adverse effect of antipsychotic medications. In our case study a 30 year-old Iranian male with schizophrenia was experiencing recurrent priapism associated with quetiapine use. There are three interesting facts about this case: Firstly, the patient suffered priapism after even low dose consumption of quetiapine. Secondly, this case had experienced priapism with risperidone, olanzapine, and even clozapine in the past, suggesting a possible pharmacodynamic interaction of antipsychotics and inner biological traits in this particular case. Thirdly, priapism induced by low dose quetiapine was resolved after cigarette smoking.

Comorbidity of narcolepsy and schizophrenia in an adolescent patient

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Mu-Hong Chen

2014-11-01

Full Text Available A 13-year-old boy suffered from hypersomnia, fragmented nighttime sleep, and cataplexy since age 10 years, and then developed prominent psychotic symptoms (i.e., auditory and visual hallucination, hallucinatory behavior, delusions of reference, and misidentification that occurred persistently during the wakeful and consciously clear period when he was aged 12 years. The child underwent additional medical evaluation and testing, and comorbidity of narcolepsy and schizophrenia was diagnosed. The child's psychotic symptoms and narcolepsy improved significantly upon treatment with methylphenidate 30 mg, olanzapine 25 mg, and haloperidol 10 mg. In this case, the child's symptomology of narcolepsy and schizophrenia and the dilemma of the use of antipsychotics and psychostimulants are representative examples of the diagnostic and therapeutic challenges in adolescent psychiatry.

Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

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Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

2016-01-01

Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180

Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics

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Olsen, Christina Kurre; Brennum, Lise Tøttrup; Kreilgaard, Mads

2008-01-01

response behaviour correlates well with the relationship between human dopamine D2 receptor occupancy and clinical effect. The aim of the present study was to evaluate how pharmacokinetic/pharmacodynamic (PK/PD) predictions of therapeutic effective steady-state plasma levels by means of conditioned...... the rat dopamine D2 receptor occupancy levels providing 50% response in the conditioned avoidance response test and the dopamine D2 receptor occupancy levels reported from responding schizophrenic patients treated with antipsychotics. Predictions of therapeutically effective steady-state levels...... for sertindole (+dehydrosertindole) and olanzapine were 3-4-fold too high whereas for haloperidol, clozapine and risperidone the predicted steady-state EC50 in conditioned avoidance responding rats correlated well with the therapeutically effective plasma levels observed in patients. Accordingly, the proposed PK...

Clozapine-induced rabbit syndrome: a case report

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Cicek Hocaoglu

2009-10-01

Full Text Available Rabbit syndrome (RS is an antipsychoticinduced rhythmic motion of the mouth/lips resembling the chewing movements of a rabbit. The movement consists of a vertical-only motion, at about 5 Hz, with no involvement of the tongue. Long-term exposure to typical antipsychotics has clearly been associated with RS, but little is known of the risk of RS due to exposure to newer atypical antipsychotics. There have been isolated reports of RS in patients treated with the atypical agents risperidone, aripiprazole, olanzapine, and clozapine. We present the case history of a 44-year old female patient treated for paranoid schizophrenia for 22 years and RS during her last 10-month clozapine treatment. Background information from the literature is also discussed.

Body weight gain induced by a newer antipsychotic agent reversed as negative symptoms improved.

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Koga, M; Nakayama, K

2005-07-01

We describe a patient in whom improvement in negative symptoms contributed to early weight loss and subsequent long-term improvement in weight management. Case report. A 26-year-old woman with schizophrenia gained 7 kg over the course of 1 year after starting treatment with olanzapine. However, as negative symptoms gradually improved with treatment, she became motivated to diet and exercise regularly. She quickly lost 9 kg and subsequently maintained optimal weight (55 kg; body mass index, 24.1 kg/m(2) ). Important strategies for minimizing weight gain in patients taking antipsychotic agents include improving negative symptoms of avolition and apathy, regular monitoring of body weight and potential medical consequences of overweight and obesity, and educating the patient about the importance of diet and regular exercise.

Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

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Maurizio Pompili

2016-10-01

Full Text Available Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia. We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior.

Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

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Pinaki Chakravarty

2016-01-01

Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

Tratamento farmacológico do transtorno bipolar: as evidências de ensaios clínicos randomizados Pharmacological treatment of bipolar disorder: evidence from randomized clinical trials

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Flávio Kapczinski

2005-01-01

Full Text Available O presente artigo é uma síntese das evidências provenientes de ensaios clínicos randomizados sobre o tratamento do transtorno bipolar. A metodologia para a busca do material disponível é descrita, e os resultados são apresentados. Com o melhor nível de evidência disponível, ou seja, revisões sistemáticas de mais de um ensaio clínico randomizado ou pelo menos um ensaio clínico randomizado, temos as seguintes recomendações: 1 a mania aguda pode ser tratada com Lítio, Valproato, Carbamazepina, e antipsicóticos; 2 a depressão bipolar pode ser tratada com antidepressivos (com risco aumentado de virada para mania, com lamotrigina e a associação fluoxetina/olanzapina e 3 a manutenção do transtorno bipolar pode ser realizada com o lítio, valproato, carbamazepina, olanzapina e lamotrigina (quando o objetivo for a profilaxia da depressão bipolar. A não existência de ensaios clínicos publicados não significa que determinadas intervenções não sejam úteis.The present article is a synthesis of the published clinical trials about the treatment of Bipolar disorder (BD. The methodology used to search the literature is described and results are presented. Using the best available evidence (systematic reviews of clinical trials or at lest one randomized clinical trial the following is recommended: 1 acute mania can be treated with lithium, carbamazepine, valrpoate and antipsychotics; 2 acute depression can be treated with lamotrigine, olanzapine/fluoxetine combination and with antidepressants (with an increased risk of switch into mania; 3 maintenance can be performed using lithium, valproate, olanzapine and lamotrigine (when the aim is prophylaxis of bipolar depression. The absence of published results about certain interventions does not mean that such interventions are not useful.

[Conference report: Belgian consensus on metabolic problems associated with atypical antipsychotics].

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De Nayer, A; De Hert, M; Scheen, A; Van Gaal, L; Peuskens, J

2007-01-01

The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. As a consequence, there is a shift in attention toward physical health

How large are the differences between originator and generic prices? Analysis of five molecules in 16 European countries

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Sabine Vogler

2012-12-01

Full Text Available OBJECTIVE: To survey the price differences between originators and generics for a selected basket of molecules and to analyze similarities and differences with regard to the countries included and their generic policies. METHODS: Ex-factory prices as of November 2011 of five molecules provided from the Pharma Price Information (PPI service of the Austrian Health Institute were analyzed for 16 European countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, the Netherlands, Norway, Portugal, Spain, Switzerland, Sweden, UK. The selected molecules were gemcitabine, mycophenolate mofetil, olanzapine, risperidone and sumatriptan. For a specific presentation (same pack size, dosage and pharmaceutical form of each molecule, the prices of the original product and the “most common generic” as defined by PPI were compared. RESULTS: Considerable variations among the extent of price differences between originator and generic were identified (gemicitabine: lowest price difference of 1.4% between originator and generic in Belgium and highest difference of 73.4% in Portugal; mycophenolate mofetil: 3.4% Norway – 71.7% Netherlands; olanzapine: 0.1% Spain – 97.1% Sweden; risperidone: 0.9% Netherlands – 97.3% UK; sumatriptan: 5.8% Greece – 95.0% Denmark. Further, no difference at all between originator and generic prices was found for some molecules in a few countries (Norway: for 4 of the 5 molecules analyzed; Spain: 3; Belgium: 2; in Austria, France and Greece for one molecule respectively. For the five molecules of the sample, Greece, Spain, Ireland and Norway consistently displayed lower price differences whereas Denmark, Finland and Sweden tended to show higher differences between originator and generic prices. CONCLUSION: Even if this research is illustrative and not representative due to the small sample size, results suggest confirming large differences across Europe. It appears that countries (e.g. Denmark

Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

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DuMouchel, William; Fram, David; Yang, Xionghu; Mahmoud, Ramy A; Grogg, Amy L; Engelhart, Luella; Ramaswamy, Krishnan

2008-01-01

This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. There are consistent and substantial differences between atypical antipsychotic drugs in the

A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report

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Storm Christian

2009-02-01

Full Text Available Abstract Introduction A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction. Case presentation A 22-year-old Caucasian man was admitted unconscious with a body temperature of 42°C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000®, Medivance Inc., USA, originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa® for schizophrenia. Conclusion Numerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa® medication. Frequently hyperthermia has been observed

Use of antipsychotics in the treatment of depressive disorders

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Ping WANG; Tianmei SI

2013-01-01

There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.

Smoking in Schizophrenia: an Updated Review.

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Šagud, Marina; Vuksan-Ćusa, Bjanka; Jakšić, Nenad; Mihaljević-Peleš, Alma; Rojnić Kuzman, Martina; Pivac, Nela

2018-06-01

Patients with schizophrenia continue to have the highest rate of both smoking and heavy nicotine dependence. The interaction between smoking and schizophrenia is complex. There is evidence of the shared genetic background. Recent preclinical and clinical research has further investigated self-medication hypothesis, given that nicotine might alleviate cortical dysfunction. While prior research indicated some favorable effects of smoking on cognitive performance, particulatly on attention/vigilance, recent studies did not confirm those findings. Lower severity of negative symptoms in smokers was not confirmed across studies. Cigarette smoking decreases clozapine and olanzapine concentrations. There is no consistent evidence of favorable effects of nicotine on symptoms in schizophrenia, but the evidence of detrimental effects of smoking on general health is highly consistent. Smoking cessation should be a priority in patients with schizophrenia.

The Safety of Second-Generation Antipsychotics During Pregnancy

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Damkier, Per; Videbech, Poul

2018-01-01

The issue of antipsychotic treatment during pregnancy is subject to substantial uncertainty and some controversy among healthcare providers, specifically pertaining to second-generation antipsychotics (SGAs) that are subject to a large gap in safety data during pregnancy compared...... with antidepressants. The amount of safety data for the use of SGAs during pregnancy is rapidly increasing, thus constantly changing the level of evidence. We performed a clinically focused review on the safety of SGA during pregnancy. Twenty-three studies provided various pregnancy outcomes for 14,382 pregnant women...... exposed to an SGA during pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not associated with increased risks of major congenital malformations, whereas risperidone and paliperidone may be associated with a very minor increased risk of congenital malformations. Safety data...

Benzodiazepines for psychosis-induced aggression or agitation

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Zaman, Hadar; Sampson, Stephanie J; Beck, Alison Ls

2017-01-01

of global state, clearly more people receiving placebo showed no improvement in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI 0.40 to 0.97, very low quality evidence). Benzodiazepines versus antipsychoticsWhen compared with haloperidol, there was no observed effect for benzodiazepines...... improved when receiving benzodiazepines compared with olanzapine (n = 150, 1 RCT, RR 1.84, 95% CI 1.06 to 3.18, very low quality evidence). People receiving benzodiazepines were less likely to experience extrapyramidal effects in the medium term compared to people receiving haloperidol (n = 233, 6 RCTs, RR...... 0.13, 95% CI 0.04 to 0.41, low quality evidence).Benzodiazepines versus combined antipsychotics/antihistaminesWhen benzodiazepine was compared with combined antipsychotics/antihistamines (haloperidol plus promethazine), there was a higher risk of no improvement in people receiving benzodiazepines...

2016 updated MASCC/ESMO consensus recommendations

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Einhorn, Lawrence H; Rapoport, Bernardo; Navari, Rudolph M

2017-01-01

PURPOSE: This review summarizes the recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting as agreed at the MASCC/ESMO Antiemetic Guidelines update meeting in Copenhagen in June...... receiving high-dose chemotherapy with stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4) is recommended before chemotherapy. For patients undergoing multiple-day chemotherapy-induced nausea...... and vomiting, a 5-HT3 receptor antagonist, dexamethasone, and aprepitant, are recommended before chemotherapy for the prophylaxis of acute emesis and delayed emesis. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests the use of 10 mg oral olanzapine, daily for 3 days...

Could Reward-disturbances caused by antipsychotic medication lead to weight gain?

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Nielsen, Mette Ødegaard; Rostrup, Egill; Nørbak-Emig, Henrik

2014-01-01

BACKGROUND The reward system is known to be central to the regulation of appetite. Further, disturbances of the brain reward system are suggested to play an important role in the development of central psychopathological symptoms in schizophrenia. Antipsychotic medication partly acts by modulating...... the reward system and most antipsychotics cause some degree of weight gain. Recently, a relation between weight gain caused by one week of olanzapine treatment and change in reward signalling was found in healthy volunteers1. To our knowledge there are no previous studies examining how the effect...... of antipsychotic treatment on the reward system relate to weight gain in patients. METHODS 50 antipsychotic-naïve first-episode patients with schizophrenia and 40 healthy controls were included in the study at baseline. 38 patients and 31 healthy controls were re-examined after six weeks where patients were...

Efeitos adversos metabólicos de antipsicóticos e estabilizadores de humor Metabolic side effects of antipsychotics and mood stabilizers

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Paulo José Ribeiro Teixeira

2006-08-01

use of lithium and valproic acid once again directed the attention to their metabolic effects. This study aims to review the medical literature with regard to metabolic side effects associated with the use of antipsychotics and mood stabilizers. METHOD: Research was carried out at MEDLINE and LILACS through October 2005. CONCLUSION: Metabolic side effects remain a major concern for psychopharmacology. Clinically relevant weight gain occurs frequently in patients taking antipsychotics and mood stabilizers, particularly clozapine, olanzapine, lithium, and valproic acid. Clozapine and olanzapine are also associated with higher incidence of diabetes mellitus and dyslipidemias, either due to weight gain or because of a direct deleterious action on glucose metabolism. Incidence of obesity and other metabolic disorders is lower with risperidone when compared to olanzapine or clozapine. Carbamazepine is associated with lower weight gain when compared to lithium or valproic acid. Drugs such as haloperidol, ziprasidone, aripiprazole and lamotrigine are not associated with significant weight gain or with higher incidence of diabetes mellitus. They are alternatives for patients more likely to develop these adverse effects.

Depressão resistente a tratamento: uma revisão das estratégias farmacológicas de potencialização de antidepressivos Treatment-resistant depression: review of pharmacologic antidepressant strategies

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Milena Antunes Santos

2006-01-01

, LILACS and Cochrane Library, from 1990 to June 2006 using the words treatment, resistant, refractory, depression and the medical subject headings depression, drug resistance and augmentation. Double-blind controlled trials and reviews were included. We also consulted reference of the articles in order to obtain studies and original articles of historical value from before 1990. RESULTS: There were 17 double-blind trials with lithium, six with thyroid hormone, two with buspirone, six with pindolol one with carbamazepine, two with lamotrigine and four with olanzapine. Forty-one percent of the trials with lithium, 60% of those with thyroid hormone and tricyclics, 0% of the ones with thyroid hormone and selective serotonin reuptake inhibitors (SSRI, 50% of those with pindolol, 100% of those with carbamazepine and 40% of the ones with olanzapine were favorable. No trials with buspirone were favorable. The only trial with lamotrigine did not show efficacy using the main outcome measures. Otherwise, there was superiority over placebo on secondary measures. CONCLUSION: Only lithium and thyroid hormone showed efficacy as antidepressant augmentation strategies for TRD. Olanzapine was reasonably studied and did not prove its efficacy. There were just a few studies on buspirone and pindolol and they were not favorable to them. Carbamazepine was studied very little. Lamotrigine was not adequately evaluated.

Asenapine for bipolar disorder

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Scheidemantel T

2015-12-01

Full Text Available Thomas Scheidemantel,1 Irina Korobkova,2 Soham Rej,3,4 Martha Sajatovic1,2 1University Hospitals Case Medical Center, 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Psychiatry, University of Toronto, Toronto, ON, 4Geri PARTy Research Group, Jewish General Hospital, Montreal, QC, Canada Abstract: Asenapine (Saphris® is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD. Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be

Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients

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Collet, Marie O; Caballero, Jesús; Sonneville, Romain

2018-01-01

PURPOSE: We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality. METHODS: All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed...... the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use. RESULTS: We included 1260 patients from 99 ICUs in 13 countries. Delirium...... occurred in 314/1260 patients [25% (95% confidence interval 23-27)] of whom 145 received haloperidol [46% (41-52)]. Other interventions for delirium were benzodiazepines in 36% (31-42), dexmedetomidine in 21% (17-26), quetiapine in 19% (14-23) and olanzapine in 9% (6-12) of the patients with delirium...

Lamotrigine in the treatment of psychotic depression associated with hereditary coproporphyria -- case report and a brief review of the literature.

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Takács, Rozália; Makkos, Zoltán; Kassai-Farkas, Ákos; Pusztai, Ágnes; Ungvári, Gábor S; Gazdag, Gábor

2014-03-01

We report a successful treatment with lamotrigine of a patient with hereditary coproporphyria presenting with affective and psychotic symptoms. M.F., a 38-year-old, single woman was admitted to an acute psychiatric ward because of suddenly emerging psychosis. Ms F's hereditary coproporphyria was diagnosed 9 years before the current admission. While on treatment with olanzapine (20mg/day) the psychotic symptoms have gradually disappeared. In view of her significant mood fluctuations predominantly with depressed phases, lamotrigine was started and titrated up to 125 mg/day. Ms F's mood gradually became euthymic, suicidal ideations and anxiety disappeared. At 5-month follow-up, while still on lamotrigine, her porphyria was asymptomatic. To the best of our knowledge, this is the first report about the safe administration of lamotrigine in hereditary coproporphyria. Lamotrigine did not trigger an acute porphyric attack as confirmed by clinical and laboratory findings.

Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription

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Thomas J Reilly

2017-03-01

Full Text Available Objectives: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. Methods: We present a case report of a patient who developed this syndrome with various sequelae. Results: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. Conclusions: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

[Eating disorders in psychiatric patients during treatment with second generation antipsychotics].

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Vasilenko, L M; Gorobets, L N; Bulanov, V S; Litvinov, A V; Ivanova, G P; Tsarenko, M A; Polyakovskaya, T P

2015-01-01

To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMIobesity grade 2-3 in 38 patients (BMI>30 kg/m²). Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these we developed recommendations for management of patients treated with second generation antipsychotics.

Course of Neuropsychiatric Symptoms during Flares of Systemic Lupus Erythematosus (SLE

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Gareth Garrett

2017-01-01

Full Text Available We present the case of a seventeen-year-old girl who presents with an interesting course of neuropsychiatric symptoms during several flares of SLE. The patient was diagnosed at the age of thirteen and has had four flares in total. The latter two flares included cutaneous and neuropsychiatric symptoms. The most recent flare occurred when she was aged seventeen. She had cutaneous symptoms which coincided with an episode of hypomania. Her mental state further deteriorated following steroid treatment. She exhibited affective and psychotic symptoms. Treatment with cyclophosphamide and olanzapine was associated with an improvement in both cutaneous and neuropsychiatric symptoms. Previously aged sixteen the patient had presented with cutaneous symptoms and a moderate depressive episode which was also exacerbated by steroid treatment. The patient’s mood improved when the dose of oral steroids was reduced to a daily dose of 15–20 mg prednisolone.

[Mania associated with Usher syndrome type II].

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Praharaj, Samir Kumar; Acharya, Mahima; Sarvanan, Arul; Kongasseri, Sreejayan; Behere, Rishikesh V; Sharma, P S V N

2012-01-01

Usher syndrome (or Hallgren syndrome) is an autosomal recessive genetic disorder characterized by sensorineural deafness, retinitis pigmentosa, and variable vestibular deficit; Usher syndrome type II is the most common form. Various neuropsychiatric disorders have been reported to occur in those with Usher syndrome, including schizophrenia-like disorder, atypical psychosis, recurrent depressive illness, neurotic disorder, and mental retardation; however, bipolar disorder is not common in those with Usher syndrome. Herein we describe a 30-year-old male with Usher syndrome type II that developed features indicative of a probable manic episode. The patient had complete remission of symptoms in response to treatment with olanzapine 20 mg d-1. In persons with dual sensory impairment there are inherent problems with assessment and diagnosis is difficult due to their limited communication abilities. The diagnosis of Usher syndrome depends heavily on behavioral observation and disturbances in vegetative functions.

Entomophagy and coprophagy in undifferentiated schizophrenia.

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Lingeswaran, Anand; Vijayakumar, Vinayak; Dinesh, John

2009-01-01

Coprophagia or the ingestion of feces, considered to be a variant of pica, has been associated with medical disorders like seizure disorders, cerebral atrophy, and tumors and with psychiatric disorders like mental retardation, alcoholism, depression, obsessive compulsive disorder, schizophrenia, schizoaffective disorder, fetishes, delirium, and dementia. But entomophagy or the practice of eating live or dead insects as food by humans has only been reported as part of eating habits by some cultures in the world and not in association with any medical or neuropsychiatric disorders. Till date, there is no report in medical literature of entomophagy as an association with any neuropsychiatric or medical illnesses. Coprophagy and entomophagy has not been together reported as well. We describe the first ever case report of a 19-year- old male patient diagnosed with undifferentiated schizophrenia and associated with both entomophagy and coprophagy. His schizophrenic symptoms, the entomophagic, coprophagic behaviors improved with olanzapine therapy. Entomophagy and coprophagy, two very unusual human behaviors, can be seen in association with schizophrenia.

Current and Emerging Directions in the Treatment of Eating Disorders

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Tiffany A. Brown

2012-01-01

Full Text Available Eating disorders are a significant source of psychiatric morbidity in young women and demonstrate high comorbidity with mood, anxiety, and substance use disorders. Thus, clinicians may encounter eating disorders in the context of treating other conditions. This review summarizes the efficacy of current and emerging treatments for anorexia nervosa (AN, bulimia nervosa (BN, and binge eating disorder (BED. Treatment trials were identified using electronic and manual searches and by reviewing abstracts from conference proceedings. Family based therapy has demonstrated superiority for adolescents with AN but no treatment has established superiority for adults. For BN, both 60 mg fluoxetine and cognitive behavioral therapy (CBT have well-established efficacy. For BED, selective serotonin reuptake inhibitors, CBT, and interpersonal psychotherapy have demonstrated efficacy. Emerging directions for AN include investigation of the antipsychotic olanzapine and several novel psychosocial treatments. Future directions for BN and BED include increasing CBT disseminability, targeting affect regulation, and individualized stepped-care approaches.

Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

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Miroshnichenko, Igor I; Baymeeva, Natalia V

2018-04-07

A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost.

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Mortimer, A; Williams, P; Meddis, D

2003-01-01

Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.

Is atomoxetine effective in some comorbid mental disorders in ADHD?

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Cesneková D.

2016-09-01

Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD is connected with high level of psychiatric comorbidity in paediatric population. Depressive disorder is common comorbid disorder co-existing with ADHD. Atomoxetine is worldwide approved for treatment of ADHD in paediatric population; in addition atomoxetine is effective and safe in treatment of some comorbid disorders in ADHD. Pharmacotherapy of depression is limited and residual symptoms are common. Fluoxetine is currently considered to be the gold standard of treatment of depression, but effectiveness of acute phase of treatment is not sufficient. Atomoxetine as a selective noradrenaline reuptake inhibitor or olanzapine as a multi receptors antagonist drug in combination with fluoxetine could be perspective augmented treatment strategy of depression just for their antidepressant effect. The aim of our following study is to evaluate and compare effectiveness and safety of monotherapy and combined/augmented therapy in acute phase of depression treatment in adolescence, as well as introduce complex modern research methodology of effectiveness and safety of treatment.

[Pharmacotherapy in the treatment of borderline personality disorder].

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Alliani, Daniela; Tarantelli, Silvia

2009-01-01

The aim of this study is to bring together the previous studies on pharmacotherapy of borderline disorder from the oldest to the recent ones, mainly focusing on atypical antipsychotic, whose success has been underlined in recent medical literature with peculiar reference to olanzapine. Since the '80 the pharmacotherapy in borderline personality disorder has been playing an increasing role in the interest of scientific community and in the medical practice as indicated by APA guidelines (2000). Nowadays the pharmacological approach, supported by some experimental outcomes, follow a so called "dimensional" standard. The targets of this standard drug approach are specific psychopathological "dimensions" of the disorder and related neurotransmitters' changes in particular linked to serotoninergic and dopaminergic systems, both supported by experimental outcomes. The psychopathological dimensions to which pharmacological approach is more suitable are: impulsiveness and emotional dysregulation. During the last past years, effectiveness of atypical antipsychotic drugs became of major interest in medical treatment of borderline disorder, mainly related to their action toward the serotoninergic and dopaminergic systems.

The diagnosis and management of delirium in infancy.

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Turkel, Susan Beckwitt; Jacobson, Julienne R; Tavaré, C Jane

2013-06-01

Atypical antipsychotics have been documented to be effective in the management of delirium in adults and older children, but despite considerable need, their use has been less studied in the very young. A retrospective chart review was undertaken to describe the use of atypical antipsychotics in controlling symptoms of delirium in infants and toddlers. All psychiatric inpatient consultations performed during a 3 year period were reviewed to identify children delirium. Delirium Rating Scale (DRS) scores were retrospectively calculated when the antipsychotic was initiated and discontinued, to confirm the diagnosis of delirium and evaluate symptom severity, and then to assess symptom response to pharmacologic intervention. There were 10 boys and 9 girls in the study population (ages 7-30 months, mean 20.5 months). Olanzapine (n=16) and risperidone (n=3) were used, and length of treatment and response were comparable for both medications. Mean DRS scores decreased significantly (pdelirium symptoms in very young pediatric patients.

New onset epilepsy following unintentional durotomy in a patient on anti-psychiatric medication

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West M

2010-04-01

Full Text Available We would like to present a rare case report describing a case in which new-onset tonic-clonic seizures occurred following an unintentional durotomy during lumbar discectomy and decompression. Unintentional durotomy is a frequent complication of spinal surgical procedures, with a rate as high as 17%. To our knowledge a case of new onset epilepsy has never been reported in the literature. Although dural tears during surgery and CSF hypovolaemia are thought to be the main contributing factors, one postulates on the effects of anti-psychiatric medication with epileptogenic properties. Amisulpride and Olanzapine can lower seizure threshold and should be used with caution in patients previously diagnosed with epilepsy. However manufacturers do not state that in cases where the seizure threshold is already lowered by CSF hypotension, new onset epilepsy might be commoner. Finally, strong caution and aggressive post-operative monitoring is advised for patients with CSF hypotension in combination with possible epileptogenic medication.

Gabapentin pharmacotherapy for antipsychotic-induced akathisia: single-patient experiment and case report.

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Sullivan, Maria A; Wilbur, Robert

2014-04-01

This clinical study reports upon the efficacy of gabapentin (Neurontin) for treating severe akathisia (3 on the Barnes Akathisia Rating Scale) in two patients receiving quetiapine (Seroquel), one of whom also received olanzapine (Zyprexa) for a short period. The first patient participated in an open-label experiment in which the bedtime dose of gabapentin was discontinued three times at intervals 1 week apart, resulting in severe akathisia which was quickly terminated by taking his usual 1200 mg gabapentin dose. This patient was also taking high doses of two benzodiazepines and a beta blocker, without therapeutic effect upon his akathisia; only gabapentin was efficacious. The second case is a report of a woman taking a high dose of quetiapine for anxiety who experienced severe akathisia which was relieved by taking 1200 mg of gabapentin. Possible mechanisms of action of gabapentin are discussed. Particular attention is drawn to the difference between neuroleptic-induced akathisia and the neurological condition of restless legs syndrome.

No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

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Goto, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Moriya, Junji; Hori, Hikaru; Hayashi, Kenji; Ikenouchi-Sugita, Atsuko; Nakano-Umene, Wakako; Katsuki, Asuka; Nishimura, Joji; Korogi, Yukunori; Nakamura, Jun

2010-12-01

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

Plasma homovanillic acid and family history of psychotic disorders in bipolar I patients.

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Zumárraga, Mercedes; Dávila, Ricardo; Basterreche, Nieves; Arrue, Aurora; Goienetxea, Biotza; González-Torres, Miguel Angel; Guimón, José

2009-04-01

It has been suggested that the family history of psychotic disorders is useful in defining homogeneous groups of bipolar patients. The plasma homovanillic acid (pHVA) concentrations have been related to the effect of antipsychotic treatment in psychotic patients. We have studied the influence of a positive family history of psychotic disorders both on the variation of pHVA levels and on the relation between pHVA concentrations and the clinical response to treatment. Clinical status and pHVA levels were assessed in 58 medication free patients before and after 4 weeks of treatment with olanzapine and lithium. Clinical improvement correlated positively with pHVA levels on the 28th day of treatment only in the patients having first degree relatives with psychotic disorders. The pHVA levels did not decrease after 28 days of treatment. Our results reinforce the idea that a positive family history of psychosis in psychotic bipolar disorders may constitute a good basis for sub-grouping these patients.

Schizophrenia symptoms and functioning in patients receiving long-term treatment with olanzapine long-acting injection formulation

DEFF Research Database (Denmark)

Peuskens, Joseph; Porsdal, Vibeke; Pecenak, Jan

2012-01-01

: At baseline, 434 (36.8%) patients had minimal Positive and Negative Syndrome Scale (PANSS) symptoms but seriously impaired Heinrich Carpenter's Quality of Life Scale (QLS) functioning; 303 (25.6%) had moderate to severe symptoms and seriously impaired function; 208 (17.6%) had mild to moderate symptoms...... but good functioning, and 162 (13.7%) had minimal symptoms and good functioning. Baseline category was significantly associated with Clinical Global Impression - Severity (CGI-S), extrapyramidal symptoms, working status, age, and number of previous episodes. The majority of all patients starting OLAI...... treatment maintained or improved (62% 6 months and 52% 12 months) their symptom and functioning levels on OLAI maintenance treatment. Less than 8% of the patients showed worsening of symptoms or functioning. An improvement in category was associated with high PANSS positive and low CGI-S scores at baseline...

Psychomotor and Memory Effects of Haloperidol, Olanzapine, and Paroxetine in Healthy Subjects After Short-Term Administration

NARCIS (Netherlands)

Morrens, M.; Wezenberg, E.; Verkes, R.J.; Hulstijn, W.; Ruigt, G.S.F.; Sabbe, B.G.C.

2007-01-01

Rationale: Impaired psychomotor function has been shown to be associated with clinical and functional outcome in schizophrenia. However, few studies have investigated the short-term effects of antipsychotics on the cognitive and psychomotor functions of this patient group. Because many confounding

Psychomotor and memory effects of haloperidol, olanzapine, and paroxetine in healthy subjects after short-term administration.

NARCIS (Netherlands)

Morrens, M.; Wezenberg, E.; Verkes, R.J.; Hulstijn, W.; Ruigt, G.S.F.; Sabbe, B.G.C.

2007-01-01

RATIONALE: Impaired psychomotor function has been shown to be associated with clinical and functional outcome in schizophrenia. However, few studies have investigated the short-term effects of antipsychotics on the cognitive and psychomotor functions of this patient group. Because many confounding

Pharmacotherapy for trichotillomania.

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Rothbart, Rachel; Amos, Taryn; Siegfried, Nandi; Ipser, Jonathan C; Fineberg, Naomi; Chamberlain, Samuel R; Stein, Dan J

2013-11-08

(SSRIs) demonstrated strong evidence of a treatment effect on any of the outcomes of interest. The unpublished naltrexone study did not provide strong evidence of a treatment effect. Two studies, an olanzapine study and a N-acetylcysteine (NAC) study, reported statistically significant treatment effects. One study of clomipramine demonstrated a treatment effect on two out of three measures of response to treatment. No particular medication class definitively demonstrates efficacy in the treatment of trichotillomania. Preliminary evidence suggests treatment effects of clomipramine, NAC and olanzapine based on three individual trials, albeit with very small sample sizes.

Quetiapine monotherapy for bipolar depression

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Michael E Thase

2008-03-01

Full Text Available Michael E ThaseDepartments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; and the University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Bipolar depression is more common, disabling, and difficult-to-treat than the manic and hypomanic phases that define bipolar disorder. Unlike the treatment of so-called “unipolar” depressions, antidepressants generally are not indicated as monotherapies for bipolar depressions and recent studies suggest that - even when used in combination with traditional mood stabilizers – antidepressants may have questionable value for bipolar depression. The current practice is that mood stabilizers are initiated first as monotherapies; however, the antidepressant efficacy of lithium and valproate is modest at best. Within this context the role of atypical antipsychotics is being evaluated. The combination of olanzapine and the antidepressant fluoxetine was the first treatment to receive regulatory approval in the US specifically for bipolar I depression. Quetiapine was the second medication to be approved for this indication, largely as the result of two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession I and II. Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given once daily at bedtime were significantly more effective than placebo, with no increased risk of patients switching into mania. Pooling the two studies, quetiapine was effective for both bipolar I and bipolar II depressions and for patients with (and without a history of rapid cycling. The two doses were comparably effective in both studies. Although the efficacy of quetiapine monotherapy has been established, much additional research is necessary. Further studies are needed to more fully investigate dose-response relationships and comparing quetiapine monotherapy to other mood stabilizers

Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

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Ricardo Alberto Moreno

2004-10-01

Full Text Available O transtorno bipolar é uma condição médica complexa e até o momento não há um tratamento único comprovadamente eficaz no controle de todos aspectos da doença. Foram revisadas a literatura disponível sobre o uso de anticonvulsivantes (valproato, carbamazepina, oxcarbazepina, lamotrigina, gabapentina, topiramato, clonazepam e antipsicóticos atípicos (clozapina, risperidona, olanzapina, quetiapina, ziprasidona e aripiprazole no tratamento agudo e profilático do transtorno bipolar. Existe um acúmulo de evidências acerca da eficácia do lítio na profilaxia e de ser melhor no tratamento da mania aguda do que nos episódios depressivos. Outros dados indicam que a carbamazepina e o valproato são eficazes na mania aguda. A lamotrigina parece reduzir ciclagem e ser eficaz em episódios depressivos. Baseado nas informações disponíveis, as evidências apontam a olanzapina como o antipsicótico atípico mais apropriado no tratamento de pacientes bipolares em mania, embora existam estudos sugerindo a eficácia da risperidona, aripiprazol e da clozapina. Resultados preliminares avaliando a eficácia de ziprasidona e quetiapina no transtorno bipolar ainda são bastante limitadas. Não há dados consistentes apoiando o uso profilático dos novos antipsicóticos.Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are

Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder.

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Houthoofd, Sofie A M K; Morrens, Manuel; Sabbe, Bernard G C

2008-09-01

functioning), although the results for verbal fluency, verbal learning and memory, and reasoning and problem solving were not unanimous, and no comparative data on social cognition were available. Similar cognitive effects were found with risperidone, olanzapine, and quetiapine on the domains of verbal working memory and reasoning and problem solving, as well as verbal fluency. More research is needed on the domains in which study results were contradictory. For olanzapine versus risperidone, these were verbal and visual learning and memory and psychomotor functioning. No comparative data for olanzapine and risperidone were available for the social cognition domain. For quetiapine versus risperidone, the domains in which no unanimity was found were processing speed, attention/vigilance, nonverbal working memory, and verbal learning and memory. The limited available reports on risperidone versus clozapine suggest that: risperidone was associated with improved, and clozapine with worsened, performance on the nonverbal working memory domain; risperidone improved and clozapine did not improve reasoning and problem-solving performance; clozapine improved, and risperidone did not improve, social cognition performance. Use of long-acting injectable risperidone seemed to be associated with improved performance in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning. The results for the nonverbal working memory domain were indeterminate, and no clear improvement was seen in the social cognition domain. The domains of processing speed, verbal working memory, and visual learning and memory, as well as verbal fluency, were not assessed. The results of this review of within-group comparisons of oral risperidone suggest that the agent appeared to be associated with improved functioning in the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and

Clozapine Can Be the Good Option in Resistant Mania

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S. M. Yasir Arafat

2016-01-01

Full Text Available Bipolar mood disorder is a mental disorder with a lifetime prevalence rate of about 1% in the general population and there are still a proportion of individuals who suffer from bipolar mood disorders that are resistant to standard treatment. Reporting clozapine responsive mania that was not responding to two previous consecutive atypical antipsychotics and one typical antipsychotic was aimed at. A 17-year-old male manic patient was admitted into the psychiatry inpatient department and was nonresponsive to Risperidone 12 mg daily for 4 weeks, Olanzapine 30 mg daily for 3 weeks, and Haloperidol 30 mg daily for 3 weeks, along with valproate preparation 1500 mg daily. He was started on clozapine as he was nonresponsive to Lithium in previous episodes and did not consent to starting Electroconvulsive Therapy (ECT. He responded adequately to 100 mg clozapine and 1500 mg valproate preparation and remission happened within 2 weeks of starting clozapine. Clozapine can be a good option for resistant mania and further RCT based evidences will strengthen the options in treating resistant mania.

Clozapine-induced severe eosinophilia: report of a case with good outcome

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Carla R. B. Marcelino

2013-09-01

Full Text Available INTRODUCTION: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. METHODS: Case report and literature review. RESULTS: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils began to increase. Drug titration was stopped, but eosinophils counts continued to rise up, reaching the mark of 5200/mm³. Due to severity of psychotic symptoms and to the good response obtained with clozapine, we decided to investigate organs involvement before withdrawing the medication. As the patient had no organs involvement, clozapine was maintained and one month after eosinophils peak, it was already normalized. CONCLUSION: Eosinophilia should not necessarily lead to clozapine's withdrawal. Patients who present eosinophilia must be at rigorous observation for organs involvement, and if there is no such involvement, clozapine might be maintained, considering the possible benign and transitory nature of the eosinophils count elevation.

Use of psychotropic drugs during pregnancy and breast-feeding.

Science.gov (United States)

Larsen, E R; Damkier, P; Pedersen, L H; Fenger-Gron, J; Mikkelsen, R L; Nielsen, R E; Linde, V J; Knudsen, H E D; Skaarup, L; Videbech, P

2015-01-01

To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

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Essam Ezzeldin

2017-01-01

Full Text Available Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS assay has been developed and validated for simultaneous quantification of risperidone (RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS in rat plasma using olanzapine (OLA as internal standard (IS. Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg. Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including Cmax, tmax, and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.

Haloperidol for long-term aggression in psychosis.

Science.gov (United States)

Khushu, Abha; Powney, Melanie J

2016-11-27

Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015). We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study

ANÁLISIS COSTO-BENEFICIO DE CUATRO MEDICAMENTOS ANTIPSICÓTICOS EN PACIENTES CON ESQUIZOFRENIA EN COLOMBIA

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Diego Rosselli

2009-01-01

Full Text Available

RESUMEN
Por la menor incidencia de efectos secundarios extrapiramidales y por una mayor adherencia de los pacientes al tratamiento, los antipsicóticos atípicos de liberación prolongada constituyen una alternativa para el tratamiento de la esquizofrenia. En este análisis de costo-beneficio se compara un antipsicótico atípico de liberación prolongada (risperidona con dos medicamentos orales de nueva generación (olanzapina y clozapina y uno típico de depósito (pipotiazina.
Se empleó un modelo de árbol decisión que incorporó exclusivamente costos directos, desde la perspectiva de una EPS (“tercero pagador” y empleando las ivariables adherencia, recaídas con y sinhospitalización, y efectos adversos. Según el modelo, el empleo de risperidona inyectable de liberación prolongada durante un año de tratamiento, y de manera similar a la clozapina, ahorraría un millón de pesos al sistema al compararse con la olanzapina, y dos millones al compararse con la pipotiazina.
A esta ganancia en dinero con la risperidona inyectable se agregaría el beneficio directo e Indirecto para el paciente y su comunidad al reducir las recaídas.

Palabras clave: risperidona, depósito, antipsicóticos, esquizofrenia, costo-beneficio.

Summary

Due to the lower incidence of extrapyramidal side effects and greater adherence of patients to treatment, long-action atypical antipsychotics are an alternative for the treatment of schizophrenia. In this cost-benefit analysis we compare a long-action atypical antipsychotic (risperidone with two second-generation oral antipsychotics (olanzapine and clozapine and a “typical” prolonged action drug (pipotiazine.
We designed a decision tree that included only direct costs, from the third party payer perspective, using as main variables adherence, relapses with and without hospitalization, and side

A study on the quality of outpatient prescription of psychopharmaceuticals in the City of Zagreb 2006-2009.

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Zivković, Kresimir; Zelić-Kerep, Ana; Stimac, Danijela; Ozić, Sanja; Zivković, Nikica

2014-06-01

The lack of Croatian studies which could determine the justifiability of excessive psychopharmaceutical utilization was an encouragement to conduct this research. Furthermore, regarding the conduction of this study, it would be possible to determine whether the trend of drug utilization has increased, decreased or perhaps stabilized. The data on the outpatient utilization of psycholeptics and psychoanaleptics were collected from all Zagreb pharmacies, 2006-2009. Based on the collected data for all N05 and N06 groups of drugs, the defined daily doses (DDD) and DDD per thousand inhabitants per day (DDD/TID) have been calculated using the Anatomical-Therapeutic-Chemical classification (ATC) for 2006, 2007, 2008 and 2009. To indicate the quality of drug prescription the Drug Utilization 90% (DU 90%) method was used. Moreover, in order to determine a more precise quality of individual drug group prescriptions, the indicators have been calculated by determining the proportion of the total utilization of individual therapeutic and pharmacological therapeutic subgroups in DDD/TID a day. The utilization of anxiolytics (N05B) accounts for most of the psycholeptic utilization in the City of Zagreb throughout the entire study period. In the study period, the utilization of antidepressants has slightly increased, by 10.5%, taking the first and the last years of the period into account. In 2006, 5 benzodiazepines and the hypnotic zolpidem, as well as 5 selective serotonin reuptake inhibitors (SSRIs) and 1 third generation antipsychotic (olanzapin) were found in the DU 90% segment. In 2009, the DU 90% segment also comprised 5 benzodiazepines and the hypnotic zolpidem, as well as 6 SSRIs and 1 third generation antipsychotic (olanzapin). In the City of Zagreb, a general insight into the quality of psychopharmaceutical prescriptions indicates stability in comparison to earlier studies. The ratio index of the first generation antipsychotic utilization, compared to the third

Design and validation of standardized clinical and functional remission criteria in schizophrenia

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Mosolov, Sergey N; Potapov, Andrey V; Ushakov, Uriy V; Shafarenko, Aleksey A; Kostyukova, Anastasiya B

2014-01-01

Background International Remission Criteria (IRC) for schizophrenia were developed recently by a group of internationally known experts. The IRC detect only 10%–30% of cases and do not cover the diversity of forms and social functioning. Our aim was to design a more applicable tool and validate its use – the Standardized Clinical and Functional Remission Criteria (SCFRC). Methods We used a 6-month follow-up study of 203 outpatients from two Moscow centers and another further sample of stable patients from a 1-year controlled trial of atypical versus typical medication. Diagnosis was confirmed by International Classification of Diseases Version 10 (ICD10) criteria and the Mini-International Neuropsychiatric Interview (MINI). Patients were assessed by the Positive and Negative Syndrome Scale, including intensity threshold, and further classified using the Russian domestic remission criteria and the level of social and personal functioning, according to the Personal and Social Performance Scale (PSP). The SCFRC were formulated and were validated by a data reanalysis on the first population sample and on a second independent sample (104 patients) and in an open-label prospective randomized 12-month comparative study of risperidone long-acting injectable (RLAI) versus olanzapine. Results Only 64 of the 203 outpatients (31.5%) initially met the IRC, and 53 patients (26.1%) met the IRC after 6 months, without a change in treatment. Patients who were in remission had episodic and progressive deficit (39.6%), or remittent (15%) paranoid schizophrenia, or schizoaffective disorder (17%). In addition, 105 patients of 139 (51.7%), who did not meet symptomatic IRC, remained stable within the period. Reanalysis of data revealed that 65.5% of the patients met the SCFRC. In the controlled trial, 70% of patients in the RLAI group met the SCFRC and only 19% the IRC. In the routine treatment group, 55.9% met the SCFRC and only 5.7% the IRC. Results of the further independent

Tratamento farmacológico da gagueira: evidências e controvérsias Pharmacologic treatment of stuttering: evidences and controversies

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Camila Vila-Nova

2006-01-01

the following drugs were found: citalopram + clomipramine, desipramine, paroxetine, olanzapine, pimozide, risperidone, tiapride, levetiracetam, divalproex sodium, citalopram + alprazolam, clonidine and bethanecol, as well as clinical trials with the botulinum toxin A and anesthetics. Studies with citalopram + clomipramine, paroxetine, olanzapine, citalopram + alprazolam, risperidone, clomipramine and desipramine, levetiracetam, divalproex sodium, lidocaine and botulinum toxin A showed positive results. However, the great majority of pharmacological studies in this area are case series or clinical trials with small samples. CONCLUSION: Enough evidences do not exist that justify the use of a specific treatment for stuttering. The presented studies indicate the necessity of accomplishment of more double-blind placebo-controlled trials involving larger samples.

Update on quetiapine in the treatment of bipolar disorder: results from the BOLDER studies

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Prashant Gajwani

2007-01-01

Full Text Available Prashant Gajwani1, David J Muzina2, David E Kemp3, Keming Gao1, Joseph R Calabrese11Case Western Reserve University (CWRU School of Medicine, 2Cleveland Clinic Lerner College of Medicine of CWRU, 3Case Western Reserve University, Cleveland OH, USAAbstract: The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same.Keywords: bipolar disorder, quetiapine, BOLDER studies

Patient satisfaction with psychotropic drugs: sensitivity to change and relationship to clinical status, quality-of-life, compliance and effectiveness of treatment. Results from a nation-wide 6-month prospective study.

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Gasquet, Isabelle; Tcherny-Lessenot, Stéphanie; Lépine, Jean-Pierre; Falissard, Bruno

2006-12-01

To see if patient satisfaction with psychotropics (PSP) could be used as a patient-oriented outcome variable in the evaluation of PSP drugs in clinical epidemiological studies, relationships between PSP, clinical status, QoL, compliance and the type of antipsychotic were analyzed. Elements of validation of PSP were also assessed. In a 6-month prospective study, 933 schizophrenic outpatients with initiation or change to their antipsychotic treatment were enrolled. Psychiatrists completed five CGI-SCH scales (positive, negative, cognitive, depressive and global), hospitalization, compliance, and prescription variables. Patients completed PSP, EuroQoL scales, sexual function and compliance variables. A satisfactory structural equation model was obtained showing significant relationships PSP/compliance (coef.=0.16), QoL/PSP (coef.=0.37), clinical status/QoL (coef.=0.61), clinical status/compliance (coef.=0.09). Patients receiving olanzapine were more satisfied than patients receiving other atypicals (coef.=012) and had better clinical status than patients treated with typicals (coef.=0.08). Evolution of PSP was related to clinical status, QoL, and continuation of treatment (all Pmeasure was not sufficiently sensitive to change. Multi-item questionnaires evaluating different dimensions are needed.

Phelan-McDermid syndrome due to SHANK3 mutation in an intellectually disabled adult male: successful treatment with lithium.

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Egger, Jos I M; Verhoeven, Willem M A; Groenendijk-Reijenga, Renske; Kant, Sarina G

2017-09-28

For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in the SHANK3 gene. Its core psychopathological phenotype comprises symptoms from the bipolar spectrum for which generally treatment with a mood-stabilising anticonvulsant in combination with an atypical antipsychotic seems to be most effective. In addition to two elsewhere published adolescent patients, we here describe in detail the history of an adult male patient with PMS caused by a SHANK3 mutation in whom successive treatment regimens with antipsychotics and mood-stabilising anticonvulsants were all ineffective. Ultimately, addition of lithium to existing olanzapine therapy led to enduring stabilisation of mood and behaviour. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Design of a dual nanostructured lipid carrier formulation based on physicochemical, rheological, and mechanical properties

International Nuclear Information System (INIS)

Vitorino, Carla; Alves, Luís; Antunes, Filipe E.; Sousa, João J.; Pais, Alberto A. C. C.

2013-01-01

The synergy between nanostructured lipid carriers (NLC) and chemical penetration enhancers provides the basis for a promising strategy to effectively deliver drugs through the skin. In the present work, focus is given to the study of the interaction of limonene, ethanol, and Carbopol Ultrez ® 10NF, as the gelling agent, with a co-encapsulating NLC dispersion, containing both olanzapine and simvastatin. The analysis is based on rheological, mechanical, and physicochemical properties. The nanoparticle size ranged from 130 to 400 nm, depending on the system considered. The inclusion of carbopol resulted in a considerable increase in the NLC particle size, which was attributed to carbomer bridging nanoparticles, resulting in some particle aggregation. Rheological measurements indicated that the viscosity of the neat carbopol hydrogel was reduced by the enhancers and to a higher extent by the presence of NLC. A more apolar medium can be pointed out as a general explanation, while a polymer/nanoparticle hydrophobic interaction coupled with surfactant/polymer H-bonding provides the rationale for the NLC effect. The inclusion of enhancers and a carbomer largely contributed to the physicochemical stability of the NLC formulation, as revealed by the low transmission profiles and more negative zeta potential values

The psychopharmacology of aggressive behavior: a translational approach: part 2: clinical studies using atypical antipsychotics, anticonvulsants, and lithium.

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Comai, Stefano; Tau, Michael; Pavlovic, Zoran; Gobbi, Gabriella

2012-04-01

Patients experiencing mental disorders are at an elevated risk for developing aggressive behavior. In the past 10 years, the psychopharmacological treatment of aggression has changed dramatically owing to the introduction of atypical antipsychotics on the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.This review (second of 2 parts) uses a translational medicine approach to examine the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis (serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid) and the neuropharmacological rationale for using atypical antipsychotics, anticonvulsants, and lithium in the therapeutics of aggressive behavior. A critical review of all clinical trials using atypical antipsychotics (aripiprazole, clozapine, loxapine, olanzapine, quetiapine, risperidone, ziprasidone, and amisulpride), anticonvulsants (topiramate, valproate, lamotrigine, and gabapentin), and lithium are presented. Given the complex, multifaceted nature of aggression, a multifunctional combined therapy, targeting different receptors, seems to be the best strategy for treating aggressive behavior. This therapeutic strategy is supported by translational studies and a few human studies, even if additional randomized, double-blind, clinical trials are needed to confirm the clinical efficacy of this framework.

Transient splenium lesions in presurgical epilepsy patients: incidence and pathogenesis

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Nelles, M.; Falkenhausen, M. von; Urbach, H. [University of Bonn Medical Center, Department of Radiology/Neuroradiology, Bonn (Germany); Bien, C.G.; Kurthen, M. [University of Bonn Medical Center, Department of Epileptology, Bonn (Germany)

2006-07-15

Transient splenium corporis callosi (SCC) lesions are related to rapid reduction of antiepileptic drugs (AEDs). The range of substances with predilection for SCC changes, their pathophysiology and their occurrence are still unknown. In a prospective 2-year study an epilepsy-dedicated MRI protocol supplemented by DWI and ADC maps was performed after AED withdrawal for diagnostic seizure provocation in all patients with pharmacoresistant seizures locally admitted to the Department of Epileptology. Of 891 presurgical epilepsy patients, 6 (0.7%) had SCC lesions with cytotoxic edema on DWI. Carbamazepine combined with other AEDs was administered in five of those patients. In the study period we observed identical lesions in a schizophrenic patient treated with olanzapine and citalopram, in a patient with oropharyngeal carcinoma treated with alkylating agents, and in a hypernatremic patient following neurohypophyseal granular cell tumor surgery. Transient SCC lesions are related to rapid AED reduction but may occur in similar conditions with fluid balance alterations. We contribute further clinical data in this field to better classify the pharmaceuticals that are prone to the described cerebral cytotoxic side effects in the SCC and to clarify their incidence among presurgical epilepsy patients. (orig.)

Rapid Tranquilization for Psychiatric Patients with Psychomotor Agitation: What is Known About it?

Science.gov (United States)

de Almeida, Clayton Gonçalves; Del Grossi Moura, Mariana; Barberato-Filho, Silvio; de Sá Del Fiol, Fernando; Motta, Rogério Heládio Lopes; de Cássia Bergamaschi, Cristiane

2017-12-01

Rapid tranquilization is an intervention used in control of agitation or aggression in patients with mental disorders. This study synthesized the available evidence regarding efficacy and safety of drugs used for rapid tranquilization in psychiatric patients with psychomotor agitation. It is an overview study of systematic reviews and meta-analysis of randomized controlled trials (RCT) identified in the database MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library and LILACS until April 2015. A team of reviewers, in pairs and independently, identified eligible studies and assessed methodological quality using AMSTAR. Data were extracted from four studies (61 RCT, 8021 participants). The association of haloperidol with promethazine (H + P) promoted tranquilization and presented better safety profile, with moderate quality evidence. Olanzapine demonstrated benefit towards tranquilization and good safety profile, but needed additional administration to keep tranquilization. There was no benefit in the use of haloperidol alone or associated to another psychotropic to most outcomes evaluated. The evidence was of low quality to most of the interventions. H + P was considered a good option for rapid tranquilization, however, more RCT are necessary to confirm the efficacy and safety of the available interventions.

Weight change by baseline BMI from three-year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database.

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Bushe, Chris J; Slooff, Cees J; Haddad, Peter M; Karagianis, Jamie L

2013-04-01

The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data. Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI 30 kg/m²). Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43-48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15-27) in the obese BMI cohort; 7% (95% CI: 6-8) of the underweight/normal cohort and 19% (95% CI: 13-27) of the obese cohort lost ≥7% baseline weight. BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change.

Management of Agitation Following Aneurysmal Subarachnoid Hemorrhage: Is There a Role for Beta-Blockers?

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Fayaz Ibrahim

2012-01-01

Full Text Available Introduction. Stroke is a leading cause of mortality and morbidity in the United States. About 20% of the stroke is hemorrhagic and about 50% of these is due to aneurysmal subarachnoid hemorrhage. A troublesome neuropsychiatric complication of subarachnoid hemorrhage is agitation/aggression. Case Presentation. A 45-year-old man with no prior psychiatric history, sustained subarachnoid hemorrhage. After initial stabilization for 2 days, he underwent craniotomy and clipping of anterior cerebral communicating artery aneurysm. Treatment was continued with labetalol, nimodipine, and levetiracetam. Beginning postoperative day 4, patient developed episodes of confusion and agitation/aggression. Switching of Levetiracetam to valproate did not show any improvement. Psychiatry team tried to manage him with intense nursing intervention and different medications like olanzapine, valproate, lorazepam, and haloperidol. However, patient continued to be agitated and aggressive. Switching from labetalol to metoprolol resulted in dramatic improvement within 3 days. Discussion. Antipsychotics and benzodiazepines are often not sufficiently effective in the control of agitation/aggression in patients with traumatic brain injury and similar conditions. Our case report and the literature review including a cochrane review suggests that beta-blockers may be helpful in this situation.

Transient splenium lesions in presurgical epilepsy patients: incidence and pathogenesis

International Nuclear Information System (INIS)

Nelles, M.; Falkenhausen, M. von; Urbach, H.; Bien, C.G.; Kurthen, M.

2006-01-01

Transient splenium corporis callosi (SCC) lesions are related to rapid reduction of antiepileptic drugs (AEDs). The range of substances with predilection for SCC changes, their pathophysiology and their occurrence are still unknown. In a prospective 2-year study an epilepsy-dedicated MRI protocol supplemented by DWI and ADC maps was performed after AED withdrawal for diagnostic seizure provocation in all patients with pharmacoresistant seizures locally admitted to the Department of Epileptology. Of 891 presurgical epilepsy patients, 6 (0.7%) had SCC lesions with cytotoxic edema on DWI. Carbamazepine combined with other AEDs was administered in five of those patients. In the study period we observed identical lesions in a schizophrenic patient treated with olanzapine and citalopram, in a patient with oropharyngeal carcinoma treated with alkylating agents, and in a hypernatremic patient following neurohypophyseal granular cell tumor surgery. Transient SCC lesions are related to rapid AED reduction but may occur in similar conditions with fluid balance alterations. We contribute further clinical data in this field to better classify the pharmaceuticals that are prone to the described cerebral cytotoxic side effects in the SCC and to clarify their incidence among presurgical epilepsy patients. (orig.)

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

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Eduardo Henrique Teixeira

2013-01-01

Full Text Available Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA. All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.

Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute major cardiovascular events in young and middle-aged adults

DEFF Research Database (Denmark)

Pasternak, Björn; Svanström, Henrik; Ranthe, Mattis F

2014-01-01

BACKGROUND: A number of serious cardiovascular safety concerns related to the use of atypical antipsychotics, compared with no use, have emerged, but nearly all reports are from studies of older patients. We aimed to compare the risk of cardiovascular events between the three most commonly used...

Des recommandations probantes pour surveiller l’innocuité des antipsychotiques de deuxième génération chez les enfants et les adolescents

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Pringsheim, Tamara; Panagiotopoulos, Constadina; Davidson, Jana; Ho, Josephine

2012-01-01

��ADG. Le risque de prise de poids, d’augmentation de l’indice de masse corporelle et de taux lipidiques anormaux est plus élevé à l’utilisation d’olanzapine, suivie de la clozapine et de la quétiapine. Quant au risque d’effets secondaires neurologiques des traitements, il est plus élevé à l’utilisation de rispéridone, d’olanzapine et d’aripiprazole. Des interventions de surveillance pertinentes des effets secondaires amélioreront la qualité des soins des enfants traités à l’aide de ces médicaments. PMID:24082813

A Clinical Update on Delirium: From Early Recognition to Effective Management

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Joaquim Cerejeira

2011-01-01

Full Text Available Delirium is a neuropsychiatric syndrome characterized by altered consciousness and attention with cognitive, emotional and behavioural symptoms. It is particularly frequent in elderly people with medical or surgical conditions and is associated with adverse outcomes. Predisposing factors render the subject more vulnerable to a congregation of precipitating factors which potentially affect brain function and induce an imbalance in all the major neurotransmitter systems. Early diagnosis of delirium is crucial to improve the prognosis of patients requiring the identification of subtle and fluctuating signs. Increased awareness of clinical staff, particularly nurses, and routine screening of cognitive function with standardized instruments, can be decisive to increase detection rates of delirium. General measures to prevent delirium include the implementation of protocols to systematically identify and minimize all risk factors present in a particular clinical setting. As soon as delirium is recognized, prompt removal of precipitating factors is warranted together with environmental changes and early mobilization of patients. Low doses of haloperidol or olanzapine can be used for brief periods, for the behavioural control of delirium. All of these measures are a part of the multicomponent strategy for prevention and treatment of delirium, in which the nursing care plays a vital role.

Design of a dual nanostructured lipid carrier formulation based on physicochemical, rheological, and mechanical properties

Energy Technology Data Exchange (ETDEWEB)

Vitorino, Carla [University of Coimbra, Centro de Estudos Farmaceuticos (CEF), Faculty of Pharmacy (Portugal); Alves, Luis; Antunes, Filipe E. [University of Coimbra, Department of Chemistry (Portugal); Sousa, Joao J. [University of Coimbra, Centro de Estudos Farmaceuticos (CEF), Faculty of Pharmacy (Portugal); Pais, Alberto A. C. C., E-mail: pais@qui.uc.pt [University of Coimbra, Department of Chemistry (Portugal)

2013-10-15

The synergy between nanostructured lipid carriers (NLC) and chemical penetration enhancers provides the basis for a promising strategy to effectively deliver drugs through the skin. In the present work, focus is given to the study of the interaction of limonene, ethanol, and Carbopol Ultrez{sup Registered-Sign} 10NF, as the gelling agent, with a co-encapsulating NLC dispersion, containing both olanzapine and simvastatin. The analysis is based on rheological, mechanical, and physicochemical properties. The nanoparticle size ranged from 130 to 400 nm, depending on the system considered. The inclusion of carbopol resulted in a considerable increase in the NLC particle size, which was attributed to carbomer bridging nanoparticles, resulting in some particle aggregation. Rheological measurements indicated that the viscosity of the neat carbopol hydrogel was reduced by the enhancers and to a higher extent by the presence of NLC. A more apolar medium can be pointed out as a general explanation, while a polymer/nanoparticle hydrophobic interaction coupled with surfactant/polymer H-bonding provides the rationale for the NLC effect. The inclusion of enhancers and a carbomer largely contributed to the physicochemical stability of the NLC formulation, as revealed by the low transmission profiles and more negative zeta potential values.

Treatment strategy in schizophrenia combined with eating disorder.

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Dadić-Hero, Elizabeta; Ružić, Klementina; Grahovac, Tanja; Valković, Toni; Petranović, Duška

2011-03-01

Like any other patient, a schizophrenic patient can get a physical illness, too. As such patients tend to ignore reality and neglect themselves and are stigmatized by society, due to which their physical symptomatology is often ignored, physical illness can remain undetected. If the schizophrenic patient is observed and adequate care is provided by the family, family doctor and a psychiatrist, it is possible to recognize the physical illness and intervene promptly. We are presenting a case of a female patient who has been treated for schizophrenia for a number of years. The treatment was mostly ambulatory (i.e. the patient was hospitalized twice) and consisted of first-generation antipsychotics. During the past two years, for reasons unknown, the patient stopped taking regular meals and as a result lost significant body weight, became apathetic and withdrawn, started avoiding social contacts and neglected personal hygiene. She reportedly took the psychopharmaca regularly, but rarely attended psychiatric follow-up consultations. Due to substantial weight loss and hypotonia, correction of antipsychotic was made and internist treatment administered. The choice of olanzapine was not an accidental one. We decided to take advantage of its side effect for the treatment of an anorectic syndrome. Interdisciplinary cooperation proved to be a justified decision.

A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

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López-Muñoz, Francisco; De Berardis, Domenico; Fornaro, Michele; Vellante, Federica; di Giannantonio, Massimo; Povedano-Montero, Francisco J; Póveda Fernández-Martín, Maria; Rubio, Gabriel; Álamo, Cecilio

2017-01-01

A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

Structured physical exercise improves neuropsychiatric symptoms in acute dementia care: a hospital-based RCT.

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Fleiner, Tim; Dauth, Hannah; Gersie, Marleen; Zijlstra, Wiebren; Haussermann, Peter

2017-08-29

The primary objective of this trial is to investigate the effects of a short-term exercise program on neuropsychiatric signs and symptoms in acute hospital dementia care. Within a hospital-based randomized controlled trial, the intervention group conducted a 2-week exercise program with four 20-min exercise sessions on 3 days per week. The control group conducted a social stimulation program. Effects on neuropsychiatric signs and symptoms were measured via the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change, the Neuropsychiatric Inventory, and the Cohen-Mansfield Agitation Inventory. The antipsychotic and sedative dosage was quantified by olanzapine and diazepam equivalents. Eighty-five patients were randomized via minimization to an intervention group (IG) and a control group (CG). Seventy patients (82%) (mean age 80 years, 33 females, mean Mini Mental State Examination score 18.3 points) completed the trial. As compared to the CG (n = 35), the IG (n = 35) showed significantly reduced neuropsychiatric signs and symptoms. Especially, agitated behavior and lability improved. There were no between-group differences concerning antipsychotic and benzodiazepine medication. This exercise program is easily applicable in hospital dementia care and significantly reduces neuropsychiatric signs and symptoms in patients suffering from predominantly moderate stages of dementia. German Clinical Trial Register DRKS00006740 . Registered 28 October 2014.

Pressure ulcers induced by drug administration: A new concept and report of four cases in elderly patients.

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Mizokami, Fumihiro; Takahashi, Yoshiko; Hasegawa, Keiko; Hattori, Hideyuki; Nishihara, Keiji; Endo, Hidetoshi; Furuta, Katsunori; Isogai, Zenzo

2016-04-01

Drug-induced akinesia is a potential cause of pressure ulcers. However, pressure ulcers that are caused by drug-induced akinesia are not considered an adverse drug reaction (ADR). We propose that drug-induced pressure ulcers (DIPU) are pressure ulcers that are caused by an external force that is experienced after drug administration, and we considered resolution of these ulcers after drug discontinuation to be a supportive finding. In this report, we reviewed the medical records of pressure ulcer cases from a 300-bed hospital. Among 148 patients, four patients with pressure ulcers met the criterion for DIPU. In these cases, the suspected DIPU were related to treatment with olanzapine, fluvoxamine, valproic acid, clotiazepam, triazolam and rilmazafone. These drugs were administrated to manage the patients' behavioral and psychological symptoms that accompanied dementia. The DIPU in these patients were categorized as stage IV according to the National Pressure Ulcer Advisory Panel criteria. Discontinuation of the causal drugs led to significant improvements or complete healing of the pressure ulcers, and the patients subsequently recovered their mobility. Therefore, we propose that DIPU are potential ADR that have been overlooked in clinical practice. Thus, recognition of DIPU as an ADR may be important in preventing and appropriately managing pressure ulcers among elderly patients. © 2015 Japanese Dermatological Association.

[Mineralization of the basal ganglia as the supposed cause of poor tolerance of zuclopenthixol in a patient with long-term untreated paranoid schizophrenia].

Science.gov (United States)

Wichowicz, Hubert M; Wilkowska, Alina; Banecka-Majkutewicz, Zyta; Kummer, Łukasz; Konarzewska, Joanna; Raczak, Alicja

2013-01-01

Formations described as intracranial calcifications can appear in the course of diseases of the central nervous system, other systems and organs (e.g. endocrine), but also as a disorder of idiopathic character. They are frequently located in subcortical nuclei and usually constitute an incidental finding. This report presents the case of a patient suffering from paranoid schizophrenia for approximately 40 years, who did not agree to any treatment and was hospitalized against her will because she was the threat to the lives of others. She was treated with zuklopentixol resulting in positive symptoms reduction and considerable improvement in social functioning. Unfortunately neurological symptoms appeared: bradykinesis, rigidity--of the type of the lead pipe, balance, posture and gait abnormalities, disturbances in precise hands movements, double-sided Rossolimo's sign, plantar reflex without the participation of the big toe on the left. Neuroimaging studies have demonstrated changes in the form of lenticular nuclei calcification and reduction of signal intensity in posterior parts of both putamens. Neurological symptoms decreased significantly after switching to atypical neuroleptic (olanzapine), and the patient did not require any additional treatment. Mineralization of the basal ganglia can often be associated with psychiatric disorders and it shouldn't be neglected because it can require modification of pharmacotherapy or additional neurological treatment.

Pharmacotherapy of eating disorders.

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Davis, Haley; Attia, Evelyn

2017-11-01

Medications are commonly prescribed in the treatment of eating disorders. In this review, we discuss relevant medications used for the treatment of bulimia nervosa, binge eating disorder (BED), and anorexia nervosa. We focus on recent research developments, where applicable, in addition to discussing important findings from older studies to provide a complete synopsis of the current evidence base for eating disorder treatment using pharmacologic agents. Medications are generally useful for patients with bulimia nervosa and BED. For bulimia nervosa, antidepressant medications are the primary pharmacologic treatment and limited new research has been completed. For BED, lisdexamfetamine is reported to be generally well tolerated and effective, and is the first medication to be indicated by the US Food and Drug Administration for treatment of BED. For anorexia nervosa, there is limited evidence supporting benefits of medications. Second-generation antipsychotics, particularly olanzapine, appear to demonstrate some benefit for weight gain in anorexia nervosa, although are not advised as a stand-alone treatment. Transdermal administration of hormonal agents is also being explored for improving bone health in anorexia nervosa. Although pharmacotherapy has established utility in bulimia nervosa and BED, further research on medications for the treatment of eating disorders, particularly anorexia nervosa, is necessary.

Persistent psychotic symptoms after long-term heavy use of mephedrone: A two-case series.

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Barrio, Pablo; Gaskell, Matthew; Goti, Javier; Vilardell, Sergi; Fàbregas, Josep Maria

2016-06-15

Mephedrone (4-methylmethcathinone) is a synthetic stimulant drug of the cathinone class. Similar effects to those of cocaine and ecstasy are reported by users, with a high addictive potential. Given its increasing rate of consumption in Europe, it is getting more and more attention from the addiction field. In spite of that, little is known about the long-term consequences of prolonged heavy use. The two following cases might depict some of them. Case 1 was a middle-age man who reported three years of intravenous use of mephedrone. He used to binge for several days in a row. Psychotic symptoms appeared after a few months, especially paranoid delusions. Sent to aftercare in a therapeutic community, delusions kept reappearing after prolonged abstinence. A good response to risperidone was observed. Case 2 was a young man who used mephedrone heavily for two years, always snorted. Upon admission to the therapeutic community, the patient reported auditory hallucinations that partially remitted with olanzapine. Both cases showed a good insight and no personality deterioration. Given its similarities to other substances that are known to induce psychotic symptoms, and the increasing consumption of mephedrone around Europe, similar cases are expected in the near future. Conventional antipsychotic treatment seems a reasonable pharmacological approach.

Atypical antipsychotic medications to control symptoms of delirium in children and adolescents.

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Turkel, Susan Beckwitt; Jacobson, Julienne; Munzig, Elizabeth; Tavaré, C Jane

2012-04-01

Atypical antipsychotics have been documented to be effective in the management of delirium in adults, but despite considerable need, their use has been less studied in pediatric patients. A retrospective chart review was done to describe the use of atypical antipsychotics in controlling symptoms of delirium in children and adolescents. Pharmacy records at Children's Hospital Los Angeles were reviewed to identify patients to whom antipsychotic agents were dispensed over a 24-month period. Psychiatric inpatient consultations during the same 24-month period were reviewed. Patients 1-18 years old diagnosed with delirium given antipsychotics constituted the study population. Delirium Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when possible, at time antipsychotic was started to confirm the initial diagnosis of delirium and evaluate symptom severity, and again when antipsychotic was stopped, to assess symptom response. Olanzapine (n=78), risperidone (n=13), and quetiapine (n=19) were used during the 2 years of the study. Mean patient age, length of treatment, and response were comparable for the three medications. For patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores decreased significantly (pdelirium symptoms in pediatric patients while underlying etiology was addressed.

Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST).

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Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A

2015-06-01

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Metabolic Syndrome in Schizophrenia: A Non‑systematic Review

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Marta Nascimento

2012-12-01

Full Text Available Background: The link between mental illness and metabolic disturbances has been recognized since the beginning of the last century. The debate concerning medical morbidity in schizophrenia intensified during the last twenty years, especially after the introduction of atypical antipsychotics. Aims: To highlight some features of the metabolic syndrome in this population, specifically epidemiological data, underlying mechanisms and antipsychotic therapy. Methods: Non‑systematic review of literature. Results and Conclusions: Despite the different criteria used for the definition of metabolic syndrome, it is clear today that the schizophrenic population has the highest rate of metabolic syndrome. Additionally, the prevalence of the metabolic syndrome in this population demonstrates a geographical distribution similar to the general population. Although it hasn’t been recognized for years, schizophrenic patients’ vulnerability to develop metabolic disturbances isn’t entirely related to antipsychotic therapy. Actually, it results from an interaction of multiple factors, including hereditary, genetic, biochemical and environmental ones (which include antipsychotic therapy. Moreover, they are not exclusively explained by weight gain. Metabolic disturbances are one of the main concerns related to general psychopharmacology. The differences between typical and atypical antipsychotics in terms of metabolic syndrome are not completely established. However, clozapine and olanzapine are recognized to have the worst metabolic profile, amongst all atypical antipsychotics.

Obsessive-Compulsive Disorder with Suicide Obsessions in a First Responder without Previous Diagnosis of OCD or History of Suicide Attempts.

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Rachamallu, Vivekananda; Song, Michael M; Liu, Haiying; Giles, Charles L; McMahon, Terry

2017-01-01

Obsessive-compulsive disorder (OCD) is a distressing and often debilitating disorder characterized by obsessions, compulsions, or both that are time-consuming and cause impairment in social, occupational, or other areas of functioning. There are many published studies reporting higher risk of suicidality in OCD patients, as well as studies describing increased risk of suicidality in OCD patients with other comorbid psychiatric conditions such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Existing case reports on OCD with suicide as the obsessive component describe patients with long standing diagnosis of OCD with suicidal ideations or previous suicide attempts. This report describes the case of a 28-year-old male, who works as a first responder, who presented with new onset symptoms characteristic of MDD and PTSD, with no past history of OCD or suicidality who developed OCD with suicidal obsessions. Differentiating between suicidal ideation in the context of other psychiatric illnesses and suicidal obsessions in OCD is critical to ensuring accurate diagnosis and timely provision of most appropriate treatment. The combination of exposure and response prevention therapy and pharmacotherapy with sertraline and olanzapine was effective in helping the patient manage the anxiety and distress stemming from the patient's OCD with suicidal obsession.

Mixed states in bipolar disorder - changes in DSM-5 and current treatment recommendations.

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Betzler, Felix; Stöver, Laura Apollonia; Sterzer, Philipp; Köhler, Stephan

2017-11-01

Mixed states in affective disorders represent a particular challenge in clinical routine, characterized by a complicated course of treatment and a worse treatment response. Clinical features of mixed states and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria are presented and critical discussed. We then performed a systematic review using the terms 'bipolar', 'mixed' and 'randomized' to evaluate current treatment options. For pharmacological treatment of mixed states in total, there is still insufficient data from RCTs. However, there is some evidence for efficacy in mixed states from RCTs for atypical antipsychotics, especially olanzapine, aripiprazole and asenapine as well as mood stabilizers as valproate and carbamazepine. Mixed states are of a high clinical relevance and the DSM-5 criteria substantially reduced the diagnostic threshold. Besides advantages of a better characterization of patients with former DSM-IV-defined mixed episodes, disadvantages arise for example differential diagnoses with a substantial overlap in symptoms such as borderline personality disorders. Atypical antipsychotics, valproate and carbamazepine demonstrated efficacy in a limited sample of RCTs. The number of RCTs in the treatment of mixed states is highly limited. Furthermore, nearly all studies were funded by pharmaceutical companies which may lead to an underestimation of classical mood stabilizers such as lithium.

Metabolic Syndrome in Schizophrenia: A Non‑systematic Review

Directory of Open Access Journals (Sweden)

Marta Nascimento

2013-11-01

Full Text Available Background: The link between mental illness and metabolic disturbances has been recognized since the beginning of the last century. The debate concerning medical morbidity in schizophrenia intensified during the last twenty years, especially after the introduction of atypical antipsychotics. Aims: To highlight some features of the metabolic syndrome in this population, specifically epidemiological data, underlying mechanisms and antipsychotic therapy. Methods: Non‑systematic review of literature. Results and Conclusions: Despite the different criteria used for the definition of metabolic syndrome, it is clear today that the schizophrenic population has the highest rate of metabolic syndrome. Additionally, the prevalence of the metabolic syndrome in this population demonstrates a geographical distribution similar to the general population. Although it hasn’t been recognized for years, schizophrenic patients’ vulnerability to develop metabolic disturbances isn’t entirely related to antipsychotic therapy. Actually, it results from an interaction of multiple factors, including hereditary, genetic, biochemical and environmental ones (which include antipsychotic therapy. Moreover, they are not exclusively explained by weight gain. Metabolic disturbances are one of the main concerns related to general psychopharmacology. The differences between typical and atypical antipsychotics in terms of metabolic syndrome are not completely established. However, clozapine and olanzapine are recognized to have the worst metabolic profile, amongst all atypical antipsychotics.

Imbalanced Kynurenine Pathway in Schizophrenia

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Magdalena E. Kegel

2014-01-01

Full Text Available Several studies suggest a role for kynurenic acid (KYNA in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN. Here we investigate the levels of QUIN in cerebrospinal fluid (CSF of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22 and those of controls (n = 26 were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36. CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls ( P = 0.027. In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

Design and validation of standardized clinical and functional remission criteria in schizophrenia

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Mosolov SN

2014-01-01

Full Text Available Sergey N Mosolov,1 Andrey V Potapov,1 Uriy V Ushakov,2 Aleksey A Shafarenko,1 Anastasiya B Kostyukova11Department of Mental Disorders Therapy, Moscow Research Institute of Psychiatry, Moscow, Russia; 2Moscow Psychiatric Outpatient Services #21, Moscow, RussiaBackground: International Remission Criteria (IRC for schizophrenia were developed recently by a group of internationally known experts. The IRC detect only 10%–30% of cases and do not cover the diversity of forms and social functioning. Our aim was to design a more applicable tool and validate its use – the Standardized Clinical and Functional Remission Criteria (SCFRC.Methods: We used a 6-month follow-up study of 203 outpatients from two Moscow centers and another further sample of stable patients from a 1-year controlled trial of atypical versus typical medication. Diagnosis was confirmed by International Classification of Diseases Version 10 (ICD10 criteria and the Mini-International Neuropsychiatric Interview (MINI. Patients were assessed by the Positive and Negative Syndrome Scale, including intensity threshold, and further classified using the Russian domestic remission criteria and the level of social and personal functioning, according to the Personal and Social Performance Scale (PSP. The SCFRC were formulated and were validated by a data reanalysis on the first population sample and on a second independent sample (104 patients and in an open-label prospective randomized 12-month comparative study of risperidone long-acting injectable (RLAI versus olanzapine.Results: Only 64 of the 203 outpatients (31.5% initially met the IRC, and 53 patients (26.1% met the IRC after 6 months, without a change in treatment. Patients who were in remission had episodic and progressive deficit (39.6%, or remittent (15% paranoid schizophrenia, or schizoaffective disorder (17%. In addition, 105 patients of 139 (51.7%, who did not meet symptomatic IRC, remained stable within the period. Reanalysis of

The psychopharmacology algorithm project at the Harvard South Shore Program: an update on schizophrenia.

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Osser, David N; Roudsari, Mohsen Jalali; Manschreck, Theo

2013-01-01

This article is an update of the algorithm for schizophrenia from the Psychopharmacology Algorithm Project at the Harvard South Shore Program. A literature review was conducted focusing on new data since the last published version (1999-2001). The first-line treatment recommendation for new-onset schizophrenia is with amisulpride, aripiprazole, risperidone, or ziprasidone for four to six weeks. In some settings the trial could be shorter, considering that evidence of clear improvement with antipsychotics usually occurs within the first two weeks. If the trial of the first antipsychotic cannot be completed due to intolerance, try another until one of the four is tolerated and given an adequate trial. There should be evidence of bioavailability. If the response to this adequate trial is unsatisfactory, try a second monotherapy. If the response to this second adequate trial is also unsatisfactory, and if at least one of the first two trials was with risperidone, olanzapine, or a first-generation (typical) antipsychotic, then clozapine is recommended for the third trial. If neither trial was with any these three options, a third trial prior to clozapine should occur, using one of those three. If the response to monotherapy with clozapine (with dose adjusted by using plasma levels) is unsatisfactory, consider adding risperidone, lamotrigine, or ECT. Beyond that point, there is little solid evidence to support further psychopharmacological treatment choices, though we do review possible options.

Drugs and dilated cardiomyopathies: A case/noncase study in the French PharmacoVigilance Database.

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Montastruc, Guillaume; Favreliere, Sylvie; Sommet, Agnès; Pathak, Atul; Lapeyre-Mestre, Maryse; Perault-Pochat, Marie-Christine; Montastruc, Jean-Louis

2010-03-01

To evaluate putative associations between drugs and dilated cardiomyopathy. We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were all the observations with dilated cardiomyopathy registered into the FPVD between 1 January 1990 and 30 June 2007. Noncases were all other reports other than those studied. Anthracyclines were used as positive controls. Data were expressed as reporting odds ratio (ROR) with their 95% confidence intervals. Out of the 258 729 adverse drug reaction (ADR) reports recorded in the FPVD between 1 January 1990 and 30 June 2007, 47 (22 men, mean age 49 years) were defined as dilated cardiomyopathy. In these 47 patients, 67 drugs were 'suspect'. A significant ROR was found with cytotoxic (epirubicin, mitoxantrone, cyclophosphamide, gemcitabine, fluorouracil) and antiretroviral (lamividune, zidovudine, abacavir) but also with isotretinoin, prednisone, appetite suppressant (clobenzorex) and psychotropic [antipsychotic (clozapine, olanzapine), lithium, antidepressant (clomipramine, amitriptyline, fluvoxamine)] drugs. The present study describes an association between some drugs and reports of dilated cardiomyopathies. This relationship involves not only some already suspected drugs (anthracyclines, antiretrovirals), but also other drugs (antipsychotics, lithium, antidepressants, retinoids) less known to induce such an ADR. Despite the mandatory limits of this kind of study (underreporting, confounding factors . . .), these data represent a pharmacovigilance signal and could contribute to establish further prospective studies in order to confirm such signals.

Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study.

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Fervaha, Gagan; Agid, Ofer; Takeuchi, Hiroyoshi; Foussias, George; Remington, Gary

2014-07-01

The field of schizophrenia is redefining optimal outcome, moving beyond clinical remission to a more comprehensive model including functional recovery and improved subjective well-being. Although numerous studies have evaluated subjective outcomes within the domain of subjective quality of life in patients with schizophrenia, less is known about global evaluations of subjective well-being. This study examined the effects of antipsychotic medication on overall life satisfaction in patients with chronic schizophrenia. Data were drawn from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, where participants with a DSM-IV diagnosis of schizophrenia were randomized to receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under double-blind conditions (N=753). The primary outcome measure was prospective change in subjectively evaluated overall life satisfaction scores following 12 months of antipsychotic treatment. Psychopathology, medication side effects and functional status were also evaluated, among other variables. Patients experienced modest improvements in overall life satisfaction (d=0.22, p0.05). Change in severity of positive, negative, and depressive symptoms as well as functional status each demonstrated a small, albeit statistically significant, association with change in life satisfaction (r=0.10-0.21, p׳slife satisfaction scores (explained variance satisfaction with life. Clinicians should be aware that these two domains are not inextricably linked. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

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Olivares, J M; Rodriguez-Morales, A; Diels, J; Povey, M; Jacobs, A; Zhao, Z; Lam, A; Villalobos Vega, J C; Cuéllar, J Alonso; de Castro, F J Alberca; Quintero, C Morillo-Velarde; Martíin, J F Román; Domínguez, P Tabares; Ojeda, J L Prados; Cortés, S Sanz; Cala, F I Mata; Marín, C Gutiérrez; Castro, L Moyano; Duaso, M A Haza; Albarracín, J Requena; Vergara, G Narbona; Benítez, A Fernández; Cleries, F Mayoral; Pérez-Brian, J M García-Herrera; Aragón, A Bordallo; Navarro, J C Rodríguez; Biedma, J A Algarra; de Pedro, R Bravo; González, J F Delgado; López, M E Jaén; Moreno, H Díaz; López, J A Soto; Rodríguez, E Ojeda; de Hoyos, C Martínez; Sacristán, M Pardilla; Martín, M D Molina; Ballesteros, E Martín; Rodríguez, P A Sopelana; Menéndez, L Fernández; Rivas, R Santos; del Pino Cuadrado, P; Lauffer, J Correas; Solano, J J Rodríguez; Martínez, J M Fernández; Solano, F García; Rodríguez, P García-Lamberde; Rodríguez, J A Romero; Cano, T Rodríguez; Fortacin, M Ducaju; Lobeiras, J M Blanco; Sampedro, J M Piñeiro; Bravo, A Pérez; Pellicer, A Fernández; López, M D Alonso; Liste, J Fraga; Fernández, M Riobo; Losada, A Casas; Mendez, R Vazquez-Noguerol; Romero, S Agra; Blanco, J J Blanco; Bonaselt, I Tortajada; Mahia, M C García; del Valle, E Ferrer Gómez; Yañez, P Quiroga; Camarasa, M Gelabert; Alonso, J A Barbado; Mendez, G Florez; Feliz, F Doce; Lamela, M A López; Piñero, M Vega; Alvarado, P Fuentes; Gómez, I López; Martín, P Fadon; Gómez, J L Santos; López, A García; Jiménez, A Rodríguez; Nafs, A Escudero; Barquero, N Casas; Ortiz, R Fernández-Villamor; Noguera, J L Velez; Carrasco, P Ruiz; Muñoz, J Martín; Palma, M Masegoza; Hortelano, C Marín; Bonome, L Sánchez; Sevilla, J Sánchez; Juan, J M Mongil San; Ramos, J M García; Muñoz, J L Vallejo; Guisasola, J Elorza; Vazquez, L Santamaria; Guerras, F Campo; Nebot, F J Arrufat; Fernández, F J Baron; Nicolau, A L Palomo; Subirats, R Catala; Kidias, M Messays; Navarro, V Fabregat; García, B Frades; del Rosal, F Mejias; de Vicente Muñoz, T; Ballester, J Año; Lieb, P Malabia; Martel, A Delgado; Bea, E Roca; Joaquim, I Grau; Enjuanes, F Boatas; Piñol, M Bañuelos; Carbonell, E Fontova I; Muñoz, R Martín; Giribets, C Argila; Sans, L Albages; Blanco, A Serrano; Felipe, M Arcega; Muñoz, P González; Villanueva, A Pons; Arroyo, M Bernardo; Borri, R Coronas; Fallada, S Miret; Merola, M Celma; Rodon, E Parellada; Palmes, J R Pigem; Martínez, E Pérez; Catala, J Matarredona; Coca, A Sandoval; Ferrandiz, F Pascual; Paya, E Ferrandiz; Caballero, G Iturri; Bonet, A Franco; Figueras, J Fluvia; Pagador, P Moreno; Garibo, M Medina; Camo, V Pérez; Carrillo, C Sanz; Valero, C Pelegrin; Rebollo, F J Caro; García Campayo, J; Sala Ayma, J M Sala; Roig, M Martínez; de Uña Mateos, M A; Bertolin, R García; García, A Martín; Mazo, F Jiménez; Velasco, J L Galvez; Pérez, L Santa Maria; Casado, C Jiménez; Barba, J J Mancheño; Diaz, M Conde; Rubio, J P Alcon; Mandoli, A Soler; Herrero, A Uson; Martínez, A Rodríguez; Serrano, P Salgado; Rodríguez, E Nieto; Montesinos, J Segui; Macia, J Ferragud; Mateos Marcos, A Mateos; Soto, J V Pérez-Fuster; Dumont, M Verdaguer; Pagan, J Parra; Martínez, V Balanza; Santiuste de Pablos, M; Delgado, C Espinosa; Quiles, M D Martínez; López, F J Manzanera; Navarro, P Pozo; Torres, A Micol; Ingles, F J Martínez; Arias-Camison, J M Salmeron; Manzano, J C López; Peña, R Villanueva; Guitarte, G Petersen; Fontecilla, H Blasco; Romero, J Barjau; Gil, R Sanz; Lozano, J Marín; Adanez, L Donaire; Zarranz Herrera-Oria, I; Jiménez, J Pérez; Vaz, F Carrato; García, O Sanz; Anton, C Contreras; Casula, R Reixach; Hernandez, M C Natividad; Escabias, F Teba; Torresano, J Rodríguez; Pérez-Villamil, A Huidobro; Estevez, L; Figuero, M Aragües; Muñoz de Morales, A; Calvin, J L Rodríguez; Criado, M Delgado; Rodríguez, V Molina; Ambrosolio, E Balbo; Madera, P M Holgado; Alfaro, G Ponce; Vidal, M M Rojas; Valtuille, A García; Ruiz, O; Cabornero, G Lucas; Echevarria Martínez de Bujo, M; Mallen, M J Maicas; Puigros, J Santandreu; Martorell, A Liñana; Forteza, A Clar; Arrebola, E Rodríguez; Rodríguez de la Torre, M; Saiz, C G Anton; Bardolet I Casas, C; Linde, E Rodríguez; De Arce Cordon, R; Molina, E M Padial; Carazo, F J Ruiz; Romero, J J Muro; Cano, D Vico; Dorado, M Soria; Velazquez, S Campos; Sánchez, A J Rodríguez; Leon, S Ocio; Sánchez, K Pachas; Benitez, M Henry; Zugarramurai, A Intxausti; Contreras, M A; De la Varga González, M; Marín, P Barreiro; Robina, F Gómez; García, M Sánchez; Pérez, F J Otero; Bros, P Cubero; Gómez, A Carrillo; de Dios Molina Martín, J; Perera, J L Carrasco; Averbach, M C; Perera, J L Carrasco; Palancares, E Goenaga; Gallego de Dios, M T; Rojo, C Fernández; Iglesias, S Sánchez; Merino, M I Rubio; Mestre, N Prieto; Urdaniz, A Pérez; Sánchez, J M Martínez; Seco, R Gordo; Muñoz, J Franco; Agut, M Mateos; Lozano, M L Blanco; Herguedas, F Martín; Pena, A Torcal; García, J Vicente; Martínez, A Varona; Sanz Granado, O Sanz; Fernández, M A Medina; Canseco, J M Moran; López, P A Megia; Martín, M A Franco; Barrio, J A Espina; Ubago, J Giner; Bennassar, M Roca; Díez, J M Olivares; Fleta, J L Hernandez; Fortes, F Porras; López, C Arango; Medina, O; Alvarez, D Figuera; Roca, J M Peña; Valladolid, G Rubio; Tavera, J A Furquet; García-Castrillon Sales, J A; Llordes, I Batalla; Melgarejo, C Anchuistegui; Cañas de la Paz, F; Callol, V Vallés; García, M Bousoño; García, J Bobes; Leal, F J Vaz; Corrales, E Cáceres; Iglesias, E Sánchez; Gómez, M A Carreiras; Serrano, G García; Chillarón, E G Román; Aguado, F J Samino; Castillo, J J Molina; González, A González; Vázquez, J Gallardo; Peralvarez, M Bolivar; Diaz, M Rios; Mesa, M Ybarzabal; Artiles, F J Acosta; Chao, M Ajoy; Mesa, M Ybarzabal; del Rosario Santana, P; Escudero, M A García; Berenguer, M Molla; Llacer, J M Bonete; Berna, J A Juan; Ortiz, J Barragán; Pardell, L Tost; Hernández-Alvarez de Sotomayor, C; Méndez, M R Cejas; Garate, R Cabrera; Múgica, B Díaz; González, M Caballero; Domingo, J Pujol; Navarro, C Sáez; Vera, G Selva; Cuquerella, M A; Monzo, J Lonjedo; Boada, P Cervera; Pérez, M F Martín; Parrado, E Carrasco; Sánchez, J J Yañez; Fernández, J Calvo

2009-06-01

The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

Catatonic Dilemma in a 33-Year-Old Woman: A Discussion

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Alexander Koch

2013-01-01

Full Text Available Case. We report a case of catatonia with elevated CK, elevated temperature, and hypoferritinemia after abrupt discontinuation of clozapine in a patient with known proneness to catatonic symptoms. Reinstatement of clozapine therapy was contraindicated due to leukopenia. Neuroleptic malign syndrome could not be ruled out by the administration of quetiapine; this prevented the quick use of other potent D2 antagonists. Some improvement was achieved through supportive therapy, high dose of lorazepam, and a series of 10 ECT sessions. Returning to baseline condition was achieved by a very careful increase of olanzapine. Discussion. Catatonic symptoms in schizophrenia as well as in NMS might be caused by a lack of striatal dopamine (CS or dopamine D2 antagonism (NMS. CS might be a “special” kind of schizophrenia featuring both hypo- and hyperactivity of dopaminergic transmission. ECT has been described as a “psychic rectifier” or a “reset for the system.” The desirable effect of ECT in cases of CS might be dopaminergic stimulation in the striatum and decrease of both the dopaminergic activity in the limbic system and the serotonergic activity on 5-HT2 receptors. The desirable effect of ECT in NMS would be explained by activation of dopaminergic transmission and/or liberation of dopaminergic receptors from the causative neuroleptics.

Second-generation antipsychotics and risk of cerebrovascular accidents in the elderly.

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Percudani, Mauro; Barbui, Corrado; Fortino, Ida; Tansella, Michele; Petrovich, Lorenzo

2005-10-01

Concern has been recently raised for risperidone and olanzapine, possibly associated with cerebrovascular events in placebo-controlled trials conducted in elderly subjects with dementia. We investigated the relationship between exposure to second-generation antipsychotics (SGAs) and occurrence of cerebrovascular accidents in the elderly. From the regional database of hospital admissions of Lombardy, Italy, we extracted all patients aged 65 or older with cerebrovascular-related outcomes for the year 2002. From the regional database of prescriptions reimbursed by the National Health Service, we extracted all patients aged 65 or older who received antipsychotic prescriptions during 2001. The 2 databases were linked anonymously using the individual patient code. The proportions of cerebrovascular accidents were 3.31% (95% confidence interval, 2.95-3.69) in elderly subjects exclusively exposed to SGAs and 2.37% (95% confidence interval, 2.19-2.57) in elderly subjects exclusively exposed to first-generation antipsychotics. After background group differences were controlled for, exposure to SGAs significantly increased the risk of accidents. The analysis of cerebrovascular events in elderly subjects exposed to each individual SGA, in comparison with exposure to haloperidol, showed a significantly increased risk for risperidone only (adjusted odds ratio, 1.43; 95% confidence interval, 1.12-1.93). These data provide preliminary epidemiological evidence that exposure to SGAs, in comparison with exposure to first-generation antipsychotics, significantly increased the risk of cerebrovascular accidents in the elderly.

Do We Really Know How to Treat a Child with Bipolar Disorder or One with Severe Mood Dysregulation? Is There a Magic Bullet?

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Rajeev Jairam

2012-01-01

Full Text Available Background. Despite controversy, bipolar disorder (BD is being increasingly diagnosed in under 18s. There is scant information regarding its treatment and uncertainty regarding the status of “severe mood dysregulation (SMD” and how it overlaps with BD. This article collates available research on treatment of BD in under 18s and explores the status of SMD. Methods. Literature on treatment of BD in under 18s and on SMD were identified using major search engines; these were then collated and reviewed. Results. Some markers have been proposed to differentiate BD from disruptive behaviour disorders (DBD in children. Pharmacotherapy restricted to short-term trials of mood-stabilizers and atypical-antipsychotics show mixed results. Data on maintenance treatment and non-pharmacological interventions are scant. It is unclear whether SMD is an independent disorder or an early manifestation of another disorder. Conclusions. Valproate, lithium, risperidone, olanzapine, aripiprazole and quetiapine remain first line treatments for acute episodes in the under 18s with BD. Their efficacy in maintenance treatment remains unclear. There is no validated treatment for SMD. It is likely that some children who are currently diagnosed with BD and DBD and possibly most children currently diagnosed with SMD will be subsumed under the proposed category in the DSM V of disruptive mood dysregulation disorder with dysphoria.

Cycloserine Induced Late Onset Psychosis and Ethambutol Induced Peripheral Neuropathy Associated with MDR-TB Treatment in an Indian Patient- A Rare Case Report.

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Holla, Sadhana; Amberkar, Mohan Babu; Bhandarypanambur, Rajeshkrishna; Kamalkishore, Meenakumari; Janardhanan, Manju

2015-02-01

Adverse reactions and toxicity inevitably accompany all treatment courses for drug-resistant TB. Our case underscores the importance of awareness regarding neuropsychiatric adverse reactions due to MDR-TB therapy and reversible nature of it. Cycloserine induced psychosis is most life threatening complication and sometimes could be fatal. A 42-year-old male on MDR-TB therapy got admitted for his persistent psychotic complaints like hallucinations, delusions and suicidal ideations, despite being treated with quetiapine/olanzapine. Eventually patient was rehabilitated, cycloserine was stopped and psychotic events regressed slowly. Other culprit drugs like ethambutol and levofloxacin causing psychosis was ruled out because there was no relapse of psychotic events despite being continued with these drugs. He also complained of tingling, numbness, swaying, pain and weakness. On examination, he had distal motor weakness in lower limbs, tandem gait positive, altered position sense, and tenderness over toes and positive Romberg's sign with ataxia. He was diagnosed to have drug induced sensorimotor peripheral neuropathy. All these symptoms persisted after stopping cycloserine and patient continued to have neuropathy with ethambutol and ethionamide. Considering the nature of neuropathy which was mild, mixed sensorimotor and resolved completely after 2-3 weeks of stopping, it was more in favour of ethambutol. However, we could not rule out the possibility of ethionamide or (ethionamide + ethambutol) causing neuropathy or both could have accelerated the neurotoxic effects of cycloserine which remained elusive.

[A naturalistic study: 100 consecutive episodes of acute agitation in a psychiatric emergency department].

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Pascual, J C; Madre, M; Puigdemont, D; Oller, S; Corripio, I; Díaz, A; Faus, G; Perez, V; Alvarez, E

2006-01-01

Psychomotor agitation is a common event in psychiatric emergency services (PES) with a prevalence of approximately 10 %. There is no general consensus on to how to manage psychomotor agitation; benzodiazepines, typical antipsychotics and now atypical antipsychotics have demonstrated similar efficacy. The aim of our study was to describe the epidemiology and clinical management of agitation in "real-life" in a psychiatric emergency service. A naturalistic study was performed in acutely agitated patients recruited consecutively in a psychiatric emergency service. Demographics, clinical and therapeutic characteristics were analyzed. Efficacy was assessed by the Excitement Component of the Positive and Negative Syndrome Scale (PANSS-EC) and the Agitation-Calmness Evaluation Scale (ACES). Pragmatic variables such as the need for second pharmacological intervention and the need for physical restraints were assessed. The study included 100 patients with psychomotor agitation. Mean age was 36.2 % and 54% were women. The most prevalent diagnoses were psychotic disorder (48 %) and personality disorder (24 %). Physical restraint was required in 39 % of patients and 52 % accepted oral treatment. Haloperidol was the most frequent oral treatment and olanzapine was the most frequent intramuscular treatment. A naturalistic approach provides data based on clinical reality in psychiatric emergency services. Strict research designs of clinical trials of efficacy imply sample selection biases and are generally distanced from the clinical reality. Atypical antipsychotics have become the first-line treatment in acute agitation

Can lipid nanoparticles improve intestinal absorption?

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Mendes, M; Soares, H T; Arnaut, L G; Sousa, J J; Pais, A A C C; Vitorino, C

2016-12-30

Lipid nanoparticles and their multiple designs have been considered appealing nanocarrier systems. Bringing the benefits of these nanosystems together with conventional coating technology clearly results in product differentiation. This work aimed at developing an innovative solid dosage form for oral administration based on tableting nanostructured lipid carriers (NLC), coated with conventional polymer agents. NLC dispersions co-encapsulating olanzapine and simvastatin (Combo-NLC) were produced by high pressure homogenization, and evaluated in terms of scalability, drying procedure, tableting and performance from in vitro release, cytotoxicity and intestinal permeability stand points. Factorial design indicated that the scaling-up of the NLC production is clearly feasible. Spray-drying was the method selected to obtain dry particles, not only because it consists of a single step procedure, but also because it facilitates the coating process of NLC with different polymers. Modified NLC formulations with the polymers allowed obtaining distinct release mechanisms, comprising immediate, delayed and prolonged release. Sureteric:Combo-NLC provided a low cytotoxicity profile, along with a ca. 12-fold OL/3-fold SV higher intestinal permeability, compared to those obtained with commercial tablets. Such findings can be ascribed to drug protection and control over release promoted by NLC, supporting them as a versatile platform able to be modified according to the intended needs. Copyright © 2016 Elsevier B.V. All rights reserved.

Dementia.

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Butler, Rob; Radhakrishnan, Raghavakurup

2012-09-10

Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or vascular)? What are the effects of treatments on behavioural and psychological symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), antidepressants (clomipramine, fluoxetine, imipramine, sertraline), antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy, benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT), cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and statins.

Change in Prolactin Levels in Pediatric Patients Given Antipsychotics for Schizophrenia and Schizophrenia Spectrum Disorders: A Network Meta-Analysis

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Chakrapani Balijepalli

2018-01-01

Full Text Available Background. Treatment of schizophrenia with first- and second-generation antipsychotics has been associated with elevated prolactin levels, which may increase the risk for prolactin-related adverse events. Methods. Randomized controlled trials (RCTs included in a recent systematic review were considered for this analysis. A Bayesian network meta-analysis was used to compare changes in prolactin levels in pediatric patients diagnosed with schizophrenia or schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs. Results. Five RCTs, including 989 patients combined, have evaluated the changes in prolactin for pediatric patients after 6 weeks of treatment with risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone. In the overall study population, treatment with risperidone was associated with the highest increase in mean prolactin levels compared to other SGAs. Patients treated with risperidone 4–6 mg/day were found to experience the greatest increases (55.06 ng/ml [95% CrI: 40.53–69.58] in prolactin levels, followed by risperidone 1–3 mg/day, paliperidone 3–6 mg/day, and paliperidone 6–12 mg/day. Conclusions. This study shows that there are differences in SGAs ability to cause hyperprolactinemia. Further, there is clear evidence of safety concerns with risperidone and paliperidone treatment in adolescent schizophrenia patients. Registration. PROSPERO CRD42014009506.

Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics.

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Li, Xiaohua; Rosborough, Kelley M; Friedman, Ari B; Zhu, Wawa; Roth, Kevin A

2007-02-01

Glycogen synthase kinase-3 (GSK3) has been recognized as an important enzyme that modulates many aspects of neuronal function. Accumulating evidence implicates abnormal activity of GSK3 in mood disorders and schizophrenia, and GSK3 is a potential protein kinase target for psychotropics used in these disorders. We previously reported that serotonin, a major neurotransmitter involved in mood disorders, regulates GSK3 by acutely increasing its N-terminal serine phosphorylation. The present study was undertaken to further determine if atypical antipsychotics, which have therapeutic effects in both mood disorders and schizophrenia, can regulate phospho-Ser-GSK3 and inhibit its activity. The results showed that acute treatment of mice with risperidone rapidly increased the level of brain phospho-Ser-GSK3 in the cortex, hippocampus, striatum, and cerebellum in a dose-dependent manner. Regulation of phospho-Ser-GSK3 was a shared effect among several atypical antipsychotics, including olanzapine, clozapine, quetiapine, and ziprasidone. In addition, combination treatment of mice with risperidone and a monoamine reuptake inhibitor antidepressant imipramine or fluoxetine elicited larger increases in brain phospho-Ser-GSK3 than each agent alone. Taken together, these results provide new information suggesting that atypical antipsychotics, in addition to mood stabilizers and antidepressants, can inhibit the activity of GSK3. These findings may support the pharmacological mechanisms of atypical antipsychotics in the treatment of mood disorders.

Current treatment for anorexia nervosa: efficacy, safety, and adherence

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Lindsay P Bodell

2010-10-01

Full Text Available Lindsay P Bodell, Pamela K KeelDepartment of Psychology, Florida State University, Tallahassee, FL, USAAbstract: Anorexia nervosa (AN is a serious psychiatric illness associated with significant medical and psychiatric morbidity, psychosocial impairment, increased risk of death, and chronicity. Given the severity of the disorder, the establishment of safe and effective treatments is necessary. Several treatments have been tried in AN, but few favorable results have emerged. This paper reviews randomized controlled trials in AN, and provides a synthesis of existing data regarding the efficacy, safety, and adherence associated with pharmacologic and psychological interventions. Randomized controlled trials for the treatment of AN published in peer-reviewed journals were identified by electronic and manual searches. Overall, pharmacotherapy has limited benefits in the treatment of AN, with some promising preliminary findings associated with olanzapine, an antipsychotic agent. No single psychological intervention has demonstrated clear superiority in treating adults with AN. In adolescents with AN, the evidence base is strongest for the use of family therapy over alternative individual psychotherapies. Results highlight challenges in both treating individuals with AN and in studying the effects of those treatments, and further emphasize the importance of continued efforts to develop novel interventions. Treatment trials currently underway and areas for future research are discussed.Keywords: anorexia nervosa, treatment, pharmacotherapy, psychotherapy, randomized controlled trials

Efficacy of Adjunctive Treatments Added to Olanzapine or Clozapine for Weight Control in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

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Yun-Jung Choi

2015-01-01

Full Text Available Objectives. This study was conducted to review systematically adjunctive treatments for weight reduction in patients with schizophrenia and compare efficacies of clinical trials through meta-analysis, so as to provide effective clinical guideline regarding weight control for patients taking atypical antipsychotics. Methods. Candidate clinical trials were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Fourteen randomized clinical trials were included for systematic review and meta-analysis from 132 potential trials. The Comprehensive Meta-Analysis version 2 was used for meta-analysis. Results. Difference in means and significances from meta-analyses regarding weight control by adjunctive treatments showed that topiramate, aripiprazole, or sibutramine was more effective than metformin or reboxetine. Psychiatric evaluations did not show statistically significant changes between treatment groups and placebo groups except topiramate adjunctive treatments. Adverse effects regarding adjunctive therapies were tolerable and showed statistically no significances compared to control groups. Conclusion. Though having several reports related to exacerbation of psychiatric symptoms, topiramate and aripiprazole are more efficacious than other medications in regard to weight reduction and less burden of critical adverse effects as well as being beneficial for clinical improvement.

Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.

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Moreno, Carmen; Merchán-Naranjo, Jessica; Alvarez, Mar; Baeza, Inmaculada; Alda, Jose A; Martínez-Cantarero, Carmen; Parellada, Mara; Sánchez, Bernardo; de la Serna, Elena; Giráldez, Marisa; Arango, Celso

2010-03-01

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p or = 1 obesity-related complication at follow-up. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Development of a Medication Monitoring System for an Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT Team

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Nicole B. Washington, DO, Assistant Professor

2012-01-01

Full Text Available Purpose: The primary goal was to improve medication management oversight for a severely mentally ill (SMI community-based population by developing a medication monitoring system based on current guidelines to optimize pharmacotherapy and minimize potential medication-related adverse effects. The secondary goal was improvement in coordination of care between healthcare providers. Methods: Guidelines for medication used for psychiatric indications were reviewed. A database of medication for psychiatric indications with monitoring recommendation was developed. Results: Medication regimens for 68 members of the Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT program qualified for review. Fourteen medications, carbamazepine, chlorpromazine, clozapine, fluphenazine and fluphenazine long-acting injections (LAI, haloperidol and haloperidol LAI, lithium, lurasidone, olanzapine, paliperidone and paliperidone LAI, perphenazine, quetiapine, risperidone and risperidone LAI, valproic acid/divalproex, and ziprasidone, were identified. In total, 111 medications are used on a monthly basis. Each member receives more than one medication qualifying for review. Additional monitoring parameters that were evaluated included changes in laboratory orders for members with insulin-dependent diabetes. Annual lipid panels were changed to every 6 months, if applicable. Conclusions and Future Directions: This medication monitoring program was developed to help ensure IMPACT members receive the most effective care and minimize potential medication-related adverse effects. The secondary goal was to improve coordination of care. Medication monitoring will be added as a continuous quality assurance measure. Lab results will be reviewed at least monthly. The medication monitoring program will be evaluated annually.

The role of asenapine in the treatment of manic or mixed states associated with bipolar I disorder

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Pompili M

2011-05-01

Full Text Available Maurizio Pompili1,2, Paola Venturini1, Marco Innamorati1, Gianluca Serafini1, Ludovica Telesforo1, David Lester3, Roberto Tatarelli1, Paolo Girardi11Department of Neurosciences, Mental Health and Sensory Functions, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy; 2McLean Hospital, Harvard Medical School, Boston, MA, USA; 3The Richard Stockton College of New Jersey, Pomona, NJ, USABackground: Bipolar disorders (BD are of particular public health significance as they are prevalent, severe and disabling, and often associated with elevated risks of premature mortality. The aim of this concise overview is to investigate the role of asenapine in the treatment of manic and mixed states associated with BD type 1 disorder.Method: MedLine, Excerpta Medica and PsycINFO searches were performed to identify papers in English published over the past 7 years. Search terms were "asenapine", "manic" OR "mixed states", "bipolar I disorder". Subjects included in this study suffered from BD type 1 disorder.Results: To date, only four studies of asenapine for the treatment of manic or mixed episodes associated with BD type 1 have been published.Conclusion: Research indicates that asenapine is generally well-tolerated, and that asenapine is efficacious and not inferior to olanzapine in the treatment of mixed or manic episodes associated with BD type 1 in the short-term and long-term.Keywords: asenapine, bipolar disorder, side effects

Altered consciousness states and endogenous psychoses: a common molecular pathway?

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Ciprian-Ollivier, J; Cetkovich-Bakmas, M G

1997-12-19

Interest in the role of indolamines in the pathogenesis of psychoses has been renewed in recent years by the development of atypical antipsychotic drugs such as clozapine, olanzapine, and risperidone, which act on serotonin receptors. Discovery of the hallucinogenic compounds called methylated indolealkyalamines (MIAs) (e.g. N,N-dimethylserotonin, or bufotenin, and N,N-dimethyltryptamine, or DMT) led proponents of the transmethylation hypothesis of schizophrenia to theorize that through some inborn error of metabolism, serotonin or tryptamine might undergo the addition of extra methyl radicals, thereby forming MIAs with hallucinogenic properties. Various studies have attempted to detect the excretion of MIAs, especially DMT, in the body fluids of psychotic patients and normal controls. Some of these studies have demonstrated elevated MIA concentrations in psychotic patients, including those with schizophrenia, compared with normal persons, and others have not. A number of variables may account for these contradictory findings. The mechanism whereby the beverage ayahuasca, which is used in certain cure and divination rituals in the Amazon Basin, exerts its hallucinogenic effects may serve as a model to explain the mechanism underlying hallucinogenic symptoms in schizophrenia and may lend support to the transmethylation hypothesis. Certain studies suggest that specific perceptual disturbances manifested by schizophrenic patients could contribute to progressive deterioration and negative symptomatology. All these findings point to the need for further study of the neurophysiology of MIAs and their pathogenetic role in endogenous psychoses.

Prophylaxis and management of antineoplastic drug induced nausea and vomiting in children with cancer

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Sidharth Totadri

2016-10-01

Full Text Available Antineoplastic drug induced nausea and vomiting (AINV is a major adverse event which deeply impacts the quality of life of children with cancer. It additionally causes distress to parents and negatively impacts compliance to therapy. A robust AINV prophylaxis regimen is essential to achieve complete control; and prevent anticipatory, breakthrough and refractory AINV. With a wide array of available anti-emetics, standard guidelines for their use are crucial to ensure uniform and optimum prophylaxis. Chemotherapeutic agents are classified as having high, moderate, low or minimal emetic risk based on their potential to cause emesis in the absence of prophylaxis. Three drug regimen with aprepitant, ondansetron/granisetron and dexamethasone is recommended for protocols with high emetic risk. Although approved in children ≥12 years, there is mounting evidence for the use of aprepitant in younger children too. In protocols with moderate and low emetic risk, combination of ondansetron/granisetron and dexamethasone; and single agent ondansetron/granisetron are recommended, respectively. Metoclopramide is an alternative when steroids are contraindicated. Olanzapine and lorazepam are useful drugs for breakthrough AINV and anticipatory AINV. Knowledge of pediatric dosage, salient adverse events, drug interactions as well as cost of drugs is essential to prescribe anti-emetics accurately and safely in resource constrained settings. Non pharmacological interventions such as hypnosis, acupressure and psychological interventions can benefit a sub-group of patients without significant risk of adverse events.

The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings

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de Boer, Marrit K.; Castelein, Stynke; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

2015-01-01

A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce. PMID:25721311

Delirium Associated With Fluoxetine Discontinuation: A Case Report.

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Fan, Kuang-Yuan; Liu, Hsing-Cheng

Withdrawal symptoms on selective serotonin reuptake inhibitor (SSRI) discontinuation have raised clinical attention increasingly. However, delirium is rarely reported in the SSRI discontinuation syndrome. We report a case of delirium developing after fluoxetine discontinuation in a 65-year-old female patient with major depressive disorder. She experienced psychotic depression with limited response to treatment of fluoxetine 40 mg/d and quetiapine 100 mg/d for 3 months. After admission, we tapered fluoxetine gradually in 5 days because of its limited effect. However, delirious pictures developed 2 days after we stopped fluoxetine. Three days later, we added back fluoxetine 10 mg/d. Her delirious features gradually improved, and the clinical presentation turned into previous psychotic depression state. We gradually increased the medication to fluoxetine 60 mg/d and olanzapine 20 mg/d in the following 3 weeks. Her psychotic symptoms decreased, and there has been no delirious picture noted thereafter. Delirium associated with fluoxetine discontinuation is a much rarer complication in SSRI discontinuation syndrome. The symptoms of SSRI discontinuation syndrome may be attributable to a rapid decrease in serotonin availability. In general, the shorter the half-life of any medication, the greater the likelihood patients will experience discontinuation symptoms. Genetic vulnerability might be a potential factor to explain that SSRI discontinuation syndrome also occurred rapidly in people taking long-half-life fluoxetine. The genetic polymorphisms of both pharmacokinetic and pharmacodynamic pathways might be potentially associated with SSRI discontinuation syndrome.

Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder.

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Brar, Jaspreet S; Ganguli, Rohan; Pandina, Gahan; Turkoz, Ibrahim; Berry, Sally; Mahmoud, Ramy

2005-02-01

Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). BT may be an effective method for weight reduction in patients with chronic psychotic illness.

Pharmacokinetic-pharmacodynamic analysis of antipsychotics-induced extrapyramidal symptoms based on receptor occupancy theory incorporating endogenous dopamine release.

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Matsui-Sakata, Akiko; Ohtani, Hisakazu; Sawada, Yasufumi

2005-06-01

We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

[Lithium and anticonvulsants in the treatment of mania and in the prophylaxis of recurrences].

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Salvi, Virginio; Cat Berro, Alberto; Bechon, Elisa; Bogetto, Filippo; Maina, Giuseppe

2011-01-01

A mood stabilizer is an agent effective in treating both poles of the illness and at the same time being able to prevent both manic and depressive episodes in bipolar disorder. According to a broader definition, a mood stabilizer should be effective in decreasing the frequency or severity of any type of episode in bipolar disorder, without worsening the frequency or severity of episodes of opposite polarity. According to this, anticonvulsants and atypical antipsychotics can be considered as mood stabilizers. In this paper we review the use of lithium and other anticonvulsants that have proved effective in randomized controlled trials of the treatment of manic episodes and prevention of recurrences of bipolar disorder. Lithium and valproate are considered as first-line treatment options for acute mania while evidence regarding carbamazepine is insufficient to consider it as a first-line agent. Patients who fail to respond to first-line treatments may benefit from the adjunct of an atypical antipsychotic such as olanzapine, quetiapine, risperidone or aripiprazole. Lithium retains the strongest evidence of efficacy in the prophylaxis of manic episodes, lamotrigine in the prevention of depressive episodes. Valproate and carbamazepine have no indication for long-term treatment of bipolar disorder. Lithium can still be considered a gold standard in the treatment of manic episodes as well as in the prophylaxis of recurrences. Other anticonvulsants should be employed in particular situations, such as valproic acid in the treatment of mania and lamotrigine in the prevention of depressive recurrences.

Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children

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Eiji Kirino

2014-01-01

Full Text Available Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.

Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

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Beninger, Richard J

2006-12-01

Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

Treatment of anorexia nervosa with long-term risperidone in an outpatient setting: case study.

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Kracke, Elsa J; Tosh, Aneesh K

2014-01-01

There are currently few studies focusing on the efficacy of long-term atypical antipsychotics to treat anorexia nervosa in the pediatric population. This case report follows the treatment of a 17 year-old female with anorexia nervosa over her four-year undergraduate career. After two years of multidisciplinary treatment, low-dose risperidone was initiated due to persistence of her disease. She expressed decreased rigidity around meal times, her weight improved and she had resumption of menses. She was compliant with treatment through graduation and maintained her weight gain. Atypical antipsychotics are a treatment option in the management of anorexia nervosa. Risperidone has not been studied as frequently as olanzapine for eating disorders. Risperidone was chosen for its more favorable side effect profile and decreased cost to the patient. Previous studies on anorexia nervosa treatment have occurred during inpatient treatment and have limited follow-up due to patients' refusal to initiate or maintain medication compliance. This case presents 17 months of outpatient data. The efficacy of risperidone therapy was evaluated with frequent weight checks, subjective decrease in rigidity, serial complete metabolic panels, and restoration of menses. In this case report, an adolescent female treated with low-dose risperidone had decreased rigid thinking, weight gain and resolution of secondary amenorrhea without medication side effects. Therefore, the atypical antipsychotic risperidone may be an effective long-term outpatient treatment option for patients with anorexia nervosa.

[Comparison of medical and economic benefits of antipsychotics in the treatment of schizophrenia in France].

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Druais, S; Doutriaux, A; Cognet, M; Godet, A; Lançon, C; Levy, P; Samalin, L; Guillon, P

2017-08-01

The course of schizophrenia can vary widely, and patients experience remission phases alternating with relapse episodes, which generally lead to hospitalisation and have a significant impact on the burden of disease. The prevalence of schizophrenia in France is estimated to be approximately 600,000 people, with an incidence of 10,000 new patients per year. Patients with schizophrenia represent the largest group of hospitalised patients in French public institutions and specialised centres, and the French authorities recognise that the management of schizophrenia is a major public health concern. The Haute Autorité de Santé (HAS) and most of the evidence-based guidelines for the maintenance treatment of schizophrenia recommend long-acting injectable (LAI) antipsychotics to be used predominantly in the prevention of relapse for non-compliant patients; however, in clinical practice, the use of LAIs remains low. This analysis aimed to estimate and to compare the cost-effectiveness of the most common antipsychotic strategies in France in the management of schizophrenia. A Markov model was developed to simulate the progression of a cohort of patients with schizophrenia through four health states (stable treated, stable non-treated, relapse and death) and considered up to three lines of treatment to account for changes in treatment management. Antipsychotics including aripiprazole LAI (ALAI), olanzapine LAI (OLAI), paliperidone LAI (PLAI), risperidone LAI (RLAI), haloperidol decanoate (HD) and oral olanzapine (OO) were compared in terms of costs and clinical outcomes. Thus, costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over five years based on three-month cycles from a French health insurance perspective with a discount rate of 4 %. Patients were considered to be stabilised after clinical decompensation and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or

Pathophysiology and treatment of psychosis in Parkinson's disease: a review.

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Zahodne, Laura B; Fernandez, Hubert H

2008-01-01

between deep brain stimulation surgery and PD psychosis.When reduction in anti-PD medications to the lowest tolerated dose does not improve psychosis, further intervention may be warranted. Several atypical antipsychotic agents (i.e. clozapine, olanzapine) have been shown to be efficacious in reducing psychotic symptoms in PD; however, use of clozapine requires cumbersome monitoring and olanzapine leads to motor worsening. Studies of ziprasidone and aripiprazole are limited to open-label trials and case reports and are highly variable; however, it appears that while each may be effective in some patients, both are associated with adverse effects. While quetiapine has not been determined efficacious in two randomized controlled trials, it is a common first-line treatment for PD psychosis because of its tolerability, ease of use and demonstrated utility in numerous open-label reports. Cholinesterase inhibitors currently represent the most promising pharmacological alternative to antipsychotics. Tacrine is rarely tried because of hepatic toxicity, and controlled trials with donepezil have not shown significant reductions in psychotic symptoms, due perhaps to methodological limitations. However, results from an open-label study and a double-blind, placebo-controlled trial involving 188 hallucinating PD patients support the efficacy of rivastigmine. With regard to non-pharmacological interventions, case reports suggest that electroconvulsive therapy has the potential to reduce psychotic symptoms and may be considered in cases involving concurrent depression and/or medication-refractory psychosis. Limited case reports also suggest that specific antidepressants (i.e. clomipramine and citalopram) may improve psychosis in depressed patients. Finally, studies in the schizophrenia literature indicate that psychological approaches are effective in psychosis management but, to date, this strategy has been supported only qualitatively in PD, and further studies are warranted.

Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

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Vik-Mo Audun O

2006-10-01

Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

Síndrome de Cotard associada ao uso de ecstasy Cotard’s syndrome induced by ecstasy

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Rodrigo Nicolato

2007-01-01

Full Text Available O termo ecstasy é usado para descrever diversas substâncias que compartilham estruturas químicas e efeitos semelhantes, referindo-se mais comumente a 3,4-metilenodioximetanfetamina (3,4-MDMA. Os efeitos psíquicos da MDMA são, sobretudo, alucinógenos e estimulantes. A tendência atual considera o delírio de Cotard como sendo a crença delirante de estar morto ou de que seus órgãos estejam paralisados ou podres, independentemente do diagnóstico do paciente. Neste artigo, relatamos o caso clínico de um paciente que apresentou quadro psicótico com delírios hipocondríacos e alucinações olfativas com características de síndrome de Cotard associado ao uso crônico de ecstasy. Foi medicado com olanzapina e obteve remissão completa dos sintomas.The term ecstasy is used to describe various substances that share similar chemical structures and effects, often referring to 3,4-methylenedioxy-N-methylamphetamine (3,4-MDMA. MDMA psychic effects are mainly hallucinatory and stimulatory. Current trends consider Cotard’s delusion as a delusional belief of being dead or having paralyzed or rotten organs, independent of the diagnosis the patient has received. This case report is about a psychotic episode where the patient presented with hypochondriac delusion and olfactory hallucinations resembling Cotard’s syndrome and associated with ecstasy abuse. He was given olanzapine and achieved total remission from symptoms.