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Sample records for antipsychotics zyprexa olanzapine

  1. The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.

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    Andrew P Morgan

    Full Text Available The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.

  2. Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

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    Marić Nađa P.

    2008-01-01

    Full Text Available INTRODUCTION Olanzapine is a second generation antipsychotic (SGA with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline was associated with good initial response (PANSS reduction 20% in the first two weeks and the improvement was maintained further on (PANSS reduction 50% after 16 weeks. Significant increase (20 kg, 40% in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2. CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

  3. Heart rate variability in schizophrenic patients switched from typical antipsychotic agents to amisulpride and olanzapine. 3-month follow-up.

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    Wang, Ying-Chieh; Yang, Cheryl C H; Bai, Ya-Mei; Kuo, Terry B J

    2008-01-01

    Schizophrenia is a severe mental disorder that requires lifelong treatment, and therefore information on the cardiovascular safety and tolerance of antipsychotics is of significant clinical importance. Atypical antipsychotics have been used to treat schizophrenia patients since the 1990s, and more and more patients have been switched to these from typical antipsychotics; however, there is still no accessible evaluation tool for assessing cardiovascular safety. In this study, we used a computer-assisted 5-min measurement of resting heart rate variability (HRV) in schizophrenia patients who were switched to atypical antipsychotic agents (amisulpride and olanzapine) due to severe side effects (tardive dyskinesia). In 15 patients who switched to amisulpride and 18 to olanzapine, HRV was evaluated before the medication was switched, and patients were followed up every month for 3 months after the switch. Frequency-domain analyses of short-term and stationary respiratory rate (RR) intervals were performed to evaluate low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF in normalized units (LF%). Our results showed significant increases in the mean, variance and HF of RR intervals in the amisulpride group, but not in the olanzapine group. These results indicate that amisulpride has a more vagotonic effect, suggesting greater cardiovascular safety as compared with olanzapine when subjects are switched from typical antipsychotic agents.

  4. Improvement in hyperprolactinemia and reproductive comorbidities in patients with schizophrenia switched from conventional antipsychotics or risperidone to olanzapine.

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    Kinon, Bruce J; Ahl, Jonna; Liu-Seifert, Hong; Maguire, Gerald A

    2006-06-01

    This open-label, prospective, 4-month study in hyperprolactinemic patients with schizophrenia explored whether prolactin levels decrease after switching antipsychotic therapy to olanzapine. A secondary objective was to determine if reproductive morbidities and sexual dysfunction occurring with hyperprolactinemia improved with prolactin normalization. Clinically stable patients with schizophrenia, who had hyperprolactinemia defined as >18.8 ng/ml for males and >24.2 ng/ml for females, were randomized to: remain on current therapy (n=27) or switch to olanzapine, 5-20 mg/day, (n=27). Baseline prolactin levels in female patients randomized to receive olanzapine (n=14) were 66.3+/-38.7 ng/ml and were 82.0+/-37.6 (p=.32) in those remaining on their pre-study antipsychotic medication (n=14). In male patients, baseline prolactin levels were 33.7+/-12.1 and 33.5+/-13.8 ng/ml (p=.97), respectively, for those randomized to olanzapine (n=13) or remaining on pre-study treatment (n=13). At study end, patients switched to olanzapine experienced significant reductions in mean serum prolactin levels of 19.8+/-18.1 ng/ml in males (p=.02), and 32.3+/-47.5 ng/ml in females (p=.01), but prolactin continued to be elevated in patients who remained on pre-study antipsychotic treatment. After switching to olanzapine treatment, male patients experienced significantly (p=.03) increased free testosterone levels but there were no significant improvements in total testosterone levels; some female patients experienced improved menstrual cycling, as well as resolution of galactorrhea and gynecomastia, and sexual functioning was significantly improved in both genders. Patients switched to olanzapine, as well as those remaining on their pre-study medication, maintained clinical stability, their symptoms continued to improve, although there were no significant between-treatment differences in improvement. Treatment-emergent adverse events did occur in both treatment groups; however, they were not

  5. 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

  6. Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States

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    Smolen Lee J

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator, quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. Methods A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs, treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. Results The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544 followed by generic risperidone ($9,080. In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719. The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. Conclusion The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and

  7. Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study

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    Sacristán Jose A

    2001-12-01

    Full Text Available Abstract Background In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. Method Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10, and treatment compliance was measured using a physician-rated 4 point categorical scale. Results A total of 2128 patients initiated treatment (as monotherapy with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. Conclusion Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS.

  8. Olanzapine

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    ... bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) in ... Olanzapine may cause side effects. Tell your doctor if any of these ... difficulty walking constipation weight gain dry mouth pain in arms, legs, ...

  9. Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute major cardiovascular events in young and middle-aged adults

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    Pasternak, Björn; Svanström, Henrik; Ranthe, Mattis F

    2014-01-01

    risperidone (n = 14,134). The primary outcome was any major cardiovascular event (composite of cardiovascular mortality, acute coronary syndrome, or ischemic stroke) within 1 year following treatment initiation. Cox regression was used to estimate hazard ratios (HRs) while on current antipsychotic monotherapy...... in the outpatient setting, adjusting for an outcome-specific disease risk score. RESULTS: The crude rate of any major cardiovascular event was 5.3 per 1,000 person-years among olanzapine users, 3.4 in quetiapine users, and 5.2 in risperidone users. Compared with risperidone, the risk of any major cardiovascular.......9 to 2.0) events for quetiapine. CONCLUSIONS: Among young and middle-aged outpatients, the risk of acute major cardiovascular events was similar with use of olanzapine, quetiapine, and risperidone. Although moderate relative differences cannot be ruled out, any differences are small in absolute terms....

  10. Schizophrenic patients treated with clozapine or olanzapine perform better on theory of mind tasks than those treated with risperidone or typical antipsychotic medications.

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    Savina, Ioulia; Beninger, Richard J

    2007-08-01

    Theory of mind (ToM), the ability to attribute mental states to others, is associated with medial prefrontal cortical (mPFC) activity and is impaired in schizophrenia. Olanzapine or clozapine but not typical antipsychotics or risperidone preferentially affect c-fos expression in mPFC in animals. We tested the hypothesis that schizophrenic patients treated with different antipsychotics would perform differently on ToM tasks. Groups receiving Typicals (n=23), Clozapine (n=18), Olanzapine (n=20) or Risperidone (n=23) and a Control group of healthy volunteers (n=24) were matched for age, gender, handedness and education. ToM functioning was assessed with picture sequence, second-order belief and faux-pas tests. Schizophrenic groups performed similarly to controls on non-ToM conditions. The Olanzapine and Clozapine groups performed similarly to Controls on ToM tasks. The Typicals and Risperidone groups performed worse than the other groups on ToM tasks. We concluded that ToM performance of schizophrenic patients is influenced by the antipsychotic they are taking. Our results suggest that olanzapine or clozapine but not typicals or risperidone may improve or protect ToM ability.

  11. The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: comparison with aripiprazole, ziprasidone, bifeprunox and F15063.

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    Assié, Marie-Bernadette; Carilla-Durand, Elisabeth; Bardin, Laurent; Maraval, Mireille; Aliaga, Monique; Malfètes, Nathalie; Barbara, Michèle; Newman-Tancredi, Adrian

    2008-09-11

    Several novel antipsychotics activate serotonin 5-HT1A receptors as well as antagonising dopamine D2/3 receptors. Such a pharmacological profile is associated with a lowered liability to produce extrapyramidal side effects and enhanced efficacy in treating negative and cognitive symptoms of schizophrenia. However, 5-HT1A receptor agonists increase plasma corticosterone and many antipsychotics disturb the regulation of glucose. Here, we compared the influence on plasma glucose and corticosterone of acute treatments with 'new generation' antipsychotics which target dopamine D2/3 receptors and 5-HT1A receptors, with that of atypical antipsychotics, and with haloperidol. Olanzapine and clozapine, antipsychotics that are known to produce weight gain and diabetes in humans, both at 10 mg/kg p.o., substantially increased plasma glucose (from 0.8 to 1.7 g/l) at 1 h after administration, an effect that returned to control levels after 4 h. In comparison, F15063 (40 mg/kg p.o.) was without effect at any time point. Olanzapine and clozapine dose-dependently increased plasma glucose concentrations as did SLV313 and SSR181507. Haloperidol and risperidone had modest effects whereas aripiprazole, ziprasidone and bifeprunox, antipsychotics that are not associated with metabolic dysfunction in humans, and F15063 had little or no influence on plasma glucose. The same general pattern of response was found for plasma corticosterone levels. The present data provide the first comparative study of conventional, atypical and 'new generation' antipsychotics on glucose and corticosterone levels in rats. A variety of mechanisms likely underlie the hyperglycemia and corticosterone release observed with clozapine and olanzapine, whilst the balance of dopamine D2/3/5-HT1A interaction may contribute to the less favourable impact of SLV313 and SSR181507 compared with that of bifeprunox and F15063.

  12. DEVELOPMENT AND BIOEQUIVALENCE STUDY OF OLANZAPINE 10mg TABLETS

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    Ravindra Waykar et al

    2012-09-01

    Full Text Available Generic drugs are lower-cost versions of patent-expired original brand-name medications. According to guidelines of regulatory agencies of the Canada, US and European Union, a generic drug must be “identical, or bioequivalent to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use”. Bioequivalence is decreed when the ratio of the generic to the reference compound for the area-under-the-curve and maximum plasma concentration (Cmax fall within a 0.80–1.25 range. The present study was to develop Olanzapine Tablets and compare pharmacokinetic profile of Zyprexa 10 mg film-coated tablets, Zyprexa Velotabs 10 mg orodispersible tablets and Olanzapine 10mg tablets. Multi media dissolution studies in 0.1N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were carried out for Reference (Zyprexa Velotab 10 mg and Zyprexa 10 mg and test product (i.e. Olanzapine 10 mg. A single centre, open-label, single-dose, randomised, 3-way crossover bioequivalence study, performed under fasting conditions. Based on the results obtained, it can be concluded that the test olanzapine (Treatment A is bioequivalent to both references Zyprexa Velotab (Treatment B and Zyprexa (Treatment C following a 10 mg dose under fasting conditions. All formulations were well tolerated, with no major side effects and no relevant differences in safety profiles were observed between the preparations, particularly with respect to the number and pattern of adverse event.

  13. Incidence of tardive dyskinesia with risperidone or olanzapine in the elderly: results from a 2-year, prospective study in antipsychotic-naïve patients.

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    Woerner, Margaret G; Correll, Christoph U; Alvir, Jose Ma J; Greenwald, Blaine; Delman, Howard; Kane, John M

    2011-07-01

    Tardive dyskinesia (TD) rates with second-generation antipsychotics (SGAs) are considered to be low relative to first-generation antipsychotics (FGAs), even in the particularly vulnerable elderly population. However, risk estimates are unavailable for patients naïve to FGAs. Therefore, we aimed to determine the TD incidence in particularly vulnerable, antipsychotic-naïve elderly patients treated with the SGA risperidone or olanzapine. The present work describes a prospective inception cohort study of antipsychotic-naïve elderly patients aged 55 years identified at New York Metropolitan area in-patient and out-patient geriatric psychiatry facilities and nursing homes at the time of risperidone or olanzapine initiation. At baseline, 4 weeks, and at quarterly periods, patients underwent assessments of medical and medication history, abnormal involuntary movements, and extra-pyramidal signs. TD was classified using Schooler-Kane criteria. Included in the analyses were 207 subjects (age: 79.8 years, 70.0% female, 86.5% White), predominantly diagnosed with dementia (58.9%) or a major mood disorder (30.9%), although the principal treatment target was psychosis (78.7%), with (59.4%) or without (19.3%) agitation. With risperidone (n=159) the cumulative TD rate was 5.3% (95% confidence interval (CI): 0.7, 9.9%) after 1 year (mean dose: 1.0±0.76 mg/day) and 7.2% (CI: 1.4, 12.9%) after 2 years. With olanzapine (n=48) the cumulative TD rate was 6.7% (CI: 0, 15.6%) after 1 year (mean dose: 4.3±1.9 mg/day) and 11.1% (CI: 0, 23.1%) after 2 years. TD risk was higher in females, African Americans, and patients without past antidepressant treatment or with FGA co-treatment. The TD rates for geriatric patients treated with risperidone and olanzapine were comparable and substantially lower than previously reported for similar patients in direct observation studies using FGAs. This information is relevant for all patients receiving antipsychotics, not just the especially

  14. 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; Frimurer, Thomas; Schwartz, Thue W; Levy, Finn Olav; Andressen, Kjetil Wessel

    2015-07-15

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We 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-mediated degradation of 5-HT7 receptors and also interfered with G protein activation. In addition, we tested whether receptor degradation was mediated by the GPCR-associated sorting protein-1 (GASP-1). We show that GASP-1 binds the 5-HT7 receptor and regulates the clozapine-mediated degradation. Mutations of the identified motifs and residues, located in or close to Helix-VIII of the 5-HT7 receptor, modified antipsychotic-stimulated binding of proteins (such as GASP-1), possibly by altering the flexibility of Helix-VIII, and also interfered with G protein activation. Taken together, our data demonstrate that binding 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.

  15. Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.

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    Bobes, Julio; Cañas, Fernando; Rejas, Javier; Mackell, Joan

    2004-12-01

    Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

  16. A Case of Olanzapine-Induced Fever

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    Yang, Cho-Hsiang; Chen, Ying-Yeh

    2017-01-01

    Olanzapine, a frequently used second-generation antipsychotic, has rarely been implicated as a cause of drug-induced fever in the absence of neuroleptic malignant syndrome. We describe a patient who developed isolated fever following olanzapine monotherapy, which subsided after discontinuation of olanzapine. Blockade of dopaminergic receptors and elevated cytokines concentration are possible mechanisms of fever development during treatment with olanzapine. This case calls for attention to olanzapine-induced fever in clinical practice. PMID:28138204

  17. 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.

  18. Development and validation of a HPLC-UV method for the simultaneous determination of the antipsychotics clozapine, olanzapine and quetiapine, several beta-blockers and their metabolites.

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    Gracia, Margarete Silva; Köppl, Alexandra; Unholzer, Sandra; Haen, Ekkehard

    2017-03-07

    A simple, accurate and selective column-switching high performance liquid chromatography (HPLC) method was developed and validated for simultaneous quantification of six beta-blockers (metoprolol MET, timolol TIM, bisoprolol BIS, propranolol PRO, carvedilol CAR and nebivolol NEB), three of their metabolites (α-hydroxy metoprolol α-HMET, N-desisopropyl propranolol DIPRO and 4'-hydroxy carvedilol 4-HCAR), three antipsychotics (olanzapine OLA, clozapine CLO and quetiapine QUE) and three of their metabolites (N-desmethyl olanzapine DMOLA, N-desmethyl clozapine DMCLO and N-desalkyl quetiapine DAQUE) in human serum. After pretreatment on a Merck LiChrospher RP-4 ADS column (25 μm) drugs were separated on a Phenomenex Gemini Phenyl Hexyl 110 A column (250 mm x 4.6 mm, 5 μm) using a gradient mixture of acetonitrile and potassium dihydrogen phosphate buffer pH 3.1 (containing 10 % methanol) as a mobile phase at a flow rate of 1ml/min. The total analysis time was 40 min. For detection of the analytes, four different UV wavelengths were used: 215 nm, 226 nm, 242 nm and 299 nm. The method was validated according to the guidelines of the Society of Toxicology and Forensic Chemistry (GTFCh) in terms of selectivity, linearity, accuracy, precision and stability and successfully applied for the analysis of the 15 described analytes in human serum.

  19. 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

    DEFF Research Database (Denmark)

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

    2015-01-01

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We...... 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...

  20. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

    DEFF Research Database (Denmark)

    Vidarsdottir, Solrun; Roelfsema, Ferdinand; Streefland, Trea;

    2009-01-01

    BACKGROUND: Treatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth...

  1. Focus on olanzapine.

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    Green, B

    1999-01-01

    Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine) is a novel antipsychotic agent of the theinobenzodiazepine class developed by Eli Lilly & Co. It has a pleotrophic pharmacology and affects the dopaminergic, serotonergic, muscarinic and adrenergic systems. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to additional serotonergic effects. Clinical studies and trials suggest that olanzapine is comparable or superior to haloperidol and may be superior to risperidone in terms of efficacy and side-effect profiles. The starting dose of olanzapine is a single dose of 10 mg. The drug reaches peak plasma levels in 5-8 h, and has a half-life of about 35 h, depending on metabolism. The recommended maximum dose is 20 mg daily, but higher doses have been employed. Abnormalities of the QTc interval on ECG are unlikely to occur and so there is no need for a baseline ECG as with sertindole, which has recently been withdrawn. The most common side-effects are somnolence and weight gain. About 40% of patients in clinical trials gain weight--especially if they are on a high starting dose and if they were underweight pre-treatment. Reported evidence to date suggests that olanzapine is relatively less likely to produce sexual dysfunction. In general, weight gain and sexual dysfunction are of great concern to people taking antipsychotics and the side-effect profile of any antipsychotic may affect compliance. Olanzapine's general efficacy and side-effect profile suggest that, unforeseen post-marketing complications notwithstanding, olanzapine deserves a major place in the first-line management of psychotic disorders.

  2. Olanzapine reduces physical activity in rats exposed to activity-based anorexia : possible implications for treatment of anorexia nervosa?

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; van Elburg, Annemarie A; Kas, Martien J H; van Engeland, Herman; Adan, Roger A H

    2005-01-01

    BACKGROUND: Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduc

  3. Pharmacogenetics of olanzapine metabolism.

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    Söderberg, Mao Mao; Dahl, Marja-Liisa

    2013-08-01

    The pharmacokinetics of the atypical antipsychotic, olanzapine, display large interindividual variation leading to multiple-fold differences in drug exposure between patients at a given dose. This variation in turn gives rise to the need for individualized dosing in order to avoid concentration-dependent adverse effects or therapeutic failure. Genetically determined differences in olanzapine metabolism represent a less studied source of variability in comparison to environmental and physiological factors. In this review, we summarize available in vitro and in vivo data addressing the influence of polymorphisms in drug-metabolizing enzymes on olanzapine serum exposure. The polymorphic CYP2D6 enzyme appears to have no significant influence on olanzapine steady-state serum concentrations. The formation of the various olanzapine metabolites is influenced by polymorphisms in the genes coding for CYP1A2, CYP1A expression regulator AHR, UGT1A4 and UGT2B10, as well as FMO3. An impact on steady-state olanzapine serum concentrations has been suggested for variants of CYP1A2 and UGT1A4, with somewhat conflicting findings. The potential involvement of FMO1 and CYP3A43 in olanzapine disposition has also been suggested but needs future validation.

  4. Olanzapine induced neuroleptic malignant syndrome.

    Science.gov (United States)

    Patra, Bichitra Nanda; Khandelwal, Sudhir K; Sood, Mamta

    2013-01-01

    An 18 year old male diagnosed as a case of bipolar affective disorder (BPAD), developed neuroleptic malignant syndrome (NMS) following treatment with olanzapine (20 mg per day), an atypical antipsychotic drug. NMS is usually seen with typical antipsychotic drugs. The patient was diagnosed as a case of NMS, offending agent was immediately withdrawn and prompt treatment with bromocriptine and levodopa produced a good recovery. The various features of the case are discussed in view of the potential mortality of the syndrome.

  5. 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

    DEFF Research Database (Denmark)

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

    2005-01-01

    It is unclear to what degree antipsychotic therapy confounds longitudinal imaging studies and post-mortem studies of subjects with schizophrenia. To investigate this problem, we developed a non-human primate model of chronic antipsychotic exposure. Three groups of six macaque monkeys each were...

  6. Olanzapine-induced tardive oculogyric crises

    Directory of Open Access Journals (Sweden)

    Amar D Bavle

    2013-01-01

    Full Text Available Tardive syndromes are much lower in prevalence in second generation antipsychotics (SGA than in the typical antipsychotics. Although, olanzapine, which is an SGA, has a high risk of causing weight gain, metabolic syndrome, raised blood sugar, and dyslipidemias; it is widely used as the risk of developing extrapyramidal syndromes (EPS is low. Among the various forms of EPS, tardive syndromes are the most feared, tardive dyskinesia, tardive akathisia, and tardive dystonia are the commonest tardive syndromes, the others being less common. Tardive oculogyric crises (TOC are a rare form of tardive dystonia. This patient had TOC with prolonged unsupervised treatment with low-dose olanzapine. Added to that, she developed weight gain that was alarmingly high and such high gain in weight with olanzapine, to our knowledge, has not been reported. She responded to a low dose of trihexiphenydyl, and on stopping olanzapine and adding aripiprazole, has started losing weight.

  7. Olanzapine induced neuroleptic malignant syndrome

    Directory of Open Access Journals (Sweden)

    Bichitra Nanda Patra

    2013-01-01

    Full Text Available An 18 year old male diagnosed as a case of bipolar affective disorder (BPAD, developed neuroleptic malignant syndrome (NMS following treatment with olanzapine (20 mg per day, an atypical antipsychotic drug. NMS is usually seen with typical antipsychotic drugs. The patient was diagnosed as a case of NMS, offending agent was immediately withdrawn and prompt treatment with bromocriptine and levodopa produced a good recovery. The various features of the case are discussed in view of the potential mortality of the syndrome.

  8. Olanzapine-Induced Hypertriglyceridemia Resulting in Necrotizing Pancreatitis

    Science.gov (United States)

    Roy-Chaudhury, Prabir; Yadlapalli, Ganesh

    2016-01-01

    Olanzapine is an atypical antipsychotic agent that was approved by the Food and Drug Administration in 1996 for treatment of psychotic disorders, bipolar disorder, and schizophrenia. Since that time, numerous case reports have been published that describe the association of olanzapine and the development of pancreatitis. Furthermore, 3 reports suggest the mechanism of olanzapine-induced hypertriglyceridemia as the etiology of this progression. We report a case of a 36-year-old man who developed necrotizing pancreatitis secondary to olanzapine-induced hypertriglyceridemia. This case, to our knowledge, is the most severe case of this progression and the first case requiring plasmapheresis for acute management.

  9. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    Directory of Open Access Journals (Sweden)

    Mishra Biswaranjan

    2007-10-01

    Full Text Available Neuroleptic malignant syndrome (NMS is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presentations of NMS have often varied, and we report another atypicality in presentation of NMS due to olanzapine use.

  10. [The comparative study on the efficacy of the combination of serotonin reuptake inhibitor antidepressants and antipsychotics in the treatment of recurrent depressive disorders].

    Science.gov (United States)

    D'iakonov, A L; Lobanova, I V

    2012-01-01

    A combination of serotonin reuptake inhibitor antidepressants (prozac and stimulaton) with atypical antipsychotics (zyprexa and solian) reduced depression in patients with recurrent depressive disorders during 10 days. The effect was evenly distributed between 10, 20 and 40 days of treatment. Other symptoms had a peculiar dynamics depending on the therapy. By the end of the study, similar effects were achieved for all groups. The addition of antipsychotics to antidepressant treatment insignificantly increased the number of adverse events.

  11. Hyperglycemia and antipsychotic medications.

    Science.gov (United States)

    Haupt, D W; Newcomer, J W

    2001-01-01

    Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and

  12. Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2014-01-01

    Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R) of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks) combination treatment of betahistine (an H1R agonist and H3R antagonist) and olanzapine (O+B) reduced (-45%) body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d.) and betahistine (9.6 mg/kg, t.i.d.) significantly reduced (-51.4%) weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT). The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

  13. Olanzapine-induced ischemic colitis

    Directory of Open Access Journals (Sweden)

    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.

  14. Olanzapine discontinuation emergent recurrence in bipolar disorder

    Directory of Open Access Journals (Sweden)

    Manu Arora

    2014-01-01

    Full Text Available Objective: The efficacy of atypical antipsychotics including olanzapine in acute treatment of manic episode has been established, whereas its role in maintenance treatment is not clear. Materials and Methods: Thirteen patients of bipolar disorder who were on regular treatment with mood stabilizer and subsequently relapsed into mania or depressive episode after discontinuation of olanzapine were studied for various socio-demographic and clinical factors using retrospective chart review. Results: There was no correlation found between the period of tapering olanzapine, time to recurrence of episode after discontinuation, and the dosage of olanzapine at the time of discontinuation. The predominant early signs of relapse after discontinuation of olanzapine included sleep disturbance (72.7%, lack of insight for change in behavior (72.7%, irritability (54.5%, and elevated mood (45.5%. Conclusion: Mood stabilizer alone as a maintenance therapy of bipolar disorder may be inadequate for long-term management. A low dose of olanzapine along with mood stabilizers might be useful for prevention of recurrence in bipolar disorder.

  15. Atypical antipsychotic drugs and tardive dyskinesia: relevance of D2 receptor affinity.

    Science.gov (United States)

    Bressan, Rodrigo A; Jones, Hugh M; Pilowsky, Lyn S

    2004-03-01

    Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

  16. Antipsychotic medication prescribing trends in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Riyaz Ahmed Siddiqui

    2016-08-01

    Conclusions: Atypical antipsychotics are more commonly used as compared to the typical ones. Atypical antipsychotics like olanzapine, resperidone and quetiapine are preferred because of their lesser propensity to cause extrapyramidal adverse effects and they also helps in improving negative symptoms of schizophrenia. [Int J Basic Clin Pharmacol 2016; 5(4.000: 1417-1420

  17. Antipsychotics for the management of psychosis in Parkinson's disease: systematic review and meta-analysis

    OpenAIRE

    Jethwa, Ketan Dipak; Onalaja, Oluwademilade A.

    2015-01-01

    Background Antipsychotics can exacerbate motor symptoms in Parkinson's disease psychosis. Aims To systematically review the literature on the efficacy and acceptability of antipsychotics for Parkinson's disease psychosis. Method Randomised controlled trials comparing an antipsychotic with placebo were systematically reviewed. Results The final selection list included nine studies using quetiapine (3), clozapine (2), olanzapine (3) and pimavanserin (1). A narrative synthesis and meta-analyses ...

  18. Effects of olanzapine on regional C-Fos expression in rat forebrain.

    Science.gov (United States)

    Robertson, G S; Fibiger, H C

    1996-02-01

    Compared to typical antipsychotic drugs, clozapine produces a unique pattern of Fos-like immunoreactive neurons in the rat forebrain. It has been proposed, therefore, that this approach may be useful in identifying other agents with clozapine's therapeutic profile. In the present study, we examined the ability of olanzapine to increase the number of Fos-like immunoreactive neurons in the striatum, nucleus accumbens, lateral septal nucleus, and prefrontal cortex. Olanzapine (5, 10 mg/kg) produced dose-dependent increases in the number of Fos-positive neurons in the nucleus accumbens and lateral septal nucleus, important components of the limbic system that may mediate some of the therapeutic actions of neuroleptics. Olanzapine also produced dose-dependent increases in the number of Fos-positive neurons in the dorsolateral striatum, an effect that correlates with the ability of neuroleptics to produce extrapyramidal side-effects. The effects of olanzapine on regional c-fos expression are not therefore identical to clozapine, which is without effect in the dorsolateral striatum. However, olanzapine-induced increases in the dorsolateral striatum were considerably smaller than those generated in the nucleus accumbens suggesting that at low, potentially therapeutic doses olanzapine may not generate significant extrapyramidal side effects. Olanzapine also increased the number of Fos-positive neurons in medical prefrontal cortex, an action unique to clozapine and a few other atypical antipsychotics. These findings are consistent with the hypothesis that olanzapine is an atypical antipsychotic in the sense that it does not produce significant extrapyramidal side-effects at low therapeutic doses. However, extrapyramidal side-effects at higher doses can be predicted by these results. Finally, olanzapine's actions in the medial prefrontal cortex may be predictive of a clozapine-like profile with respect to actions on negative symptoms in schizophrenia. Additional clinical

  19. Risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine

    NARCIS (Netherlands)

    Schillevoort, I; de Boer, A; Herings, R M; Roos, R A; Jansen, P A; Leufkens, H G

    2001-01-01

    OBJECTIVE: To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS. METHODS: Data were obtained from the PHARMO-database, containing filled prescriptions of 450,000 community-dwellin

  20. Olanzapine-induced tender pitting pre-tibial edema

    Directory of Open Access Journals (Sweden)

    Kaliaperumal Mathan

    2015-01-01

    Full Text Available Antipsychotic-induced edema is uncommonly encountered in clinical practice. We report a case of tender pitting pre-tibial edema with olanzapine in a woman with no medical comorbidities. The peculiar distribution of edema resulted in diagnostic confusion necessitating specific investigations. Eventually, the edema resolved following complete stoppage of the drug, but caused distress to the patient and the caregiver.

  1. Switch to quetiapine in antipsychotic agent-related hyperprolactinemia.

    Science.gov (United States)

    Keller, R; Mongini, F

    2002-12-01

    Novel antipsychotics (clozapine, risperidone, olanzapine, quetiapine) are effective in treating psychotic symptoms, also in neurological disease. Hyperprolactinemia is a side effect related to antipsychotics that can cause galactorrhea, gynecomastia, amenorrhea, anovulation, impaired spermatogenesis, decreased libido and sexual arousal, impotence, and anorgasmia, consequent to removal of tonic dopaminergic inhibition of prolactin secretion via hypothalamic dopaminergic receptor blockade in the tuberoinfundibolar tract. Hyperprolactinemia occurs more frequently during treatment with risperidone and olanzapine compared with clozapine and quetiapine. The therapeutic algorithm to antipsychotic-relatedhyperprolactinemia is the following: reduction in antipsychotic dose, addition of cabergoline, bromocriptine, amantadine, and/or switch to another antipsychotic. We propose switching to quetiapine in symptomatic hyperprolactinemia related to antipsychotics and describe five cases.

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

    DEFF Research Database (Denmark)

    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...

  3. Neuroleptic malignant syndrome induced by atypical antipsychotics.

    Science.gov (United States)

    Farver, Debra K

    2003-01-01

    A review of the English literature confirms that neuroleptic malignant syndrome (NMS) occurs with both traditional and atypical antipsychotic medications. Published reports of NMS induced by the traditional antipsychotics have given the practitioner valuable information on the prevention and treatment of this adverse effect. Case reports have also been published concerning NMS and clozapine, risperidone, olanzapine and quetiapine. By evaluating the case reports of atypical antipsychotic-induced NMS, valuable information may be obtained concerning similarities or differences from that induced by the traditional antipsychotics. The case reports of NMS with atypical antipsychotics were evaluated for diagnosis, age/sex of patient, risk factors, antipsychotic doses and duration of use, symptoms of NMS, and clinical course.

  4. Use of Antipsychotics in Children Is Criticized%阻止精神病药"标签外"用途

    Institute of Scientific and Technical Information of China (English)

    Gardiner Harris; 雪梅

    2008-01-01

    @@ Risperdal (risperidone) 和 Zyprexa (olanzapine)是两种近年来十分常用的精神障碍治疗药.随着近年美国被诊断出患有双相情感障碍的儿童数量突然增加,包括上述两种抗精神病药物在内的一系列药物如Seroquel (quetiapine)、Abilify (aripiprazole)和Geodon(ziprasidone)用于儿童的处方量也迅速上升.

  5. Preventing olanzapine-induced weight gain using betahistine: a study in a rat model with chronic olanzapine treatment.

    Directory of Open Access Journals (Sweden)

    Jiamei Lian

    Full Text Available Olanzapine is the one of first line antipsychotic drug for schizophrenia and other serious mental illness. However, it is associated with troublesome metabolic side-effects, particularly body weight gain and obesity. The antagonistic affinity to histamine H1 receptors (H1R of antipsychotic drugs has been identified as one of the main contributors to weight gain/obesity side-effects. Our previous study showed that a short term (2 weeks combination treatment of betahistine (an H1R agonist and H3R antagonist and olanzapine (O+B reduced (-45% body weight gain induced by olanzapine in drug-naïve rats. A key issue is that clinical patients suffering with schizophrenia, bipolar disease and other mental disorders often face chronic, even life-time, antipsychotic treatment, in which they have often had previous antipsychotic exposure. Therefore, we investigated the effects of chronic O+B co-treatment in controlling body weight in female rats with chronic and repeated exposure of olanzapine. The results showed that co-administration of olanzapine (3 mg/kg, t.i.d. and betahistine (9.6 mg/kg, t.i.d. significantly reduced (-51.4% weight gain induced by olanzapine. Co-treatment of O+B also led to a decrease in feeding efficiency, liver and fat mass. Consistently, the olanzapine-only treatment increased hypothalamic H1R protein levels, as well as hypothalamic pAMPKα, AMPKα and NPY protein levels, while reducing the hypothalamic POMC, and UCP1 and PGC-1α protein levels in brown adipose tissue (BAT. The olanzapine induced changes in hypothalamic H1R, pAMPKα, BAT UCP1 and PGC-1α could be reversed by co-treatment of O+B. These results supported further clinical trials to test the effectiveness of co-treatment of O+B for controlling weight gain/obesity side-effects in schizophrenia with chronic antipsychotic treatment.

  6. Antipsychotics dosage and antiparkinsonian prescriptions

    Directory of Open Access Journals (Sweden)

    Gasquet Isabelle

    2007-09-01

    Full Text Available Abstract Background To study the link between the dosage of several antipsychotics and the prescription of antiparkinsonians in an observational study. Methods In the context of a national naturalistic prospective observational study, a database containing all the prescriptions from 100 French psychiatrists during the year 2002 was analysed. The inclusion criteria were a diagnosis of schizophrenia or schizoaffective disorder and age over 18. The mean dosage of antipsychotics with and without antiparkinsonians was compared. Since there were multiple prescriptions for a given subject, generalised mixed linear models were also used to study the link between antiparkinsonian prescription and antipsychotic dosage. Results antiparkinsonians were prescribed to 32,9% of the patients. Two groups of antipsychotics were observed relating to differences in dosage when an antiparkinsonian was co prescribed or not : a first group, where the mean dosage was higher with antiparkinsonians (risperidone, amisulpride and haloperidol and a second group (clozapine, olanzapine, in which antiparkinsonian co prescription was not related to the dosage of antipsychotics. Conclusion As a conclusion, it can be said that it is important to consider the dosage and the type of antipsychotic in the treatment of patients suffering of schizophrenia, because neurological side effects are frequent and can impair quality of life. Moreover the prescription of antiparkinsonians can lead to different side effects such anticholinergic effects.

  7. Intramuscular Olanzapine – a UK case series of early cases

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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.

    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, clozapin

  10. 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, clozapin

  11. Postinjection Delirium/Sedation Syndrome with Olanzapine Depot Injection

    Science.gov (United States)

    Sarangula, Sadhvi Mythili; Mythri, Starlin Vijay; Sanjay, Y.; Reddy, M. S.

    2016-01-01

    After 1 year of introduction of olanzapine long-acting injectable (LAI) in India, many psychiatrists believe that it is a very affordable, well-tolerated, and effective second generation long-acting antipsychotic depot compared to not well tolerated but cheap first generation antipsychotic depots and to other second generation depots which are costly. However, reports of its possible adverse events in clinical settings are not yet published. We report what probably might be the first case of postinjection delirium/sedation syndrome (PDSS) in India. Although the occurrence is uncommon, incorrect understanding of this event may hinder the future use of the potentially useful olanzapine LAI. We review the available literature on the proposed diagnostic guidelines, mechanism of this event, precautions, and management of PDSS. PMID:27570354

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

    Directory of Open Access Journals (Sweden)

    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

  13. Evaluation of proximal therapeutic effect and distal social function restoration of olanzapine on schizophrenia patients%奥氮平对精神分裂症患者近期疗效及远期社会功能恢复效果评价

    Institute of Scientific and Technical Information of China (English)

    王长虹; 赵峥; 李晏; 潘苗; 刘旭

    2002-01-01

    Objective To evaluate the efficacy and prognosis of olanzapine in treatment of the schizophrenia. Methods A randomized controlled clinical study was performed to compare the efficacy and prognosis of olanzapine to that of chlorpromazine. 60 patients with schizophrenia were divided two groups. 32cases were treated with olanzapine. 28 cases were treated with chlorpromazine .Results The significant effect rate and effective rate on olanzapine group were 63% and 82% respectively ; which in chlorpromazine group were 32% and 50% .There were less side effects, and less recurrent rate in olanzapine. Conclusion Olanzapine is one of the safe and effective atypical antipsychotic for schizophrenia with significantly fewer side effects.

  14. Reducing olanzapine-induced weight gain side effect by using betahistine: a study in the rat model.

    Science.gov (United States)

    Deng, Chao; Lian, Jiamei; Pai, Nagesh; Huang, Xu-Feng

    2012-09-01

    Olanzapine is effective at treating multiple domains of schizophrenia symptoms. However, it induces serious metabolic side effects. Antipsychotic drug's antagonistic affinity to histamine H₁ receptors has been identified as a main contributor for weight gain/obesity side effects. This study therefore investigated whether a combined treatment of betahistine (a H₁ receptor agonist and H₃ receptor antagonist) could reduce the body weight/obesity induced by olanzapine. Female Sprague Dawley rats were treated orally with olanzapine (1 mg/kg, t.i.d.) and/or betahistine (2.67 mg/kg, t.i.d.), or vehicle for two weeks. Rats treated with olanzapine exhibited significant body weight gain and increased food intake. Co-treatment of olanzapine with betahistine significantly prevented (-45%) weight gain and reduced feeding efficiency compared to sole olanzapine treatment. Betahistine treatment alone had no effect on weight gain and food intake. Olanzapine reduced locomotor activity, but not betahistine. These findings demonstrate that olanzapine-induced body weight gain can partially be reduced by co-treatment with betahistine. Betahistine has H₃ receptor antagonistic effects to increase histamine release, which may augment its direct agonistic effects on H₁ receptors. These findings have important implications for clinical trials using betahistine to control antipsychotic-induced obesity side effects.

  15. Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity

    OpenAIRE

    Zhao, Changjiu; Li, Ming

    2012-01-01

    Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum Days 6–8, Sprague-Dawley mother rats were given a single injection of ster...

  16. The metabolic effects of olanzapine and topiramate in rats and humans

    NARCIS (Netherlands)

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

    2011-01-01

    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,

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

    NARCIS (Netherlands)

    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 mech

  18. Olanzapine-induced Fos expression in the rat forebrain; cross-tolerance with haloperidol and clozapine

    NARCIS (Netherlands)

    Sebens, JB; Koch, T; Ter Horst, GJ; Korf, J

    1998-01-01

    Acute administration of the atypical antipsychotic drug olanzapine (5 mg kg(-1) i.p.) increased the number of Fos-positive cells moderately in the prefrontal cortex and the striatum; more pronounced were the effects in the nucleus accumbens, the lateral septum, the hypothalamic paraventricular nucle

  19. The role of hypothalamic pathways in the metabolic side effects of Olanzapine

    NARCIS (Netherlands)

    Girault, E.M.

    2013-01-01

    Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side effects are currently unknown. In this thesis, we showed that both acute and chronic administration of Ola

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

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2014-06-01

    olanzapine-LAI and oral olanzapine. Conclusion: In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time. Results did not significantly differ between olanzapine-LAI and oral olanzapine. Keywords: antipsychotics, functioning, olanzapine long-acting injection, quality of life, schizophrenia

  1. Improvement of dumping syndrome and oversecretion of glucose-dependent insulinotropic polypeptide following a switch from olanzapine to quetiapine in a patient with schizophrenia.

    Science.gov (United States)

    Watanabe, Aiko; Fukui, Naoki; Suzuki, Yutaro; Motegi, Takaharu; Igeta, Hirofumi; Tsuneyama, Nobuto; Someya, Toshiyuki

    2015-01-01

    Among the most important adverse effects of antipsychotics is abnormal glucose metabolism, which includes not only hyperglycemia but hyperinsulinemia and hypoglycemia. We have previously described five patients who experienced hypoglycemia during treatment with antipsychotics. Thus, an anamnesis of gastric surgery, which often causes dumping syndrome, and treatment with antipsychotics may synergistically induce hypoglycemia. We describe here a patient with schizophrenia under treatment of olanzapine and an anamnesis of gastric surgery, who experienced late dumping syndrome, hyperinsulinemia and overactivation of glucose-dependent insulinotropic polypeptide. Dumping syndrome, however, was improved after the patient was switched from olanzapine to quetiapine.

  2. [Dementia with Lewy bodies; 2 patients with exacerbation due to an atypical antipsychotic, but with a favorable response to the cholinesterase inhibitor rivastigmine

    NARCIS (Netherlands)

    Scheepmaker, A.J.T.M.; Horstink, M.W.I.M.; Hoefnagels, W.H.L.; Strijks, F.E.

    2003-01-01

    In two patients, men aged 80 and 75 years with cognitive deterioration, hallucinations and parkinsonism, the clinical diagnosis 'dementia with Lewy bodies' was established. Treatment with an atypical antipsychotic, risperidone and olanzapine respectively, resulted in an exacerbation of the parkinson

  3. 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.

    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

  4. Metabolic side effects of antipsychotic agents: a prospective study in a teaching hospital.

    Directory of Open Access Journals (Sweden)

    Ankesh Barnwal

    2012-07-01

    Full Text Available Background: Antipsychotic drugs have propensity to produce side effects like extrapyramidal syndrome, hyperglycemia, lipid abnormalities and weight gain. As data from India related to this aspect are scarce, this study was carried out.Aims and Objectives: To study metabolic effects of antipsychotic drugs using biochemical parameters and to compare metabolic effects of different antipsychotic agents.Materials and methods: This was a prospective study of patients attending the psychiatry outpatient department from September 2007 to May 2008. Each patient enrolled was followed up for 12weeks or less till the antipsychotics were prescribed. Body weight,fasting blood glucose, fasting lipid profile were recorded at baseline and at subsequent visits.Results: Out of 45 patients, 33 completed the study. Bipolar disorder (31% was the most frequent diagnosis followed by brief psychotic disorder (22%, schizophrenia (20% and others.Olanzapine was the most frequently prescribed antipsychotic drug (56% followed by risperidone (24% and haloperidol (20%. 84% received single antipsychotic drug. After 12weeks of therapy all antipsychotics caused significant weight gain (p<0.001, olanzapine caused significant rise in fasting blood glucose (p<0.001 and serum cholesterol (p<0.001. All antipsychotics caused significant rise in serum triglyceride level (p<0.01 Conclusion: All antipsychotics can cause significant abnormalities in carbohydrate and lipid metabolism. Selection of antipsychotics, particularly the newer ones requires consideration of co morbidities like obesity, diabetes mellitus and dyslipidemias. During antipsychotic drug therapy periodic monitoring for metabolic abnormalities is advisable.

  5. Effects of intracerebroventricular (ICV) olanzapine on insulin sensitivity and secretion in vivo: an animal model.

    Science.gov (United States)

    Hahn, Margaret K; Chintoh, Araba; Remington, Gary; Teo, Celine; Mann, Steve; Arenovich, Tamara; Fletcher, Paul; Lam, Loretta; Nobrega, Jose; Guenette, Melanie; Cohn, Tony; Giacca, Adria

    2014-03-01

    The atypical antipsychotics (AAPs) have been associated with an increased risk of type 2 diabetes. While weight gain associated with AAPs is a risk factor for diabetes, preclinical work suggests that among these medications, olanzapine, when given peripherally in a single dose, causes pronounced effects on insulin sensitivity and secretion. Given a critical role of the hypothalamus in control of glucose metabolism, we examined the effect of central administration of olanzapine. Sprague-Dawley rats were treated with a single 75 μg intracerebroventricular (ICV) dose of olanzapine and tested using separate hyperinsulinemic-euglycemic and hyperglycemic clamps. Dosing of olanzapine was established based on inhibition of amphetamine-induced locomotion. In contrast to the single dosing peripheral paradigm, there was no effect of central olanzapine on insulin sensitivity, either with respect to hepatic glucose production or peripheral glucose uptake. Analogous to the peripheral model, a single ICV dose of olanzapine followed by the hyperglycemic clamp decreased insulin (p=0.0041) and C-peptide response (p=0.0039) to glucose challenge as compared to vehicle, mirrored also by a decrease in the steady state glucose infusion rate required to maintain hyperglycemia (p=0.002). In conclusion, we demonstrate novel findings that at least part of the effect of olanzapine on beta-cell function in vivo is central.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Use of antipsychotics in the treatment of depressive disorders

    Institute of Scientific and Technical Information of China (English)

    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.

  8. [Treatment of tics in Tourette syndrome with atypical antipsychotic drugs].

    Science.gov (United States)

    Sindø, Ingrid; Jørgensen, Jan Ib

    2002-08-05

    We reviewed articles in English dealing with research into the effect of atypical antipsychotic drugs on tic reduction in Tourette's syndrome. In Denmark, there are four registered atypical antipsychotic drugs; clozapine, sulpiride, olanzapine, and risperidone. The topic of interest is the effectiveness and side effects of these drugs as compared to the conventional antipsychotic, pimozide, which is today the preferred pharmacological treatment of Tourette's syndrome among the antipsychotics. The conclusion is that risperidone would be a good first-line antipsychotic drug for the treatment of Tourette's syndrome. It is as effective as pimozide, its side effect profile is overall much more favourable, and unlike pimozide it does not contain the risk of causing heart arrhythmia.

  9. 奥氮平与氟哌啶醇治疗老年性谵妄的随机对照观察%Olanzapine and haloperidol for senile delirium: A randomized controlled observation

    Institute of Scientific and Technical Information of China (English)

    胡华; 邓伟; 杨辉; 刘玉

    2006-01-01

    啶醇组次之,对照组起效最慢(P<0.01).结论:奥氮平与氟哌啶醇治疗老年性谵妄疗效相当,但奥氮平起效更快.%BACKGROUND: Delirium is an acute organic brain syndrome caused by various reasons, and it is common in elderly patients. Antipsychotics treatment is an important method to control delirium.OBJECTIVE: To observe the efficacy of new antipsychotic agent of olanzapine and the traditional antipsychotic agent of haloperidol in treating senile delirium.DESIGN: A randomized controlled observation. SETTING: Mental Health Center, the First Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 175 inpatients with senile delirium were selected from the First Affiliated Hospital of Chongqing University of Medical Sciences from September 2001 to September 2003, they were randomly divided into olanzapine treatment group (n=74), haloperidol treatment group (n=72) and a control group(n=29). There were 111 males (63.4%) and 64 females (36.6%). Delirium had occurred for a duration of 30 minutes to 17 days, with an average of (3.02±2.71) days. The enrolled patients were classified according to the etiological factors of delirium: metabolic (n=68), toxic (n=47), structural (n=25) and infectious (n=35).METHODS: Different treatments were used in different groups. Control group (n=29): The patients were only given somatic treatment aiming at delirium, and not any drug for central nervous system was used. Olanzapine group (n=74): Besides the somatic treatment aiming at delirium, the patients were given olanzapine (Zyprexa, produced by Eli Lilly and Company,5 mg/tablet) taken orally or sublingually (fasted patients), the initial dosage was 1.25-2.5 mg per day, and then adjusted to 1.25-20 mg per day. Haloperidol group (n=72): Besides the somatic treatment aiming at delirium, they were treated with intramuscular injection of haloperidol (2.5-10 mg per day). The effects were prospectively observed for 1 week.The scores were observed before enrollment

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

    DEFF Research Database (Denmark)

    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...

  11. Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.

    Science.gov (United States)

    Srivastava, Manish; Brito-Dellan, Norman; Davis, Mellar P; Leach, Marie; Lagman, Ruth

    2003-06-01

    Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed.

  12. Hematological Side Effects of Atypical Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  13. Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology.

    Science.gov (United States)

    Kotler, Moshe; Strous, Rael D; Reznik, Ilya; Shwartz, Sima; Weizman, Abraham; Spivak, Baruch

    2004-01-01

    Several recent studies, albeit limited in sample number, design and generalizability, have suggested that augmentation of atypical antipsychotic medication (such as clozapine and olanzapine) with sulpiride, a substituted benzamide antipsychotic medication, may play a role in the management of treatment-resistant psychotic conditions. The objective of this study was to investigate any change in clinical symptomatology or side-effect profile in treatment-resistant schizophrenia patients receiving sulpiride in addition to olanzapine. Seventeen patients with treatment-resistant chronic schizophrenia, who were receiving olanzapine monotherapy for at least 6 months before study commencement, were randomized in a 1:1 fashion to receive either adjunctive treatment with sulpiride (study group) or to continue their pre-study treatment with olanzapine with no medication augmentation (control group), each for a period of 8 weeks. Changes in measures of positive and negative symptoms, anxiety, depression and extrapyramidal symptoms were assessed at baseline and at 8 weeks. Study observations indicated no significant differences in the changes in positive or negative symptomatology between patients receiving a combined regimen of olanzapine with sulpiride (600 mg/ day) augmentation and controls. However, a significantly greater improvement of depressive symptomatology (P Depression) was noted in the sulpiride augmentation group. These data indicate improvement in depressive symptomatology with sulpiride augmentation of olanzapine in treatment-resistant chronic schizophrenia patients.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Olanzapine-induced Priapism in a Child with Asperger’s Syndrome

    Science.gov (United States)

    Bozkurt, Hasan; Şahin, Serkan

    2017-01-01

    Background: Priapism is a potentially painful and prolonged erection that occurs in the absence of any stimulation. Olanzapine has been reported to induce priapism in several adult cases with schizophrenia and/or mood disorders but very rarely reported in children. Case Report: 9-year-old male with Asperger’s Syndrome (AS) referred to our clinic with the complaints of inattention, hyperactivity and impulsivity. He was diagnosed with attention deficit hyperactivity disorder (ADHD) and given methylphenidate treatment which ameliorated his ADHD symptoms. He started to have severe loss of appetite after methylphenidate treatment so olanzapine 2.5 mg/day was added to cope with severe inappetence. However he experienced priapism after olanzapine and priapism resolved after ceasing the drug. His mother restarted olanzapine because he benefited from olanzapine. But the same episodes occurred soon after olanzapine again and his mother had to stop the medication. Conclusion: Because atypical antipsychotics are now widely used in children, unusual side effects such as priapism should be taken into consideration for the differential diagnosis. PMID:28251031

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

    Directory of Open Access Journals (Sweden)

    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

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

    OpenAIRE

    Albaugh, Vance L.; Judson, Jessica G.; She, Pengxiang; Lang, Charles H.; Maresca, Kevin P.; Joyal, John L.; Christopher J Lynch

    2010-01-01

    Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; while 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...

  18. 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...

  19. Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of the Dopamine D-2 Receptor Occupancy of Olanzapine in Rats

    NARCIS (Netherlands)

    Johnson, Martin; Kozielska, Magdalena; Reddy, Venkatesh Pilla; Vermeulen, An; Li, Cheryl; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    2011-01-01

    A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol

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

    DEFF Research Database (Denmark)

    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...

  1. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Severe tardive dystonia on low dose short duration exposure to atypical antipsychotics: Factors explored

    Directory of Open Access Journals (Sweden)

    Nilanjan C Chandra

    2017-01-01

    Full Text Available Tardive dystonia (TD is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics.

  5. Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study.

    Science.gov (United States)

    Yang, S-Y; Kao Yang, Y-H; Chong, M-Y; Yang, Y-H; Chang, W-H; Lai, C-S

    2007-04-01

    To compare the prevalence of extrapyramidal syndrome (EPS) between the first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), the co-prescribing rate of anti-Parkinson drugs (APDs) of each antipsychotic drug was analyzed using population database. Fourteen antipsychotics had been prescribed during the 5-year study period. Among the SGAs, quetiapine had the lowest crude co-prescribing rate of APDs (27.09%), whereas risperidone had the highest rate (66.50%). Among the FGAs, thioridazine and loxapine had the lowest (60.99%) and highest rates (96.35%), respectively. The rankings of the co-prescribing rate of APDs among antipsychotics, in increasing order, were quetiapine, clozapine, olanzapine, thioridazine, zotepine, chlorpromazine, risperidone, sulpiride, clotiapine, flupentixol, haloperidol, zuclopentixol, trifluoperazine, and loxapine. The results indicate that the risk of EPS appears to be lower in SGAs than in FGAs; however, the considerably high rate of EPS in some of the newer generation of antipsychotics warrants clinical attention.

  6. Severe Tardive Dystonia on Low Dose Short Duration Exposure to Atypical Antipsychotics: Factors Explored

    Science.gov (United States)

    Chandra, Nilanjan C.; Sheth, Shabina A.; Mehta, Ritambhara Y.; Dave, Kamlesh R.

    2017-01-01

    Tardive dystonia (TD) is a serious side effect of antipsychotic medications, more with typical antipsychotics, that is potentially irreversible in affected patients. Studies show that newer atypical antipsychotics have a lower risk of TD. As a result, many clinicians may have developed a false sense of security when prescribing these medications. We report a case of 20-year-old male with hyperthymic temperament and borderline intellectual functioning, who developed severe TD after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine. The goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features, hyperthymic temperament, or borderline intellectual functioning suggestive of organic brain damage, who are more prone to develop adverse effects such as TD and monitor the onset of TD in patients taking atypical antipsychotics.

  7. Influence of olanzapine on QT variability and complexity measures of heart rate in patients with schizophrenia.

    Science.gov (United States)

    Bär, Karl-Jürgen; Koschke, Mandy; Berger, Sandy; Schulz, Steffen; Tancer, Manuel; Voss, Andreas; Yeragani, Vikram K

    2008-12-01

    Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability. This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients. However, the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated, applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias. We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls. New nonlinear parameters (approximate entropy, compression entropy, fractal dimension) of heart rate variability and also the QT-variability index were calculated. In accordance with previous results, we have observed reduced complexity of heart rate regulation in untreated patients. Furthermore, the QT-variability index was significantly increased in unmedicated patients, indicating increased repolarization lability. Reduction of the heart rate regulation complexity after olanzapine treatment was seen, as measured by compression entropy of heart rate. No change in QT variability was observed after treatment. This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction. Olanzapine treatment seems to have very little additional impact in regard to the QT variability. However, the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function, which may increase the risk for cardiac mortality. Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics.

  8. Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

    Science.gov (United States)

    Molina, Vicente; Gispert, Juan D; Reig, Santiago; Pascau, Javier; Martínez, Raúl; Sanz, Javier; Palomo, Tomás; Desco, Manuel

    2005-01-01

    The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

  9. The impact of antipsychotic polytherapy costs in the public health care in Sao Paulo, Brazil.

    Directory of Open Access Journals (Sweden)

    Denise Razzouk

    Full Text Available 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

  10. 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

  11. Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting.

    Science.gov (United States)

    Navari, Rudolph M

    2014-01-05

    Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. Olanzapine has five times the affinity for 5-HT2 receptors than D2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D2, 5-HT2c, and 5-HT3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.

  12. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs.

    Science.gov (United States)

    Trollor, Julian N; Chen, Xiaohua; Sachdev, Perminder S

    2009-01-01

    Neuroleptic malignant syndrome (NMS) is a rare but potentially severe idiosyncratic adverse reaction usually seen in the context of treatment with antipsychotic drugs. Although NMS is historically associated with the classic or 'typical' antipsychotic drugs, it is also a potential adverse effect of atypical antipsychotic drugs. The widespread use of atypical antipsychotic drugs highlights the need to examine the data relating to the symptomatology, diagnosis, classification and management of NMS with these newer agents. We used MEDLINE and EMBASE to identify NMS case reports and systematic reviews published to June 2008 related to the atypical antipsychotic drugs clozapine, olanzapine, risperidone, paliperidone, aripiprazole, ziprasidone, amisulpride and quetiapine. Case reports and reviews were systematically examined. Our review suggests that, in general, NMS associated with atypical antipsychotic drugs manifests in a typical manner. One notable exception is clozapine-induced NMS, which appears less likely to manifest with extrapyramidal features, including rigidity and tremor. The available literature highlights the divergence of opinion relating to the core diagnostic features of NMS and its conceptualization as a categorical versus dimensional disorder. Both these issues have relevance for the identification of atypical or milder forms of NMS, which are sometimes seen with atypical antipsychotic drugs.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    Roke, Y.; van Harten, P. N.; 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, clozapine, ziprasidone, and quetiapine. Twenty-nine studies were selected after a literature search in the English Medline/Embase/Psychinfo/EBM databases (1965 to August, 2008). RESULTS: All antipsychotics...

  15. Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2016-04-01

    Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental

  16. The orexin-1 receptor antagonist SB-334867 blocks the effects of antipsychotics on the activity of A9 and A10 dopamine neurons: implications for antipsychotic therapy.

    Science.gov (United States)

    Rasmussen, Kurt; Hsu, Mei-Ann; Yang, Yili

    2007-04-01

    Antipsychotic drugs alter the activity of dopamine neurons in the ventral tegmental area (A10) and substantia nigra pars compacta (A9). As there is a dense projection of orexin neurons from the lateral hypothalamus to A10 dopaminergic neurons, and some antipsychotics have been shown to increase the expression of c-fos in orexin-containing cells in the hypothalamus, we hypothesized that stimulation of orexin receptors plays a role in the effects of antipsychotics on the activity of A9 and A10 dopamine cells. Single-unit recordings in anesthetized rats demonstrated the central effects of the selective orexin-1 receptor antagonist SB-334867 (2 mg/kg, intravenous), as it reversed the excitatory effects of orexin-A administration (6 microg, intracerebroventricular) on the activity of locus coeruleus (LC) cells. Recordings from midbrain dopamine neurons showed that acute administration of SB-334867 alone did not alter the number of spontaneously active A9 or A10 cells, but did reverse: (1) the increase in the number of spontaneously active A9 and/or A10 dopamine cells caused by the acute administration of haloperidol (1 mg/kg, subcutaneous) or olanzapine (10 mg/kg, s.c.) and (2) the decrease in the number of spontaneously active A9 and/or A10 dopamine cells caused by the chronic administration of haloperidol (1 mg/kg/day x 21 days, s.c.) or olanzapine (10 mg/kg/day x 21 days, s.c.). However, SB-334867 did not block a different electrophysiological effect of olanzapine, as it did not block the olanzapine-induced activation of LC cells. These results indicate that activation of orexin-1 receptors plays an important role on the effects of antipsychotic drugs on dopamine neuronal activity and may play an important role in the clinical effects of antipsychotic drugs.

  17. Efficacy of amisulpride and olanzapine for negative symptoms and cognitive impairments: An open-label clinical study

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    Subodh Kumar

    2014-01-01

    Full Text Available Background: Negative symptoms and diminished cognitive ability are also considered as core features of schizophrenia. There are many studies in which negative symptoms and cognitive impairments are individually treated with atypical antipsychotic in comparison with either a placebo or a typical antipsychotic. There is paucity of studies comparing the efficacy of olanzapine and amisulpride on improvement of negative symptoms and cognitive impairments. Aim: To examine the effectiveness of amisulpride and olanzapine in treatment of negative symptoms and cognitive impairments in schizophrenia. Materials and Methods: Total 40 adult inpatients diagnosed as schizophrenia fulfilling inclusion/exclusion criteria were included in the study with their informed consent. These patients were recruited consecutively to one of the two drug regimen group, i.e. tab Amisulpride (100-300 mg/day and tab Olanzapine (10-20 mg. Patients were evaluated on day 0 and day 60 with various rating scales like Scale for the Assessment of Negative Symptoms (SANS, Scale for the Assessment of Positive Symptoms (SAPS, Schizophrenia Cognition Rating Scale (SCoRS, Brief Psychiatric Rating Scale (BPRS, Calgary Depression Scale for Schizophrenia (CDSS, and three different scales to measure drug side effects. Results: The mean SANS score in amisulpride and olanzapine group at day 0 and day 60 were 83.89 (±12.67 and 21.00 (±11.82 and 84.40 (±13.22 and 26.75 (±12.41, respectively. The mean rank of SCoRS global in amisulpride and olanzapine group at day 0 and day 60 were 4.78 (±1.13 and 2.78 (±0.63 and 4.85 (±1.18 and 3.30 (±1.12, respectively. The percentage improvement in SANS, SAPS, SCoRS interviewer, and SCoRS global in amisulpride group are 74.96%, 13.36%, 54.14%, and 42.00%, respectively. Similarly in olanzapine group percentage improvement in SANS, SAPS, SCoRS interviewer, and SCoRS global are 68.30%, 30.28%, 35.22%, and 31.95%, respectively. There is significant

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. 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.

  1. Efficacy, tolerability and cost effectiveness of zotepine versus olanzapine in patients of acute schizophrenia

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    Saroj Kothari

    2013-10-01

    Full Text Available Background: Schizophrenia is a functional psychosis with severe personality changes and thought disorders without cerebral damage. No reports are available in literature regarding efficacy and tolerability of atypical antipsychotic drug zotepine over olanzapine a preferred drug worldwide for the treatment of schizophrenia. Therefore, present study is undertaken to evaluate efficacy, tolerability and cost effectiveness of zotepine over olanzapine in patients suffering from schizophrenia. Methods: A prospective, randomized, single blind, parallel, 6 weeks clinical study was conducted on a total of 112 patients, of schizophrenia attending psychiatry outpatient department at G. R. Medical College, Gwalior, India randomized into two groups (56 in each. Patients received either olanzapine (10-20mg or zotepine (75-150mg per day for a period of 6 week. Efficacy was measured by Positive and Negative Syndrome Scale (PANSS and Clinical Global Impression (CGI scale whereas tolerability was measured by dropout rate and frequency of adverse effects. Cost effectiveness was calculated in terms of cost incurred for improvement at the end of treatment period. Results: Both the drugs showed significant (P.0.05. Olanzapine showed significantly better (P0.05 between the two groups. Incidence of akathisia and drop out (16% and 23% with zotepine were significant (P<0.05 as compared to olanzapine (2% and 11% respectively. Conclusions: Though the efficacy of both the drugs is comparable, olanzapine appears to have better tolerability and cost effectiveness than zotepine in patients of schizophrenia. [Int J Basic Clin Pharmacol 2013; 2(5.000: 577-582

  2. 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.

  3. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum

    NARCIS (Netherlands)

    Westerink, B.H.C.; Kawahara, Y; de Boer, P; Geels, C; de Vries, J.B; Wikström, H.V; van Kalkeren, A; van Vliet, B; Kruse, C.H; Long, S.K

    2001-01-01

    Dose-effect curves were established for the effects of the antipsychotic drugs haloperidol, clozapine, olanzapine, risperidone and ziprasidone on extracellular levels of dopamine and noradrenaline in the medial prefrontal cortex, and of dopamine in the striatum. Haloperidol was more effective in sti

  4. 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

  5. Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics

    DEFF Research Database (Denmark)

    Olsen, Christina Kurre; Brennum, Lise Tøttrup; Kreilgaard, Mads

    2008-01-01

    avoidance response behaviour in rodents, correlate with clinically relevant plasma exposure for the classical antipsychotic drug haloperidol and four second generation antipsychotics: sertindole, clozapine, risperidone and olanzapine, including selected metabolites. In order to confirm the validity...... receptor occupancy required to suppress conditioned avoidance response behaviour according to EC50 measurements to be sertindole (+dehydrosertindole)=dehydrosertindole=paliperidone (the metabolite of risperidone)=haloperidol=olanzapine>risperidone>clozapine. Overall, a good agreement was observed between...... 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...

  6. Chronic betahistine co-treatment reverses olanzapine's effects on dopamine D₂ but not 5-HT2A/2C bindings in rat brains.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2015-01-02

    Olanzapine is widely prescribed for treating schizophrenia and other mental disorders, although it leads to severe body weight gain/obesity. Chronic co-treatment with betahistine has been found to significantly decrease olanzapine-induced weight gain; however, it is not clear whether this co-treatment affects the therapeutic effects of olanzapine. This study investigated the effects of chronic treatment of olanzapine and/or betahistine on the binding density of the serotonergic 5-HT2A (5-HT2AR) and 5-HT2C (5-HT2CR) receptors, 5-HT transporter (5-HTT), and dopaminergic D₂ receptors (D₂R) in the brain regions involved in antipsychotic efficacy, including the prefrontal cortex (PFC), cingulate cortex (Cg), nucleus accumbens (NAc), and caudate putamen (CPu). Rats were treated with olanzapine (1 mg/kg, t.i.d.) or vehicle for 3.5 weeks, and then olanzapine treatment was withdrawn for 19 days. From week 6, the two groups were divided into 4 groups (n=6) for 5 weeks' treatment: (1) olanzapine-only (1 mg/kg, t.i.d.), (2) betahistine-only (9.6 mg/kg, t.i.d.), (3) olanzapine and betahistine co-treatment (O+B), and (4) vehicle. Compared to the control, the olanzapine-only treatment significantly decreased the bindings of 5-HT2AR, 5-HT2CR, and 5-HTT in the PFC, Cg, and NAc. Similar changes were observed in the rats receiving the O+B co-treatment. The olanzapine-only treatment significantly increased the D₂R binding in the Cg, NAc, and CPu, while the betahistine-only treatment reduced D₂R binding. The co-treatment of betahistine reversed the D₂R bindings in the NAc and CPu that were increased by olanzapine. Therefore, chronic O+B co-treatment has similar effects on serotonin transmission as the olanzapine-only treatment, but reverses the D₂R that is up-regulated by chronic olanzapine treatment. The co-treatment maintains the therapeutic effects of olanzapine but decreases/prevents the excess weight gain.

  7. Olanzapine-induced eosinophilic pleuritis

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    Matthew Evison

    2015-01-01

    Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion.

  8. Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia.

    Science.gov (United States)

    Molina, Vicente; Sanz, Javier; Benito, Carlos; Palomo, Tomás

    2004-07-01

    The study of cerebral variables associated with response to neuroleptics holds interest from both theoretical and clinical points of view. To date, no studies have aimed to identify predictors of response to olanzapine based on cerebral measurements. Here, we used magnetic resonance to assess the relationship between volumes of the prefrontal (dorsolateral and orbitofrontal) and temporal (temporal lobe and hippocampus) cortical regions and ventricles and, on the other hand, the response to olanzapine in 16 schizophrenic patients. Data from 42 healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values, given individual age and intracranial volume. Residuals thus represent the effect of illness on regional measurements. The association between clinical change and those residuals was calculated separately for the positive, negative and total scores from the Positive and Negative Syndrome Scale (PANSS). There was a significant direct association between the degree of orbitofrontal atrophy and the improvement of positive symptoms with olanzapine. No predictors were found for change in the negative dimension. A trend was found for patients with larger ventricles to show a greater global decrease in total PANSS scores. Neither age nor duration of illness explained a significant proportion of the symptom improvement. This result, together with others from the literature, supports the idea that atypical antipsychotics may offer some benefit to patients with significant regional atrophy, and this may have implications for the choice of antipsychotic in clinical practice.

  9. Neuroanatomical substrates of the disruptive effect of olanzapine on rat maternal behavior as revealed by c-Fos immunoreactivity.

    Science.gov (United States)

    Zhao, Changjiu; Li, Ming

    2012-12-01

    Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum days 6-8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0mg/kg, sc). Maternal behavior was tested 2h later, after which rats were sacrificed and brain tissues were collected. Ten brain regions that were either implicated in the action of antipsychotic drugs and/or in the regulation of maternal behavior were examined for c-Fos immunoreactivity. Acute olanzapine treatment dose-dependently disrupted various components of maternal behavior (e.g., pup retrieval, pup licking, nest building, crouching) and increased c-Fos immunoreactivity in the medial prefrontal cortex (mPFC), nucleus accumbens shell and core (NAs and NAc), dorsolateral striatum (DLSt), ventral lateral septum (LSv), central amygdala (CeA) and ventral tegmental area (VTA), important brain areas generally implicated in the incentive motivation and reward processing. In contrast, olanzapine treatment did not alter c-Fos in the medial preoptic nucleus (MPN), ventral bed nucleus of the stria terminalis (vBST) and medial amygdala (MeA), the core brain areas directly involved in the mediation of rat maternal behavior. These findings suggest that olanzapine disrupts rat maternal behavior primarily by suppressing incentive motivation and reward processing via its action on the mesocorticolimbic dopamine systems, other limbic and striatal areas, but not by disrupting the core processes involved in the mediation of maternal behavior in particular.

  10. Cognitive effects of atypical antipsychotic drugs in first-episode drug-na?ve schizophrenic patients

    Institute of Scientific and Technical Information of China (English)

    Juan Wang; Maorong Hu; Xiaofeng Guo; Renrong Wu; Lehua Li; Jingping Zhao

    2013-01-01

    Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-na?ve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.

  11. The role of antipsychotics in the management of fibromyalgia.

    Science.gov (United States)

    Calandre, Elena P; Rico-Villademoros, Fernando

    2012-02-01

    Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2-4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the α(2)δ ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease. First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and

  12. NOVEL ATYPICAL ANTIPSYCHOTIC AGENTS

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    Vijay Vinay

    2011-05-01

    Full Text Available Antipsychotics are a group of drugs commonly but not exclusively used to treat psychosis. Antipsychotic agents are grouped in two categories: Typical and Atypical antipsychotics. The first antipsychotic was chlorpromazine, which was developed as a surgical anesthetic. The first atypical anti-psychotic medication, clozapine, was discovered in the 1950s, and introduced in clinical practice in the 1970s. Both typical and atypical antipsychotics are effective in reducing positive and negative symptoms of schizophrenia. Blockade of D2 receptor in mesolimbic pathway is responsible for antipsychotic action. Typical antipsychotics are not particularly selective and also block Dopamine receptors in the mesocortical pathway, tuberoinfundibular pathway, and the nigrostriatal pathway. Blocking D2 receptors in these other pathways is thought to produce some of the unwanted side effects. Atypical antipsychotics differ from typical psychotics in their "limbic-specific" dopamine type 2 (D2-receptor binding and high ratio of serotonin type 2 (5-HT2-receptor binding to D2. Atypical antipsychotics are associated with a decreased capacity to cause EPSs, TD, narcoleptic malignant syndrome, and hyperprolactinemia. Atypical antipsychotic agents were developed in response to problems with typical agents, including lack of efficacy in some patients, lack of improvement in negative symptoms, and troublesome adverse effects, especially extrapyramidal symptoms (EPSs and tardive dyskinesia (TD.

  13. Fever development in neuroleptic malignant syndrome during treatment with olanzapine and clozapine.

    Science.gov (United States)

    Szota, Anna; Ogłodek, Ewa; Araszkiewicz, Aleksander

    2013-01-01

    Neuroleptic malignant syndrome (NMS) is the most dangerous life-threatening complication of antipsychotic medication. It's development is connected with the blockade of dopaminergic transmission (D2 receptors) in the nigrostriatal system of the brain. Fever is one of the main symptoms of this syndrome and it's elevation is due to the activation of the immune system. Numerous studies report that treatment with clozapine (doses 37.5-600 mg) or olanzapine (doses 10-25 mg) or the use of these drugs in polytherapy cause pyrexia between 37.8-40.6 °C. Additionally, levels of proinflammatory interleukins such as IL-6, IL-1,TNF-α were increased. The aim of this article is to describe how olanzapine and clozapine influence fever development in NMS, in relation to the dose of the drug taken by schizophrenic patients including changes in immunological system.

  14. Bilateral lesions of the entorhinal cortex differentially modify haloperidol- and olanzapine-induced c-fos mRNA expression in the rat forebrain.

    Science.gov (United States)

    Seillier, A; Coutureau, E; Thiriet, N; Herbeaux, K; Zwiller, J; Di Scala, G; Will, B; Majchrzak, M

    2003-08-01

    Lesions of the entorhinal cortex are now an accepted model for mimicking some of the neuropathological aspects of schizophrenia, since evidence has accumulated for the presence of cytoarchitectonic abnormalities within this cortex in schizophrenic patients. The present study was undertaken to address the functional consequences of bilateral entorhinal cortex lesions on antipsychotic-induced c-fos expression. After a 15-day recovery period, the effect of a typical antipsychotic, haloperidol (1 mg/kg), on c-fos mRNA expression was compared with that of an atypical one, olanzapine (10 mg/kg), in both sham-lesioned and entorhinal cortex-lesioned rats. In sham-lesioned rats, both haloperidol and olanzapine induced c-fos expression in the caudal cingulate cortex, dorsomedial and dorsolateral caudate-putamen, nucleus accumbens core and shell and lateral septum. In addition, olanzapine, but not haloperidol, increased c-fos expression within the central amygdala. In entorhinal cortex-lesioned rats, haloperidol-induced c-fos expression was markedly reduced in most areas. In contrast, the olanzapine-induced c-fos expression was not altered in the nucleus accumbens shell and lateral septum of the lesioned rats. These findings reveal that entorhinal cortex lesions affect c-fos expression in a compound- and regional-dependent manner. Our results further emphasize the importance of the exploration of the mechanisms of action of antipsychotic drugs in the context of an associated cortical pathology.

  15. Postmortem redistribution of olanzapine following intramuscular administration of olanzapine pamoate in dogs.

    Science.gov (United States)

    Johnson, Jason T; Everly, Amy G; Kpakima, Felicia E Frazier; Detke, Holland C

    2015-12-01

    The potential for postmortem redistribution of olanzapine was investigated in beagle dogs. Olanzapine pamoate monohydrate was administered once every 14 days by intramuscular injection for 3 months to fed male dogs (n=15) at a dose of 20 mg/kg olanzapine (equivalent to 46 mg/kg olanzapine pamoate monohydrate). Blood samples were collected after the fifth (Day 57) and sixth (Day 71) doses to determine olanzapine and N-oxide olanzapine concentrations. On Day 71 at 72 h postdose, dogs were euthanized and placed on their backs without additional manipulation and held for postmortem blood, urine, and tissue collection at room temperature for up to 168 h postdose (96 h after euthanasia). Concentrations of olanzapine and N-oxide olanzapine were determined by liquid chromatography-mass spectroscopy/mass spectroscopy (LC-MS/MS). Postmortem olanzapine concentrations in blood increased up to seven-fold compared to the last quantified antemortem blood concentration. Olanzapine concentrations in vein tissue samples (surrogates for peripheral blood) also increased, whereas other tissue concentrations, such as myocardium, lung, liver, and kidney decreased over the postmortem period. An increase in blood concentration of olanzapine after death was observed in all but one animal, suggesting that postmortem redistribution may occur in dogs following biweekly intramuscular administration of olanzapine pamoate monohydrate. The rise in olanzapine concentrations in blood after death in this study may potentially be attributed to diffusion from multiple tissues to blood and, to a lesser extent, reduction of the N-oxide olanzapine metabolite back to olanzapine. However, the generalizability of these results to humans cannot be confirmed by the present study.

  16. 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.

  17. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

    Science.gov (United States)

    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

  18. Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview.

    Science.gov (United States)

    Pompili, Maurizio; Baldessarini, Ross J; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

    2016-10-11

    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.

  19. Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects.

    Science.gov (United States)

    Jafari, Somayeh; Fernandez-Enright, Francesca; Huang, Xu-Feng

    2012-02-01

    Antipsychotic drugs have various neuropharmacological properties as a result of their structural diversity. Despite their therapeutic benefits, most of the prescribed atypical antipsychotics can induce severe side effects, including weight gain, type II diabetes mellitus, and cardiovascular diseases. Among the developed atypical antipsychotic agents, tetracyclic dibenzodiazepine and thienobenzodiazepine compounds, particularly clozapine and olanzapine, are associated with the greatest weight gain and metabolic disturbances. However, the unique chemical structure of these compounds causes the low risk of side effects reported for typical antipsychotics (e.g. extrapyramidal symptoms and tardive dyskinesia). This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure-activity relationship studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H(1) receptors may significantly advance schizophrenia therapy.

  20. Comparative Cytochrome P450 In Vitro Inhibition by Atypical Antipsychotic Drugs

    OpenAIRE

    Guillermo Gervasini; Caballero, Maria J.; Carrillo, Juan A.; Julio Benitez

    2013-01-01

    The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5  μ M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1′-hydroxybufuralol (IC50 range, 3.5–25.5  μ M). Olanzapine inhibited CYP3A-catalyze...

  1. A suspected case of olanzapine induced hyponatremia

    Directory of Open Access Journals (Sweden)

    Ajay Kumar Bakhla

    2014-01-01

    Full Text Available Here we report a case of a 63-year-old male diagnosed with recurrent depressive disorder and current episode of severe depression with psychotic symptoms, developed hyponatremia soon after addition of olanzapine and increasing the dose of escitalopram. A possible causality association was established with olanzapine, and the possible etiological reasons of this clinically significant risk were discussed.

  2. Antipsychotic-induced hyperprolactinemia.

    Science.gov (United States)

    Bostwick, Jolene R; Guthrie, Sally K; Ellingrod, Vicki L

    2009-01-01

    Use of antipsychotic agents has been associated with hyperprolactinemia, or elevated prolactin levels; this hormonal abnormality can interfere with the functioning of reproductive, endocrine, and metabolic systems. As antipsychotic agents are increasingly used for both United States Food and Drug Administration-approved and nonapproved indications, many individuals are at risk for developing antipsychotic-induced hyperprolactinemia. First-generation antipsychotics pose the greatest risk of causing this adverse effect; however, second-generation antipsychotics, particularly risperidone and paliperidone, also often increase prolactin secretion. Hyperprolactinemia has short- and long-term consequences that can seriously affect quality of life: menstrual disturbances, galactorrhea, sexual dysfunction, gynecomastia, infertility, decreased bone mineral density, and breast cancer. Although many of these are definitively connected to elevated prolactin levels, some, such as breast cancer, require further study. Both clinicians and patients should be aware of hyperprolactinemia-associated effects. To prevent or alleviate the condition, tailoring an antipsychotic drug regimen to each individual patient is essential. In addition, the risk of hyperprolactinemia can be minimized by using the lowest effective dose of the antipsychotic agent. If the effects of prolactin are evident, the drug can be changed to another agent that is less likely to affect prolactin levels; alternatively, a dopamine agonist may be added, although this may compromise antipsychotic efficacy. Additional research is needed to clarify the appropriate level of monitoring, the long-term effects, and the optimal treatment of antipsychotic-induced hyperprolactinemia.

  3. 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

  4. Pharmacogenetics of second-generation antipsychotics.

    Science.gov (United States)

    Brennan, Mark D

    2014-04-01

    This review considers pharmacogenetics of the so called 'second-generation' antipsychotics. Findings for polymorphisms replicating in more than one study are emphasized and compared and contrasted with larger-scale candidate gene studies and genome-wide association study analyses. Variants in three types of genes are discussed: pharmacokinetic genes associated with drug metabolism and disposition, pharmacodynamic genes encoding drug targets, and pharmacotypic genes impacting disease presentation and subtype. Among pharmacokinetic markers, CYP2D6 metabolizer phenotype has clear clinical significance, as it impacts dosing considerations for aripiprazole, iloperidone and risperidone, and variants of the ABCB1 gene hold promise as biomarkers for dosing for olanzapine and clozapine. Among pharmacodynamic variants, the TaqIA1 allele of the DRD2 gene, the DRD3 (Ser9Gly) polymorphism, and the HTR2C -759C/T polymorphism have emerged as potential biomarkers for response and/or side effects. However, large-scale candidate gene studies and genome-wide association studies indicate that pharmacotypic genes may ultimately prove to be the richest source of biomarkers for response and side effect profiles for second-generation antipsychotics.

  5. Antipsychotic polypharmacy in a regional health service: a population-based study

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    Bernardo Miguel

    2012-05-01

    Full Text Available Abstract Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain, focusing on the use of clozapine and long-acting injections (LAI. Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA from the Anatomical Therapeutic Chemical classification (ATC code N05A (except lithium were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9% corresponded to an antipsychotic combination, 47,386 (66.7% to monotherapy and 13,763 (19.4% to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1% and oral risperidone (36.4% were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8% revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%. Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%. A total of 3.800 patients (5.4% were given LAI antipsychotics, and 2.662 of these (70.1% were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine.

  6. Diabetic control and atypical antipsychotics: a case report

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    Gaston Romina

    2008-05-01

    Full Text Available Abstract Introduction People with schizophrenia are at increased risk of developing metabolic disturbances. This risk may be further exacerbated by the use of antipsychotic agents. Research is still ongoing to determine the metabolic impact of antipsychotics on glucose regulation. In this case report we review some of the possible mechanisms of action of antipsychotic medication on glucose regulation. Case presentation We present the case of a 50-year-old man diagnosed with paranoid schizophrenia who developed type 2 diabetes mellitus whilst on treatment with second generation antipsychotics (SGA. His diabetes was controlled by a combination of antidiabetic drugs that were associated with his psychotropic treatment. Due to deterioration in his mental state, the patient was admitted on two occasions to a psychiatric unit during which his prescribed medication (olanzapine and risperidone was discontinued and changed to aripiprazole. On both occasions, the patient suffered hypoglycaemic episodes and his antidiabetic treatment had to be adjusted accordingly. The patient did not require any antidiabetic treatment whilst on aripiprazole during the follow up period. Conclusion Clinicians face regular dilemmas in trying to find the right balance between achieving control over a patient's mental illness and reducing any adverse effects associated with the prescribed medication. In patients receiving concomitant antidiabetic therapy, caution should be exercised when changing from one SGA to another. Whilst more longitudinal data are required, a trial of alternative SGAs, including aripiprazole in those developing type 2 diabetes and impaired glucose tolerance may be a worthwhile therapeutic option.

  7. 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.

  8. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Directory of Open Access Journals (Sweden)

    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

  9. Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions.

    Science.gov (United States)

    Iasevoli, Felice; Fiore, Germano; Cicale, Maria; Muscettola, Giovanni; de Bartolomeis, Andrea

    2010-05-15

    Homer1a and Yotiao are two post-synaptic density proteins at the crossroad of dopamine-glutamate neurotransmission. Homer1a has been implicated in the pathophysiology of schizophrenia and is differentially induced by typical and atypical antipsychotics, perhaps according to their dopaminergic profile. Yotiao has been involved in glutamate and dopamine post-synaptic signalling. Here, we seek to determine whether Homer1a and Yotiao might be implicated in post-synaptic response to antipsychotics with affinity to different dopamine D(2) receptors: haloperidol (0.8mg kg(-1)), risperidone (3mg kg(-1)), olanzapine (2.5mg kg(-1)) and (-)-sulpiride (50mg kg(-1)). Homer1a expression was significantly induced by haloperidol compared to vehicle and to atypical antipsychotics in almost all striatal sub-regions. Atypical antipsychotics induced the gene in the lateral putamen and in the core of the accumbens only. All antipsychotics, with the exclusion of sulpiride, elicited a dorsolateral-to-ventromedial distribution pattern of Homer1a expression. No significant induction was detected for Yotiao. These results suggest that the quantitative and topographical pattern of Homer1a expression may putatively be related to antipsychotics affinity and/or occupancy at dopamine D(2) receptors.

  10. Predictors of effect of atypical antipsychotics on speech

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    Preeti Sinha

    2015-01-01

    Full Text Available Background: Most of the studies have looked into the effect of typical antipsychotics on speech secondary to tardive dyskinesia. Aims: This study was aimed to explore the factors predicting the effect of atypical antipsychotic medications on the production of speech. Materials and Methods: One hundred and forty patients on stable regimen of three or more months on risperidone (92, olanzapine (28, aripiprazole (14, and clozapine (6 were recruited for the study. Speech was assessed by maximum phonation duration task, s/z ratio, diadochokinetic task, acoustic analysis and Frenchay Dysarthria Assessment (FDA. Extrapyramidal symptoms (EPS were assessed by Simpson Angus scale. Statistical Analysis: Spearman correlation analysis was carried out to find the association between speech parameters and continuous variables. Effect of EPS, duration and dose of antipsychotic treatment on speech parameters was compared using Mann-Whitney test. Results: The risperidone group differ from other antipsychotics groups significantly in s/z ratio (0.07, FDA-total (0.23 and FDA-reflex (0.25. People who took antipsychotic for more than 2 years had lower score of FDA-palate (P = 0.042, and FDA-respiratory (P = 0.04 and higher values in noise-harmonic ratio (P = 0.011 and maximum /fundamental frequency (MFF for males (P = 0.02. Effect of EPS was seen on MFF for males (spearman correlation coefficient = 0.34 and on almost all sections of FDA (spearman correlation coefficients = -0.2 to -0.33. Conclusion: Both duration of use and propensity of atypical antipsychotics to cause EPS can influence the speech performance of the patients. This information can be useful, particularly in people with the requirement of high quality speech.

  11. 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

  12. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to Counteract Olanzapine-Associated Weight Gain.

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    Barak, Nir; Beck, Yaffa; Albeck, Joseph H

    2016-06-01

    Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted.

  13. 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 BACKGROUND: 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. METHODS: 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  14. Effects of olanzapine and betahistine co-treatment on serotonin transporter, 5-HT2A and dopamine D2 receptor binding density.

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    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2013-12-02

    Olanzapine is widely used in treating multiple domains of schizophrenia symptoms but induces serious metabolic side-effects. Recent evidence has showed that co-treatment of betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for preventing olanzapine-induced weight gain/obesity, however it is not clear whether this co-treatment affects on the primary therapeutic receptor binding sites of olanzapine such as serotonergic 5-HT2A receptors (5-HT2AR) and dopaminergic D2 receptors (D2R). Therefore, this study investigated the effects of this co-treatment on 5-HT2AR, 5-HT transporter (5-HTT) and D2R bindings in various brain regions involved in antipsychotic efficacy. Female Sprague Dawley rats were administered orally (t.i.d.) with either olanzapine (1mg/kg), betahistine (2.7 mg/kg), olanzapine plus betahistine (O+B), or vehicle (control) for 2 weeks. Quantitative autoradiography was used to detect the density of [(3)H]ketanserin, [(3)H]paroxetine and [(3)H]raclopride binding site to 5-HT2AR, 5-HTT and D2R. Compared to the controls, olanzapine significantly decreased [(3)H]ketanserin bindings to 5-HT2AR in the prefrontal cortex, cingulate cortex, and nucleus accumbens. Similar changes in 5-HT2AR bindings in these nuclei were also observed in the O+B co-treatment group. Olanzapine also significantly decreased [(3)H]paroxetine binding to 5-HTT in the ventral tegmental area and substantia nigra, however, both olanzapine only and O+B co-treatment did not affect [(3)H]raclopride binding to D2R. The results confirmed the important role of 5-HT2AR in the efficacy of olanzapine, which is not influenced by the O+B co-treatment. Therefore, betahistine co-treatment would be an effective combination therapy to reduce olanzapine-induced weight gain side-effects without affecting olanzapine's actions on 5-HT2AR transmissions.

  15. Borderline personality disorder: bipolarity, mood stabilizers and atypical antipsychotics in treatment.

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    Belli, Hasan; Ural, Cenk; Akbudak, Mahir

    2012-10-01

    In this article, it is aimed to review the efficacies of mood stabilizers and atypical antipsychotics, which are used commonly in psychopharmacological treatments of bipolar and borderline personality disorders. In this context, common phenomenology between borderline personality and bipolar disorders and differential features of clinical diagnosis will be reviewed in line with the literature. Both disorders can demonstrate common features in the diagnostic aspect, and can overlap phenomenologically. Concomitance rate of both disorders is quite high. In order to differentiate these two disorders from each other, quality of mood fluctuations, impulsivity types and linear progression of disorders should be carefully considered. There are various studies in mood stabilizer use, like lithium, carbamazepine, oxcarbazepine, sodium valproate and lamotrigine, in the treatment of borderline personality disorder. Moreover, there are also studies, which have revealed efficacies of risperidone, olanzapine and quetiapine as atypical antipsychotics. It is not easy to differentiate borderline personality disorder from the bipolar disorders. An intensively careful evaluation should be performed. This differentiation may be helpful also for the treatment. There are many studies about efficacy of valproate and lamotrigine in treatment of borderline personality disorder. However, findings related to other mood stabilizers are inadequate. Olanzapine and quetiapine are reported to be more effective among atypical antipsychotics. No drug is approved for the treatment of borderline personality disorder by the entitled authorities, yet. Psychotherapeutic approaches have preserved their significant places in treatment of borderline personality disorder. Moreover, symptom based approach is recommended in use of mood stabilizers and atypical antipsychotics.

  16. Eosinophilic myocarditis during treatment with olanzapine

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

    2016-01-01

    BACKGROUND: Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical...... fatal cases of eosinophilic myocarditis associated with the use of olanzapine. CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post......-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...

  17. 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

  18. Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients.

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    Ruaño, G; Goethe, J W; Caley, C; Woolley, S; Holford, T R; Kocherla, M; Windemuth, A; de Leon, J

    2007-05-01

    Atypical antipsychotics induce pre-diabetic symptoms in some but not all patients, characterized most notably by elevated weight. The side effect profiles of the various drugs in the class differ, however, raising the possibility of drug-specific mechanisms for similar side effects. We used physiogenomic analysis, an approach previously employed to study the genetics of drug and diet response, to discover and compare genetic associations with weight profiles observed in patients treated with olanzapine and risperidone as an approach to unraveling contrasting mechanistic features of both drugs. A total of 29 single nucleotide polymorphisms (SNPs) were selected from 13 candidate genes relevant to two potential pharmacological axes of psychotropic-related weight profiles, appetite peptides and peripheral lipid homeostasis. We applied physiogenomic analysis to a cross-section of 67 and 101 patients being treated with olanzapine and risperidone, respectively, and assessed genetic associations with the weight profiles. Weight profiles in patients treated with olanzapine were significantly associated with SNPs in the genes for apolipoprotein E, apolipoprotein A4 and scavenger receptor class B, member 1. Weight profiles in patients treated with risperidone were significantly associated with SNPs in the genes for leptin receptor, neuropeptide Y receptor Y5 and paraoxonase 1. These results are consistent with contrasting mechanisms for the weight profile of patients treated with these drugs. Genes associated with olanzapine weight profiles may be related to peripheral lipid homeostatic axes, whereas those associated with risperidone's may be related to brain appetite peptide regulation. Future physiogenomic studies will include neurotransmitter receptor SNPs and validation in independent samples.

  19. Report of a Rare Case of Olanzapine and Risperidone Induced Hypomania

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    AR Zahiroddin

    2006-07-01

    Full Text Available Introduction & Objective: Hypomania is a mood disorder with symptoms of constantly high expansive or irritable mood. After a 4-day period, the patient feels to be in need of less sleep, being talkative, or feeling pressure if not treated kindly, having flight of ideas, distractibility, and increase in goal oriented activities (including social, occupational, educational or sexual activities and being extravagant. Hypomania could be a mood episode of bipolar I and II mood disorder or cyclothymia and could be resulted from consumption of drugs, materials, Electro Convulsive Therapy (ECT or photo therapy. Case: The present report is the case of a 57-year old married woman, who has had a record of bipolar I mood disorder since 30 years ago. The patient was hospitalized once in psychiatry hospital and referred to psychiatry office 2 years ago. She has been under medication therapy by lithium 600 mg, nortriptyline 75 mg, and colonazpam 1 mg. She has taken risperidone 2 mg, the symptoms of hypomania have revealed. After stopping the consumption of risperidone, the treatment continued by lithium tablet 900 mg, eskazina tablet 4 mg, nortriptyline 75 mg for one day. She was under care for 15 months and then due to muscle complications of lithium, pessimism, auditory and visual hallucination, she was recommended to take olanzapine tablet 5 mg once every night. Two days after taking olanzapine the symptoms of hypomania revealed. Consumption of olanzapine was then stopped and the symptoms disappeared and she was brought under control after taking sodiumvalproate tablet. Conclusion: Rarely could Hypomania be a mood episode induced by consuming atypical antipsychotics such as risperidone and olanzapine.

  20. Conventional and atypical antipsychotics in the elderly : a review.

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    Gareri, Pietro; De Fazio, Pasquale; Stilo, Mariagrazia; Ferreri, Guido; De Sarro, Giovambattista

    2003-01-01

    Psychoses are major mental disorders marked by derangement of personality and loss of contact with reality, and are common in the elderly. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients, the most studied of which are the dopaminergic, serotonergic and glutamatergic systems. In particular, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Treatment with antipsychotics is very common in the elderly and often indispensable. However, for successful treatment it is essential to have an adequate multidimensional assessment of the geriatric patient and of his or her polypathology and polypharmacy, together with knowledge of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug interactions.Conventional antipsychotics such as haloperidol, chlorpromazine, promazine, tiapride and zuclopenthixol are D(2)-receptor antagonists and inhibit dopaminergic neurotransmission in a dose-related manner. They decrease the intensity of all psychotic symptoms, although not necessarily to the same extent and with the same time course. Negative symptoms may persist to a much more striking extent than delusions, hallucinations and thought disorders, and there is a dose-related incidence of extrapyramidal side effects (EPS). Newer antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and ziprasidone, have a different receptor-binding profile, interacting with both D and 5-HT receptors; they less frequently cause EPS and are better tolerated in the elderly. Their use is advantageous because they are effective both on positive and negative symptoms of schizophrenia and may also be used in the treatment of behavioural disturbances in elderly and/or demented individuals. The use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine, risperidone, quetiapine

  1. Antipsychotic-induced Hyperprolactinemia

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    Suheyla Dogan Bulut

    2015-06-01

    Full Text Available Prolactin provides the growth of the mammary gland during pregnancy and synthesis and preparation of breast milk for lactation. Antipsychotics and antidepressants that are frequently used in psychiatry, cause hyperprolactinemia. The prevalent opinion is that especially typical antipsychotics increase prolactin levels primarily by blocking D2 receptors in the anterior pituitary. The effects of atypical antipsychotics on hyperprolactinemia vary. Hyperprolactinemia causes galactorrhea, gynecomastia, sexual dysfunction, infertility, acne, hirsutism in women, weight gain, obesity and mood changes in addition to menstrual irregularities such as oligomenorrhea, polymenorrhea and amenorrhea. In the long term, hyperprolactinemia may cause reduction in bone density and osteoporosis. Hyperprolactinemia as a side effect of antipsychotics drugs and its treatment will be reviewed in this article. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 109-124

  2. Incident users of antipsychotics

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    Baandrup, Lone; Kruse, Marie

    2016-01-01

    initial antipsychotic prescribing patterns and associated use of mental health care services. METHOD: Population-based cohort study linking the following Danish national registers: the Central Psychiatric Research Register, the Register of Medicinal Product Statistics, and Statistics Denmark. RESULTS....... As a consequence of the range of adverse effects associated with antipsychotic drug use, the documented widespread off-label prescribing practices warrant careful monitoring for adverse effects and prompt discontinuation in case of an unfavorable risk-benefit ratio....

  3. Atypical antipsychotics suppress production of proinflammatory cytokines and up-regulate interleukin-10 in lipopolysaccharide-treated mice.

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    Sugino, Haruhiko; Futamura, Takashi; Mitsumoto, Yasuhide; Maeda, Kenji; Marunaka, Yoshinori

    2009-03-17

    There is considerable evidence that schizophrenia is associated with immune system dysregulation. For example, blood and cerebrospinal fluid (CSF) levels of proinflammatory cytokines are significantly increased in schizophrenic patients, and their normalization correlates with improvement in psychotic symptoms. In fact, typical and atypical antipsychotics are reported to modulate immune function in in vitro and in vivo studies. In the present study, we examined the anti-inflammatory effect of antipsychotics, clozapine, olanzapine, risperidone and haloperidol, on serum cytokine levels in lipopolysaccharide (LPS)-treated mice. Atypical antipsychotics, such as clozapine, olanzapine and risperidone, but not haloperidol, suppressed tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, and up-regulated IL-10. Moreover, only clozapine, robustly increased the serum levels of IL-10. Clozapine reproduced its anti-inflammatory feature in polyinsinic-polycytidylic acid sodium salt (Poly[I:C])-induced inflammation. Thus, the anti-inflammatory effect of clozapine would adapt to inflammation induced by some varieties of antigens. Several receptor ligands, such as 8-OH-DPAT, ketanserin, prazosin and scopolamine, were also examined as to their anti-inflammatory effects on serum cytokine levels in LPS-treated mice. Ketanserin and prazosin, but not 8-OH-DPAT nor scopolamine, behaved similarly to atypical antipsychotics. However, the remarkable increase of serum IL-10 level observed in clozapine was not detected in ketanserin and prazosin. These results suggest the unique efficacy of atypical antipsychotics in the suppression of proinflammatory cytokines, and the increase of anti-inflammatory cytokine, IL-10.

  4. Olanzapine versus haloperidol: Which can control stuttering better?

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    Vahid Shaygannejad

    2013-01-01

    Conclusions: It seems that olanzapine does have better impact in controlling stuttering, and it may be recommended to prescribe olanzapine for stutters as the first choice to control the stuttering under a careful follow-up.

  5. The influence of antipsychotic therapy on the cognitive functions of schizophrenic patients

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    Tybura, Piotr

    2013-07-01

    Full Text Available Aim: The aim of the present study was twofold: 1. to compare the efficacy of three antipsychotics (ziprasidone, olanzapine and perazine in schizophrenia 2. to compare the improvement in cognitive functioning between groups treated with the three different neuroleptics. Method: A total of 58 Caucasian patients diagnosed with paranoid schizophrenia were recruited into the study group. We used the Polish version of the CIDI (Composite International Diagnostic Interview to obtain ICD-10 diagnoses. The intensity of psychopathological symptoms was examined using the PANSS. The patients were randomly assigned to treatment with perazine, olanzapine or ziprasidone administered as monotherapy for 3 months. The treatment efficacy was measured as a change in the PANSS (Positive and Negative Syndrome Scale total score from baseline (T0 to 3 months (T1. The WCST (The Wisconsin Card Sorting Test was used to measure working memory and executive functions in the evaluated patients.Wilcoxon’s and Kruskal-Wallis tests were applied to compare changes in the PANSS scores between the treatment groups. To analyze the cognitive functions, Kruskal-Wallis test for the WCST parameters was used. Results: The three antipsychotics similarly reduced the total PANSS score. The WCST parameters in the 3 groups of examined patients using the Kruskal-Wallis test revealed some differences between the three administered antipsychotics. Conclusions: Results suggest that the short-term efficacy of the atypical (olanzapine, ziprasidone and typical (perazine antipsychotic drugs did not differ. Based on the analysis, a conclusion can be drawn that the three neuroleptics provided similar improvements in cognitive functioning.

  6. 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.

  7. Betahistine co-treatment ameliorates dyslipidemia induced by chronic olanzapine treatment in rats through modulation of hepatic AMPKα-SREBP-1 and PPARα-dependent pathways.

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    Liu, Xuemei; Lian, Jiamei; Hu, Chang-Hua; Deng, Chao

    2015-10-01

    Second-generation antipsychotics including olanzapine are associated with weight gain, dyslipidemia and other metabolic disorders. Both animal and clinical studies have shown that co-treatment with betahistine (a histamine H1 receptor agonist/H3 receptor antagonist) is effective in controlling olanzapine-induced weight gain. In the present study, we investigate whether co-treatment with betahistine is able to prevent dyslipidemia induced by chronic olanzapine treatment and the underlying mechanisms. Female rats were orally administered with olanzapine (1 mg/kg, t.i.d.) for 3.5 consecutive weeks and then a 2.5-week drug withdrawal. Then, rats were divided into 4 groups for 5 weeks treatment: (1) vehicle, (2) olanzapine-only (1 mg/kg, t.i.d.), (3) betahistine-only (9.6 mg/kg, t.i.d.), and (4) olanzapine and betahistine (O+B) co-treatment. After completing treatment, hepatic mRNA expression was measured by qRT-PCR, while the protein levels were detected by western blot. In our study, olanzapine-only treatment significantly increased triglyceride accumulation and non-esterified fatty acids (NEFA), and upregulated mRNA expression of sterol regulatory element binding protein 1 (SREBP-1) and its target genes, while these alterations were ameliorated by O+B co-treatment. Hepatic AMP-activated protein kinase α (AMPKα) was activated in the O+B co-treatment group, with a significant reduction in nuclear SREBP-1 protein expression but an increased expression of peroxisome proliferator-activated receptor-α (PPARα) and its-responsive molecule(CPT1A), compared with olanzapine-only treatment. In addition, olanzapine significantly increased hepatic histamine H1 receptors, while O+B co-treatment significantly reversed them to normal levels. This study provided the first evidence that betahistine could act on hepatic H1 receptors via modulation of AMPKα-SREBP-1 and PPARα-dependent pathways to ameliorate olanzapine-induced dyslipidemia in rats.

  8. 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 (p<0,02). No changes in HDL concentrations. There was positive relationship 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells

    Science.gov (United States)

    Filatova, Elena; Kasian, Anastasiya; Kolomin, Timur; Rybalkina, Ekaterina; Alieva, Anelya; Andreeva, Lyudmila; Limborska, Svetlana; Myasoedov, Nikolay; Pavlova, Galina; Slominsky, Petr; Shadrina, Maria

    2017-01-01

    Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABAA receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method. As test substances, in addition to Selank, we selected the major GABAA receptor ligand, GABA, the atypical antipsychotic, olanzapine, and combinations of these compounds (Selank and GABA; Selank and olanzapine). We found no changes in the mRNA levels of the genes studied under the effect of Selank. The combined effect of GABA and Selank led to nearly complete suppression of changes in expression of genes in which mRNA levels changed under the effect of GABA. When Selank was used in conjunction with olanzapine, the expression alterations of more genes were observed compared with olanzapine alone. The data obtained indicate that Selank has no direct effect on the mRNA levels of the GABAergic system genes in neuroblastoma IMR-32 cells. At the same time, our results partially confirm the hypothesis that the peptide may affect the interaction of GABA with GABAA receptors. Our data also suggest that Selank may enhance the effect of olanzapine on the expression of the genes studied. PMID:28293190

  11. Effects of lactational exposure of olanzapine and risperidone on hematology and lymphoid organs histopathology: a comparative study in mice neonates.

    Science.gov (United States)

    Mishra, Akash C; Mohanty, Banalata

    2010-05-25

    Body weight gain, sexual/reproductive dysfunction and hematological abnormalities are serious consequences of atypical antipsychotics treatment. No attempts however have been made preclinically to elucidate the adverse hematological impacts. Presently, effects of lactational exposure of olanzapine (4, 8 and 10 mg/kg) and risperidone (1 and 2 mg/kg) on hematology as well as lymphoid organ histopathology of mice neonates were investigated. Both olanzapine and risperidone transfers through milk and make the neonates susceptible to their adverse side effects. Corticosterone elevation tendency of both the drugs further enhance the susceptibility for immune dysfunction. Analysis of total and differential leukocytes counts revealed neutropenia with all the doses of olanzapine but only with risperidone 2mg/kg. Weight analysis and histopathology of thymus and spleen indicated a state of suppression; less in the risperidone-exposed groups. Significant plasma corticosterone elevation occurred on 4 and 8 mg/kg olanzapine exposures but not with 10 mg/kg as well as with both the risperidone doses. Elevation of plasma prolactin levels occurred dose-dependently for both the drugs. Hematological toxicity (neutropenia) might be the direct toxic effects of the drugs/unstable metabolites on circulating neutrophils and/or on the bone marrow hemopoietic cells. Direct toxicity of the drugs might also have suppressed the lymphoid organs thymus and spleen. Further, it could be associated to hormonal imbalance induced by adverse pharmacological effects of the drugs on the endocrine system. Suppression of lymphoid organs in olanzapine groups might have resulted because of corticosteronemia and hyperprolactinemia, while in risperidone it could be mediated by pronounced hyperprolactinemic effect alone.

  12. 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.

  13. 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.

  14. 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....

  15. Efficacy and safety of atypical antipsychotic drugs (quetiapine, risperidone, aripiprazole and paliperidone compared with placebo or typical antipsychotic drugs for treating refractory schizophrenia: overview of systematic reviews

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    Tamara Melnik

    Full Text Available CONTEXT AND OBJECTIVE: According to some cohort studies, the prevalence of refractory schizophrenia (RS is 20-40%. Our aim was to evaluate the effectiveness and safety of aripiprazole, paliperidone, quetiapine and risperidone for treating RS. METHODS: This was a critical appraisal of Cochrane reviews published in the Cochrane Library, supplemented with reference to more recent randomized controlled trials (RCTs on RS. The following databases were searched: Medical Literature Analysis and Retrieval System Online (Medline (1966-2009, Controlled Trials of the Cochrane Collaboration (2009, Issue 2, Embase (Excerpta Medica (1980-2009, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs (1982-2009. There was no language restriction. Randomized controlled trials, systematic reviews and meta-analyses evaluating atypical antipsychotics for treating RS were included. RESULTS: Seven Cochrane systematic reviews and 10 additional RCTs were included in this review. The data generally showed minor differences between the atypical antipsychotics evaluated and typical antipsychotics, regarding improvement in disease symptoms, despite better adherence to treatment with atypical antipsychotics. Risperidone was specifically evaluated in patients with RS in one of the systematic reviews included, with favorable outcomes, but without definitive superiority compared with other drugs of proven efficacy, like amisulpride, clozapine and olanzapine. CONCLUSIONS: The findings underscore the difficulty in treating these patients, with high dropout rates and treatment patterns of modest improvement in assessments of effectiveness. Atypical antipsychotics have advantages over typical antipsychotics mainly through their better safety profile, which leads to better adherence to treatment. A combination of antipsychotics may also be an option for some refractory patients.

  16. Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2014-08-08

    Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

  17. Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.

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    Kensuke Sakuma

    Full Text Available Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs, raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR. Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist, olanzapine (antagonist, and aripiprazole (partial agonist all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.

  18. Antipsychotic poisoning in young children: a systematic review.

    Science.gov (United States)

    Isbister, Geoffrey K; Balit, Corrine R; Kilham, Henry A

    2005-01-01

    The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children

  19. Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans.

    Science.gov (United States)

    Donohoe, Dallas R; Weeks, Kathrine; Aamodt, Eric J; Dwyer, Donard S

    2008-01-01

    Antipsychotic drugs are increasingly being prescribed for children and adolescents, and are used in pregnant women without a clear demonstration of safety in these populations. Global effects of these drugs on neurodevelopment (e.g., decreased brain size) have been reported in rats, but detailed knowledge about neuronal effects and mechanisms of action are lacking. Here we report on the evaluation of a comprehensive panel of antipsychotic drugs in a model organism (Caenorhabditis elegans) that is widely used to study neuronal development. Specifically, we examined the effects of the drugs on neuronal migration and axonal outgrowth in mechanosensory neurons visualized with green fluorescent protein expressed from the mec-3 promoter. Clozapine, fluphenazine, and haloperidol produced deficits in the development and migration of ALM neurons and axonal outgrowth in PLM neurons. The defects included failure of neuroblasts to migrate to the proper location, and excessive growth of axons past their normal termination point, together with abnormal morphological features of the processes. Although the antipsychotic drugs are potent antagonists of dopamine and serotonin receptors, the neurodevelopmental deficits were not rescued by co-incubation with serotonin or the dopaminergic agonist, quinpirole. Other antipsychotic drugs, risperidone, aripiprazole, quetiapine, trifluoperazine and olanzapine, also produced modest, but detectable, effects on neuronal development. This is the first report that antipsychotic drugs interfere with neuronal migration and axonal outgrowth in a developing nervous system.

  20. Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

    Directory of Open Access Journals (Sweden)

    Bo Wang

    Full Text Available Following Food and Drug Administration (FDA approval, many drugs are prescribed for non-FDA-approved ("off-label" uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs. We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone. FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications. Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63. Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79.The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Association study of olanzapine-induced weight gain and therapeutic response with SERT gene polymorphisms in female schizophrenic patients.

    Science.gov (United States)

    Bozina, Nada; Medved, Vesna; Kuzman, Martina Rojnic; Sain, Ivica; Sertic, Jadranka

    2007-09-01

    We investigated the relationships between L/S promoter (SERTPR) and l/s intron2 (SERTin2) genetic variants of serotonin transporter (SERT) polymorphisms with olanzapine-induced weight gain and treatment response in 94 female schizophrenic patients treated with olanzapine for up to 3 months. Body mass index (BMI) was calculated for each patient prior to olanzapine administration and 3 months afterwards. To assess and evaluate improvement of clinical psychotic symptoms and therapeutic response to the antipsychotic, all patients were rated using the Positive and Negative Syndrome ScaLe (PANSS). Overall, the presence of S SERTPR allelic variant and SS genotype was associated with significantly higher weight gain in subjects who were non-obese at the time of admission. The presence of L SERTPR variant was associated with significantly better treatment response measured with total PANSS and general PANSS subscale, while the presence of l SERTin2 variant determined better treatment response only in several items. No evidence of linkage disequilibrium between the two loci was found in the sample. These findings identify genetic factors associated with oLanzapine-induced weight gain and treatment response in femaLe schizophrenic patients.

  4. Olanzapine use in a manic patient during second and third trimester pregnancy

    Directory of Open Access Journals (Sweden)

    Choi L

    2014-02-01

    Full Text Available Lynn Choi, Soo-Hyun Joo, Jong-Hyun Jeong Department of Psychiatry, St Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea Abstract: Women with bipolar disorder have a high risk for symptom exacerbation during pregnancy and the risk is elevated further when mood stabilizers are discontinued. This report describes a 31-year-old bipolar woman who discontinued medication before pregnancy but had to resume her pharmacotherapy due to manic episodes that recurred during the second trimester. Olanzapine, an atypical antipsychotic, was administered from week 25 of gestation and then replaced with quetiapine in week 35 of gestation. Even though a consensus on clinical interventions for pregnant patients with symptom relapse has not been reached, clinicians should still discuss pregnancy and therapeutic management with every female bipolar patient of childbearing age. This discussion is important because treatment can be managed most effectively in these individuals if pregnancy is planned. Ultimately, clinical decisions should be made on a case-by-case basis, weighing the risks to the mother and fetus between the disorder itself and the teratogenicity of pharmacotherapy. Keywords: pregnancy, bipolar disorder, olanzapine, manic

  5. Differential effect of antipsychotics on place navigation of rats in the Morris water maze. A comparative study between novel and reference antipsychotics.

    Science.gov (United States)

    Skarsfeldt, T

    1996-03-01

    A group of novel neuroleptics (e.g. olanzapine, seroquel, sertindole and ziprasidone) and already marketed compounds (e.g. clozapine, haloperidol and risperidone) were tested for acute effect on spatial learning and memory in Morris' water maze task. Young rats were trained for 4 consecutive days (three trials/day) to find a platform situated beneath the water surface. Two compounds, sertindole and seroquel, were without effect on spatial performance, whereas clozapine impaired performance on the first 2 test days but showed no effect compared to the controls on the last 2 test days. Ziprasidone and olanzapine markedly impaired spatial memory without affecting motor function (measured by the swimming speed). Risperidone and haloperidol also impaired performance but in addition both compounds significantly lowered the swimming speed. The present study indicates that several of the compounds impair spatial learning in Morris water maze. This might be of clinical importance in the treatment of schizophrenics, as many of these patients already show severe cognitive deficits. Therefore, certain antipsychotics could worsen the preexisting memory deficits in schizophrenic patients and this aspect should be considered before antipsychotic treatment.

  6. Simultaneous Estimation of Fluoxetine HCl and Olanzapine in Bulk Drug and Pharmaceutical Formulation by Using UV-Visible Spectroscopy Method

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    Rubesh kumar S

    2011-01-01

    Full Text Available Present work is to carry out an analytical method development and validation of Fluoxetine HCl (FLU and Olanzapine (OLZ in bulk drug and pharmaceutical dosage form. The developed method is based upon simultaneous equations (Vierodt’s method by using UV/Visible spectroscopy. Both drugs come in the categories of anti- depressant and anti-psychotic agent. The developed method can be used for the simultaneous estimation of FLU and OLZ in pharmaceutical dosage form without separating from each other or from the excipients. Primarily the λ max of Fluoxetine HCl (FLU and Olanzapine (OLZ was determined as 226 and 258 nm respectively. The suggested method is validated by using ICH validation parameters like accuracy, precession, linearity and LOD and LOQ respectively. Accuracy study showed percentage recovery in the range of 97-102% w/w respectively. Precision studies were carried out for 6 successive absorbance and studied for their percentage relative standard deviation (%RSD was < 2%, LOD and LOQ was studied and the limit of detection and limit of quantification were found to be was 1-100 µg/ml for Olanzapine and Fluoxetine HCl, the slope of interception Y=0.23x6+0.054 (R2 0.993 and Y=0.222x6-0.014 (R 2 0.995 respectively. Relative standard deviation for Fluoxetine hydrochloride and Olanzapine were 0.4904 and 0.53969, the co-relation coefficient were 0.997 and 0.825 respectively. This procedure was applied successfully for the analysis of FLU and OLZ in bulk drug and Pharmaceutical preparations.

  7. 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

  8. New users of antipsychotic medication

    DEFF Research Database (Denmark)

    Baandrup, L; Kruse, M

    2016-01-01

    BACKGROUND: Treatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing...

  9. Arterial Stiffness in Patients Taking Second-generation Antipsychotics

    Science.gov (United States)

    Fındıklı, Ebru; Gökçe, Mustafa; Nacitarhan, Vedat; Camkurt, Mehmet Akif; Fındıklı, Hüseyin Avni; Kardaş, Selçuk; Şahin, Merve Coşgun; Karaaslan, Mehmet Fatih

    2016-01-01

    Objective That treatment with second-generation antipsychotics (SGAs) causes metabolic side effects and atherosclerosis in patients with schizophrenia and bipolar disorder (BD) is well-known. Increased arterial stiffness is an important marker of arteriosclerosis and has been identified as an independent risk factor for cardiovascular diseases. We measured pulse wave velocity (PWV) as a marker of arteriosclerosis in patients with schizophrenia and BD who use SGAs. Methods Patients and controls were collected from our psychiatry outpatient clinics or family medicine. Mental illness was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Mean age, gender, systolic and diastolic blood pressure, body mass index, Framingham risk score (FRS), etc. were determined. Simultaneous electrocardiography and pulse wave were recorded with an electromyography device. The photo-plethysmographic method was used to record the pulse wave. Inclusion criteria included use of SGAs for at least the last six months. Patients with diseases that are known to cause stiffness and the use of typical antipsychotics were excluded. Results Ninety-six subject (56 patients, 40 controls) were included in our study. There were 49 females, 47 males. Patients had schizophrenia (n=17) and BD (n=39). Their treatments were quetiapine (n=15), risperidone (n=13), olanzapine (n=15), and aripiprazole (n=13). Although differences in mean age, gender, and FRS in the patient and control groups were not statistically significant (p=1), PWV was greater in patients in the antipsychotic group (p=0.048). Conclusion This study supported the liability to stiffness in patients with schizophrenia and BD. Using SGAs may contribute to arterial stiffness in these patients. PMID:27776389

  10. 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

  11. Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

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    Park, Young-Min; Lee, Seung-Hwan; Lee, Bun-Hee; Lee, Kyu Young; Lee, Kye-Seong; Kang, Seung-Gul; Lee, Hwa-Young; Kim, Won

    2016-05-30

    The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (pprolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients.

  12. Use of antipsychotics and benzodiazepines in patients with psychiatric emergencies: Results of an observational trial

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    Schacht Alexander

    2008-07-01

    Full Text Available Abstract Background Conventional antipsychotics augmented with benzodiazepines have been the standard acute treatment for psychiatric emergencies for more than 50 years. The inability of patients to give informed consent limits randomised, controlled studies. This observational study on immediate therapy for aggression and impulse control in acutely agitated patients (IMPULSE evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications (AP in a non-interventional setting. Methods This was a comparative, non-randomised, prospective, open-label, observational study. Treatment over the first 5 days was classified according to whether any olanzapine, risperidone, or haloperidol was included or not. Documentations (PANSS-excited component, CGI-aggression, CGI-suicidality, tranquilisation score were at baseline (day 1 and days 2–6 after start of AP. Results During the short treatment-period, PANSS-EC and CGI-aggression scores improved in all cohorts. 68.7% of patients treated with olanzapine, 72.2% of patients treated with risperidone, and 83.3% of patients treated with haloperidol received concomitant benzodiazepines (haloperidol vs. non-haloperidol: p Conclusion Current medication practices for immediate aggression control are effective with positive results present within a few days. In this study, concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol.

  13. 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

  14. Prior haloperidol, but not olanzapine, exposure augments the pursuit of reward cues: implications for substance abuse in schizophrenia.

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    Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

    2013-05-01

    Drug abuse and addiction are excessively common in schizophrenia. Chronic antipsychotic treatment might contribute to this comorbidity by inducing supersensitivity within the brain's dopamine system. Dopamine supersensitivity can enhance the incentive motivational properties of reward cues, and reward cues contribute to the maintenance and severity of drug addiction. We have shown previously that rats withdrawn from continuous haloperidol (HAL) treatment (via subcutaneous minipump) develop dopamine supersensitivity and pursue reward cues more vigorously than HAL-naive rats following an amphetamine (AMPH) challenge. Atypical antipsychotic drugs are thought to be less likely than typicals to produce dopamine supersensitivity. Thus, we compared the effects of HAL and the atypical antipsychotic olanzapine (OLZ) on the pursuit of reward cues. Rats were trained to associate a light-tone cue with water then treated with HAL or OLZ. Following antipsychotic withdrawal, we assessed AMPH-induced enhancement of lever pressing for the cue. Withdrawal from HAL, but not from OLZ, enhanced this effect. HAL, but not OLZ, also enhanced AMPH-induced psychomotor activation and c-fos mRNA expression in the caudate-putamen. Thus, prior HAL, but not OLZ, enhanced conditioned reward following an AMPH challenge, and this was potentially linked to enhanced behavioral sensitivity to AMPH and AMPH-induced engagement of the caudate-putamen. These findings suggest that HAL, but not an atypical like OLZ, modifies reward circuitry in ways that increase responsiveness to reward cues. Because enhanced responsiveness to reward cues can promote drug-seeking behavior, it should be investigated whether atypical antipsychotics might be a preferential option in schizophrenic patients at risk for drug abuse or addiction.

  15. 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

  16. A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation

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    Katagiri Hideaki

    2013-01-01

    Full Text Available Abstract Background Olanzapine rapid-acting intramuscular (IM injection is an atypical antipsychotic drug already used overseas and recently approved in Japan. The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC total score. Methods We conducted a placebo-controlled, randomized, double-blind, parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR. Patients were randomized to 2 treatment groups: IM olanzapine (10 mg or IM placebo. The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection. Treatment groups were compared with an analysis of variance model which included treatment and site as factors. During the 24-hour treatment period, safety was assessed by clinical examination and laboratory investigations, electrocardiograms, extrapyramidal symptoms scales, and recording spontaneously reported adverse events. Results Of the 91 randomized patients, 90 patients (45 IM olanzapine-group; 45 IM placebo-group were in the full analysis set. The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection (mean±standard deviation was −9.2±4.5 for the IM olanzapine group and −2.8±5.6 for the IM placebo group. The difference between treatment groups was statistically significant (p Conclusion The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure, PANSS-EC. Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable, and could be a new option for treatment

  17. Amisulpride a selective dopamine antagonist and atypical antipsychotic: results of a meta-analysis of randomized controlled trials.

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    Leucht, Stefan

    2004-03-01

    The pharmacological profiles of the atypical antipsychotics, clozapine, olanzapine, quetiapine and risperidone, all show a combined serotonin (5-HT2) and dopamine type-2 (D2) receptor antagonism. Amisulpride, a highly selective dopamine D2/D3 receptor antagonist that binds preferentially to receptors in the mesolimbic system, is also an 'atypical' antipsychotic despite having a different receptor-affinity profile. A meta-analysis of 18 clinical trials was undertaken to compare the efficacy and safety of amisulpride with conventional antipsychotics. The improvement in mental state was assessed using the Brief Psychiatric Rating Scale (BPRS) or the Scale for the Assessment of Negative Symptoms (SANS). In a pooled analysis of 10 studies of acutely ill patients, amisulpride was significantly more effective than conventional neuroleptics with regard to improvement of global symptoms. Amisulpride is, to date, the only atypical antipsychotic for which several studies on patients suffering predominantly from negative symptoms have been published. In four such studies, amisulpride was significantly superior to placebo. Three small studies with conventional neuroleptics as a comparator showed only a trend in favour of amisulpride in this regard. Amisulpride was associated with fewer extrapyramidal side-effects and fewer drop-outs due to adverse events than conventional neuroleptics. These results clearly show that amisulpride is an 'atypical' antipsychotic, and they cast some doubt on the notion that combined 5-HT2-D2 antagonism is the only reason for the high efficacy against negative symptoms and fewer extrapyramidal side-effects.

  18. 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.

  19. A TYPICAL ANTIPSYCHOTIC: A REVIEW

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    Mukesh Ratnaparkhi

    2010-12-01

    Full Text Available Recent advances in understanding the pathophysiology of underlying psychotic disorder and subsequent development of new antipsychotic drugs to treat these diseases have altered clinicians? pharmacological approach. It has also helped researcher to produce a new generation antipsychotic agents (NGA which could show better clinical results. However methodical approach as well as in-depth research in this area has provided several potent atypical antipsychotic agents. Now days all the atypical antipsychotics agents are FDA approved and being frequently used for pharmacotherapy of schizophrenia, acute mania, bipolar mania, psychotic agitation, bipolar maintenance, and other indications. Atypical antipsychotics are associated with the numbers of clinical benefits such as higher rate of responders, efficiency in patients with refractory disease, lower risk of suicides, better functional capacity and an improved quality of life and thus, have showed their efficacy against previous modes of treatment. The present review highlights the advantages, disadvantages as well as risk factors associated with novel antipsychotic agent with a view to outline their future scope.

  20. The role of histaminergic H1 and H3 receptors in food intake: a mechanism for atypical antipsychotic-induced weight gain?

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    Deng, Chao; Weston-Green, Katrina; Huang, Xu-Feng

    2010-02-01

    Atypical antipsychotics such as olanzapine and clozapine are effective at treating the multiple domains of schizophrenia, with a low risk of extra-pyramidal side-effects. However a major downfall to their use is metabolic side-effects particularly weight gain/obesity, which occurs by unknown mechanisms. The present paper explores the potential candidature of histaminergic neurotransmission in the mechanisms of atypical antipsychotic-induced weight gain, with a focus on the histaminergic H1 and H3 receptors. Olanzapine and clozapine have a high affinity for the H1 receptor, and meta-analyses show a strong correlation between risk of weight gain and H1 receptor affinity. In addition, olanzapine treatment decreases H1 receptor binding and mRNA expression in the rat hypothalamus. Furthermore, a complex role is emerging for the histamine H3 receptor in the control of hunger. The H3 receptor is a pre-synaptic autoreceptor that inhibits the synthesis and release of histamine, and a heteroreceptor that inhibits other neurotransmitters such as serotonin (5-HT), noradrenaline (NA) and acetylcholine (ACh), which are also implicated in the regulation of food intake. Thus, the H3 receptor is in a prime position to regulate food intake, both through its control of histamine and its influence on other feeding pathways. We proposed that a mechanism for atypical antipsychotic-induced weight gain may be partly through the H3 receptor, as a drug-induced decrease in H1 receptor activity may decrease histamine tone through the H3 autoreceptors, compounding the weight gain problem. In addition, atypical antipsychotics may affect food intake by influencing 5-HT, NA and ACh release via interactions with the H3 heteroreceptor.

  1. Effects of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c-fos mRNA in the retrosplenial cortex after administration of dizocilpine.

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    Fujimura, M; Hashimoto, K; Yamagami, K

    2000-06-09

    In this study, we examined the effect of clozapine, olanzapine, risperidone and haloperidol on the neuropathology (i.e. neuronal vacuolization) and the expression of Fos-like protein and c-fos mRNA in the retrosplenial cortex of female Sprague-Dawley rats induced by the NMDA receptor antagonist dizocilpine. Pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, blocked the neuronal vacuolization produced by dizocilpine (0.5 mg/kg, s.c.) in the rat retrosplenial cortex in a dose-dependent manner. Furthermore, pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, significantly attenuated the expression of Fos-like protein in the retrosplenial cortex induced by dizocilpine (0.5 mg/kg, s.c.) in a dose-dependent manner. The marked expression of c-fos mRNA in the rat retrosplenial cortex induced by the administration of dizocilpine (0.5 mg/kg, s.c.) was significantly attenuated by pretreatment (15 min) with clozapine (10 mg/kg) or olanzapine (10 mg/kg), but not risperidone (10 mg/kg) or haloperidol (10 mg/kg). The present results suggest that pharmacologically relevant doses of clozapine or olanzapine, but not risperidone or haloperidol, block the neuropathological changes and the expression of Fos-like protein and c-fos mRNA in the rat retrosplenial cortex elicited by the administration of dizocilpine. It is possible that the blockade of dizocilpine-induced neuropathological changes by clozapine and olanzapine may be related to the unique antipsychotic actions of these drugs in schizophrenic patients, although this remains to be verified.

  2. Involvement of oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes.

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    Eftekhari, Aziz; Azarmi, Yadollah; Parvizpur, Alireza; Eghbal, Mohammad Ali

    2016-01-01

    1. Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown. 2. In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p lysosomal involvement following the initiation of oxidative stress in hepatocytes.

  3. A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice

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    Bodén R

    2013-03-01

    Full Text Available Robert Bodén,1,2 Gunnar Edman,3,4 Johan Reutfors,2 Claes-Göran Östenson,3 Urban Ösby3,4 1Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden; 2Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 4Department of Psychiatry, Tiohundra AB, Norrtälje, Sweden Abstract: It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08–3.04, reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01–2.97; and OR = 2.03, 95% CI 1.32–3.13, hypertension with perphenazine (OR = 2.00, 95% CI 1.21–3.59, and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05–0.89 and positively with haloperidol (OR = 2.02, 95% CI 1.18–3.48. There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In

  4. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe.

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    Emanuel Raschi

    Full Text Available BACKGROUND: Antipsychotics (APs have been associated with risk of torsade de Pointes (TdP. This has important public health implications. Therefore, (a we exploited the public FDA Adverse Event Reporting System (FAERS to characterize their torsadogenic profile; (b we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010 were analyzed based on the following criteria: (1 ≥ 4 cases of TdP/QT abnormalities; (2 Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers; (3 ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD; (4 Significant ROR for VA/SCD; (5 Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled to group E (unclear/uncertain signal: only 2/5 criteria. Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID. RESULTS: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone. In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia to 13.99 (France, 2009. Considerable increment of Group A agents was found in several Countries (+3.47 in France: the exposure to olanzapine increased across all Countries (+1.84 in France and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009. Among Group B drugs, levomepromazine peaked 3.78 (Serbia; fluphenazine 1.61 (Slovenia. CONCLUSIONS: This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  5. 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.

  6. Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

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    Misiak, Błażej; Frydecka, Dorota; Beszłej, Jan A; Moustafa, Ahmed A; Tybura, Piotr; Kucharska-Mazur, Jolanta; Samochowiec, Agnieszka; Bieńkowski, Przemysław; Samochowiec, Jerzy

    2016-07-01

    We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms.

  7. Olanzapine-induced changes in glucose metabolism are independent of the melanin-concentrating hormone system.

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    Girault, Elodie M; Toonen, Pim W; Eggels, Leslie; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, Andries

    2013-11-01

    Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. Chagnon et al. showed that the common allele rs7973796 of the prepro-melanin-concentrating hormone (PMCH) gene is associated with a greater body mass index in Ola-treated schizophrenic patients. As PMCH encodes for the orexigenic neuropeptide melanin-concentrating hormone (MCH), it was hypothesized that MCH is involved in Ola-induced metabolic changes. We have recently reported that the intragastric infusion of Ola results in hyperglycaemia and insulin resistance in male rats. In order to test in vivo the possible involvement of the PMCH gene in the pathogenesis of Ola side-effects, we administered Ola intragastrically in wild-type (WT) and PMCH knock-out (KO) rats. Our results show that glucose and corticosterone levels, as well as endogenous glucose production, are elevated by the infusion of Ola in both WT and KO animals. Thus, the lack of MCH does not seem to affect the acute effects of Ola on glucose metabolism. On the other hand, these effects might be obliterated by compensatory changes in other hypothalamic systems. In addition, possible modulatory effects of the MCH KO on the long term effects of Ola, i.e. increased adiposity, body weight gain, have not been investigated yet.

  8. Zonisamide prevents olanzapine-associated hyperphagia, weight gain, and elevated blood glucose in rats.

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    Wallingford, Nicholas M; Sinnayah, Puspha; Bymaster, Frank P; Gadde, Kishore M; Krishnan, Ranga K; McKinney, Anthony A; Landbloom, Ronald P; Tollefson, Gary D; Cowley, Michael A

    2008-11-01

    Olanzapine (OLZ), one of the second-generation atypical antipsychotics (SGAs), has shown relative advantages in patient adherence and outcomes. However, OLZ has also been associated with a higher incidence of weight gain than most other SGAs. Excessive weight gain may in turn contribute to long-term health concerns for some individuals. Zonisamide (ZNS), a medication approved in the United States as an adjunct in the management of epilepsy, has a diverse pharmacological profile, including sodium channel blockade, monoamine enhancement, and inhibition of carbonic anhydrase. ZNS has also been reported to cause weight loss in both humans and rodents. We hypothesized that this profile might be beneficial when co-administered with OLZ. To test this hypothesis, we evaluated the effects of OLZ on body weight, as well as the pathways known to regulate feeding behavior and arousal in the Sprague-Dawley rat. As indicated via c-Fos expression, we found an OLZ-induced activation in the nucleus accumbens and orexin neurons in the lateral hypothalamus. An OLZ-associated development of hyperphagia, weight gain and elevated blood glucose in the rat was also found. These outcomes were attenuated and reversed in the presence of concomitant ZNS. These results suggest the hypothesis that ZNS may effectively treat or prevent weight gain or metabolic changes associated with the SGAs. Future studies of this combination in patients through appropriately designed human clinical studies are encouraged.

  9. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    van Marum, Rob J.; Wegewijs, Michelle A.; Loonen, Anton J. M.; Beers, Erna

    2007-01-01

    Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Methods Case reports of hypothermia in APD-users found in PUBMED or E

  10. Hypothermia following antipsychotic drug use

    NARCIS (Netherlands)

    Marum, R.J. van; Wegewijs, M.A.; Loonen, A.J.M.; Beers, E.

    2007-01-01

    Objective: Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method: Case reports of hypothermia in APD-users found in PUBMED or

  11. Antipsychotic treatments; Focus on lurasidone

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    Tomiki eSumiyoshi

    2013-08-01

    Full Text Available The introduction of atypical antipsychotic drugs (AAPDs, or second-generation antipsychotics, with clozapine as the prototype, has largely changed the clinicians’ attitudes towards the treatment of mental illnesses including, but not limited to schizophrenia. Initially, there was optimism that AAPDs would be superior over typical antipsychotic drugs (TAPDs, or first-generation antipsychotic drugs, in terms of efficacy for various phenomenological aspects, including cognitive impairment, and less likelihood of causing adverse events. However, these views have been partly challenged by results from recent meta-analysis studies. Specifically, cardio-metabolic side effects of AAPDs, in spite of a relative paucity of extrapyramidal symptoms, may sometimes limit the use of these agents. Accordingly, attempts have been made to develop newer compounds, e.g. lurasidone, with the aim of increasing efficacy and tolerability. Further investigations are warranted to determine if a larger proportion of patients will be benefitted by treatment with AAPDs compared to TAPDs in terms of remission and recovery.

  12. Pharmacogenetics and antipsychotic treatment response.

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    Naumovska, Z; Nestorovska, A K; Filipce, A; Sterjev, Z; Brezovska, K; Dimovski, A; Suturkova, L J

    2015-01-01

    Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorder. The lack of antipsychotic response and treatment-induced side-effects, such as neuroleptic syndrome, polydipsia, metabolic syndrome, weight gain, extrapyramidal symptoms, tardive dyskinesia or prolactin increase, are the two main reasons for non-compliance and increased morbidity in schizophrenic patients. During the past decades intensive research has been done in order to determine the influence of genetic variations on antipsychotics dosage, treatment efficacy and safety. The present work reviews the molecular basis of treatment response of schizophrenia. It highlights the most important findings about the impact of functional polymorphisms in genes coding the CYP450 metabolizing enzymes, ABCB1 transporter gene, dopaminergic and serotonergic drug targets (DRD2, DRD3, DRD4, 5-HT1, 5HT-2A, 5HT-2C, 5HT6) as well as genes responsible for metabolism of neurotransmitters and G signalling pathways (5-HTTLPR, BDNF, COMT, RGS4) and points their role as potential biomarkers in everyday clinical practice. Pharmacogenetic testing has predictive power in the selection of antipsychotic drugs and doses tailored according to the patient's genetic profile. In this perception pharmacogenetics could help in the improvement of treatment response by using different medicinal approaches that would avoid potential adverse effects, reduce stabilization time and will advance the prognosis of schizophrenic patients.

  13. Second generation antipsychotic-induced obsessive-compulsive symptoms in schizophrenia: a review of the experimental literature.

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    Fonseka, Trehani M; Richter, Margaret A; Müller, Daniel J

    2014-11-01

    Second generation antipsychotics (SGAs) have been implicated in the de novo emergence and exacerbation of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Among SGAs, clozapine, olanzapine, and risperidone are the most prominent agents associated with these sequelae, according to case reports. Comorbid OCS can impede recovery by compromising treatment benefits, medication compliance, and clinical prognoses. Previous reviews of SGA-induced OCS have predominantly focused on descriptive case reports, with limited attention paid toward experimental findings. To address this paucity of data, we sought to review the effects of SGAs on OCS in schizophrenia in the experimental literature, while addressing the role of different treatment (duration, dose, serum levels) and pharmacogenetic factors. Our findings suggest that clozapine confers the greatest risk of OCS in schizophrenia, with 20 to 28% of clozapine-treated patients experiencing de novo OCS, in addition to 10 to 18% incurring an exacerbation of pre-existing OCS. Clozapine can also yield full threshold obsessive-compulsive disorder (OCD), in some cases. Olanzapine is another high risk drug for secondary OCS which occurs in 11 to 20% of schizophrenic patients receiving olanzapine therapy. At this time, there is insufficient experimental evidence to characterize the effects of other SGAs on OCS. Despite some experimental support for the involvement of longer treatment duration and genetic factors in mediating drug-induced OCS, more research is needed to clearly elucidate these associations. Based on these results, schizophrenic patients should be routinely monitored for OCS throughout the course of SGA treatment, particularly when clozapine or olanzapine is administered.

  14. No evidence for a role of the peroxisome proliferator-activated receptor gamma (PPARG) and adiponectin (ADIPOQ) genes in antipsychotic-induced weight gain.

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    Brandl, Eva J; Tiwari, Arun K; Zai, Clement C; Chowdhury, Nabilah I; Lieberman, Jeffrey A; Meltzer, Herbert Y; Kennedy, James L; Müller, Daniel J

    2014-10-30

    Antipsychotics frequently cause changes in glucose metabolism followed by development of weight gain and/or diabetes. Recent findings from our group indicated an influence of glucose-related genes on this serious side effect. With this study, we aimed to extend previous research and performed a comprehensive study on the peroxisome proliferator-activated receptor gamma (PPARG) and the adiponectin (ADIPOQ) genes. In 216 schizophrenic patients receiving antipsychotics for up to 14 weeks, we investigated single-nucleotide polymorphisms in or near PPARG (N=24) and ADIPOQ (N=18). Statistical analysis was done using ANCOVA in SPSS. Haplotype analysis was performed in UNPHASED 3.1.4 and Haploview 4.2. None of the PPARG or ADIPOQ variants showed significant association with antipsychotic-induced weight gain in our combined sample or in a refined subsample of patients of European ancestry treated with clozapine or olanzapine after correction for multiple testing. Similarly, no haplotype association could withstand multiple test correction. Although we could not find a significant influence of ADIPOQ and PPARG on antipsychotic-induced weight gain, our comprehensive examination of these two genes contributes to understanding the biology of this serious side effect. More research on glucose metabolism genes is warranted to elucidate their role in metabolic changes during antipsychotic treatment.

  15. Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.

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    Oka, Takuro; Hamamura, Takashi; Lee, Youmei; Miyata, Shinji; Habara, Toshiaki; Endo, Shiro; Taoka, Hideki; Kuroda, Shigetoshi

    2004-11-26

    Acute administration of typical and atypical antipsychotics has been reported to induce regionally distinct patterns of c-Fos expression in the rat forebrain. Furthermore, atypical index, the difference in the extent of increased Fos-like immunoreactivity (Fos-LI) in the nucleus accumbens (NAc) shell versus the dorsolateral striatum (DLSt), has been proposed to classify antipsychotics into typical or atypical antipsychotics. The present study was conducted to investigate the atypical properties of 24 antipsychotics that are used in Japan and blonanserin, a novel 5-HT2A and D2 receptor antagonist. We systematically examined the effects of the drugs on Fos-LI in the NAc and DLSt in the rat brain using immunohistochemistry and calculated the atypical index, comparing with those of haloperidol and clozapine. Floropipamide, oxypertine, nemonapride, pimozide and mosapramine, as well as clozapine, olanzapine, quetiapine and risperidone, showed high positive atypical index. Zotepine, perospirone, sulpiride, moperone, sultopride, thioridazine, carpipramine, clocapramine and blonanserin showed moderate ones. In contrast, fluphenazine, bromperidol, timiperone, spiperone, propericiazine, perphenazine, chlorpromazine and levomepromazine had negative atypical index like haloperidol. These results suggest that not only so-called atypical antipsychotics, but also several conventional drugs, possess atypical properties.

  16. Formulation and characterization of nanoemulsion of olanzapine for intranasal delivery.

    Science.gov (United States)

    Kumar, Mukesh; Misra, Ambikanandan; Pathak, Kamla

    2009-01-01

    The objective was to formulate an olanzapine nanoemulsion that could potentially deliver the drug directly to the brain following intranasal administration. The nanoemulsions were prepared using the water titration method. The mucoadhesive character was imparted by the addition of 0.5%w/w chitosan and 0.5%w/w polycarbophil and was characterized for drug content, pH, percentage transmittance, globule size, zeta potential, and PDI. The composition (%w/w) of the optimized olanzapine nanoemulsion was capmul MCM, tween 80, and a mixture of 1:1 ratio of polyethylene glycol 400 and ethanol, and aqueous phase in a ratio of 15:35:17.5:32.5. The optimized olanzapine nanoemulsion exhibited a high diffusion coefficient and no nasal cilio-toxicity. The drug release followed the Higuchi model. The optimized nanoemulsions were found to be stable for 3 months.

  17. Binding of lurasidone, a novel antipsychotic, to rat 5-HT7 receptor: analysis by [3H]SB-269970 autoradiography.

    Science.gov (United States)

    Horisawa, Tomoko; Ishiyama, Takeo; Ono, Michiko; Ishibashi, Tadashi; Taiji, Mutsuo

    2013-01-10

    Lurasidone is a novel antipsychotic agent with high affinity for dopamine D(2) and serotonin 5-HT(7), 5-HT(2A), and 5-HT(1A) receptors. We previously reported that in addition to its antipsychotic action, lurasidone shows beneficial effects on mood and cognition in rats, likely through 5-HT(7) receptor antagonistic actions. In this study, we evaluated binding of lurasidone to 5-HT(7) receptors in the rat brain by autoradiography using [(3)H]SB-269970, a specific radioligand for 5-HT(7) receptors. Brain slices were incubated with 4 nM [(3)H]SB-269970 at room temperature and exposed to imaging plates for 8 weeks before phosphorimager analysis. Using this method, we first investigated 5-HT(7) receptor distribution. We found that 5-HT(7) receptors are abundantly localized in brain limbic structures, including the lateral septum, thalamus, hypothalamus, hippocampus, and amygdala. On the other hand, its distribution was moderate in the cortex and low in the caudate putamen and cerebellum. Secondly, binding of lurasidone, a selective 5-HT(7) receptor antagonist SB-656104-A and an atypical antipsychotic olanzapine to this receptor was examined. Lurasidone, SB-656104-A (10–1000 nM), and olanzapine (100–10,000 nM) showed concentration-dependent inhibition of [(3)H]SB-269970 binding with IC(50) values of 90, 49, and 5200 nM, respectively. Similar inhibitory actions of these drugs were shown in in vitro [(3)H]SB-269970 binding to 5-HT(7) receptors expressed in Chinese hamster ovary cells. Since there was no marked species difference in rat and human 5-HT(7) receptor binding by lurasidone (K(i) = 1.55 and 2.10 nM, respectively), these findings suggest that binding to 5-HT(7) receptors might play some role in its beneficial pharmacological actions in schizophrenic patients.

  18. ATYPICAL ANTIPSYCHOTICS FROM SCRATCH TO THE PRESENT

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    Ashish Chauhan*, Amit Mittal, Pradeep Kumar Arora

    2013-01-01

    Full Text Available Mental illness constitutes the second-largest disease burden in the United States. Psychosis is one of the most common and severe mental illnesses. It is an extremely devastating condition characterised by delusions, hallucinations, distortion of thoughts and deteriorating social functioning experiences. Psychosis in all human societies has approximately same incidence of occurrence as in accordance to “anthropo-parity principle.” It has large economic impact on various aspects of cognition, health, and quality of life which has devastated effects on its sufferers and facing them large economic burden. Psychosis (Schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyper-stimulation of dopamine function in the brain, particularly in the mesolimbic pathway. Consequences of antipsychotic treatment are far reaching and expensive. Detrimental extrapyramidal side effects associated with conventional antipsychotics and non-compliance among patients limits long term treatment with conventional antipsychotics. It gives rise to a new class, atypical antipsychotics owning low propensity to cause EPS, efficacy against refractory cases and better control over negative symptoms, better tolerance and compliance along with lower relapse rate and safer adverse effect profile. Atypical antipsychotics have revolutionized the treatment of psychosis, now being the treatment of choice for patients with psychosis. The positive therapeutic experience with the atypical antipsychotics in the treatment of psychosis and their favourable effects outweighs their unfavourable adverse effects. Though atypical antipsychotics are widely prescribed in the treatment of schizophrenia, however not a single atypical antipsychotic drug having any exceptional efficacy and safety profile. Thus, there is still a lot of research needed to be carried out in the development of novel atypical antipsychotics. This review is comprehensive appraisal about

  19. Clinical consequences of switching from olanzapine to risperidone and vice versa in outpatients with schizophrenia: 36-month results from the worldwide schizophrenia outpatients health outcomes (W-SOHO study

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    Hong Jihyung

    2012-12-01

    Full Text Available Abstract Background With many atypical antipsychotics now available in the market, it has become a common clinical practice to switch between atypical agents as a means of achieving the best clinical outcomes. This study aimed to examine the impact of switching from olanzapine to risperidone and vice versa on clinical status and tolerability outcomes in outpatients with schizophrenia in a naturalistic setting. Methods W-SOHO was a 3-year observational study that involved over 17,000 outpatients with schizophrenia from 37 countries worldwide. The present post hoc study focused on the subgroup of patients who started taking olanzapine at baseline and subsequently made the first switch to risperidone (n=162 and vice versa (n=136. Clinical status was assessed at the visit when the first switch was made (i.e. before switching and after switching. Logistic regression models examined the impact of medication switch on tolerability outcomes, and linear regression models assessed the association between medication switch and change in the Clinical Global Impression-Schizophrenia (CGI-SCH overall score or change in weight. In addition, Kaplan-Meier survival curves and Cox-proportional hazards models were used to analyze the time to medication switch as well as time to relapse (symptom worsening as assessed by the CGI-SCH scale or hospitalization. Results 48% and 39% of patients switching to olanzapine and risperidone, respectively, remained on the medication without further switches (p=0.019. Patients switching to olanzapine were significantly less likely to experience relapse (hazard ratio: 3.43, 95% CI: 1.43, 8.26, extrapyramidal symptoms (odds ratio [OR]: 4.02, 95% CI: 1.49, 10.89 and amenorrhea/galactorrhea (OR: 8.99, 95% CI: 2.30, 35.13. No significant difference in weight change was, however, found between the two groups. While the CGI-SCH overall score improved in both groups after switching, there was a significantly greater change in those who

  20. Effect of novel antipsychotic drugs on phencyclidine-induced stereotyped behaviour and social isolation in the rat social interaction test.

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    Sams-Dodd, F

    1997-06-01

    Phencyclidine (PCP) induces stereotyped behaviour and social isolation in rats; comparisons with clinical observations have suggested that these behaviours may mimic certain aspects of the positive and the negative symptoms, respectively, of an acute schizophrenic episode. Novel antipsychotics are effective in treating the positive symptoms in schizophrenic patients and have also shown some promise in treating the negative symptoms. In the present study the effects of the novel antipsychotics remoxipride (2.5-20 mg/kg), risperidone (0.02-0.63 mg/kg), sertindole (0.01-2.5 mg/kg), olanzapine (0.16-2.5 mg/kg) and quetiapine (0.16-10 mg/kg) on PCP-induced behaviours were determined. The drugs were administered daily for 3 or 21 days in combination with vehicle or 2.0 mg/kg of PCP for the last 3 days of the administration regime, and the rats were tested using the social interaction test. The antipsychotic drugs all reliably reduced the level of PCP-induced stereotyped behaviour and had distinct effects on PCP-induced social isolation. Comparison with clinical findings suggests that the PCP-induced behaviours respond to treatment with antipsychotic drugs in a manner that correlates well with clinical observations, and that this animal model of schizophrenia may be useful for evaluating novel drug candidates. However, the study also showed that additional experiments are required to determine the specificity by which antipsychotic drugs alleviate PCP-induced behaviours because most of the drugs also affected considerably the behaviour of the control animals.

  1. Movement disorders in elderly users of risperidone and first generation antipsychotic agents: a Canadian population-based study.

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    Irina Vasilyeva

    Full Text Available BACKGROUND: Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines, particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results. METHODS: A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS in new users of risperidone compared to new users of FGAs. RESULTS: After controlling for potential confounders (demographics, comorbidity and medication use, risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22-0.67; 0.45, 95% CI: 0.28-0.73; 0.50, 95% CI: 0.33-0.77; 0.65, 95% CI: 0.45-0.94, respectively. At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54-1.05. CONCLUSIONS: In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS

  2. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

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    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard

    2015-06-01

    Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic

  3. Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

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    Ana Maria Volpato

    2013-09-01

    Full Text Available Objective: Atypical antipsychotics (AAPs promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. Method: A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. Results: This review provides consistent results concerning the side effects of olanzapine (OL and clozapine (CLZ, whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. Conclusions: Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles.

  4. 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.

  5. Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia.

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    Hill, S Kristian; Sweeney, John A; Hamer, Robert M; Keefe, Richard S E; Perkins, Diana O; Gu, Hongbin; McEvoy, Joseph P; Lieberman, Jeffrey A

    2008-03-01

    Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n = 367) and 12-week (n = 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes.

  6. 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.

  7. 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

  8. 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

  9. Olanzapine-induced weight gain is associated with the -759C/T and -697G/C polymorphisms of the HTR2C gene.

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    Godlewska, B R; Olajossy-Hilkesberger, L; Ciwoniuk, M; Olajossy, M; Marmurowska-Michałowska, H; Limon, J; Landowski, J

    2009-08-01

    Weight gain, a serious problem associated with some antipsychotic drugs, notably olanzapine and clozapine, was suggested to be associated with -759C/T polymorphism of the 5-HT2C receptor gene. This study aimed to examine a potential association of two functional polymorphisms of the promoter region of this gene: -759C/T (rs3813929) and -697G/C (rs518147), with weight gain after 6 weeks of olanzapine monotherapy. It included 107 patients with schizophrenia; among them 36 are first-episode drug-naive patients. Analysis was carried out by PCR-restriction fragment length polymorphism. A protective effect of -759T and -697C alleles was found: significantly less patients with -697C (3/51) and no patient with -759T (0/28) alleles experienced body mass index increase >or=10% (P=0.0006 and 0.002, respectively). The same was true for drug-naive patients possessing any of the variant alleles. There was a significant association of haplotypes with a >or=10% body mass index increase (P=0.001). On the basis of the additional statistical analysis, the more important role of -697C allele was suggested.

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

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    Jafari, Somayeh; Huang, Xu-Feng; Andrews, Jessica L; Fernandez-Enright, Francesca

    2013-01-01

    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 that of Olz

  11. A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment.

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    Song, Hong-tao; Sun, Xin-yang; Zhang, Liang; Zhao, Lin; Guo, Zhong-min; Fan, Hui-min; Zhong, Ai-fang; Niu, Wei; Dai, Yun-hua; Zhang, Li-yi; Shi, Zheng; Liu, Xiao-ping; Lu, Jim

    2014-07-01

    Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p treatment in the patient group, the symptomatology scores were significantly lower (p treatment (p treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses.

  12. Acute Metabolic Effects of Olanzapine Depend on Dose and Injection Site

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    Candice M. Klingerman

    2015-11-01

    Full Text Available Atypical antipsychotics (AAPs, such as olanzapine (OLZ, are associated with metabolic side effects, including hyperglycemia. Although a central mechanism of action for the acute effects on glycemia has been suggested, evidence for peripheral versus central effects of AAPs has been mixed and has not been explored for an effect of OLZ on the respiratory exchange ratio (RER. Here, we tested the hypothesis that some inconsistencies in the glycemic responses are likely a result of different doses and central sites of injection. We also compared the effects of central versus peripherally administered OLZ on the RER of unsedated rats. Third ventricle infusion of OLZ at 0.3 mg/kg caused hyperglycemia within 30 minutes, with a higher dose (1.8 mg/kg needed to elicit a similar response in the lateral ventricles. In contrast, 3 mg/kg of OLZ was needed to raise blood glucose within 30 minutes when given intragastrically, and 10 mg/kg resulted in a prolonged hyperglycemia lasting at least 60 minutes. Third ventricle injection of OLZ significantly decreased RER after 75 minutes, whereas intragastric OLZ resulted in a faster drop in RER after 30 minutes. Since changes in glycemia were most sensitive when OLZ was infused into the third ventricle, but effects on RER were more rapidly and efficaciously observed when the drug was given peripherally, these results raise the likelihood of a dual mechanism of action involving hypothalamic and peripheral mechanisms. Some discrepancies in the literature arising from central administration appear to result from the injection site and dose.

  13. 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

  14. Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation.

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    Dong, E; Nelson, M; Grayson, D R; Costa, E; Guidotti, A

    2008-09-09

    Cortical GABAergic dysfunction, a hallmark of both schizophrenia (SZ) and bipolar (BP) disorder pathophysiologies may relate to the hypermethylation of GABAergic gene promoters (i.e., reelin and GAD67). Benefits elicited by a combination of atypical antipsychotics with valproate (VPA) (a histone deacetylase inhibitor that may also activate brain DNA demethylation) in SZ or BP disorder treatment prompted us to investigate whether the beneficial action of this association depends on induction of a putative DNA demethylase activity. To monitor this activity, we measured the ratio of 5-methyl cytosine to unmethylated cytosine in reelin and GAD67 promoters in the mouse frontal cortex and striatum. We compared normal mice with mice pretreated with l-methionine (5.2 mmol/kg s.c. twice a day for 7 days) to hypermethylate promoters, including reelin and GAD67. Clinically relevant doses of clozapine (CLZ) (3.8 to 15 micromol/kg twice a day s.c. for 3 days) and sulpiride (SULP) (12.5 to 50 micromol/kg twice a day for 3 days) but not clinically relevant doses of haloperidol (HAL) (1.3 to 4 micromol/kg twice a day s.c. for 3 days) or olanzapine (OLZ) (4 to 15 micromol/kg twice a day for 3 days) exhibited dose-related increases in the cortical and striatal demethylation of hypermethylated reelin and GAD67 promoters. These effects of CLZ and SULP were dramatically potentiated by a clinically relevant VPA dose (0.5 mmol/kg twice a day for 3 days). By activating a DNA demethylase, the association of CLZ or SULP with VPA may facilitate a chromatin remodeling that normalizes the GABAergic gene expression down-regulation detected in the telencephalic regions of SZ and BP patients.

  15. Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio

    2009-01-01

    The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

  16. A placebo controlled trial on add-on modafinil on the anti-psychotic treatment emergent hyperglycemia and hyperlipidemia

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    Pathapati Lakshmi Prasuna

    2014-01-01

    Full Text Available Modafinil is non stimulant drug which is marketed for mainly Narcolepsy and daytime drowsiness. The clinical experience and Summary of Product Characteristics (SPC of the drug also mentions Anorexia as one of the side effects. Anorexia can have a direct impact on the carbohydrate and fat intake, which may, in turn, regulate antipsychotic induced dyslipidemia and Hyperglycaemia. Aim: To compare the effects of Modafinil- ADDON with Placebo add on with olanzapine, Clozapine and Risperidone in drug naive subjects and people who were started on the drugs within 15days of assessment. Materials and Methods: Randomized, Double blind, Placebo controlled study, which was conducted at two centres, one at department of Psychiatry, S.V Medical College, Tirupati and the other at Asha hospitals, Hyderabad. Seventy two patient were randomised, sixty three patients have completed the total study period of three months.The dose of Modafinil was 200 mgs constantly as Flexible doses of Olanzapine, Clozapine and Risperidone as per clinical need was given. A baseline, three week and twelve week assessments of Fasting blood Glucose and fasting Serum cholesterol were made and the groups were compared on these parameters. Results: From baseline to week 3 there was a significant raise in Fasting serum cholesterol followed by a fall from week 3 to week 12 in the Modafinil addon group, though it could not be considered a drug for hypercholesteremia like Statins in controlling hyperlipidaemia. The implications of these findings were discussed.

  17. Metabolic Impairments Precede Changes in Hunger and Food Intake Following Short-Term Administration of Second-Generation Antipsychotics.

    Science.gov (United States)

    Teff, Karen L; Rickels, Karl; Alshehabi, Erica; Rickels, Michael R

    2015-10-01

    The second-generation antipsychotics (SGAs) are associated with weight gain and an increased incidence of metabolic diseases. The metabolic impairments are assumed a consequence of increased body adiposity secondary to central nervous system-associated increases in food intake. We have previously reported that, independent of weight gain, 9 days of olanzapine administration to control subjects is associated with insulin resistance and increases in postprandial levels of insulin and glucagon-like peptide 1 to a mixed meal challenge. This current report describes previously unpublished data on the effects of the SGAs olanzapine and aripiprazole compared with placebo on detailed hunger and satiety responses over the 12-day inpatient evaluation as well as postprandial ghrelin and leptin responses prior to and following administration of the 2 SGAs. We found no changes in hunger, fullness, or in the orexigenic hormone ghrelin or satiety hormone leptin, consistent with our previous report indicating no change in weight during this study. The results indicate that the SGAs are associated with metabolic changes prior to changes in hunger, satiety, and food intake, and this temporal separation suggests that there are differential mechanisms mediating SGA-associated changes in metabolism and food intake.

  18. Antipsychotic drug binding in the substantia nigra: an examination of high metoclopramide binding in the brains of normal, Alzheimer's disease, Huntington's disease, and Multiple Sclerosis patients, and its relation to tardive dyskinesia.

    Science.gov (United States)

    Chen, Sheng; Seeman, Philip; Liu, Fang

    2011-02-01

    This project was done in order to determine why the annual incidence of metoclopramide-associated tardive dyskinesia is much higher than that for the commonly used antipsychotics. To test the hypothesis that metoclopramide tardive dyskinesia may be associated with high concentrations of metoclopramide in the substantia nigra under clinical conditions, the nonspecific binding of tritiated antipsychotics to the dissected melaninized regions of postmortem human substantia nigra was measured. The nonspecific binding at 1 nM [³H]ligand was 7.3, 4.2, 2.6, 0.91 and 0.66 fmoles/mg for [³H]haloperidol, [³H]clozapine, [³H]raclopride, [³H]metoclopramide, and [³H]olanzapine, respectively. After adjusting these values for the known free concentrations of these drugs in plasma or spinal fluid, the amounts that would be bound under clinical conditions would be 231, 113, 15, 11, and 3.4 fmoles/mg for metoclopramide, clozapine, raclopride, haloperidol, and olanzapine, respectively. Using rat striatum as baseline to define antipsychotic binding to nonnigral tissue, the excess amount of binding to the Alzheimer nigral tissue under clinical conditions would be 209, 19, 0, 3.4 and 0.8 fmole/mg for metoclopramide, clozapine, raclopride, haloperidol, and olanzapine, respectively, with a similar pattern for nigral tissues from Huntington and Multiple Sclerosis patients. The high accumulation of metoclopramide is sufficiently high to cause nigral nerve cell membrane damage by metoclopramide's detergent-like action, possibly explaining metoclopramide's toxic ability to elicit early tardive dyskinesia. In addition, the nonspecific binding of metoclopramide was much higher in Alzheimer-diseased substantia nigra, consistent with the fact that older individuals are relatively more vulnerable to metoclopramide tardive dyskinesia.

  19. A Non-Interventional Naturalistic Study of the Prescription Patterns of Antipsychotics in Patients with Schizophrenia from the Spanish Province of Tarragona.

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    Ana M Gaviria

    Full Text Available The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes.To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain.A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013.The most used antipsychotic was risperidone, identified in 463 (26.3% patients, followed by olanzapine in 249 (14.1%, paliperidone in 225 (12.7%, zuclopenthixol in 201 (11.4%, quetiapine in 141 (8%, aripiprazole in 100 (5.7%, and clozapine in 100 (5.7%. Almost 8 out of 10 patients (79.3% were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6% were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94-40.97, LAI (OR 9.99, 95% CI 6.45-15.45, psychiatric co-medications (OR 4.25, 95% CI 2.72-6.64, and paliperidone (OR 3.13, 95% CI 1.23-7.92 were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35-0.83 and older age (OR 0.98, 95% CI 0.97-0.99 were related to a low polypharmacy probability.Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy is associated with the use of quetiapine or

  20. Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic, NPY and AMPK pathways.

    Science.gov (United States)

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao

    2014-10-01

    Olanzapine is widely used to treat schizophrenia and other disorders, but causes adverse obesity and other metabolic side-effects. Both animal and clinical studies have shown that co-treatment with betahistine (a histaminergic H1 receptor agonist and H3 receptor antagonist) is effective for ameliorating olanzapine-induced weight gain/obesity. To reveal the mechanisms underlying these effects, this study investigated the effects of co-treatment of olanzapine and betahistine (O+B) on expressions of histaminergic H1 receptor (H1R), AMP-activated protein kinase (AMPK), neuropeptide Y (NPY), and proopiomelanocortin (POMC) in the hypothalamus associated with reducing olanzapine-induced weight gain. Olanzapine significantly upregulated the mRNA and protein expressions of H1R, while O+B co-treatment significantly downregulated the H1R levels, compared to the olanzapine-only treatment group. The NPY mRNA expression was significantly enhanced by olanzapine, but it was significantly reversed by O+B co-treatment. The hypothalamic H1R expression was positively correlated with total food intake, and NPY expression. Olanzapine also increased AMPKα activation measured by the AMPKα phosphorylation (pAMPKα)/AMPKα ratio compared with controls, whereas O+B co-treatment decreased the pAMPKα/AMPKα ratio, compared with olanzapine only treatment. The pAMPKα/AMPKα ratio was positively correlated with total food intake and H1R expression. Although olanzapine administration decreased the POMC mRNA level, this level was not affected by O+B co-treatment. Therefore, these results suggested that co-treatment with betahistine may reverse olanzapine-induced body weight gain via the H1R-NPY and H1R-pAMPKα pathways.

  1. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  2. 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

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. Antipsychotic Medicines for Schizophrenia and Bipolar Disorder: What You Should Know

    Science.gov (United States)

    Antipsychotic Drugs for Schizophrenia and Bipolar Disorder: What You Should Know What are antipsychotic drugs? Antipsychotics are prescription drugs used to treat schizophrenia. They can also be used— ...

  4. Adolescent olanzapine sensitization is correlated with hippocampal stem cell proliferation in a maternal immune activation rat model of schizophrenia.

    Science.gov (United States)

    Chou, Shinnyi; Jones, Sean; Li, Ming

    2015-08-27

    Previous work established that repeated olanzapine (OLZ) administration in normal adolescent rats induces a sensitization effect (i.e. increased behavioral responsiveness to drug re-exposure) in the conditioned avoidance response (CAR) model. However, it is unclear whether the same phenomenon can be detected in animal models of schizophrenia. The present study explored the generalizability of OLZ sensitization from healthy animals to a preclinical neuroinflammatory model of schizophrenia in the CAR. Maternal immune activation (MIA) was induced via polyinosinic:polycytidylic acid (PolyI:C) administration into pregnant dams. Behavioral assessments of offspring first identified decreased maternal separation-induced pup ultrasonic vocalizations and increased amphetamine-induced hyperlocomotion in animals prenatally exposed to PolyI:C. In addition, repeated adolescent OLZ administration confirmed the generalizability of the sensitization phenomenon. Using the CAR test, adolescent MIA animals displayed a similar increase in behavioral responsiveness after repeated OLZ exposure during both the repeated drug test days as well as a subsequent challenge test. Neurobiologically, few studies examining the relationship between hippocampal cell proliferation and survival and either antipsychotic exposure or MIA have incorporated concurrent behavioral changes. Thus, the current study also sought to reveal the correlation between OLZ behavioral sensitization in the CAR and hippocampal cell proliferation and survival. 5'-bromodeoxyuridine immunohistochemistry identified a positive correlation between the magnitude of OLZ sensitization (i.e. change in avoidance suppression induced by OLZ across days) and hippocampal cell proliferation. The implications of the relationship between behavioral and neurobiological results are discussed.

  5. Determination of olanzapine by spectrophotometry using permanganate

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    Nagaraju Rajendraprasad

    2009-09-01

    Full Text Available Two new spectrophotometric methods using permanganate as the oxidimetric reagent for the determination of olanzapine (OLP were developed and validated as per the current ICH guidelines. The methods involved the addition of known excess of permanganate to OLP in either acid or alkaline medium followed by the determination of unreacted permanganate at 550 nm (method A or bluish-green color of manganate at 610 nm (method B. The decrease in absorbance in method A or increase in absorbance in method B as a function of concentration of OLP was measured and related to OLP concentration. Under optimized conditions, Beer's law was obeyed over the ranges 2.0 to 20 and 1.0 to 10 μg mL-1 in method A and method B, respectively. The calculated molar absorptivity values were 1.34 x 10(4 and 2.54 x 10(4 l mol-1cm-1 for method A and method B respectively, and the respective Sandell sensitivities were 0.0233 and 0.0123 μg cm-2. The LOD and LOQ for method A were calculated to be 0.37 and 1.13 μg mL-1and the corresponding values for method B were 0.16 and 0.48 μg mL-1. Intermediate precision, expressed as RSD was in the range 0.51 to 2.66 %, and accuracy, expressed as relative error ranged from 0.79 to 2.24 %. The proposed methods were successfully applied to the assay of OLP in commercial tablets with mean percentage recoveries of 102 ±1.59 % (method A and 101 ±1.53 % (method B. The accuracy and reliability of the methods were further confirmed by performing recovery tests via standard addition procedure.Dois métodos espectrofotométricos novos, usando o permanganato como o reagente oxidimétrico para a determinação da olanzapina (OLP foram utilizados e validados de acordo com as diretrizes atuais do ICH. Os métodos envolveram a adição de excesso conhecido de permanganato à OLP em meio ácido ou alcalino, determinando-se o permanganato que não reagiu em 550 nm (método A, ou pela cor verde-azulada do manganato a 610 nm (método B. A diminuição da

  6. A randomized open-label comparison of the impact of olanzapine versus risperidone on sexual functioning

    NARCIS (Netherlands)

    Knegtering, H; Boks, M; Blijd, C; Castelein, S; Van den Bosch, RJ; Wiersma, D

    2006-01-01

    The objective of this study was to compare sexual functioning in patients treated with olanzapine or risperidone. This open-label trial included 46 patients randomized to olanzapine (5-15mg/d) or risperidone (1-6mg/d) for 6 weeks. We used sexual dysfunction was assessed by a semistructured interview

  7. Neurobehavioral and metabolic long-term consequences of neonatal maternal deprivation stress and adolescent olanzapine treatment in male and female rats.

    Science.gov (United States)

    Llorente-Berzal, Alvaro; Mela, Virginia; Borcel, Erika; Valero, Manuel; López-Gallardo, Meritxell; Viveros, Maria-Paz; Marco, Eva M

    2012-03-01

    Early maternal deprivation (MD), 24h of dam-litter separation on postnatal day (PND) 9, has been proposed as a suitable animal model to investigate some neuropsychiatric disorders with a base in neurodevelopment that also compromises metabolic and endocrine homeostasis. Atypical antipsychotics are frequently prescribed to children and adolescents as first-line treatment for several mental disorders despite the adverse metabolic effects frequently reported. However, persistent long-term effects after adolescent drug therapy have been scarcely investigated. In the present study we aimed to investigate the long-lasting metabolic and behavioral effects of MD in combination with the administration of an atypical antipsychotic, i.e. olanzapine, during adolescence. For that purpose, male and female Wistar rats not exposed (control group, Co) and exposed to the MD protocol were administered with oral olanzapine (Olan, 7.5mg/kg/day) or vehicle (Vh, 1mM acetic acid) in drinking water from PND 28 to PND 49. Body weight gain, glycaemia and plasma triglyceride (TG) levels were evaluated as relevant metabolic parameters. MD significantly diminished body weight gain, while Olan administration only induced a subtle decrease in body weight gain among female animals in the long-term. Olan discontinuation decreased plasma TG levels in adult rats, an effect that was counteracted by neonatal exposure to the MD protocol. Both MD and Olan treatment impaired cognitive function in the novel object recognition test, although no interaction between treatments was observed. Neither MD nor Olan administration affected psychotic-related symptoms evaluated in the prepulse inhibition task, although animals treated with Olan showed an increased reactivity to the first acoustic stimulus. MD diminished the corticosterone stress-induced response among females, and reduced the expression of CB1 receptors in the hippocampus of both male and female rats. Notably, Olan administration tended to

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

    Directory of Open Access Journals (Sweden)

    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

  9. Eosinophilic myocarditis during treatment with olanzapine - report of two possible cases

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical...... similarity between olanzapine and clozapine, we hypothesized the existence of such an association. We searched the spontaneous adverse drug reports database of the Danish Health and Medicines Authority for olanzapine and myocarditis in the period from October 21, 1996 to - June 03, 2015. We identified two...... fatal cases of eosinophilic myocarditis associated with the use of olanzapine. CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post...

  10. 奥氮平所致难治性迟发性肌张力障碍1例%Case report of refractory tardive dystonia induced by olanzapine

    Institute of Scientific and Technical Information of China (English)

    孙振晓; 王相立

    2014-01-01

    Tardive dystonia (TDt), a cluster of extrapyramidal symptoms that are caused by long-term use of antipsychotic medication, is characterized by difficulty in autonomic movements of skeletal (voluntary) muscles and consequent deformations of the body. TDt is rarely seen among patients taking olanzapine, but olanzapine was the precipitating antipsychotic medication in this 22-year old male patient with schizophrenia who developed lip puckering, persistent involuntary torticollis, muscular pain, axial dystonia and unstable gait after taking a standard dose of olanzapine regularly for about one year. His symptoms did not resolve after his olanzapine was stopped. Four months of treatment with clozapine combined with magnesium valproate, vitamin E, tiapride, and lorazepam did not lead to any improvement in the dystonia.%迟发性肌张力障碍是长期使用抗精神病药物所致的一系列锥体外系症状,主要特征包括骨骼肌肉(随意肌)自主运动困难和随后的躯体变形。迟发性肌张力障碍在服用奥氮平患者中罕见,但本文报道中奥氮平正是这名22岁男性精神分裂症患者的促发抗精神病药物,他坚持服用标准剂量的奥氮平大约1年后出现撅嘴、持续不自主斜颈、肌肉疼痛、轴向肌张力障碍和步态不稳的症状。停用奥氮平后,他的症状没有缓解。氯氮平合并丙戊酸镁、维生素E、硫必利和劳拉西泮治疗四个月也没有让肌张力障碍得到任何改善。

  11. 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.

  12. Newer antipsychotics and the rabbit syndrome

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    Masalehdan Azadeh

    2007-06-01

    Full Text Available Abstract Background Rabbit syndrome is a movement disorder that is associated with long-term exposure to neuroleptic medications. Of particular interest and importance is the risk of rabbit syndrome with exposure to the newer atypical antipsychotics. Our recent experience with such a case brought to light the importance of exploring this risk. Methods MEDLINE and PubMed (1972–2006 databases were searched for English language articles using the keywords rabbit syndrome, tardive dyskinesia, antipsychotic, extrapyramidal symptoms and side effects. A recent case study is used to expand upon the literature available on newer antipsychotics and rabbit syndrome. Results We reviewed papers that addressed the following aspects of rabbit syndrome 1 the clinical manifestations 2 prevalence and risk factors, 3 etiopathogenesis 4 older antipsychotics and rabbit syndrome 5 newer antipsychotics, 6 treatment options. Moreover, we report a case of RS in a 50 year old white female, diagnosed with bipolar I disorder, that, after the discontinuation of risperidone, developed involuntary movements of the mouth that were fine, rhythmic and rapid, along the vertical axis, and without involvement of the tongue. After the re-introduction of risperidone, the symptoms decreased in a few hours and disappeared after 3 days. Conclusion Eleven cases of rabbit syndrome have been documented since the implementation of newer antipsychotics. Future research is needed to better understand the etiopathogenesis of rabbit syndrome in psychiatric populations treated with the atypical antipsychotics. Understanding the differences and similarities of rabbit syndrome and tardive dyskinesia is crucial to the creation of a successful treatment paradigm.

  13. Association between antipsychotic/antidepressant drug treatments and hospital admissions in schizophrenia assessed using a mental health case register

    Science.gov (United States)

    Cardinal, Rudolf N; Savulich, George; Mann, Louisa M; Fernández-Egea, Emilio

    2015-01-01

    Background: The impact of psychotropic drug choice upon admissions for schizophrenia is not well understood. Aims: To examine the association between antipsychotic/antidepressant use and time in hospital for patients with schizophrenia. Methods: We conducted an observational study, using 8 years’ admission records and electronically generated drug histories from an institution providing secondary mental health care in Cambridgeshire, UK, covering the period 2005–2012 inclusive. Patients with a coded ICD-10 diagnosis of schizophrenia were selected. The primary outcome measure was the time spent as an inpatient in a psychiatric unit. Antipsychotic and antidepressant drugs used by at least 5% of patients overall were examined for associations with admissions. Periods before and after drug commencement were compared for patients having pre-drug admissions, in mirror-image analyses correcting for overall admission rates. Drug use in one 6-month calendar period was used to predict admissions in the next period, across all patients, in a regression analysis accounting for the effects of all other drugs studied and for time. Results: In mirror-image analyses, sulpiride, aripiprazole, clozapine, and olanzapine were associated with fewer subsequent admission days. In regression analyses, sulpiride, mirtazapine, venlafaxine, and clozapine–aripiprazole and clozapine–amisulpride combinations were associated with fewer subsequent admission days. Conclusions: Use of these drugs was associated with fewer days in hospital. Causation is not implied and these findings require confirmation by randomized controlled trials. PMID:27336041

  14. Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

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    Tomiki eSumiyoshi

    2013-10-01

    Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

  15. 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

  16. Antipsychotic treatment of schizophrenia: an update.

    Science.gov (United States)

    Bruijnzeel, Dawn; Suryadevara, Uma; Tandon, Rajiv

    2014-10-01

    The primary objectives in the treatment of schizophrenia are to reduce the frequency and severity of psychotic exacerbation, ameliorate a broad range of symptoms, and improve functional capacity and quality of life. Treatment includes pharmacotherapy and a range of psychosocial interventions. Antipsychotics are the cornerstone of pharmacological treatment for schizophrenia. The sixty-five antipsychotics available in the world are classified into two major groups: first-generation (conventional) agents (FGAs) and second-generation (atypical) agents (SGAs). Whereas clozapine is found to be more efficacious than other agents among otherwise treatment-refractory schizophrenia patients, other differences in efficacy between antipsychotic agents are minor. There are, however, pronounced differences in adverse effect profiles among the 65 antipsychotic medications. Although the 14 SGAs differ "on average" from the 51 FGAs in terms of being associated with a lower risk of EPS and greater risk of metabolic side-effects, substantial variation within the two classes with regard to both risks and other relevant clinical properties undermines the categorical distinction between SGAs and FGAs. Choice of antipsychotic medication should be based on prior treatment response, individual preference, medical history and individual patient vulnerabilities. An individualized treatment approach with ongoing risk-benefit monitoring and collaborative decision-making is outlined. Even as rapid neuroscience advances promise revolutionary improvements in the future, a thoughtful and disciplined approach can provide enhanced outcomes for all schizophrenia patients today.

  17. FMRI, antipsychotics and schizophrenia. Influence of different antipsychotics on BOLD-signal.

    Science.gov (United States)

    Röder, Christian H; Hoogendam, Janna Marie; van der Veen, Frederik M

    2010-01-01

    In the last decade, functional Magnetic Resonance Imaging (FMRI) has been increasingly used to investigate the neurobiology of schizophrenia. This technique relies on changes in the blood-oxygen-level-dependent (BOLD) - signal, which changes in response to neural activity. Many FMRI studies on schizophrenia have examined medicated patients, but little is known about the effects of antipsychotic medication on the BOLD-signal. In this review we investigated to what extent studies in patients with schizophrenia (SC), who were treated with different antipsychotics, could give insight in the effects of antipsychotics on the BOLD-signal. A PubMed search was performed using the search items "schizophrenia", "FMRI", "antipsychotics" and "schizophrenia", "BOLD", "antipsychotics". Only articles in which there were at least two groups of patients with different treatments or in which patients were scanned twice with different treatments were selected. 18 articles, published between 1999 and 2009, fulfilled these criteria. Paradigms and results of these studies were compared regarding differences induced by the administered antipsychotics. This analysis showed no general effect of antipsychotics on the BOLD-signal. However, there is some evidence that the extent of blockade of the dopamine (DA) D(2) receptor does influence the BOLD-signal. Higher affinity to the dopamine D2 receptor, as expressed by a higher/lower inhibition constant (Ki) seems to cause a decrease in BOLD-signal.

  18. Osteoporosis Associated with Antipsychotic Treatment in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Haishan Wu

    2013-01-01

    Full Text Available Schizophrenia is one of the most common global mental diseases, with prevalence of 1%. Patients with schizophrenia are predisposed to diabetes, coronary heart disease, hypertension, and osteoporosis, than the normal. In comparison with the metabolic syndrome, for instance, there are little reports about osteoporosis which occurs secondary to antipsychotic-induced hyperprolactinaemia. There are extensive recent works of literature indicating that osteoporosis is associated with schizophrenia particularly in patients under psychotropic medication therapy. As osteoporotic fractures cause significantly increased morbidity and mortality, it is quite necessary to raise the awareness and understanding of the impact of antipsychotic-induced hyperprolactinaemia on physical health in schizophrenia. In this paper, we will review the relationship between schizophrenia, antipsychotic medication, hyperprolactinaemia, and osteoporosis.

  19. Schizophrenia risk gene CAV1 is both pro-psychotic and required for atypical antipsychotic drug actions in vivo.

    Science.gov (United States)

    Allen, J A; Yadav, P N; Setola, V; Farrell, M; Roth, B L

    2011-08-16

    Caveolin-1 (Cav-1) is a scaffolding protein important for regulating receptor signaling cascades by partitioning signaling molecules into membrane microdomains. Disruption of the CAV1 gene has recently been identified as a rare structural variant associated with schizophrenia. Although Cav-1 knockout (KO) mice displayed no baseline behavioral disruptions, Cav-1 KO mice, similar to schizophrenic individuals, exhibited increased sensitivity to the psychotomimetic N-methyl-D-aspartate receptor antagonist phencyclidine (PCP). Thus, PCP disruption of prepulse inhibition (PPI) and PCP-induced mouse locomotor activity were both enhanced by genetic deletion of Cav-1. Interestingly, genetic deletion of Cav-1 rendered the atypical antipsychotics clozapine and olanzapine and the 5-HT(2A)-selective antagonist M100907 ineffective at normalizing PCP-induced disruption of PPI. We also discovered that genetic deletion of Cav-1 attenuated 5-HT(2A)-induced c-Fos and egr-1 expression in mouse frontal cortex and also reduced 5-HT(2A)-mediated Ca(2+) mobilization in primary cortical neuronal cultures. The behavioral effects of the 5-HT(2A) agonist (2,5-dimethoxy-4-iodoamphetamine) including head twitch responses and disruption of PPI were also attenuated by genetic deletion of Cav-1, indicating that Cav-1 is required for both inverse agonist (that is, atypical antipsychotic drug) and agonist actions at 5-HT(2A) receptors. This study demonstrates that disruption of the CAV1 gene--a rare structural variant associated with schizophrenia--is not only pro-psychotic but also attenuates atypical antipsychotic drug actions.

  20. Antipsychotic agents: efficacy and safety in schizophrenia

    Directory of Open Access Journals (Sweden)

    de Araújo AN

    2012-11-01

    Full Text Available Arão Nogueira de Araújo,1 Eduardo Pondé de Sena,1,2 Irismar Reis de Oliveira,1,3 Mario F Juruena41Postgraduation Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, Brazil; 4Stress and Affective Disorders Program, Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, BrazilAbstract: Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA and third generation antipsychotics (TGA, other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.Keywords: antipsychotic agents, schizophrenia, pharmacology, safety

  1. How can lipid nanocarriers improve transdermal delivery of olanzapine?

    Science.gov (United States)

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

    2016-11-23

    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.

  2. Use of second-generation antipsychotics in the acute inpatient management of schizophrenia in the Middle East

    Directory of Open Access Journals (Sweden)

    Alkhadhari S

    2015-04-01

    Full Text Available Sulaiman Alkhadhari,1 Nasser Al Zain,2 Tarek Darwish,3 Suhail Khan,4 Tarek Okasha,5 Hisham Ramy,5 Talaat Matar Tadros6 1Kuwait Center for Mental Health, Safat, Kuwait; 2Al Amal Complex for Mental Health Hospital, Dammam, Saudi Arabia; 3Behavioural Science Pavilion, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 4Jeddah Psychiatric Hospital, Jeddah, Saudi Arabia; 5Institute of Psychiatry, Ain Shams University, Cairo, Egypt; 6Ibrahim Bin Hamad Obaidallah and Seif Bin Ghubash Hospitals, Ras Alkhaimah, United Arab Emirates Background: Management of acute psychotic episodes in schizophrenic patients remains a significant challenge for clinicians. Despite treatment guidelines recommending that second-generation antipsychotics (SGAs should be used as monotherapy, first-generation antipsychotics, polypharmacy, and lower than recommended doses are frequently administered in clinical practice. Minimal data exist regarding the use of SGAs in the Middle East. The objective of this study was to examine the discrepancies between current clinical practice and guideline recommendations in the region. Methods: RECONNECT-S Beta was a multicenter, noninterventional study conducted in Egypt, Kuwait, Saudi Arabia, and the United Arab Emirates to observe the management of schizophrenic patients who were hospitalized due to an acute psychotic episode. Patients underwent one visit on the day of discharge. Demographic and medical history, together with data on antipsychotic treatment and concomitant medication during the hospitalization period and medication recommendations at discharge were recorded. Results: Of the 1,057 patients, 180 (17.0% and 692 (65.5% received SGAs as monotherapy and in combination therapy, respectively. Overall, the most frequently administered medications were given orally, and included risperidone (40.3%, olanzapine (32.5%, and quetiapine (24.6%; the doses administered varied between countries and deviated from the recommended

  3. A single-blind, randomized comparison of olanzapine at a starting dose of 5 mg versus 20 mg in acute schizophrenia.

    Science.gov (United States)

    Mauri, Massimo Carlo; Colasanti, Alessandro; Rossattini, Matteo; Moliterno, Donatella; Baldi, Marialuisa L; Papa, Pietro

    2006-01-01

    Acute psychotic episodes represent critical situations during the course of schizophrenia. Olanzapine (OLZ), a second-generation antipsychotic, is efficacious in acute settings at dosages of 5 to 20 mg/d, and it can be considered a first-line treatment for patients with an acute episode of schizophrenia. The aim of this study was to evaluate the efficacy and tolerability of OLZ at a starting dose of 5 mg versus 20 mg in acute schizophrenic patients and to compare titration versus nontitration.Fifty-one schizophrenic inpatients were randomly assigned to receive OLZ at 5 mg/d (26 patients, group 1) or 20 mg/d (25 patients, group 2) as a starting dosage during an exacerbation phase. In group 1, the OLZ dosage was increased to a mean dosage of 10.55 (+/- 4.00) mg/d. Group 2 received OLZ at a fixed dose of 20 mg throughout the hospitalization period. Olanzapine was significantly and clinically effective on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale, PANSS positive symptoms, and Hamilton Rating Scale for Depression in both groups. There were no significant differences between groups 1 and 2 in the percent improvement in BPRS, Positive and Negative Syndrome Scale, PANSS positive symptoms, PANSS negative symptoms, or Hamilton Rating Scale for Depression; but group 2 was significantly superior in the mean percent improvement in the BPRS items of anxiety (P < 0.001) and suspiciousness (P < 0.05). In conclusion, the higher doses evidence more efficacy on anxiety and suspiciousness, so it seems to be useful to begin therapy with a full dose of the drug to obtain the maximum effect without any significant side effects.

  4. 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

    Several clinical reports have demonstrated that most antipsychotics of the new generation, but not the typical antipsychotic haloperidol, induce weight gain in schizophrenic patients. Since weight gain induces serious health complications in humans, it is crucial to test upcoming antipsychotic co...

  5. Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

    Directory of Open Access Journals (Sweden)

    Montemagni C

    2016-04-01

    Full Text Available Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL Torino 1 (TO1, Azienda Ospedaliero-Universitaria (AOU Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other

  6. The quality of lactation studies including antipsychotics

    NARCIS (Netherlands)

    Hummels, Hazel; Bertholee, Daphne; van der Meer, Douwe; Smit, Jan Pieter; Wilffert, Bob; ter Horst, Peter

    2016-01-01

    The aim of this study is to determine the quality of lactation studies that investigated antipsychotics in breast milk according to the Food and Drug Administration (FDA) and International Lactation Consultant Association (ILCA) draft guidelines. We used the draft FDA and ILCA guidelines to review t

  7. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

    Science.gov (United States)

    Navari, Rudolph M.; Qin, Rui; Ruddy, Kathryn J.; Liu, Heshan; Powell, Steven F.; Bajaj, Madhuri; Dietrich, Leah; Biggs, David; Lafky, Jacqueline M.; Loprinzi, Charles L.

    2016-01-01

    BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.) PMID:27410922

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Betahistine decreases olanzapine-induced weight gain and somnolence in humans.

    Science.gov (United States)

    Barak, Nir; Beck, Yaffa; Albeck, Joseph H

    2016-03-01

    Olanzapine's efficacy in schizophrenia is attributed to antagonism of dopamine and serotonin receptors. Olanzapine is also a potent histamine-H1 antagonist that results in weight gain and somnolence. Betahistine is a centrally acting histamine-H1 agonist, and therefore may reduce olanzapine's effect on histamine receptors in the brain. Olanzapine's high affinity for the histamine-H1 receptor warrants the use of high doses of betahistine. Forty-eight healthy women were recruited and randomized to receive either betahistine 144 mg/day or matching placebo for 4 weeks. Due to the high dose of betahistine, olanzapine was started only on the second week and titrated up to 10 mg/day, and co-administration continued for an additional 2 weeks. Only nominal differences in adverse events were noted between the treatment groups. Betahistine caused a 37% reduction in mean weight gain (1.24 kg in the betahistine arm vs. 1.93 kg in the placebo arm; p=.049) and 60% reduction in the mean increase in daytime Epworth sleepiness scores (1.82 units in the betahistine group vs. 3.57 units in the placebo group; p=.042). The present study suggests that betahistine-olanzapine co-administration, in healthy female subjects, yields an acceptable safety profile with mitigation of weight gain and somnolence. This should be further tested in a patient cohort.

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

    Science.gov (United States)

    Evers, Simon S; van Vliet, André; van Vugt, Barbara; Scheurink, Anton J W; van Dijk, Gertjan

    2016-04-01

    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 effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 ± 11 years; BW: 84 ± 12 kg; BMI=25.5 ± 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (PTPM. Using multiple regression analysis, BW gain was the key factor explaining metabolic disturbances (e.g., plasma insulin- LDL interaction: PTPM treatment, nor its circulating levels, contributed to variation observed in ΔBW. In a second multiple regression analysis, we observed that a low baseline thyrotropin profile (TSHAUC) before the start of drug treatment was associated with an increase in ΔBW over the course of drug treatment (PTPM treatment did attenuate OLZ induced BW gain (PTPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is associated with improvement in brief psychiatric rating scores (BPRS); adjunctive TPM treatment may be a solution specifically for those subjects susceptible to OLZ-induced rapid weight gain who-on a therapeutic level-benefit most of OLZ treatment.

  12. Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα-SREBP Pathway in 3T3-L1 Cells.

    Science.gov (United States)

    Li, Yanjie; Zhao, Xiaomin; Feng, Xiyu; Liu, Xuemei; Deng, Chao; Hu, Chang-Hua

    2016-11-09

    The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR) on olanzapine (OLZ)-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO) staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG) and total cholesterol (TC) by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of Sterol regulatory element binding proteins 1 (SREBP1), fatty acid synthase (FAS), peroxisome proliferator activated receptor-γ (PPARγ), SREBP2, low-density lipoprotein receptor (LDLR), and hydroxymethylglutaryl-coenzyme A reductase (HMGR) genes compared with OLZ alone. Consistently, the co-treatment downregulated protein levels of SREBP1, SREBP2, and LDLR by 57.71% ± 9.42%, 73.05% ± 11.82%, and 59.46% ± 9.91%, respectively. In addition, co-treatment reversed the phosphorylation level of AMP-activated protein kinase-α (AMPKα), which was reduced by OLZ, determined via the ratio of pAMPKα:AMPKα (94.1%) compared with OLZ alone. The results showed that BBR may prevent lipid metabolism disorders caused by OLZ by reversing the degree of SREBP pathway upregulated and the phosphorylation of AMPKα downregulated. Collectively, these results indicated that BBR could be used as a potential adjuvant to prevent dyslipidemia and obesity caused by the use of second-generation antipsychotic medication.

  13. Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα–SREBP Pathway in 3T3-L1 Cells

    Science.gov (United States)

    Li, Yanjie; Zhao, Xiaomin; Feng, Xiyu; Liu, Xuemei; Deng, Chao; Hu, Chang-Hua

    2016-01-01

    The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR) on olanzapine (OLZ)-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO) staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG) and total cholesterol (TC) by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of Sterol regulatory element binding proteins 1 (SREBP1), fatty acid synthase (FAS), peroxisome proliferator activated receptor-γ (PPARγ), SREBP2, low-density lipoprotein receptor (LDLR), and hydroxymethylglutaryl-coenzyme A reductase (HMGR) genes compared with OLZ alone. Consistently, the co-treatment downregulated protein levels of SREBP1, SREBP2, and LDLR by 57.71% ± 9.42%, 73.05% ± 11.82%, and 59.46% ± 9.91%, respectively. In addition, co-treatment reversed the phosphorylation level of AMP-activated protein kinase-α (AMPKα), which was reduced by OLZ, determined via the ratio of pAMPKα:AMPKα (94.1%) compared with OLZ alone. The results showed that BBR may prevent lipid metabolism disorders caused by OLZ by reversing the degree of SREBP pathway upregulated and the phosphorylation of AMPKα downregulated. Collectively, these results indicated that BBR could be used as a potential adjuvant to prevent dyslipidemia and obesity caused by the use of second-generation antipsychotic medication. PMID:27834848

  14. Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα–SREBP Pathway in 3T3-L1 Cells

    Directory of Open Access Journals (Sweden)

    Yanjie Li

    2016-11-01

    Full Text Available The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR on olanzapine (OLZ-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG and total cholesterol (TC by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of Sterol regulatory element binding proteins 1 (SREBP1, fatty acid synthase (FAS, peroxisome proliferator activated receptor-γ (PPARγ, SREBP2, low-density lipoprotein receptor (LDLR, and hydroxymethylglutaryl-coenzyme A reductase (HMGR genes compared with OLZ alone. Consistently, the co-treatment downregulated protein levels of SREBP1, SREBP2, and LDLR by 57.71% ± 9.42%, 73.05% ± 11.82%, and 59.46% ± 9.91%, respectively. In addition, co-treatment reversed the phosphorylation level of AMP-activated protein kinase-α (AMPKα, which was reduced by OLZ, determined via the ratio of pAMPKα:AMPKα (94.1% compared with OLZ alone. The results showed that BBR may prevent lipid metabolism disorders caused by OLZ by reversing the degree of SREBP pathway upregulated and the phosphorylation of AMPKα downregulated. Collectively, these results indicated that BBR could be used as a potential adjuvant to prevent dyslipidemia and obesity caused by the use of second-generation antipsychotic medication.

  15. Tardive dyskinesia in children treated with atypical antipsychotic medications.

    Science.gov (United States)

    Wonodi, Ikwunga; Reeves, Gloria; Carmichael, Dana; Verovsky, Ilene; Avila, Matthew T; Elliott, Amie; Hong, L Elliot; Adami, Helene M; Thaker, Gunvant K

    2007-09-15

    Recent years have witnessed increased antipsychotic treatment of children despite limited long-term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic-naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African-American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European-American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side-effect profile of the atypical antipsychotic drugs in children may be much different than that in adults.

  16. Behavioral indices in antipsychotic drug discovery.

    Science.gov (United States)

    Porsolt, Roger D; Moser, Paul C; Castagné, Vincent

    2010-06-01

    Schizophrenia is characterized by three major symptom classes: positive symptoms, negative symptoms, and cognitive deficits. Classical antipsychotics (phenothiazines, thioxanthenes, and butyrophenones) are effective against positive symptoms but induce major side effects, in particular, extrapyramidal symptoms (EPS). The discovery of clozapine, which does not induce EPS and is thought effective against all three classes of symptom, has driven research for novel antipsychotics with a wider activity spectrum and lower EPS liability. To increase predictiveness, current efforts aim to develop translational models where direct parallels can be drawn between the processes studied in animals and in humans. The present article reviews existing procedures in animals for their ability to predict compound efficacy and EPS liability in relation to their translational validity. Rodent models of positive symptoms include procedures related to dysfunction in central dopamine and glutamatergic (N-methyl-D-aspartate) and serotonin (5-hydroxytryptamine) neurotransmission. Procedures for evaluating negative symptoms include rodent models of anhedonia, affective flattening, and diminished social interaction. Cognitive deficits can be assessed in rodent models of attention (prepulse inhibition) and of learning/memory (object and social recognition, Morris water maze and operant-delayed alternation). The relevance of the conditioned avoidance response is also discussed. A final section reviews procedures for assessing EPS liability, in particular, parkinsonism (catalepsy in rodents), acute dystonia (purposeless chewing in rodents, dystonia in monkeys), akathisia (defecation in rodents), and tardive dyskinesia (long-term antipsychotic treatment in rodents and monkeys). It is concluded that, with notable exceptions (attention, learning/memory, EPS liability), current predictive models for antipsychotics fall short of clear translational validity.

  17. Schizophrenia, antipsychotics and risk of hip fracture

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Jensen, Signe O W; Nielsen, Jimmi

    2013-01-01

    -morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture...

  18. Side effects of antipsychotic agents--neuroleptic malignant syndrome.

    Science.gov (United States)

    Cvjetković-Bosnjak, Mina; Soldatović-Stajić, Branislava

    2010-01-01

    Summary - Neuroleptic malignant syndrome is a rare, potentially life-threatening complication which is an unpredictable, idiosyncratic reaction to antipsychotics. In patients receiving traditional antipsychotics, neuroleptic malignant syndrome occurs with an incidence of 0.2-3.3%. However, neuroleptic malignant syndrome also appears in patients treated with atypical antipsychotics, especially Clozapine. A possible cause of neuroleptic malignant syndrome is blockade of dopamine receptors in the nigrostriatal tracts or hypothalamic nuclei. If signs and symptoms of the Neuroleptic malignant syndrome are identified in time, full recovery is possible. This is a report of a female patient with neuroleptic malignant syndrome treated by traditional antipsychotics. As soon as neuroleptic malignant syndrome symptoms were recognized, the antipsychotic drugs were discontinued, symptomatic therapy was initiated and symptoms of neuroleptic malignant syndrome disappeared. However, the patient's psychotic symptoms persisted and an atypical antipsychotic was administered. During the next few days the psychotic symptoms gradually disappeared and the patient accomplished good recovery.

  19. Sexual dysfunction with antihypertensive and antipsychotic agents.

    Science.gov (United States)

    Smith, P J; Talbert, R L

    1986-05-01

    The physiology of the normal sexual response, epidemiology of sexual dysfunction, and the pharmacologic mechanisms involved in antihypertensive- and antipsychotic-induced problems with sexual function are discussed, with recommendations for patient management. The physiologic mechanisms involved in the normal sexual response include neurogenic, psychogenic, vascular, and hormonal factors that are coordinated by centers in the hypothalamus, limbic system, and cerebral cortex. Sexual dysfunction is frequently attributed to antihypertensive and antipsychotic agents and is a cause of noncompliance. Drug-induced effects include diminished libido, delayed orgasm, ejaculatory disturbances, gynecomastia, impotence, and priapism. The pharmacologic mechanisms proposed to account for these adverse effects include adrenergic inhibition, adrenergic-receptor blockade, anticholinergic properties, and endocrine and sedative effects. The most frequently reported adverse effect on sexual function with the antihypertensive agents is impotence. It is seen most often with methyldopa, guanethidine, clonidine, and propranolol. In contrast, the most common adverse effect on sexual function with the antipsychotic agents involves ejaculatory disturbances. Thioridazine, with its potent anticholinergic and alpha-blocking properties, is cited most often. Drug-induced sexual dysfunction may be alleviated by switching to agents with dissimilar mechanisms to alter the observed adverse effect while maintaining adequate control of the patient's disease state.

  20. Postprandial prolactin suppression appears absent in antipsychotic-treated male patients

    DEFF Research Database (Denmark)

    Coello, Klara; Broberg, Brian Villumsen; Bak, Nikolaj;

    2015-01-01

    INTRODUCTION: Hyperprolactinemia is a common side-effect of antipsychotic treatment. Antipsychotics and hyperprolactinemia are both considered risk factors of metabolic disturbances and diabetes. Investigations on prolactin response to meal ingestion in antipsychotic-treated patients are missing...

  1. Serum prolactin levels and sexual dysfunctions in antipsychotic medication, such as risperidone : a review

    NARCIS (Netherlands)

    Knegtering, H; Lambers, PA; Prakken, G; ten Brink, C

    2000-01-01

    Classical antipsychotic drugs increase the level of serum prolactin. The atypical antipsychotic clozapine barely increases prolactin levels. An open naturalistic study in the University Hospital of Groningen suggests that treatment with risperidone in comparison to classical antipsychotics seems to

  2. Antipsychotic-Induced Neuroleptic Malignant Syndrome After Cardiac Surgery.

    Science.gov (United States)

    Moll, Vanessa; Ward, Ceressa T; Zivot, Joel B

    2016-07-01

    We report a case of neuroleptic malignant syndrome (NMS) in a postoperative cardiac surgery patient after the administration of typical and atypical antipsychotics for the treatment of delirium. On postoperative day 8, the patient's temperature peaked at 40.6°C. Agitation, rigidity, elevation in creatine kinase, and leukocytosis were associated findings. NMS was suspected on postoperative day 10. All antipsychotics were discontinued; dantrolene infusions and fluid therapy were initiated. After 2 days of NMS treatment, the patient's symptoms resolved. The temporal relationship between discontinuation of all antipsychotics, initiation of dantrolene, and clinical improvement supports the diagnosis of antipsychotic-induced NMS.

  3. 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

    To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first-trimester expos......To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first......-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432....../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...

  4. Spectrum of binge eating symptomatology in patients treated with clozapine and olanzapine.

    Science.gov (United States)

    Theisen, F M; Linden, A; König, I R; Martin, M; Remschmidt, H; Hebebrand, J

    2003-01-01

    The authors explored the binge eating symptomatology in 74 patients receiving clozapine (N = 57) or olanzapine (N = 17), and compared body mass index (BMI, kg/m(2)) and weight gain in patients with and without binge eating symptomatology. Subjects who screened positively for binge eating were interviewed using a modified version of the Questionnaire on Eating and Weight Patterns (QEWP). Current BMIs were assessed cross-sectionally, BMIs at initiation of clozapine/olanzapine treatment retrospectively. Thirty-seven subjects (50%) screened positively. Taking clozapine and olanzapine together, 6/27 (22.2%) females and 3/47 (6.4%) males fulfilled criteria for binge eating disorder, 3/27 (11.1%) females and 2/47 (4.3%) males for bulimia nervosa. Patients who screened positively showed higher current BMIs (26.8 +/- 3.9 vs. 24.7 +/- 3.7 kg/m(2)) and higher BMI increments during clozapine/olanzapine treatment (3.9 +/- 3.1 vs. 2.6 +/- 3.4 kg/m(2)) than patients who screened negatively. We conclude that clozapine/olanzapine may induce binge eating and full blown eating disorders which may have predictive value for weight gain. For future research in this field we suggest a novel DSM-IV research classification "Medication-induced eating disorders".

  5. Delusion symptoms and response to antipsychotic treatment are associated with the 5-HT2A receptor polymorphism (102T/C) in Alzheimer's disease: a 3-year follow-up longitudinal study.

    Science.gov (United States)

    Angelucci, Francesco; Bernardini, Sergio; Gravina, Paolo; Bellincampi, Lorenza; Trequattrini, Alberto; Di Iulio, Fulvia; Vanni, Diego; Federici, Giorgio; Caltagirone, Carlo; Bossù, Paola; Spalletta, Gianfranco

    2009-01-01

    Although the etiology of psychotic symptoms (hallucinations and delusions) in Alzheimer's disease is still not known, alterations in serotonergic neurotransmission have been proposed. In a 3-year follow-up study, we evaluated the association of serotonin (5-HT) receptor 5-HT2a 102T/C polymorphism (allelic variants CC, CT and TT) with psychotic symptom severity and response to treatment with atypical antipsychotics (risperidone, olanzapine and quietapine) in 80 patients with a diagnosis of probable Alzheimer's disease. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity (FxS) of psychotic and other behavioral symptoms. There was a significant difference in the NPI FxS delusion score among the three variants of the 5-HT2a 102T/C polymorphism, with patients carrying the TT genotype the most delusional during the follow-up period. In particular, NPI FxS delusion score was higher in TT than in CC genotype at year 2. Moreover, patients with delusion symptoms carrying the CT and TT genotypes were resistant to the treatment with antipsychotic drugs. Thus our study, although at preliminary level, suggests that the presence of T allele of the 102T/C polymorphism in patients with Alzheimer's disease is associated with both increased presence of delusion symptoms and treatment-resistance to second generation antipsychotic drugs.

  6. Differential effects of classical and atypical antipsychotic drugs on rotenone-induced neurotoxicity in PC12 cells.

    Science.gov (United States)

    Tan, Qing-Rong; Wang, Xin-Zhao; Wang, Chuan-Yue; Liu, Xiao-Jun; Chen, Yun-Chun; Wang, Huai-Hai; Zhang, Rui-Guo; Zhen, Xue-Chu; Tong, Yao; Zhang, Zhang-Jin

    2007-12-01

    Although classical and atypical antipsychotics may have different effects against neurotoxicity, the underlying mechanisms remain to be elucidated. In the present study, we compared the atypical agents, risperidone (RIP), olanzapine (OLZ), and quetiapine (QTP), with the classical agent haloperidol (HAL) in reducing cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor, in PC12 cells. We also determined whether there were differential effects of RIP and HAL on the expression of brain-derived neurotrophic factor (BDNF), signal transducers and activators of transcription-3 (STAT-3), and the immediate early gene c-fos, as well as intracellular levels of calcium. Exposure to 6 muM rotenone for 24 h resulted in a significant decrease in cell viability and apoptotic alteration. The rotenone-induced cytotoxicity was dose-dependently worsened by pretreatment with HAL, but significantly improved by the aforementioned atypical agents at low doses. Real-time PCR analysis revealed that HAL pretreatment significantly increased BDNF mRNA expression but did not alter c-fos and STAT-3 expression compared to rotenone-exposed cells. Unlike HAL, RIP pretreatment produced a significant elevation of all the three substance mRNA expression and the expression intensity was 2.6- to 4.6-fold greater than HAL. Pretreatment with RIP, but not HAL, also effectively prevented an elevation of intracellular levels of calcium provoked by rotenone. These results suggest that the protective effects of atypical antipsychotics are associated with a greater capacity to enhance pro-cell survival factors, therapeutic biomarker expression, and blockade of calcium influx. This may provide an alternative for explaining therapeutic advantages of atypical agents observed in clinical use.

  7. Effects of antipsychotics on microRNA expression of peripheral blood in schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Xin-yang SUN

    2015-01-01

    Full Text Available Objective To observe the changes in microRNA (miRNA expression levels in peripheral blood of schizophrenia patients before and after treatment with antipsychotics. Methods Sixty-one consecutive patients with schizophrenia (case group and 62 normal controls (control group hospitalized to the 102nd Hospital of PLA from July 2012 to May 2013 were involved in this study. The relative expression levels of 9 miRNAs (miR-181b, miR-195, miR-132, miR-212, miR-30e, miR-346, miR-34a, miR-432, miR-7 in the peripheral blood plasma of patients in two groups were determined by real-time fluorescence quantitative PCR. Twenty-five schizophrenia patients with total score of Positive and Negative Syndrome Scale (PANSS >70 were selected to determine the miRNA expression levels before and 3 and 6 weeks after antipsychotics (including olanzapine, quetiapine, ziprasidone and risperidone treatment, and the clinical symptoms and treatment effect in different stages of therapy were assessed by PANSS, Global Assessment Scale (GAS, and Clinical Global Impression scale (CGI. Results The expression levels of miR-181b, miR-30e, miR-346, miR-34a and miR-7 in case group were significantly higher than those in control group (P70, the expression level of miR-132 lowered 3 weeks after treatment (P0.05. The expression of miR-132, miR-195, miR-30e and miR-432 were significantly correlated with the PANSS total score and GAS score along with the treatment course (P<0.05. Conclusion The miR-181b, miR-132, miR-30e and miR-432 may be used as biological markers for the prediction of the prognosis of patients with schizophrenia. DOI: 10.11855/j.issn.0577-7402.2014.12.09

  8. Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; Herings, RMC; Roos, RAC; Jansen, PAF; Leufkens, HGM

    2001-01-01

    Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous clinica

  9. Efeitos adversos metabólicos de antipsicóticos e estabilizadores de humor Metabolic side effects of antipsychotics and mood stabilizers

    Directory of Open Access Journals (Sweden)

    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.

  10. [3-D ultrasound-assisted gait analysis of schizophrenic patients. Comparison between conventional neuroleptics and olanzapine].

    Science.gov (United States)

    Putzhammer, Albert; Heindl, Bernhard; Müller, Jürgen; Broll, Karin; Pfeiff, Liane; Perfahl, Maria; Hess, Linda; Koch, Horst

    2003-05-01

    Schizophrenic disorders as well as neuroleptic treatment can affect locomotion. The study assessed the influence of neuroleptic treatment on human gait via ultrasonic topometric gait analysis. In a control sample the test system proved high test-retest-reliability. Spatial and temporal gait parameters were assessed in schizophrenic patients without neuroleptic treatment (n = 12) and under treatment with conventional neuroleptics (n = 14) and re-assessed after treatment change to the atypical neuroleptic olanzapine in a repeated measures design. After switch from conventional neuroleptics to olanzapine patients showed an increase of gait velocity (p step length (p gait analysis.

  11. 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...

  12. Differential RNA expression between schizophrenic patients and controls of the dystrobrevin binding protein 1 and neuregulin 1 genes in immortalized lymphocytes.

    Science.gov (United States)

    Chagnon, Y C; Roy, M-A; Bureau, A; Mérette, C; Maziade, M

    2008-03-01

    The dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1) genes have been related to schizophrenia (SZ) and bipolar disorder (BP) by several whole-genome linkage and associations studies. Few expression studies in post-mortem brains have also reported a lower or a higher expression of DTNBP1 and NRG1, respectively, in SZ. Since the difficulty to access post-mortem brains, we evaluated RNA expression of DTNBP1 and NRG1 in immortalized lymphocytes of SZ patients and unrelated-family controls. An antipsychotic stimulation was also used to challenge the genetic background of the subjects and enhance differential expression. Immortalized lymphocytes of twelve SZ and twelve controls were grown individually in the presence or not of the antipsychotic olanzapine (Zyprexa; EliLilly). RNA was extracted and pooled in four groups of three SZ and four groups of three controls, and used to probe Agilent 18K microchips. Mean gene expression values were contrasted between SZ and control groups using a T-test. For DTNBP1, RNA expression was lower in SZ than in controls before (-28%; p=0.02) and after (-30%; p=0.01) olanzapine stimulation. Similarly, NRG1 GGF2 isoform showed a lower expression in SZ before (-29%; p=0.04) and after (-33%; p=0.02) olanzapine stimulation. In contrast, NRG1 GGF isoform showed no significant difference between SZ and controls (-7%; p=0.61, +3%; p=0.86, respectively), but was slightly repressed by olanzapine in controls (-8%; p=0.008) but not in SZ (+1%; p=0.91). These results are in agreement with those observed in post-mortem brain when the isoforms involved are considered.

  13. Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis.

    Science.gov (United States)

    Boks, Marco P M; Liddle, Peter F; Russo, Sascha; Knegtering, Rikus; van den Bosch, Robert Jan

    2003-07-15

    First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of antipsychotic medication does not influence NSS, but that atypical antipsychotics are associated with less dyskinesia in the early stages of treatment.

  14. Examining dopamine D3 receptor occupancy by antipsychotic drugs via [3H]7-OH-DPAT ex vivo autoradiography and its cross-validation via c-fos immunohistochemistry in the rat brain.

    Science.gov (United States)

    Davoodi, Nima; te Riele, Paula; Langlois, Xavier

    2014-10-05

    Dopamine D3 receptors are a major target for drug discovery programs related to psychiatric disorders such as schizophrenia. The ability of a compound to occupy significant levels of D3 receptors is important for achieving therapeutic efficacy in both pre-clinical and clinical settings. Here we attempt to characterise antipsychotic drug-effects at D3 receptors by measuring receptor occupancy via ex-vivo [3H]7-OH-DPAT autoradiography, and further validating this outcome via analysis of Fos-like immunoreactivity (Fos-LI) in the rat major islands of Calleja (ICjM), a brain structure with high D3 expression. Rats were treated subcutaneously with haloperidol (0.04 mg/kg), clozapine (20 mg/kg) and olanzapine (0.63 mg/kg), the selective D2 antagonist L-741626 (2.5 mg/kg) and the selective D3 antagonist SB-277011-A (10 mg/kg). Doses were based on levels of D2 occupancy considered clinically relevant (60-80%). When measuring D3 occupancy, clozapine and SB-277011-A displayed meaningful levels of occupancy (60% and 77%, respectively), haloperidol and olanzapine showed limited occupancy (16% and 27%, respectively), whereas L-741626 showed no occupancy. There were no significant changes in ICjM Fos-LI after L-741626 and haloperidol treatment, minor but significant increases after olanzapine treatment, whereas highly significant increases were seen with SB-277011-A and clozapine. Additionally, pre-treating clozapine with the D1 antagonist SCH23390 caused a significant, albeit non-complete, reduction in Fos-LI, highlighting the D1 agonist property of clozapine. In conclusion, it appears that drugs occupying >50% D3 receptors produce robust increases in ICjM Fos-LI. This study may help to identify the appropriate D3 receptor antagonists that have the potential to be tested in the clinic.

  15. 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%.

  16. 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.

  17. The stress stability of olanzapine: studies of interactions with excipients in solid state pharmaceutical formulations.

    Science.gov (United States)

    Djordjević Filijović, Nataša; Antonijević, Milan D; Pavlović, Aleksandar; Vučković, Ivan; Nikolić, Katarina; Agbaba, Danica

    2015-03-01

    Stress stability testing represents an important part of the drug development process. It is used as an important tool for the identification of degradation products and degradation pathways, as well as for the assessment of changes in physical form of drug molecules. The impact of excipients on the stability of olanzapine confirms that levels of impurities and degradants are limiting parameters and are therefore used for stability evaluation. The major degradation product of olanzapine was identified as 2-methyl-5,10-dihydro-4H-thieno[2,3-b][1,5]benzodiazepine-4-one (III). The structure of III was determined by using LC-MS, IR and NMR. Compatibility and stress stability results demonstrated that tablet formulations of olanzapine are sensitive to temperature and moisture. In samples protected from moisture, the increase in concentration of III was shown to be highly temperature dependent and the degradation followed zero-order kinetics. In addition, studies of olanzapine with excipients and in formulated tablets revealed polymorphic phase changes in some samples, influenced by a combination of stress temperature and humidity conditions. Polymorphic transitions were monitored using x-ray powder diffraction (XRPD) analysis and exhibited no correlation between the phase change (appearance of a new polymorph) and the degradation process.

  18. Open-label study of olanzapine in children with pervasive developmental disorder.

    NARCIS (Netherlands)

    Kemner, C.; Swinkels, S.H.N.; Jonge, M.J.A. de; Tuynman-Qua, H.G.; Engeland, H.M. van

    2002-01-01

    The effects of olanzapine on the symptomatology of children with pervasive developmental disorder with emphasis on problems of communication and the safety of the drug were investigated in a 3-month open-label, open-dosage study. Participating in the study were 25 children age 6 to 16 years with a d

  19. Role of Polymeric Excipients in the Stabilization of Olanzapine when Exposed to Aqueous Environments

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    Maria Paisana

    2015-12-01

    Full Text Available Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC and microscopy (SEM for crystal size and shape. The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets’ processing and dissolution evaluation.

  20. Long-term adverse effects of novel antipsychotics.

    Science.gov (United States)

    Masand, P S; Gupta, S

    2000-11-01

    The introduction of novel antipsychotics for the treatment of patients with serious psychiatric illness has alleviated the burden of managing some of the side effects of conventional agents. However, the novel agents may also cause adverse events. The long-term adverse events of concern include weight gain, diabetes, tardive dyskinesia (TD), and those associated with hyperprolactinemia. Recent studies with the novel agents have prompted clinicians to revisit antipsychotic-induced weight gain. Clinically significant weight gain puts patients at risk for coronary heart disease, hypertension, type II diabetes, dyslipidemia, and some types of cancer. More recently, case reports of glucose abnormalities and diabetes have emerged, indicating that some novel antipsychotics may be associated with altered glucose metabolism or insulin sensitivity. The novel antipsychotics may also have a lower propensity for causing TD than the conventional antipsychotics. Side effects associated with hyperprolactinemia include galactorrhea, gynecomastia, and menstrual and sexual dysfunction. All of these adverse events can cause patients to become non-compliant and may thus predispose them to relapse. In this review, the authors summarize the literature on the long-term side effects of the novel antipsychotics and examine the severity of the problem, with recommendations for management. When selecting treatments, clinicians should consider the side-effect profiles of the various antipsychotic agents.

  1. A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report

    Directory of Open Access Journals (Sweden)

    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

  2. Clozapine regulation of p90RSK and c-Fos signaling via the ErbB1-ERK pathway is distinct from olanzapine and haloperidol in mouse cortex and striatum.

    Science.gov (United States)

    Pereira, Avril; Zhang, Betty; Malcolm, Peter; Sundram, Suresh

    2013-01-10

    Treatment of the positive psychotic symptoms of schizophrenia with standard antipsychotic drugs (APDs) is ineffective in a proportion of cases. For these treatment resistant patients the alternative is the APD clozapine which is superior to other agents but carries serious side effects. Why clozapine is uniquely effective is unknown, but we have previously postulated may involve G-protein coupled receptor (GPCR) and epidermal growth factor (EGF) receptor (ErbB1) transactivation signaling to the mitogen-activated protein kinase-extracellular signal regulated kinase (MAPK-ERK) cascade. This was based upon clozapine induced initial down-regulation and delayed ErbB1 mediated activation of the cortical and striatal ERK response in vivo distinct from other APDs. This study investigated if modulation of the ErbB1-ERK1/2 pathway by clozapine, olanzapine and haloperidol affected expression of the ERK substrates p90RSK and c-Fos, factors that regulate transcription of proteins associated with neuroplasticity and synapse formation in C57Bl/6 mice. In cortex and striatum, acute clozapine treatment induced biphasic p90RSK phosphorylation via MEK that paralleled ERK phosphorylation independent of EGF receptor blockade. By contrast, olanzapine and haloperidol caused p90RSK phosphorylation that was not concomitant with ERK signaling over a 24-hour period. For c-Fos, clozapine elevated expression 24h after administration, a timeframe consistent with ERK activation at 8h. Alternatively, haloperidol stimulation of c-Fos levels limited to the striatum was in accord with direct transcriptional regulation through ERK. The unique spatio-temporal expression of downstream nuclear markers of the ErbB1-ERK pathway invoked by clozapine may contribute to its effectiveness in treatment resistant schizophrenia.

  3. 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.

  4. Efficacy and safety of blonanserin versus other antipsychotics: a review

    Directory of Open Access Journals (Sweden)

    Anant D. Patil

    2013-12-01

    Full Text Available Although many atypical antipsychotics are available, there is a need of an atypical antipsychotic effective in all symptom domains of schizophrenia and well tolerated especially for side effects like extrapyramidal side effects, weight gain and blood prolactin elevation. Blonanserin is an atypical antipsychotic which blocks dopamine D2 and serotonin 5HT2A receptors. Its efficacy and safety has been studied in patients with schizophrenia and delirium. Blonanserin is found to be effective and well tolerated in both conditions. This article has reviewed efficacy and tolerability of blonanserin in these two psychiatry diseases. [Int J Basic Clin Pharmacol 2013; 2(6.000: 689-692

  5. Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom.

    Science.gov (United States)

    McKendrick, J; Cerri, K H; Lloyd, A; D'Ausilio, A; Dando, S; Chinn, C

    2007-08-01

    This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

  6. [Effect of antipsychotic amisulpride on immune reactivity].

    Science.gov (United States)

    Idova, G V; Al'perina, E L; Lobacheva, O A; Zhukova, E N; Cheĭdo, M A; Meniavtseva, T A; Vetlugina, T P

    2013-01-01

    The effect of atypical antipsychotic solian (amisulpride), binding predominantly to dopamine D2/D3-receptors, on the immune reactivity has been studied in mice of the CBA strain with different psychoemotional states (aggressive and submissive behavior). In addition, the effect of solian on the expression of various CD-markers of lymphocytes in has been analyzed in vitro for patients with schizophrenia diagnosis. Chronic (10 days) administration of solian in mice at a dose of 5.0 mg/kg resulted in a significant suppression of the immune response to T-dependent antigen (sheep red blood cells). This effect was manifested in animals with both psychoemotional states, but was more expressed in aggressive animals. In the in vitro system, solian produced opposite effects on the expression of surface CD receptors in lymphocytes of patients with schizophrenia. It is suggested that solian does not only affects immune function through D2 receptors of the brain, but also directly influences immunocompetent cells.

  7. [Atypical antipsychotic-induced weight gain].

    Science.gov (United States)

    Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.

  8. Indications of atypical antipsychotics in the elderly.

    Science.gov (United States)

    McKean, Andrew; Monasterio, Erik

    2015-01-01

    Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.

  9. Time trends in antipsychotic drug use in patients with dementia

    DEFF Research Database (Denmark)

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane;

    2016-01-01

    BACKGROUND: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. OBJECTIVE......: To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...

  10. Sudden cardiac death secondary to antidepressant and antipsychotic drugs.

    Science.gov (United States)

    Sicouri, Serge; Antzelevitch, Charles

    2008-03-01

    A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use.

  11. Hyperprolactinemia with antipsychotic drugs in children and adolescents.

    Science.gov (United States)

    Rosenbloom, Arlan L

    2010-01-01

    There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  12. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;

    2012-01-01

    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To i...

  13. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Arlan L. Rosenbloom

    2010-01-01

    Full Text Available There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  14. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Rosenbloom ArlanL

    2010-08-01

    Full Text Available There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  15. Enhancing the aqueous solubility and dissolution of olanzapine using freeze-drying

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    Mudit Dixit

    2011-12-01

    Full Text Available The aim of the present study was to develop an olanzapine freeze-dried tablet (FDT. The solubility and dissolution rate of poorly water-soluble olanzapine was improved by preparing a freeze-dried tablet of olanzapine using the freeze-drying technique . The FDT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was poured in to the pockets of blister packs and then was subjected to freezing and lyophilisation. The FDT was characterised by DSC, XRD and SEM and was evaluated for saturation solubility and dissolution. The samples were stored in a stability chamber to investigate their physical stability. Results obtained by DSC and X-ray were analysed and showed the crystalline state of olanzapine in FDT transformation to the amorphous state during the formation of FDT. Scanning electron microscope (SEM results suggest reduction in olanzapine particle size. The solubility of olanzapine from the FDT was observed to be nearly four and a half times greater than the pure drug. Results obtained from dissolution studies showed that olanzapine FDT significantly improved the dissolution rate of the drug compared with the physical mixture (PM and the pure drug. More than 90% of olanzapine in FDT dissolved within 5 minutes, compared to only 19.78% of olanzapine pure drug dissolved over the course of 60 minutes. In a stability test, the release profile of the FDT was unchanged, as compared to the freshly prepared FDT after 90 days of storing.O objetivo do presente estudo foi desenvolver comprimidos liofilizados de olanzapina (FDT. A solubilidade e a taxa de dissolução da olanzapina, fracamente solúvel em água, foram melhoradas com a preparação de comprimidos liofilizados de olanzapina usando a técnica de liofilização. O FDT foi preparado por dispersão do fármaco em solução aquosa de materiais altamente solúveis em água, como gelatina

  16. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    OpenAIRE

    Rosenbloom ArlanL

    2010-01-01

    There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-g...

  17. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    OpenAIRE

    Rosenbloom, Arlan L.

    2010-01-01

    There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-ge...

  18. Antipsychotics, mood stabilisers, and risk of violent crime

    OpenAIRE

    Fazel, Seena; Zetterqvist, Johan; Larsson, Henrik; Långström, Niklas; Lichtenstein, Paul

    2014-01-01

    Summary Background Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden. Methods We used linked Swedis...

  19. Síndrome neuroléptica maligna de paciente em uso de olanzapina Neuroleptic malignant syndrome in patient using olanzapine

    Directory of Open Access Journals (Sweden)

    Fabrício Lins de Medeiros

    2008-01-01

    Full Text Available A síndrome neuroléptica maligna (SNM é uma reação idiossincrásica rara, extremamente grave e potencialmente fatal ao uso de antipsicóticos, tanto típicos quanto atípicos, bem como drogas de ação dopaminérgica. O diagnóstico fundamenta-se em critérios clínicos e laboratoriais e exclusão de outras condições médicas gerais ou psiquiátricas que melhor expliquem os sintomas. Segundo o DSM-IV, os principais critérios são rigidez muscular grave e temperatura elevada, associadas ao uso de medicação antipsicótica. Foi relatado um caso de paciente com 30 anos manifestando história de transtorno afetivo bipolar, que apresentou sinais e sintomas consistentes com SNM, após três semanas de tratamento com olanzapina. Esse relato visa a discutir o risco da SNM ao uso de antipsicóticos atípicos, bem como a importância de diagnóstico precoce e intervenção imediata.Neuroleptic malignant syndrome (NMS is an idiosyncratic, serious and potentially fatal disorder observed in patients who receive treatment with neuroleptics, typical and atypical, as well as medications with dopaminergic effects. The diagnosis is based on clinical and laboratory criteria and the exclusion of other general medical or psychiatric conditions that could best explain the symptoms. The main criteria according to DSM-IV are severe rigidity and fever associated with the use of antipsychotic medication. We present a case of a 30-year-old female with history of bipolar affective disorder that developed signs and symptoms consistent with NMS after three weeks of treatment with Olanzapine. This case aims to address the risk of NMS associated atypical antipsychotic, as well as the importance of an early diagnosis and immediate intervention.

  20. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

    Directory of Open Access Journals (Sweden)

    Izchak Kohen

    2010-03-01

    Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

  1. Antipsychotic Prescriptions for Children Aged 5 Years or Younger

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    Ana Lòpez-De Fede

    2014-10-01

    Full Text Available The use of antipsychotics in very young children is of concern given the lack of empirical evidence in their efficacy and long-term impact on children’s health. This study examined the prescription of antipsychotics among children aged ≤5 years enrolled in a state Medicaid program. Secondary data analysis was conducted using the Medicaid administrative data of a southeastern state. Using SAS 9.3, descriptive statistics were performed to examine socio-demographic characteristics, psychiatric diagnoses, off-label use, receipt of medications from multiple psychotropic drug classes, and receipt of non-pharmacologic psychiatric services among children aged ≤5 years who received antipsychotic prescriptions in calendar year (CY 2011. A total of 112 children in the target age group received antipsychotics in CY 2011, the most common prescription being risperidone. The most common listed psychiatric diagnosis was attention deficit hyperactivity disorder. Two in five children received antipsychotics for off-label use. Three in four children also received medications from at least one other psychotropic drug class. More than half did not receive adjunct psychiatric services. State-level policies offering specific guidance and recommendations for antipsychotic use among very young children are urgently needed. Future research is warranted to examine long-term impact of such practices on children’s growth and development.

  2. Antipsychotics from theory to practice: integrating clinical and basic data.

    Science.gov (United States)

    Tandon, R; Milner, K; Jibson, M D

    1999-01-01

    The recent introduction of the atypical antipsychotics into the treatment arena for psychoses and related disorders comes with justifiable excitement. These newer antipsychotics offer several clinical benefits over the conventional antipsychotics, which have been the mainstays of care thus far. The primary advantage of these atypical agents is their superior side effect profiles, particularly with regard to extrapyramidal side effects (EPS). The implications from a reduction in EPS touch on virtually every aspect of pathology in schizophrenic illness, including short- and long-term movement disorders, negative symptoms, noncompliance, cognitive dysfunction, and dysphoria. It should be emphasized that while atypical antipsychotics share many clinical attributes, there are also substantial differences among them. This review will examine the pharmacology, clinical efficacy, and side effect profiles of the atypical antipsychotics and attempt to relate the attributes observed in clinical practice and clinical trials to their basic pharmacologic profiles. There is a fair, but not perfect, correspondence between the pharmacologic profiles of the different atypical antipsychotics and their respective clinical attributes. After a comparative overview of their receptor-binding profiles, a brief pharmacokinetic summary will be provided. Finally, the clinical profiles of these agents will be summarized with regard to both their efficacy and adverse effects.

  3. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

    Directory of Open Access Journals (Sweden)

    Zuardi A.W.

    2006-01-01

    Full Text Available A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD, a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

  4. Priapism in Antipsychotic Drug Use: A Rare but Important Side Effect

    Directory of Open Access Journals (Sweden)

    Igne Sinkeviciute

    2012-01-01

    Full Text Available Priapism is a rare but important side effect of antipsychotic drugs which may evolve into a urological emergency. Most antipsychotic drugs are alpha-1 adrenergic antagonists, which is thought to be the principal mechanism involved in antipsychotic-induced priapism. Other aetiologies exist, however. A case is presented with multiple episodes of priapism during the use of several different antipsychotic drugs. The case is representative of many patients treated with antipsychotic drugs, as there were hyperprolactinemia, and illicit drug use, which are known causes of priapism. Moreover, the patient used combinations of antipsychotic drugs. The case thus illustrates the etiological complexity which could delay a diagnosis of antipsychotic-induced priapism, and the problem of establishing a link between priapism and one particular ingredient of a drug combination. The case presents how a treatment regimen was finally established balancing antipsychotic efficacy to acceptable side effects and offers guidance to physicians regarding how antipsychotic-induced priapism may be resolved.

  5. Effects of Controlled Discontinuation of Long-Term Used Antipsychotics on Weight and Metabolic Parameters in Individuals With Intellectual Disability

    NARCIS (Netherlands)

    de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Visser, Frank; Hoekstra, Pieter J.

    2013-01-01

    Antipsychotics are frequently prescribed agents in individuals with intellectual disability, often for behavioral symptoms. Efficacy of antipsychotics for this is ambiguous, so discontinuation should be considered. Weight gain and metabolic dysregulation are well-known adverse effects of antipsychot

  6. Acute-Onset Type 1 Diabetes that Developed During the Administration of Olanzapine

    Science.gov (United States)

    Iwaku, Kenji; Otuka, Fumiko; Taniyama, Matsuo

    2017-01-01

    The patient was 32-year-old man, who received olanzapine for schizophrenia and developed polyuria and thirst without drinking soft-drinks after 4 months. Five months after the initiation of treatment, he developed diabetic ketoacidosis (blood glucose: 490 mg/dL, HbA1c: 15.5%). He was diagnosed with type 1 diabetes (glutamic acid decarboxylase (GAD)-Ab: 5.6 U/mL, IA-2 Ab: 5.9 U/mL, fasting C-peptide: 0.12 ng/mL) and was put on intensive insulin therapy. At four months after the onset of 1A diabetes, he experienced a honeymoon phase that was sustained until the 40th month of treatment. We hypothesize that the administration of olanzapine to a patient with pre-type 1A diabetes induced marked hyperglycemia and accelerated the onset of type 1A diabetes. PMID:28154279

  7. Plasma metabonomics study of first-Episode schizophrenia treated with olanzapine in female patients.

    Science.gov (United States)

    Qiao, Ying; Zhang, Lei; He, Shen; Wen, Hui; Yu, Yi-Min; Cao, Chun-Hua; Li, Hua-Fang

    2016-03-23

    Schizophrenia is a persistent chronic mental illness with an unknown pathogenic mechanism; no empirical laboratory-based tests are available to support the diagnosis of schizophrenia or to identify biomarkers correlated with the therapeutic effect of olanzapine. For this study, 15 female first-episode, drug-naïve patients with schizophrenia and 15 healthy female volunteers were recruited. Tests for blood glucose and lipids were conducted at baseline and after 4 weeks of treatment with olanzapine. UPLC-MS based metabonomic analysis was performed on both case and control groups to identify biomarkers of schizophrenia at baseline and to explore which biomarkers correlated with the therapeutic effect of olanzapine after a 4-week treatment. Compared with the control group, the case group showed significant changes in plasma metabolites. Thirteen distinct metabolites were identified. Among all the therapeutically effective cases, levels of these metabolites appeared to shift towards the normal trend; 8 of the identified 13 metabolites changed dramatically. The metabolites that we found are potential biomarkers for the diagnosis and treatment of schizophrenia.

  8. Spectroscopic and molecular docking studies on the interaction of the drug olanzapine with calf thymus DNA

    Science.gov (United States)

    Shahabadi, Nahid; Bagheri, Somayeh

    2015-02-01

    The present study investigated the binding interaction between olanzapine and calf thymus DNA (ct-DNA) using emission, absorption, circular dichroism, viscosity measurements and molecular modeling. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and van der Waals play main roles in the binding of the drug to ct-DNA. Spectrophotometric studies of the interaction of olanzapine with DNA have shown that it could bind to ct-DNA (Kb = 2 × 103 M-1). The binding constant is comparable to standard groove binding drugs. Competitive fluorimetric studies with Hoechst 33258 have shown that olanzapine exhibits the ability to displace the DNA-bound Hoechst 33258 indicating that binds strongly in minor groove of DNA helix. Furthermore, the drug induces detectable changes in the CD spectrum of ct-DNA as well as changes in its viscosity. All of the experimental results prove that the groove binding must be predominant. The results obtained from experimental data were in good agreement with molecular modeling studies.

  9. Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review.

    Science.gov (United States)

    Yin, John; Barr, Alasdair M; Ramos-Miguel, Alfredo; Procyshyn, Ric M

    2017-01-01

    Chronic prescription of antipsychotics seems to lose its therapeutic benefits in the prevention of recurring psychotic symptoms. In many instances, the occurrence of relapse from initial remission is followed by an increase in dose of the prescribed antipsychotic. The current understanding of why this occurs is still in its infancy, but a controversial idea that has regained attention recently is the notion of iatrogenic dopamine supersensitivity. Studies on cell cultures and animal models have shown that long-term antipsychotic use is linked to both an upregulation of dopamine D2-receptors in the striatum and the emergence of enhanced receptor affinity to endogenous dopamine. These findings have been hypothesized to contribute to the phenomenon known as dopamine supersensitivity psychosis (DSP), which has been clinically typified as the foundation of rebound psychosis, drug tolerance, and tardive dyskinesia. The focus of this review is the update of evidence behind the classification of antipsychotic induced DSP and an investigation of its relationship to treatment resistance. Since antipsychotics are the foundation of illness management, a greater understanding of DSP and its prevention may greatly affect patient outcomes.

  10. Region-specific induction of deltaFosB by repeated administration of typical versus atypical antipsychotic drugs.

    Science.gov (United States)

    Atkins, J B; Chlan-Fourney, J; Nye, H E; Hiroi, N; Carlezon, W A; Nestler, E J

    1999-08-01

    Whereas acute administration of many types of stimuli induces c-Fos and related proteins in brain, recent work has shown that chronic perturbations cause the region-specific accumulation of novel Fos-like proteins of 35-37 kD. These proteins, termed chronic FRAs (Fos-related antigens), have recently been shown to be isoforms of DeltaFosB, which accumulate in brain due to their enhanced stability. In the present study, we sought to extend earlier findings that documented the effects of acute administration of antipsychotic drugs (APDs) on induction of Fos-like proteins by investigating the ability of typical and aytpical APDs, after chronic administration, to induce these DeltaFosB isoforms in several brain regions implicated in the clinical actions of these agents. By Western blotting we found that chronic administration of the typical APD, haloperidol, dramatically induces DeltaFosB in caudate-putamen (CP), a brain region associated with the extrapyramidal side effects of this drug. A smaller induction was seen in the nucleus accumbens (NAc) and prefrontal cortex (PFC), brain regions associated with the antipsychotic effects of the drug. In contrast, chronic administration of the prototype atypical APD clozapine failed to significantly increase levels of DeltaFosB in any of the three brain regions, and even tended to reduce DeltaFosB levels in the NAc. Two putative atypical APDs, risperidone and olanzapine, produced small but still significant increases in the levels of DeltaFosB in CP, but not NAc or PFC. Studies with selective receptor antagonists suggested that induction of DeltaFosB in CP and NAc is most dependent on antagonism of D2-D3 dopamine receptors, with antagonism of D1-like receptors most involved in the PFC. Immunohistochemical analysis confirmed the greater induction of DeltaFosB in CP by typical versus atypical APDs, with no significant induction seen in PFC with either class of APD. Together, these findings demonstrate that repeated administration

  11. Sex-dependent antipsychotic capacity of 17β-estradiol in the latent inhibition model: a typical antipsychotic drug in both sexes, atypical antipsychotic drug in males.

    Science.gov (United States)

    Arad, Michal; Weiner, Ina

    2010-10-01

    The estrogen hypothesis of schizophrenia suggests that estrogen is a natural neuroprotector in women and that exogenous estrogen may have antipsychotic potential, but results of clinical studies have been inconsistent. We have recently shown using the latent inhibition (LI) model of schizophrenia that 17β-estradiol exerts antipsychotic activity in ovariectomized (OVX) rats. The present study sought to extend the characterization of the antipsychotic action of 17β-estradiol (10, 50 and 150 μg/kg) by testing its capacity to reverse amphetamine- and MK-801-induced LI aberrations in gonadally intact female and male rats. No-drug controls of both sexes showed LI, ie, reduced efficacy of a previously non-reinforced stimulus to gain behavioral control when paired with reinforcement, if conditioned with two but not five tone-shock pairings. In both sexes, amphetamine (1 mg/kg) and MK-801 (50 μg/kg) produced disruption (under weak conditioning) and persistence (under strong conditioning) of LI, modeling positive and negative/cognitive symptoms, respectively. 17β-estradiol at 50 and 150 μg/kg potentiated LI under strong conditioning and reversed amphetamine-induced LI disruption in both males and females, mimicking the action of typical and atypical antipsychotic drugs (APDs) in the LI model. 17β-estradiol also reversed MK-induced persistent LI, an effect mimicking atypical APDs and NMDA receptor enhancers, but this effect was observed in males and OVX females but not in intact females. These findings indicate that in the LI model, 17β-estradiol exerts a clear-cut antipsychotic activity in both sexes and, remarkably, is more efficacious in males and OVX females where it also exerts activity considered predictive of anti-negative/cognitive symptoms.

  12. Antipsychotic medication and prefrontal cortex activation : A review of neuroimaging findings

    NARCIS (Netherlands)

    Liemburg, Edith J.; Knegtering, Henderikus; Klein, Hans C.; Kortekaas, Rudie; Aleman, Andre

    2012-01-01

    Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which sha

  13. Representation of people with intellectual disabilities in randomised controlled trials on antipsychotic treatment for behavioural problems

    NARCIS (Netherlands)

    Scheifes, A.; Stolker, J.J.; Nijman, H.L.I.; Egberts, A.C.G.; Heerdink, E.R.

    2011-01-01

    Background Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. Aim To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems

  14. Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis

    DEFF Research Database (Denmark)

    Baandrup, Lone; Lublin, Henrik Kai Francis; Nordentoft, Merete;

    2012-01-01

    OBJECTIVE: To investigate the association of antipsychotic polypharmacy in schizophrenia with cost of primary and secondary health service use. METHOD: Comparative analysis of health service cost for patients prescribed antipsychotic polypharmacy versus antipsychotic monotherapy. Resource......, disease duration, psychiatric inpatient admissions, and treatment site as covariates. RESULTS: The sample consisted of 736 outpatients with a diagnosis in the schizophrenia spectrum. Antipsychotic polypharmacy was associated with significantly higher total health service costs compared with monotherapy...

  15. Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

    Directory of Open Access Journals (Sweden)

    Sengupta Parama

    2010-01-01

    Full Text Available Backgrounds: This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin. Materials and Methods: Albino rats were divided into three groups, namely vehicle control group (CG, olanzapine-treated group (OZ, and olanzapine plus silymarin (OZS treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP were measured in all three groups. Results: Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant. Conclusion: Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.

  16. Some adverse effects of antipsychotics: prevention and treatment.

    Science.gov (United States)

    Lader, M

    1999-01-01

    Antipsychotic medication causes a wide range of adverse effects, which can be serious and may further imperil both the physical and psychological health of schizophrenic patients. The range of side effects patients commonly encounter includes weight gain, endocrine disturbances, sedation, anticholinergic effects, hypotension, seizures, and extrapyramidal symptoms. Less common and unpredictable reactions are blood dyscrasias, cardiotoxicity, sudden death, and the neuroleptic malignant syndrome. Antipsychotic drugs differ significantly regarding their propensity to cause these reactions. Patients should undergo comprehensive health checks before an antipsychotic is prescribed, and drug therapy should be individualized to take account of any preexisting symptoms. Side effects and the wider implications of drug treatment, such as effects on occupational and social functioning, should be discussed with the patient before initiating therapy. Patients should be regularly monitored for side effects during treatment and switched to alternative therapy if side effects are serious and/or persistent.

  17. EPS profiles: the atypical antipsychotics are not all the same.

    Science.gov (United States)

    Weiden, Peter J

    2007-01-01

    Within the first few years after chlorpromazine began to be used to treat psychosis, it was observed that it could cause many kinds of neurologic reactions that resembled those seen in idiopathic Parkinson's disease. These reactions were termed "extrapyramidal side effects" (EPS) because of their resemblance to the signs of Parkinson's disease, which were associated with degeneration of the dopamine nerve tracks located in the extrapyramidal region of the central nervous system. Eventually this association of dopamine loss, antipsychotics, and parkinsonism became a central part of the dopamine hypothesis of schizophrenia. Unfortunately, this association was also used to support the hypothesis that EPS were absolutely necessary for antipsychotic efficacy--hence the term "neuroleptic" rather than "antipsychotic." This theory, now discredited, was used to justify the practice of inducing EPS as a means to gauge whether an antipsychotic would be effective. The demonstration that clozapine, an antipsychotic virtually devoid of EPS, has better efficacy for psychosis than any other "neuroleptic" disproved the theory that EPS were fundamentally linked to efficacy. Because the idea of a relationship between EPS and efficacy was so ingrained in clinical practice, clozapine was called "atypical." Our understanding of the relationship between EPS and antipsychotic response has come full circle. With the introduction of clozapine and other newer antipsychotics, it has become clear that EPS are harmful and serve no beneficial purpose. The availability of newer antipsychotics with a lower EPS burden means that, at least in theory, it is now possible to treat psychosis without EPS in the vast majority of patients. In practice, however, EPS remain a significant problem even in the era of atypical or second generation antipsychotics (SGAs). One limitation is that the concept of "atypicality," when used to denote antipsychotic efficacy without EPS, is a relative not an absolute

  18. Type 2 diabetes in children and adolescents on atypical antipsychotics.

    Science.gov (United States)

    Pramyothin, Pornpoj; Khaodhiar, Lalita

    2015-08-01

    Youth receiving treatment with antipsychotics are particularly susceptible to weight gain, type 2 diabetes (T2D), and associated metabolic disorders, which is directly associated with excess morbidity and mortality in this vulnerable population. The risk of T2D is 2- to 3-fold that of the general population, starts early in the course of treatment, and reflects the effects of weight gain in conjunction with direct effects of antipsychotics on the hypothalamus, pancreatic beta cells, and insulin-sensitive peripheral tissues. Close monitoring with early intervention through lifestyle intervention, switching away from antipsychotics with deleterious metabolic effects, and adjunctive treatment with metformin are modalities available to mitigate weight gain and improve cardiometabolic health in these patients. Despite rapidly advancing knowledge in the field, patient's access to metabolic screening and quality care remains limited. Efforts must be made to broaden reach of early cardiometabolic intervention among these patients in order to avert serious cardiovascular disease burden in the future.

  19. Pharmacokinetic studies of antipsychotics in healthy volunteers versus patients.

    Science.gov (United States)

    Cutler, N R

    2001-01-01

    In clinical trials of dopamine-blocking antipsychotics, significant adverse events may occur in healthy volunteers at dose levels that are well tolerated by schizophrenic patients. Because of these differences in tolerability, bioequivalence and pharmacokinetic studies of antipsychotics should be performed in schizophrenic patients rather than in healthy volunteers. When clozapine is the drug being investigated, pharmacokinetic and bioequivalence studies should be carried out in real-life dosage conditions because the half-life of clozapine increases with multiple doses. Under real-life conditions, the evaluation of multiple doses of clozapine in a population of schizophrenic patients can provide direct therapeutic relevance to bioavailability findings. This article discusses patient recruitment and informed consent in pharmacokinetic trials of schizophrenia, issues in studying antipsychotic agents in healthy volunteers versus schizophrenic patients, and a bioequivalency study of Clozaril (Novartis Pharmaceuticals) and generic clozapine (Creighton [Sandoz]) in schizophrenic patients.

  20. Initiation of antipsychotic treatment by general practitioners. A case-control study

    NARCIS (Netherlands)

    Boonstra, Geartsje; Grobbee, Diederick E; Hak, Eelko; Kahn, René S; Burger, Huibert

    2011-01-01

    RATIONALE, AIMS AND OBJECTIVES: Antipsychotics are approved treatment for severe conditions and have serious side effects. Antipsychotics are often prescribed off-label. Although a substantial proportion of antipsychotics are prescribed in primary care, it is largely unknown what motivates the gener

  1. Chlorpromazine equivalents versus defined daily doses : How to compare antipsychotic drug doses?

    NARCIS (Netherlands)

    Rijcken, CAW; Monster, TBM; Brouwers, JRBJ; de Jong-van den Berg, LTW

    2003-01-01

    Classic chlorpromazine (CPZ) equivalents can be used to chart relative antipsychotic potencies of antipsychotic drugs. Values of CPZ equivalents per drug are ambiguous in literature. In drug use evaluation studies, antipsychotic doses are frequently compared by use of the defined daily dose (DDD). T

  2. Antipsychotic Medication Prescription Patterns in Adults with Developmental Disabilities Who Have Experienced Psychiatric Crisis

    Science.gov (United States)

    Lunsky, Yona; Elserafi, Jonny

    2012-01-01

    Antipsychotic medication rates are high in adults with developmental disability. This study considered rates of antipsychotic use in 743 adults with developmental disability who had experienced a psychiatric crisis. Nearly half (49%) of these adults were prescribed antipsychotics. Polypharmacy was common with 22% of those prescribed antipsychotics…

  3. Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents.

    Science.gov (United States)

    Elman, Igor; Borsook, David; Lukas, Scott E

    2006-10-01

    Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies.

  4. 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

    Directory of Open Access Journals (Sweden)

    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

  5. Safety and tolerability of antipsychotics: focus on amisulpride

    Directory of Open Access Journals (Sweden)

    Mario F Juruena

    2010-10-01

    Full Text Available Mario F Juruena1, Eduardo Pondé de Sena2, Irismar Reis de Oliveira31Stress and Affective Disorders Programme, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil; 2Department of Pharmacology, Institute of Health Sciences, Federal University of Bahia, Salvador; 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, BA, BrazilAbstract: The introduction of the atypical antipsychotic drugs represents an important advance in the treatment of schizophrenia, because the therapeutic efficacy, tolerability, and safety profiles of these agents seem to be superior to that of the classical neuroleptics. As would be predicted from the pharmacologic profile of a pure D2/D3 receptor blocker, amisulpride is an atypical antipsychotic agent, effective for positive and negative symptoms, which can bring about additional improvement in the social functioning and quality of life of patients with schizophrenia. Amisulpride is effective in acute schizophrenia as determined by Clinical Global Impression scores. The major concern regarding the safety of the atypical antipsychotics is related to their propensity to induce weight gain and alter glucose and lipid metabolism. Amisulpride has one of the lowest potentials for weight gain of all the antipsychotic agents, and is associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. Amisulpride is well tolerated with regard to anxiety and insomnia, and not notably different from placebo. Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation. Amisulpride benefits patients with negative symptoms, and is the only antipsychotic to demonstrate efficacy in patients with

  6. Antipsychotic-induced life-threatening 'esophageal dyskinesia'.

    Science.gov (United States)

    Horiguchi, J; Shingu, T; Hayashi, T; Kagaya, A; Yamawaki, S; Horikawa, Y; Kitadai, Y; Inoue, M; Nishikawa, T

    1999-03-01

    We report two patients with lingual dyskinesia and complaints of food regurgitation following long-term antipsychotic therapy. Esophageal contrast radiography revealed dyskinetic movements extending from the pharynx to the upper portion of the esophagus. The elevation of intraesophageal pressure was confirmed by esophageal manometry. The dyskinetic movements almost disappeared along with improvement of lingual dyskinesia following the administration of sulpiride in one patient. Another patient suddenly died due to asphyxiation of foods before the beginning of treatment. We termed this life-threatening movement, 'esophageal dyskinesia'. It should be emphasized that 'esophageal dyskinesia' associated with lingual dyskinesia is a potentially fatal adverse reaction to antipsychotic therapy.

  7. Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine.

    Science.gov (United States)

    Ko, Françoise; Tallerico, Teresa; Seeman, Philip

    2006-08-01

    To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia.

  8. Analysis of the Utilization of Antipsychotic Drugs in 45 Hospitals of Shanghai Area during the Period of 2006-2010%上海地区45家医院2006-2010年抗精神病药利用分析

    Institute of Scientific and Technical Information of China (English)

    毛叶萌; 黄堃; 张明岛

    2011-01-01

    目的:了解上海地区45家医院2006-2010年抗精神病药的使用情况,为该类药的研究、生产、临床应用等提供参考.方法:采用回顾性方法,对上海地区45家医院2006-2010年抗精神病药的销售金额、用药频度(DDDs)及日均费用(DDC)等进行统计、分析,比较一、二、三级医院之间的用药差异.结果:该地区医院抗精神病药的DDDs和销售金额均呈逐年增长趋势,2010年药品的总DDDs和总销售金额分别是2006年的2.2倍和3.4倍;第2代抗精神病药的DDDs及销售金额均增长较快,销售金额增幅最大的是阿立哌唑,DDDs增幅最大的是奥氮平.抗精神病药的使用以口服药为主.结论:该地区医院抗精神病药销售金额的增长大于数量的增长,涨幅主要来自第2代抗精神病药.控制第2代抗精神病药的研发和生产成本,对第1、2代抗精神病药作进一步临床应用研究与评价,对具有确切疗效的第1代抗精神病药重新核价、确保生产供应,是促进抗精神病药有效、方便、经济和合理应用的有效手段.%OBJECTIVE: To probe into the utilization of antipsychotic drugs in 45 hospitals of Shanghai area during the period of 2006-2010, and to provide reference for the research, production and clinical application of these drugs.METHODS: By retrospective study, the utilization of antipsychotic drugs in 45 hospitals of Shanghai area during the period of 2006-2010 was analyzed statistically in respect of consumption sum, DDDs, DDC, etc.The difference of drug use among first, second and third level hospitals was compared.RESULTS: DDDs and consumption sum of antipsychotic drugs in Shanghai area increased year by year.Total DDDs and consumption sum of antipsychotic drugs in 2010 was 2.2 and 3.4 times as much as in 2006 respectively.The DDDs and consumption sum of second generation antipsychotic drugs increased rapidly.The increase of consumption sum of olanzapine was the biggest and aripiprazole

  9. LC-MS/MS method applied to preclinical pharmacokinetic investigation of olanzapine-loaded lipid-core nanocapsules

    Directory of Open Access Journals (Sweden)

    Frantiescoli A. Dimer

    2014-01-01

    Full Text Available In spite of different methods reported in the literature to determine olanzapine in biological fluids, all of them used high volumes of plasma. Therefore, the purpose of this paper was to develop an LC-MS/MS method using small plasma volume (0.1 mL to apply in a preclinical pharmacokinetic investigation. The method was linear over the concentration ranges of 10 - 1000 ng mL-1. Extraction recoveries, stability, and validation parameters were evaluated. Results were within the acceptable limits of international guidelines. A significant decrease in clearance led to a significant 2.26-times increase in AUC0 - 6h of olanzapine-loaded lipid-core nanocapsules compared with free-olanzapine.

  10. A hypothesis-driven association study of 28 nuclear-encoded mitochondrial genes with antipsychotic-induced weight gain in schizophrenia.

    Science.gov (United States)

    Gonçalves, Vanessa F; Zai, Clement C; Tiwari, Arun K; Brandl, Eva J; Derkach, Andriy; Meltzer, Herbert Y; Lieberman, Jeffrey A; Müller, Daniel J; Sun, Lei; Kennedy, James L

    2014-05-01

    Mitochondria are the main source of energy for neurons and have a role in many vital neuronal functions. Mitochondrial dysfunction has been described in schizophrenia, and antipsychotics such as clozapine and olanzapine have been associated with differences in gene expression in mitochondria. We investigated the hypothesis that nuclear-encoded mitochondrial genes, particularly those involved in oxidative phosphorylation or involved in oxidative stress, mitochondrial biogenesis, inflammation, and apoptosis, would be associated with antipsychotic-induced weight gain (AIWG). In total, we selected 28 genes and analyzed 60 SNPs (50 are functional), in 283 schizophrenia subjects, treated with atypical medications for up to 14 weeks. Association between AIWG (as measured by the % of weight gain from baseline) and SNP genotypes were tested using linear regression with treatment duration, baseline body weight, and medication type as covariates. We observed a significant association between rs6435326 in the NDUFS1 gene and AIWG in the subset of European patients (N=150, Pcorrected=0.02). The haplotype carrying the risk alleles of rs6435326 and two other SNPs (rs1053517 and rs1801318) in NDUFS1 was also nominally associated with percentage of weight gain (T-C-G vs A-T-A, P=0.005). In addition, stepwise linear regression was performed to select important variables predictive of the outcome, and a gene-gene interaction analysis was carried out. We observed a significant interaction between the TT risk genotype of rs6435326 in NDUFS1 and AG genotype of rs3762883 in COX18 (Pcorrected=0.001). A permutation-based test of all 60 SNPs jointly showed significant association with weight gain (P=0.02). Finally, our replication study of rs6435326, rs1053517 and rs1801318 in NDUFS1 using samples from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) showed that rs1801318 was significantly associated with AIWG (N=200, Pcorrected=0.04), and the three SNPs were

  11. Gradual vs. wait-and-gradual discontinuation in antipsychotic switching: A meta-analysis.

    Science.gov (United States)

    Takeuchi, Hiroyoshi; Thiyanavadivel, Sadhana; Agid, Ofer; Remington, Gary

    2017-02-24

    To address whether wait discontinuation (i.e., introducing the new antipsychotic while maintaining the first for a period before initiating its discontinuation) is superior to non-wait discontinuation (i.e., initiating the first antipsychotic's discontinuation when introducing the new antipsychotic) in antipsychotic switching, we conducted a meta-analysis of randomized controlled trials comparing gradual vs. wait-and-gradual antipsychotic discontinuation in patients with schizophrenia. The meta-analysis of 5 studies (n=410) demonstrated no significant differences in any clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, between the two groups. These findings indicate either strategy can be used in clinical practice.

  12. Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome.

    Science.gov (United States)

    Laika, B; Leucht, S; Heres, S; Schneider, H; Steimer, W

    2010-02-01

    Psychiatric pharmacotherapy with olanzapine is commonplace. We investigated the influence of CYP1A2*1F (-163A, rs762551) and serotonergic polymorphisms on olanzapine serum concentrations and clinical outcome in a naturalistic clinical setting. Included were 124 Caucasian psychiatric inpatients treated with olanzapine for at least 4 weeks with steady-state serum concentrations available for 73 patients. The CYP1A2*1F polymorphism was reported to affect the inducibility of CYP1A2. In our study population, CYP1A2*1F/*1F genotype alone resulted in a 22% reduction of dose-/body weight-normalized olanzapine serum concentrations compared to homo- and heterozygote carriers of CYP1A2*1A (both groups without inducers). This effect was independent of the well-known effect of inducing agents (here tobacco smoke and carbamazepine which led to on average 28% lower concentrations in CYP1A2*1A carriers and 26% lower concentrations in CYP1A2*1F/*1F carriers). Consistently, patients with the CYP1A2*1F/*1F genotype taking inducers had 22% lower concentrations compared to CYP1A2*1A carriers taking inducers. The influence of genotype alone remained significant after Bonferroni's post hoc test. Higher olanzapine concentrations were significantly correlated with better improvement of paranoid and depressive symptoms in patients with schizophrenic disorders (Spearman's r=0.5, P=0.026 and P=0.006, respectively). No relationship between serum concentrations and the side effects (DOTES) score was detected. However, patients with the 5-HTR2A intron 2 (rs7997012) AA genotype suffered from more pronounced side effects compared to carriers of the GA or GG genotype (P=0.018 and P=0.002). Short-term weight gain under olanzapine therapy was significantly lower for 5-HTR2C -759 T-allele carriers (P=0.011). Our data suggest that the CYP1A2*1F/*1F genotype exhibits a significant influence on olanzapine concentrations independent of other inducing factors. Thus, CYP1A2*1F genotyping may be useful for

  13. Antipsychotic drug use and risk of pneumonia in elderly people

    NARCIS (Netherlands)

    Knol, Wilma; Van Marum, Rob J.; Jansen, Paul A. F.; Souverein, Patrick C.; Schobben, Alfred F. A. M.; Egberts, Antoine C. G.

    2008-01-01

    OBJECTIVES: To investigate the association between antipsychotic drug use and risk of pneumonia in elderly people. DESIGN: A nested case-control analysis. SETTING: Data were used from the PHARMO database, which collates information from community pharmacies and hospital discharge records. PARTICIPAN

  14. Antipsychotic drug use and community-acquired pneumonia

    NARCIS (Netherlands)

    G. Trifirò (Gianluca)

    2011-01-01

    textabstractAntipsychotics are generally distinguished as atypical and typical agents, which are indicated in the treatment of acute and chronic psychoses and other psychiatric disorders. In April 2005, the US Food and Drug Administration issued a warning about the increased risk of all-cause mortal

  15. Antipsychotic-Induced Hyperprolactinemia and Testosterone Levels in Boys

    NARCIS (Netherlands)

    Roke, Yvette; van Harten, Peter N.; Buitelaar, Jan K.; Tenback, Diederik E.; de Rijke, Yolanda B.; Boot, Annemieke M.

    2012-01-01

    Aims: This cross-sectional study investigates the effect of antipsychotic (AP)-induced hyperprolactinemia on testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, and puberty in boys with mainly autism spectrum disorders (ASD). Method: One hundred and four physically

  16. Antipsychotic-induced hyperprolactinemia and testosterone levels in boys.

    NARCIS (Netherlands)

    Roke, Y.; Harten, P.N. van; Buitelaar, J.K.; Tenback, D.E.; Rijke, Y.B. de; Boot, A.M.

    2012-01-01

    AIMS: This cross-sectional study investigates the effect of antipsychotic (AP)-induced hyperprolactinemia on testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, and puberty in boys with mainly autism spectrum disorders (ASD). METHOD: One hundred and four physically

  17. The spectrum of subjective effects of antipsychotic medication

    NARCIS (Netherlands)

    Wolters, HA; Knegtering, R; Wiersma, D; van den Bosch, RJ

    2003-01-01

    Background: This study examined the spectrum of subjective experiences which patients attribute to the use of antipsychotic medication. Methods: We collected interview data and answers to structured questions based on a comprehensive checklist in 77 patients using various types of classical or atypi

  18. Antipsychotic induced parkinsonism in the elderly: assessment, causes and consequences

    NARCIS (Netherlands)

    Knol, W.

    2011-01-01

    Elderly people are prone to develop antipsychotic induced parkinsonism (AIP), and there are notable variations in occurrence of this adverse effect in individual elderly people. Factors that influence the variation in occurrence of AIP have not been well elucidated. The main objectives of this thesi

  19. The influence of atypical antipsychotic drugs on sexual function

    Directory of Open Access Journals (Sweden)

    Just MJ

    2015-07-01

    Full Text Available Marek J Just Department of General and Endocrine Surgery, Piekary Medical Centre, Piekary Slaskie, Poland Abstract: Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido, physiological arousal (lubrication/erection, orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic. Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. Keywords: schizophrenia, galactorrhea, hyperprolactinemia, mood disorders, anorgasmia

  20. Development of a Patient-Centered Antipsychotic Medication Adherence Intervention

    Science.gov (United States)

    Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia

    2014-01-01

    Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Single dose bioequivalence study of two brands of olanzapine 10 mg tablets in Iranian healthy volunteers.

    Science.gov (United States)

    Zakeri-Milani, P; Islambulchilar, Z; Ghanbarzadeh, S; Valizadeh, H

    2013-07-01

    This single dose, randomized, open label, 2-period and crossover study in healthy Iranian adult volunteers was conducted to compare the bioavailability of 2 branded formulations of olanzapine 10 mg tablets. 24 volunteers received one tablet of each olanzapine 10 mg formulation. Drugs were administered after a 12 h overnight fast in each of 2 treatment days which separated by a 2-week washout period. Serial blood samples were collected over a period of 72 h. Plasma was analyzed using a validated high performance liquid chromatography method with ultraviolet detection in the range of 2-24 ng/mL with a lower limit of quantitation of 1.25 ng/mL. A non-compartmental method was employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0-t, AUC0-∞ and T1/2) to test to bioequivalence. Cmax, AUC0-t and AUC0-∞ were used to test the bioequivalence after log-transformation of plasma data. The mean (SD) Cmax, AUC0-t and AUC0-∞ for the test formulation were 15.82 (3.15) ng/mL, 447.19 (100.64) ng.h/L and 570.75 (130.55) ng.h/L respectively. Corresponding values for the test formulation were 15.72 (4.25) ng/mL, 440.37 (98.75) ng.h/mL and 558.66 (129.57) ng.h/mL. For test formulation vs. the reference formulation, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t and AUC0-∞ were 97.6-110.0%, 96.4-109.4% and 97.3-109.2%. In these volunteers, based on the FDA regulatory definition, results from the pharmacokinetic analysis suggested that the test and reference formulations of olanzapine 10 mg tablets were bioequivalent.

  3. Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project.

    Science.gov (United States)

    Davis, Mellar P; Khawam, Elias; Pozuelo, Leo; Lagman, Ruth

    2002-08-01

    Advanced cancer patients are polysymptomatic and often receive multiple medications for symptom relief. Common symptoms include anorexia, weight loss, delirium and depression. Olanzapine and mirtazapine may have several advantages over older agents despite increased acquisition costs. Both medications can treat several symptoms with a low risk for drug-drug interactions and with only once- or twice-daily dosing. Drug side effects are low, compared with more conventionally used agents. The pharmacokinetics and pharmacodynamics of both agents are unique and explain many of the benefits. More research and clinical experience will be necessary to define their role in the palliation of advanced cancer.

  4. The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey

    DEFF Research Database (Denmark)

    Deurell, Maria; Weischer, Merete; Pagsberg, Anne Katrine;

    2008-01-01

    for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244...... patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail....

  5. Differential effects of olanzapine and risperidone on cognition in schizophrenia? A saccadic eye movement study

    NARCIS (Netherlands)

    Broerse, A; Crawford, TJ; den Boer, JA

    2002-01-01

    Recent studies suggest that novel antipsychotics have positive effects on certain cognitive functions in schizophrenia. The present study investigated this claim by means of saccadic paradigms, which provide a selective index of cognitive function. Thirty-three first-episode schizophrenic patients w

  6. Differences in craving for cannabis between schizophrenia patients using risperidone, olanzapine or clozapine

    NARCIS (Netherlands)

    Machielsen, Marise; Beduin, Albertine Scheltema; Dekker, Nienke; Kahn, Rene S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

    2012-01-01

    Substance abuse and psychotic disorders have a high rate of comorbidity. Both disorders are associated with changes in the dopaminergic transmission in the mesocorticolimbic pathways of the brain. Since antipsychotic medications interact with the dopamine receptors in these pathways, these medicatio

  7. A case of catatonia status-post left middle cerebral artery cerebrovascular accident, treated successfully with olanzapine.

    Science.gov (United States)

    Spiegel, David R; Klaiber, Nicholas

    2013-01-01

    Catatonia is a psychomotor phenomenon associated with psychiatric/medical conditions. We present a patient who developed catatonia status-post left middle cerebral artery infarct. With a Bush Francis Catatonia Rating Scale score of 43 on admission, treatment with olanzapine reduced this score to 2, by discharge.

  8. Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(ε-caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine.

    Science.gov (United States)

    Fonseca, Francisco N; Betti, Andresa H; Carvalho, Flávia C; Gremião, Maria P D; Dimer, Frantiescoli A; Guterres, Sílvia S; Tebaldi, Marli L; Rates, Stela M K; Pohlmann, Adriana R

    2015-08-01

    Nose-to-brain drug delivery has been proposed to overcome the low absorption of drugs in central nervous system due to the absence of brain-blood barrier in the olfactory nerve pathway. However, the presence of a mucus layer and quick clearance limit the use of this route. Herein, amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules were proposed as a mucoadhesive system to deliver olanzapine after intranasal administration. In vitro evaluations showed that these nanocapsules were able to interact with mucin (up to 17% of increment in particle size and 30% of reduction of particle concentration) and nasal mucosa (2-fold higher force for detaching), as well as to increase the retention of olanzapine (about 40%) on the nasal mucosa after continuous wash. The olanzapine-loaded amphiphilic methacrylic copolymer-functionalized PCL nanocapsules enhanced the amount of drug in the brain of rats (1.5-fold higher compared to the drug solution). In accordance with this finding, this formulation improved the prepulse inhibition impairment induced by apomorphine, which is considered as an operational measure of pre-attentive sensorimotor gating impairment present in schizophrenia. Besides, nanoencapsulated olanzapine did not affect the nasal mucosa integrity after repeated doses. These data evidenced that the designed nanocapsules are a promising mucoadhesive system for nose-to-brain delivery of drugs.

  9. Simultaneous determination of olanzapine and fluoxetine hydrochloride in capsules by spectrophotometry, TLC-spectrodensitometry and HPLC.

    Science.gov (United States)

    Tantawy, Mahmoud A; Hassan, Nagiba Y; Elragehy, Nariman A; Abdelkawy, Mohamed

    2013-03-01

    This paper describes sensitive, accurate and precise spectrophotometric, TLC-spectrodensitometric and high performance liquid chromatographic (HPLC) methods for simultaneous determination of olanzapine and fluoxetine HCl. Two spectrophotometric methods were developed, namely; first derivative (D (1)) and derivative ratio (DD (1)) methods. The TLC method employed aluminum TLC plates precoated with silica gel GF254 as the stationary phase and methanol:toluene:ammonia (7:3:0.1, by volume) as the mobile phase, where the chromatogram was scanned at 235 nm. The developed HPLC method used a reversed phase C18 column with isocratic elution. The mobile phase composed of phosphate buffer pH 4.0:acetonitrile:triethylamine (53:47:0.03, by volume) at flow rate of 1.0 mL min(-1). Quantitation was achieved with UV detection at 235 nm. The methods were validated according to the International Conference on Harmonization (ICH) guidelines. The selectivity of the proposed methods was tested using laboratory-prepared mixtures. The developed methods were successfully applied for the determination of olanzapine and fluoxetine HCl in bulk powder and combined capsule dosage form.

  10. Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: in vitro and in vivo studies.

    Science.gov (United States)

    Seju, U; Kumar, A; Sawant, K K

    2011-12-01

    Olanzapine (OZ) is a second-generation or atypical antipsychotic which selectively binds to central dopamine D₂ and serotonin (5-HT(2c)) receptors. It has poor bioavailability due to hepatic first-pass metabolism and low permeability into the brain due to efflux by P-glycoproteins. The present investigation aimed to prepare a nanoparticulate drug delivery system of OZ using poly(lactic-co-glycolic acid) (PLGA) for direct nose-to-brain delivery to provide brain targeting and sustained release. PLGA nanoparticles (NP) were prepared by the nanoprecipitation technique and characterized by entrapment efficiency, particle size, zeta potential, modulated temperature differential scanning calorimetry (MTDSC) and X-ray diffraction (XRD) studies. The NP were evaluated for in vitro release, ex vivo diffusion, toxicity and pharmacokinetic studies. The NP were 91.2±5.2 nm in diameter and had entrapment efficiency 68.91±2.31%. MTDSC studies indicated broadening of the drug peak and a shift in the polymer peak, possibly due to physical interaction or H-bonding between the carbonyl groups of PLGA and the NH groups of OZ, and also due to the plasticization effect of OZ on PLGA. XRD studies indicated a decrease in the crystallinity of OZ or amorphization. In vitro drug release showed a biphasic pattern with initial burst release and, later, sustained release (43.26±0.156% after 120 h), following the Fickian diffusion-based release mechanism. Ex vivo diffusion through sheep nasal mucosa showed 13.21±1.59% of drug diffusion in 210 min from NP. Histopathological study of sheep nasal mucosa showed no significant adverse effect of OZ-loaded NP. In vivo pharmacokinetic studies showed 6.35 and 10.86 times higher uptake of intranasally delivered NP than OZ solution delivered through intravenous (IV) and intranasal (IN) route, respectively. These results proved that OZ could be transported directly to the brain after IN delivery of PLGA NP, enhanced drug concentration in the brain and

  11. 非典型抗精神病药物对女性精神分裂症患者泌乳素水平的影响%Influence of atypical antipsychotics on the level of prolactin in female schizophrenia

    Institute of Scientific and Technical Information of China (English)

    徐开营; 张慧芳; 沈利; 赵洁

    2014-01-01

    Objective To investigate the influence of atypical antipsychotics on the level of prolactin in female schizophre-nia.Methods 18 to 45 years old female patients with schizophrenia in hospital were randomly allocated to four groups treated with olanzapine ,risperidone ,quetiapine and aripiprazole respectively ,30 cases in each group. Prolactin were measured at base-line and after 4 ,8 weeks of treatment respectively ,with menstruation and spilled milk recorded. Results The level of prolactin was increased in both olanzapine and risperidone groups (P< 0.01) ,especially in risperidone group as the treatment contin-ues. There was no significant difference between quetiapine and aripiprazole group. Conclusion Both olanzapine and risperi-done can increase the level of prolactin ,while either quetiapine or aripiprazole has no effect on the level of serum prolactin.%目的:探讨非典型抗精神病药物对女性精神分裂症泌乳素的影响。方法选择18~45岁女性精神分裂症住院患者,随机分为奥氮平组、利培酮组、喹硫平组、阿立哌唑组,每组30例。于治疗开始第0、4、8周检测血清泌乳素。并记录月经、溢乳等情况。结果与治疗前相比,奥氮平组及利培酮组患者的血清泌乳素水平升高(P<0.01),随着治疗时间的延长利培酮组患者的泌乳素水平明显升高,并有相应的临床症状;喹硫平组及阿立哌唑组患者的血清泌乳素水平无明显升高。结论奥氮平和利培酮均可引起血清泌乳素水平升高,并出现月经延迟、溢乳等症状。喹硫平及阿立哌唑对血清泌乳素无影响。

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

    Science.gov (United States)

    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.

  13. Menstrual disturbance and galactorrhea in people taking conventional antipsychotic medications.

    Science.gov (United States)

    Thangavelu, Karthik; Geetanjali, S

    2006-11-01

    Endocrine disturbances are emerging as major side effects of antipsychotic medications. Of particular note is the profile of menstrual disturbance and galactorrhea as a consequence of hyperprolactinemia (A. Weick & P. M. Haddad, 2003), a sequela of antidopaminergic action at the hypothalamopituitary axis. Research into the clinical aspects of this sensitive issue is sparse. The authors completed a cross-sectional descriptive study of 50 patients on conventional antipsychotic medications. The prevalence of menstrual disturbance was 54%, and the prevalence of amenorrhea was 12%. Symptoms of galactorrhea were present in 32% of patients. A history of pregnancy and childbirth was noted to be significantly associated with the development of galactorrhea (p = .01). The authors hypothesized that pregnancy and lactation might sensitize the hypothalamopituitary axis for further development of hyperprolactinemia due to medications.

  14. Nicotine reduces antipsychotic-induced orofacial dyskinesia in rats.

    Science.gov (United States)

    Bordia, Tanuja; McIntosh, J Michael; Quik, Maryka

    2012-03-01

    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidol-induced VCMs by ∼20% after 5 weeks, with a significant ∼60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and α6β2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced α4β2* nAChRs in both vehicle and haloperidol-treated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.

  15. Two cases of neuroleptic malignant syndrome in elderly patients taking atypical antipsychotics

    Institute of Scientific and Technical Information of China (English)

    Yuhui FENG; Xianhong YANG; Yanyan HUANG

    2013-01-01

    Summary: Neuroleptic malignant syndrome (NMS) is a rare, life-threatening adverse reaction to antipsychotic medication that typically includes high-fever, extrapyramidal symptoms, autonomic nervous system dysfunction and disturbances in consciousness. Though reported to be more common following use of the older, first generation antipsychotic medications, it can also occur in patients taking the newer, second generation antipsychotic medications. This report discusses the clinical presentation, possible etiology, pathogenesis and treatment of two cases of NMS that occurred in elderly patients after taking atypical antipsychotics. With the increasing use of atypical antipsychotic medication in elderly patients - who may be more susceptible to this adverse reaction - there is a need to increase clinical vigilance about this condition, particularly among internists and gerontologists who may be unfamiliar with this rare complication to antipsychotic medication.

  16. A perspective on molecular genetic studies of tardive dyskinesia: one clue for individualized antipsychotic drug therapy.

    Science.gov (United States)

    Ohmori, Osamu; Shinkai, Takahiro; Hori, Hiroko; Matsumoto, Chima; Nakamura, Jun

    2003-06-01

    Interindividual genetic profile differences related to antipsychotic drug therapy may be determined based on molecular genetic studies of the pathogenesis of schizophrenia and studies of antipsychotic drug responses (therapeutic as well as adverse responses). In the present article, we review molecular genetic studies of tardive dyskinesia (TD), which is a representative adverse response to antipsychotic drugs. Such studies have been performed to explore the gene-associated pharmacokinetic and pharmacodynamic processes of antipsychotic drugs. Positive associations between several genes and TD have been reported. The accumulation of results from such studies will hopefully lead to individualized antipsychotic drug therapies that involve the application of new genomic techniques, including DNA microarrays. Subsequently, antipsychotic drugs may in the future be prescribed for smaller subgroups of patients who have been classified as having a particular genetic profile.

  17. Antipsychotic drug treatment for patients with schizophrenia: theoretical background, clinical considerations and patients preferences

    DEFF Research Database (Denmark)

    Nielsen, René Ernst; Nielsen, Jimmi

    2009-01-01

      The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side-effects...... have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

  18. Adjunctive metformin for antipsychotic-induced hyperprolactinemia: A systematic review.

    Science.gov (United States)

    Bo, Qi-Jing; Wang, Zhi-Min; Li, Xian-Bin; Ma, Xin; Wang, Chuan-Yue; de Leon, Jose

    2016-03-30

    This systematic review examines adjunctive metformin therapy for the treatment of antipsychotic-induced hyperprolactinemia. A computerized search of databases in Chinese and the international databases in English provided three trials with a total of 325 patients including one randomized clinical trial (RCT) and two observational studies (single-group, before-after design). A meta-analysis could not be conducted. The quality of evidence ranged from "very low" to "moderate". Metformin patients had a significant decrease in serum prolactin level with a mean of 54.6μg/l in the three trials. In the RCT, menstruation restarted in 67% of those with menstrual disturbances versus 5% in placebo. In one observational study, 91% of patients no longer had signs or symptoms of galactorrhea. In the RCT, adverse drug reactions (ADRs) occurred at similar incidence rates among metformin and placebo patients, except that no significant increases in nausea, insomnia and agitation occurred which were not associated with discontinuations. Our systematic review indicated that adjunctive metformin significantly lowered prolactin level and relieved prolactin-related symptoms in patients with antipsychotic-induced hyperprolactinemia. Future higher quality RCTs need to verify the currently available limited evidence based on three trials which suggest that adjunctive metformin may be used effectively and safely for antipsychotic-induced hyperprolactinemia.

  19. Thalamic shape abnormalities in antipsychotic naïve schizophrenia

    Directory of Open Access Journals (Sweden)

    Vijay Danivas

    2013-01-01

    Full Text Available Background: Neurodevelopmental hypothesis of schizophrenia states abnormal pruning as one of the pathogenetic mechanism in schizophrenia. Though thalamic volume abnormalities have been documented, the shape differences of thalamus in antipsychotic-free schizophrenia in comparison with age- and sex-matched healthy volunteers need validation. Materials and Methods: We examined antipsychotic naïve schizophrenia patients ( n=60 and age- and sex-matched healthy volunteers ( n=44. The thalamic shape abnormalities were analyzed from their coded structural magnetic resonance imaging (MRI data using three-dimensional automated image analysis software, FMRIB′s (Oxford Center for the functional MRI of the brain tools-FIRST (FMRIB′s Integrated Registration and Segmentation Tool by creating deformable mesh model. Correlation with the psychopathology scores was carried out using F-statistics. Results: Patients with schizophrenia showed significant inward deformations in the regions corresponding to anterior, ventromedial, mediodorsal, and pulvinar nuclei. There was a direct correlation between negative syndrome score and the deformation in the right mediodorsal and right pulvinar nuclei. Conclusion: The inward deformations of thalamus in antipsychotic naive schizophrenia patients correspond to those nuclei which have reciprocal connections with frontal, superior temporal, and anterior cingulate regions and support the neurodevelopmental hypothesis of schizophrenia.

  20. Experimental treatment of antipsychotic-induced movement disorders

    Science.gov (United States)

    Shireen, Erum

    2016-01-01

    Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

  1. Advances in detection of antipsychotics in biological matrices.

    Science.gov (United States)

    Patteet, Lisbeth; Cappelle, Delphine; Maudens, Kristof E; Crunelle, Cleo L; Sabbe, Bernard; Neels, Hugo

    2015-02-20

    Measuring antipsychotic concentrations in human matrices is important for both therapeutic drug monitoring and forensic toxicology. This review provides a critical overview of the analytical methods for detection and quantification of antipsychotics published in the last four years. Focus lies on advances in sample preparation, analytical techniques and alternative matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is used most often for quantification of antipsychotics. This sensitive technique makes it possible to determine low concentrations not only in serum, plasma or whole blood, but also in alternative matrices like oral fluid, dried blood spots, hair, nails and other body tissues. Current literature on analytical techniques for alternative matrices is still limited and often requires a more thorough validation including a comparison between conventional and alternative results to determine their actual value. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) makes it possible to quantify a high amount of compounds within a shorter run time. This technique is widely used for multi-analyte methods. Only recently, high-resolution mass spectrometry has gained importance when a combination of screening of (un)known metabolites, and quantification is required.

  2. Atypical antipsychotics as augmentation therapy in anorexia nervosa.

    Directory of Open Access Journals (Sweden)

    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.

  3. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Science.gov (United States)

    Boonlue, Tuanthon; Subongkot, Suphat; Dilokthornsakul, Piyameth; Kongsakon, Ronnachai; Pattanaprateep, Oraluck; Suanchang, Orabhorn; Chaiyakunapruk, Nathorn

    2016-01-01

    Background Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual atypical antipsychotics therapy. Outcomes were schizophrenia-related hospitalization and total health care cost. Logistic and Poisson regression were used to evaluate the risk of hospitalization, and generalized linear model with gamma distribution was used to determine the health care cost. All analyses were adjusted by employing propensity score and multivariable analyses. All cost estimates were adjusted according to 2013 consumer price index and converted to US$ at an exchange rate of 32.85 Thai bahts/US$. Results A total of 2,354 patients were included. Of them, 166 (7.1%) patients switched to typical antipsychotics. The adjusted odds ratio for schizophrenia-related hospitalization in atypical antipsychotic switching group was 1.87 (95% confidence interval [CI] 1.23–2.83). The adjusted incidence rate ratio was 2.44 (95% CI 1.57–3.79) for schizophrenia-related hospitalizations. The average total health care cost was lower in patients with antipsychotic switching (−$64; 95% CI −$459 to $332). Conclusion Switching from atypical to typical antipsychotics is associated with an increased risk of schizophrenia-related hospitalization

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

    Directory of Open Access Journals (Sweden)

    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

  5. Case report of adjunctive use of olanzapine with an antidepressant to treat sleep paralysis

    Institute of Scientific and Technical Information of China (English)

    Jinfeng DUAN; Wanli HUANG; Mincong ZHOU; Xujuan LI; Wei CAI

    2013-01-01

    Sleep paralysis (SP) is a condiiton of unknown eitology that usually occurs when falling asleep or when awakening in which the individual remains conscious but is unable to control their voluntary movements. This case report is about a 68-year-old man with a 40-year history of symptoms of SP and associated panic attacks upon awakening. Neurological examination and neuroimaging identified no abnormaliites. Five years before the current evaluaiton he had been diagnosed with depression and treated with various anit-depressants which ameliorated, but did not cure, his SP. However, this 40-year history of SP was abruptly terminated-and did not return over the subsequent two years-atfer adjuncitve treatment with 2.5 mg olanzapine each night was added to his anitdepressant.

  6. Case report of adjunctive use of olanzapine with an antidepressant to treat sleep paralysis.

    Science.gov (United States)

    Duan, Jingfeng; Huang, Wanli; Zhou, Mincong; Li, Xujuan; Cai, Wei

    2013-10-01

    Sleep paralysis (SP) is a condition of unknown etiology that usually occurs when falling asleep or when awakening in which the individual remains conscious but is unable to control their voluntary movements. This case report is about a 68-year-old man with a 40-year history of symptoms of SP and associated panic attacks upon awakening. Neurological examination and neuroimaging identified no abnormalities. Five years before the current evaluation he had been diagnosed with depression and treated with various anti-depressants which ameliorated, but did not cure, his SP. However, this 40-year history of SP was abruptly terminated - and did not return over the subsequent two years - after adjunctive treatment with 2.5 mg olanzapine each night was added to his antidepressant.

  7. Half a century of antipsychotics and still a central role for dopamine D2 receptors.

    Science.gov (United States)

    Kapur, Shitij; Mamo, David

    2003-10-01

    A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.

  8. The Impact of Cannabis Use on the Dosage of Antipsychotic Drugs in Patients Admitted on the Psychiatric Ward at the University Hospital of the West Indies

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    P Thomas

    2015-03-01

    Full Text Available Objective: To assess the impact of cannabis use on the efficacy of antipsychotic drugs in male subjects presenting to the University Hospital of the West Indies (UHWI with psychotic episodes. Methods: Male subjects, 18–40 years old, admitted to the psychiatric ward of the UHWI between February 2013 and May 2013, diagnosed with schizophrenia, schizophreniform disorder and who tested positive for ∆9-tetrahydrocannabinol were recruited for the study. On day one, consenting subjects were assessed using the Brief Psychiatric Rating Scale (BPRS. Patients were prescribed seven days of an oral antipsychotic medication (haloperidol, chlorpromazine, risperidone, quetiapine, olanzapine. Medicated subjects were then reassessed using the BPRS on days three and seven. Statistical analysis involved the use of Student’s t-test and repeated measure analysis of variance. Results: In total, 20 subjects were recruited (mean age = 26.00 ± 5.96 years. Subjects were grouped based on the daily chlorpromazine equivalent (CPZE dose given on day one into CPZE1 (CPZE dose of 100–300mg; n = 8 and CPZE2 (CPZE dose of 400–1250 mg; n = 12. There was no significant difference in the total BPRS score between the groups on day one (CPZE1 = 41.38 ± 16.47 versus CPZE2 = 49.42 ± 25.58; p = 0.44; similar findings were obtained for the positive (26.75 ± 9.27 versus 31.83 ± 17.30; p = 0.46 and negative (14.63 ± 7.73 versus 17.58 ± 9.74; p = 0.48 symptom component on the BPRS. For subjects in CPZE1, there was no significant decrease in total BPRS score [F(2,21 = 0.07, p = 0.93] over the study period. For CPZE2, significant reduction in total BPRS scores was achieved [F(2,33 =7.12, p = 0.01], contributed by significant decrease in the positive [F(2,33 = 5.64, p = 0.02 and negative [F(2,33 = 7.53, p = 0.01 symptom components of the BPRS. Conclusion: The findings of this study purport that male cannabis users presenting with psychotic disorders may not achieve optimal

  9. Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials

    Directory of Open Access Journals (Sweden)

    Michele Fornaro

    2016-02-01

    Full Text Available Evidence supporting the use of second generation antipsychotics (SGAs in the treatment of acute depression with mixed features (MFs associated with bipolar disorder (BD is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo- controlled trials (RCTs or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI. Six RCTs and one open-label placebo-controlled studies (including post-hoc reports representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS (SMD −0.74, 95% CI −1.20 to −0.28, n SGA = 907, control = 652. Meta-analysis demonstrated that participants in receipt of SGA (n = 979 experienced a large improvement in the Montgomery–Åsberg Depression Rating Scale (MADRS scores (SMD −1.08, 95% CI −1.35 to −0.81, p < 0.001 vs. placebo (n = 678. Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable

  10. Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics.

    Science.gov (United States)

    Liou, Y-J; Bai, Y M; Lin, E; Chen, J-Y; Chen, T-T; Hong, C-J; Tsai, S-J

    2012-02-01

    The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n=171), olanzapine (n=91) and risperidone (n=194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotype-tagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P=0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316- rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P=0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene-gene interaction models (P=0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

  11. Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials

    Science.gov (United States)

    Fornaro, Michele; Stubbs, Brendon; De Berardis, Domenico; Perna, Giampaolo; Valchera, Alessandro; Veronese, Nicola; Solmi, Marco; Ganança, Licínia

    2016-01-01

    Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open-label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD −0.74, 95% CI −1.20 to −0.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery–Åsberg Depression Rating Scale (MADRS) scores (SMD −1.08, 95% CI −1.35 to −0.81, p < 0.001) vs. placebo (n = 678). Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and

  12. A VALIDATED RP-HPLC METHOD FOR THE SIMULTANEOUS ESTIMATION OF FLUOXETINE HYDROCHLORIDE AND OLANZAPINE IN PHARMACEUTICAL DOSAGE FORM

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    M.M.Eswarudu

    2012-04-01

    Full Text Available A simple, sensitive and precise reverse phase high performance liquid chromatographic method has been developed for the simultaneous estimation of Fluoxetine hydrochloride and Olanzapine in pharmaceutical dosage forms. The mobile phase consisted of Acetonitrile: pot.dihydrogen phosphate buffer: Triethylamine (0.2 % (0.1% v/v ortho phosphoric acid, PH 3.1 in the ratio of 40:60:0.2 v/v/v delivered at a flow rate of 1.0 ml / min and wavelength of detection at 233 nm. The retention times of Fluoxetine and Olanzapine were 1.96 min and 5.59 min respectively. The developed method was validated according to ICH guidelines. The proposed method can be used for determination of these drugs in combined dosage forms.

  13. Atypical antipsychotic drugs and pregnancy outcome: a prospective, cohort study.

    Science.gov (United States)

    Habermann, Frank; Fritzsche, Juliane; Fuhlbrück, Frederike; Wacker, Evelin; Allignol, Arthur; Weber-Schoendorfer, Corinna; Meister, Reinhard; Schaefer, Christof

    2013-08-01

    Women of childbearing age are often affected with psychotic disorders, requiring the use of antipsychotic medication during pregnancy. In the present study, we prospectively followed the pregnancies of 561 women exposed to second-generation antipsychotic agents (SGAs; study cohort) and compared these to 284 pregnant women exposed to first-generation antipsychotic agents (FGAs; comparison cohort I) and to 1122 pregnant women using drugs known as not harmful to the unborn (comparison cohort II). Subjects were enrolled through the Institute's consultation service. Major malformation rates of SGA exposed were higher compared to comparison cohort II (adjusted odds ratio, 2.17; 95% confidence interval, 1.20-3.91), possibly reflecting a detection bias concerning atrial and ventricular septal defects. Postnatal disorders occurred significantly more often in infants prenatally exposed to SGAs (15.6%) and FGAs (21.6%) compared to 4.2% of comparison cohort II. Cumulative incidences of elective terminations of pregnancy were significantly higher in both the study cohort (17%) and comparison cohort I (21%) compared to comparison cohort II (3%), whereas the rates of spontaneous abortions did not differ. The numbers of stillbirths and neonatal deaths were within the reference range. Preterm birth and low birth weight were more common in infants exposed to FGAs. To conclude, our findings did not reveal a major teratogenic risk for SGAs, making the better studied drugs of this group a treatment option during pregnancy. Because neonates exposed to SGAs or FGAs in the last gestational week are at higher risk of postnatal disorders, delivery should be planned in clinics with neonatal intensive care units.

  14. Loxapine for Reversal of Antipsychotic-Induced Metabolic Disturbances: A Chart Review

    Science.gov (United States)

    Jain, Seema; Andridge, Rebecca; Hellings, Jessica A.

    2016-01-01

    Loxapine substitution is a promising option for patients with autism spectrum disorder (ASD) who develop antipsychotic-induced metabolic illness. We performed a chart review of 15 adolescents and adults meeting DSM-IV-TR criteria for ASD, all with antipsychotic-associated weight gain, who received low dose loxapine in an attempt to taper or…

  15. Antipsychotic-induced catalepsy is attenuated in mice lacking the M4 muscarinic acetylcholine receptor

    DEFF Research Database (Denmark)

    Fink-Jensen, Anders; Schmidt, Lene S; Dencker, Ditte

    2011-01-01

    of the striatum, suggesting a role for muscarinic M4 receptors in the motor side effects of antipsychotics, and in the alleviation of these side effects by anticholinergics. Here we investigated the potential role of the muscarinic M4 receptor in catalepsy induced by antipsychotics (haloperidol and risperidone...

  16. Influence of antipsychotic agents on neurological soft signs and dyskinesia in first episode psychosis

    NARCIS (Netherlands)

    Boks, MPM; Liddle, PF; Russo, S; Knegtering, R; van den Bosch, RJ

    2003-01-01

    First episode psychosis patients treated with atypical antipsychotics had significantly fewer signs of dyskinesia than patients treated with classical antipsychotics, but there were no significant differences regarding the total number of neurological soft signs (NSS). This suggests that the type of

  17. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

    Science.gov (United States)

    Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2016-01-30

    Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia.

  18. Use and misuse of antipsychotic drugs in patients with dementia in Alzheimer special care units.

    Science.gov (United States)

    Nobili, Alessandro; Pasina, Luca; Trevisan, Silvia; Riva, Emma; Lucca, Ugo; Tettamanti, Mauro; Matucci, Marina; Tarantola, Massimo

    2009-03-01

    The objective of this study was to estimate the prevalence of antipsychotic use and investigate their association with behavioural and psychological symptoms of dementia (BPSD) and other clinical predictors. Patients with dementia, aged 65 and above and resident in 35 Alzheimer special care units were sequentially enrolled into a 18-month prospective observational study. Data on sociodemographic, cognitive, functional, behavioural and clinical characteristics and drug exposure were collected at baseline and at 6-month intervals up to 18 months. The prevalence of antipsychotic use and the association with BPSD and clinical predictors were analysed. Of the 349 patients with dementia enrolled in the study, 209 (60%) were taking at least one antipsychotic. Risperidone and promazine were the most frequently prescribed antipsychotic; 40.7% simultaneously received a benzodiazepine, 20% an antidepressant. More than 50% were still taking antipsychotics at 18 months of follow-up. No associations were found between antipsychotic use and level of cognitive impairment, basal activity of daily living disability and comorbidity. Multivariate analysis showed that the use of antipsychotics was highest in patients in the highest quartiles of Neuropsychiatric Inventory Scale score (III quartile, odds ratio: 1.63; 95% confidence interval: 1.19-2.23; IV quartile, odds ratio: 2.27; 95% confidence interval: 1.61-3.26). This study found high rate of use of antipsychotics in patients with dementia resident in Alzheimer special care units, frequent associations with other psychotropic medications and a strong correlation with BPSD.

  19. Antipsychotic Medication and People with Intellectual Disabilities: Their Knowledge and Experiences

    Science.gov (United States)

    Crossley, Rachel; Withers, Paul

    2009-01-01

    Background: Antipsychotics are the most frequently prescribed psychotropic medication for people with intellectual disabilities. Many people are prescribed this medication for "challenging behaviours" without having had a formal diagnosis of a psychiatric disorder. Antipsychotics have been reported to have severe side-effect profiles, which can…

  20. Bitropic D3 Dopamine Receptor Selective Compounds as Potential Antipsychotics.

    Science.gov (United States)

    Luedtke, Robert R; Rangel-Barajas, Claudia; Malik, Mahinder; Reichert, David E; Mach, R H

    2015-01-01

    Neuropsychiatric disorders represent a substantial social and health care issue. The National Institutes of Health estimates that greater than 2 million adults suffer from neuropsychiatric disorders in the USA. These individuals experience symptoms that can include auditory hallucinations, delusions, unrealistic beliefs and cognitive dysfunction. Although antipsychotic medications are available, suboptimal therapeutic responses are observed for approximately one-third of patients. Therefore, there is still a need to explore new pharmacotherapeutic strategies for the treatment of neuropsychiatric disorders. Many of the medications that are used clinically to treat neuropsychiatric disorders have a pharmacological profile that includes being an antagonist at D2-like (D2, D3 and D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved in a variety of neuronal circuits that include movement coordination, cognition, emotion, affect, memory and the regulation of prolactin. Consequently, antagonism at D2-like receptors can also contribute to some of the adverse side effects associated with the long-term use of antipsychotics including the a) adverse extrapyramidal symptoms associated with the use of typical antipsychotics and b) metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective compounds might represent an alternative strategy for the treatment of the symptoms of schizophrenia. In this review we discuss a) how bitropic Nphenylpiperazine D3 dopamine receptor selective compounds have been developed by modification of the primary (orthosteric) and secondary (allosteric or modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding selectivity ratios and b) the functional selectivity of these compounds. Examples of how these compounds might be

  1. Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

    DEFF Research Database (Denmark)

    Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, D

    2014-01-01

    effectiveness studies in children and adolescents are limited in number and size, and only a few meta-analyses based on conventional methodologies have been conducted. METHODS AND ANALYSES: We will conduct a network meta-analysis of all randomised controlled trials (RCTs) that evaluate antipsychotic therapies...... for EOS to determine which compounds are efficacious, and to determine the relative efficacy and safety of these treatments when compared in a network meta-analysis. Unlike a contrast-based (standard) meta-analysis approach, an arm-based network meta-analysis enables statistical inference from combining...

  2. Analysis of the Utilization of Antipsychotic Drugs in 26 Hospitals from Hangzhou Area during 2009-2011%杭州市26家医院2009-2011年抗精神病药利用分析

    Institute of Scientific and Technical Information of China (English)

    张霞; 徐领城; 黄堃

    2013-01-01

    OBJECTIVE:To evaluate the clinical application of antipsychotic drugs in Hangzhou area.METHODS:Using DDD and consumption sum sorting method recommended by WHO,the utilization of antipsychotic drugs in 26 hospitals from Hangzhou area during 2009-2011 were evaluated and analyzed in terms of consumption sum and its rank(B),DDDs and its rank (A),DDC and the ratio of B/A.RESULTS:The consumption sum and DDDs of antipsychotic drugs increased year by year,and consumption sum and DDDs of antipsychotic drugs in 2011 were 1.8 times of 2009.Atypical antipsychotic drugs were effective with low side effects; the consumption sum of them was 98.92% in total,and their DDDs was 70.26% of total.Risperidone,olanzapine and aripiprazole were used more frequently in Hangzhou area,and their B/A value was 1 or close to 1.These drugs had a good performance-to-price ratio.CONCLUSIONS:The atypical antipsychotics drugs occupy a leading place in consumption sum and clinical use in Hangzhou area.%目的:评价杭州市医院抗精神病药的利用情况.方法:采用世界卫生组织(WHO)推荐的限定日剂量和销售金额排序法,通过统计销售金额及排序(B)、用药频度(DDDs)及排序(A)、日均费用(DDC)和排序比(B/A),对杭州市26家医院2009-2011年抗精神病药的利用数据进行评价与分析.结果:该市医院抗精神病药的销售金额、DDDs呈逐年增长趋势,2011年的销售金额是2009年的1.8倍;非经典类抗精神病药由于不良反应少、疗效好,其年均销售金额占精神病药总销售金额的98.92%,年均DDDs占总DDDs的70.26%.利培酮、奥氮平和阿立哌唑是目前杭州地区医院应用较多的药物,其B/A值为1或逐年接近1,显示了良好的性价比.结论:该市医院非经典抗精神病药占据销售金额与临床应用的主导地位.

  3. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu

    2011-03-01

    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  4. Association of typical versus atypical antipsychotics with symptoms and quality of life in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Koichiro Fujimaki

    Full Text Available BACKGROUND: Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. METHODOLOGY AND PRINCIPAL FINDINGS: The Hasegawa Dementia Scale-Revised (HDS-R, Brief Psychiatric Rating Scale (BPRS, the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS, and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ-equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. CONCLUSION AND SIGNIFICANCE: These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia.

  5. Histamine H3-receptor inverse agonists as novel antipsychotics.

    Science.gov (United States)

    Ito, Chihiro

    2009-06-01

    Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.

  6. Current status of atypical antipsychotics for the treatment of fibromyalgia.

    Science.gov (United States)

    Rico-Villademoros, F; Calandre, E P; Slim, M

    2014-06-01

    The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms.

  7. [Antipsychotic-induced weight gain--pharmacogenetic studies].

    Science.gov (United States)

    Olajossy-Hilkesberger, Luiza; Godlewska, Beata; Marmurowska-Michałowskal, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Drug-naive patients with schizophrenia often present metabolic abnormalities and obesity. Weight gain may be the side effect of treatment with many antipsychotic drugs. Genetic effects, besides many other factors, are known to influence obesity in patients with schizophrenia treated with antipsychotics. Numerous studies of several genes' polymorphisms have been performed. -759C/T polymorphism of 5HT2C gene attracted most attention. In 5 independent studies of this polymorphism the association between T allele with the lower AP-induced weight gain was detected. No associations could be detected between weight gain and other polymorphisms of serotonergic system genes as well as histaminergic system genes. Studies of adrenergic and dopaminergic system have neither produced any unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene) confirmed the role of genetic factors in AP-induced weight gain. It is worth emphasising, that the studies have been conducted in relatively small and heterogenic groups and that various treatment strategies were used.

  8. Clinical effectiveness of atypical antipsychotics in elderly patients with psychosis.

    Science.gov (United States)

    Masand, Prakash

    2004-11-01

    The elderly represent a unique patient group in the sense that they have a high prevalence of psychotic symptoms that are a manifestation of a variety of psychiatric, neurological and organic disorders. Treatment is complicated by several factors including comorbid diagnoses (psychiatric and medical), polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics and high susceptibility to adverse events. Elderly patients require pharmacological interventions that are effective in reducing symptoms but also are well tolerated, improve everyday functioning, subjective well-being and treatment adherence and reduce family/career burden. The ability of an antipsychotic to fulfil these requirements determines its clinical effectiveness. To date, few studies have investigated the clinical effectiveness of atypical antipsychotics in elderly patients. However, clear differences exist between the available agents, particularly with regard to tolerability profiles, which have a major impact on the clinical outcome of patients. Clinicians should select an agent that is not only effective in reducing psychotic symptoms but, more importantly, one that has a low incidence of adverse events, such as extrapyramidal symptoms (EPS) and neurocognitive problems, which are of concern in the elderly.

  9. Atypical antipsychotics in first admission schizophrenia: medication continuation and outcomes.

    Science.gov (United States)

    Mojtabai, Ramin; Lavelle, Janet; Gibson, P Joseph; Bromet, Evelyn J

    2003-01-01

    This study compares the effects of atypical and conventional antipsychotic medications on treatment continuation and outcomes in a first admission sample of patients with schizophrenia treated in usual practice settings. In a sample of 189 participants with a research diagnosis of DSM-IV schizophrenia drawn from the Suffolk County Mental Health Project, we compared the effects of atypical and conventional agents on change of medication, medication gaps, and rehospitalization. For these analyses we used the method of survival analysis for recurrent events, in which the episodes of treatment rather than individual subjects are the units of analysis. In addition, we compared improvement in positive and negative symptoms from intake to 24- or 48-month followups for subjects who stayed on one type of medication or changed to atypicals from conventional antipsychotics. Atypical agents were associated with lower risk of medication change, medication gaps, and rehospitalization. Both conventional and atypical agents were associated with improvement of positive symptoms at followup, but only subjects on atypical agents at followup experienced a significant improvement in negative symptoms. We conclude that in usual practice settings, as in randomized clinical trials, atypical agents are associated with improved treatment continuation and outcomes.

  10. The therapeutic relationship and adherence to antipsychotic medication in schizophrenia.

    Directory of Open Access Journals (Sweden)

    Rosemarie McCabe

    Full Text Available OBJECTIVE: Previous research has shown that a better therapeutic relationship (TR predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia. METHODS: 134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity. RESULTS: Patient and clinician ratings of the TR were weakly inter-correlated (r(s = 0.13, p = 0.004, but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%. After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%. CONCLUSIONS: A better TR is associated with better adherence to medication among patients with schizophrenia. Patients' and clinicians' perspectives of the TR are both important, but may reflect distinct aspects.

  11. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

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    Wentzel-Larsen Tore

    2009-05-01

    Full Text Available Abstract Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA. The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800. In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in

  12. Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

    Science.gov (United States)

    Kroken, Rune A; Johnsen, Erik; Ruud, Torleif; Wentzel-Larsen, Tore; Jørgensen, Hugo A

    2009-01-01

    Background Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also

  13. Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence

    Directory of Open Access Journals (Sweden)

    Cathrin Rohleder

    2016-11-01

    Full Text Available There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC, cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial had been conducted and demonstrated that cannabidiol exerts antipsychotic properties in acute schizophrenia comparable to the antipsychotic drug amisulpride accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. However, a plethora of mechanisms of action has been suggested, but their potential relevance for the antipsychotic effects of cannabidiol needs still to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

  14. Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence

    Science.gov (United States)

    Rohleder, Cathrin; Müller, Juliane K.; Lange, Bettina; Leweke, F. M.

    2016-01-01

    There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although, results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in both rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial demonstrated that in acute schizophrenia cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug amisulpride while being accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. Although, a plethora of mechanisms of action has been suggested, their potential relevance for the antipsychotic effects of cannabidiol still needs to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials. PMID:27877130

  15. Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

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    Ludovic Samalin

    2016-11-01

    Full Text Available The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg. Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs, and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

  16. Schizophrenia, antipsychotics and risk of hip fracture: a population-based analysis.

    Science.gov (United States)

    Sørensen, Holger J; Jensen, Signe O W; Nielsen, Jimmi

    2013-08-01

    In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics consumption was found (IRR=1.13 95% CI 1.07-1.19) and both prolactin-increasing and non-prolactin-increasing antipsychotics contributed to the effect. In conclusion, several factors, including complex psychopharmacological treatment, contribute in the prediction of hip fracture in large populations. Preventive strategies should focus attention to severely ill patients with high likelihood of a receiving complex psychopharmacologic treatment and high doses of antipsychotics.

  17. Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia.

    Science.gov (United States)

    Insel, Catherine; Reinen, Jenna; Weber, Jochen; Wager, Tor D; Jarskog, L Fredrik; Shohamy, Daphna; Smith, Edward E

    2014-03-01

    Schizophrenia is characterized by an abnormal dopamine system, and dopamine blockade is the primary mechanism of antipsychotic treatment. Consistent with the known role of dopamine in reward processing, prior research has demonstrated that patients with schizophrenia exhibit impairments in reward-based learning. However, it remains unknown how treatment with antipsychotic medication impacts the behavioral and neural signatures of reinforcement learning in schizophrenia. The goal of this study was to examine whether antipsychotic medication modulates behavioral and neural responses to prediction error coding during reinforcement learning. Patients with schizophrenia completed a reinforcement learning task while undergoing functional magnetic resonance imaging. The task consisted of two separate conditions in which participants accumulated monetary gain or avoided monetary loss. Behavioral results indicated that antipsychotic medication dose was associated with altered behavioral approaches to learning, such that patients taking higher doses of medication showed increased sensitivity to negative reinforcement. Higher doses of antipsychotic medication were also associated with higher learning rates (LRs), suggesting that medication enhanced sensitivity to trial-by-trial feedback. Neuroimaging data demonstrated that antipsychotic dose was related to differences in neural signatures of feedback prediction error during the loss condition. Specifically, patients taking higher doses of medication showed attenuated prediction error responses in the striatum and the medial prefrontal cortex. These findings indicate that antipsychotic medication treatment may influence motivational processes in patients with schizophrenia.

  18. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies

    Directory of Open Access Journals (Sweden)

    Haddad PM

    2014-06-01

    Full Text Available Peter M Haddad,1,2 Cecilia Brain,3,4 Jan Scott5,6 1Neuroscience and Psychiatry Unit, University of Manchester, Manchester, 2Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK; 3Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, 4Nå Ut-teamet, Psychosis Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Academic Psychiatry, Institute of Neuroscience, Newcastle University, 6Centre for Affective Disorders, Institute of Psychiatry, London, UK Abstract: Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders

  19. Prescribing pattern of antipsychotic medications in patients with schizophrenia in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    H. K. Sushma

    2015-02-01

    Conclusions: Schizophrenia is mostly seen in males, middle age group and unemployed people. The present study showed that combination therapy is preferred for the treatment of Schizophrenia. Despite several side-effects, typical antipsychotics, especially trifluoperazine was the most commonly used drug, followed by chlorpromazine either alone or in combination. Among atypical antipsychotics, risperidone was commonly used followed by quetiapine and asenapine. Most of the patients received trihexyphenidyl, an anticholinergic drug along with antipsychotics to reduce extra pyramidal side-effects. [Int J Basic Clin Pharmacol 2015; 4(1.000: 134-138

  20. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    Science.gov (United States)

    Bakker, Ilse C A; Schubart, Chris D

    2016-01-01

    Summary In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. Learning points Prolactinoma coinciding with psychosis can represent a therapeutic challenge. In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels. Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis. PMID:27284453

  1. Entorhinal cortex volume in antipsychotic-naïve schizophrenia

    Directory of Open Access Journals (Sweden)

    Sam P Jose

    2012-01-01

    Full Text Available Background: Entorhinal cortex (ERC, a multimodal sensory relay station for the hippocampus, is critically involved in learning, emotion, and novelty detection. One of the pathogenetic mechanistic bases in schizophrenia is proposed to involve aberrant information processing in the ERC. Several studies have looked at cytoarchitectural and morphometric changes in the ERC, but results have been inconsistent possibly due to the potential confounding effects of antipsychotic treatment. Materials and Methods In this study, we have examined the entorhinal cortex volume in antipsychotic-naïve schizophrenia patients (n=40; M:F=22:18 in comparison with age, sex, and handedness, matched (as a group with healthy subjects (n=42; M:F=25:17 using a valid method. 3-Tesla MR images with 1-mm sections were used and the data was analyzed using the SPSS software. Results: Female schizophrenia patients (1.25±0.22 mL showed significant volume deficit in the right ERC in comparison with female healthy controls (1.45±0.34 mL (F=4.9; P=0.03, after controlling for the potential confounding effects of intracranial volume. However, male patients did not differ from male controls. The left ERC volume did not differ between patients and controls. Conclusions: Consistent with the findings of a few earlier studies we found a reduction in the right ERC volume in patients. However, this was limited to women. Contextually, our study finding supports the role for ERC deficit in schizophrenia pathogenesis - perhaps mediated through aberrant novelty detection. Sex-differential observation of ERC volume deficit in schizophrenia needs further studies.

  2. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

    Science.gov (United States)

    Cai, H L; Tan, Q Y; Jiang, P; Dang, R L; Xue, Y; Tang, M M; Xu, P; Deng, Y; Li, H D; Yao, J K

    2015-10-20

    Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.

  3. Nonadherence with antipsychotic medication in schizophrenia: challenges and management strategies.

    Science.gov (United States)

    Haddad, Peter M; Brain, Cecilia; Scott, Jan

    2014-01-01

    Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive

  4. Outcome of Youth with Early-Phase Schizophrenia-Spectrum Disorders and Psychosis Not Otherwise Specified Treated with Second-Generation Antipsychotics: 12 Week Results from a Prospective, Naturalistic Cohort Study

    Science.gov (United States)

    Vernal, Ditte L.; Kapoor, Sandeep; Al-Jadiri, Aseel; Sheridan, Eva M.; Borenstein, Yehonathan; Mormando, Charles; David, Lisa; Singh, Sukhbir; Seidman, Andrew J.; Carbon, Maren; Gerstenberg, Miriam; Saito, Ema; Kane, John M.; Steinhausen, Hans-Christoph

    2015-01-01

    Abstract Objectives: The purpose of this study was to assess differences in the outcomes of youth with schizophrenia-spectrum disorders (SCZ-S) and psychotic disorder not otherwise specified (PsyNOS) during early antipsychotic treatment. Methods: The study was a prospective, naturalistic, inception cohort study of youth ≤19 years old with SCZ-S (schizophrenia, schizoaffective disorder, schizophreniform disorder) or PsyNOS (PsyNOS, brief psychotic disorder) and ≤24 months of lifetime antipsychotic treatment receiving clinician's choice antipsychotic treatment. Baseline demographic, illness and treatment variables, and effectiveness outcomes were compared at 12 weeks last-observation-carried-forward across SCZ-S and PsyNOS patients, adjusting for significantly different baseline variables. Results: Altogether, 130 youth with SCZ-S (n=42) or PsyNOS (n=88), mostly antipsychotic naïve (76.9%), were prescribed risperidone (47.7%), olanzapine (19.2%), aripiprazole (14.6%), quetiapine (11.5%), or ziprasidone (6.9%). Compared with those with PsyNOS, SCZ-S youth were older (16.4±2.1 vs. 14.8±3.2, p=0.0040), and less likely to be Caucasian (19.1% vs. 42.5%, p=0.009). At baseline, SCZ-S patients had significantly higher Clinical Global Impressions-Severity (CGI-S) scores (6.0±0.9 vs. 5.5±0.8, p=0.0018) and lower Children's Global Assessment Scale (CGAS) scores (29.6±9.2 vs. 36.1±8.9, p=0.0002) and were more likely to be in the severely ill CGAS group (i.e., CGAS≤40). SCZ-S and PsyNOS patients did not differ regarding all-cause discontinuation (40.5 vs. 40.3%. p=0.49), discontinuation because of adverse effects (12.2% vs. 12.4%, p=0.97), or nonadherence (29.3% vs. 30.9%, p=0.88), but somewhat more SCZ-S patients discontinued treatment for inefficacy (19.5% vs. 7.4%, p=0.063). CGI-S and CGAS scores improved significantly in both diagnostic groups (p=0.0001, each). Adjusting for baseline differences, PsyNOS patients experienced significantly better CGI-I improvement

  5. The 2-year follow-up of schizophrenic patients treated with different antipsychotic drugs maintenance therapy%不同抗精神病药维持治疗的精神分裂症患者2年复发的随访

    Institute of Scientific and Technical Information of China (English)

    兰胜作; 陈明; 江昆伙; 黄声江; 王文华; 黄腊根; 武剑锋

    2013-01-01

    目的:探讨不同抗精神病药维持治疗的精神分裂症患者的复发率是否存在差异. 方法:对首次发病住院的425例精神分裂症患者出院时分别采用氯丙嗪(n=38),奋乃静(n=41),舒必利(n=52),氯氮平(n=81),利培酮(n=63),奥氮平(n=58),奎硫平(n=44),阿立哌唑(n=48)等8种抗精神病药维持治疗,以自制调查表及阳性和阴性症状量表(PANSS)观察其2年内复发率及服药依从性.结果:425例患者2年内总复发率为64.06%.复发率从高到低依次为氯丙嗪、奋乃静、舒必利、阿立哌唑、奎硫平、利培酮、氯氮平、奥氮平.奥氮平组的复发率显著低于氯丙嗪、奋乃静及舒必利组(x2=5.01,4.63,4.35;P均<0.05);氯氮平组的复发率显著低于氯丙嗪组、奋乃静组(x2=4.06,4.05,P均<0.05),其余各组间复发率比较均无统计学意义(P>0.05).8种药物的服药依从性差异无统计学意义(P>0.05).结论:精神分裂症首次发病患者出院后不同种类抗精神病药维持治疗2年的复发率存在差异.%Objective:Explore the relapse rate of schizophrenia with the use of different antipsychotic drugs maintenance and whether there are significant differences.Method:The first onset of schizophrenia hospitalized patients discharged chlorprumazine(n =38),perphenazine (n =41),sulpiride (n =52),clozapine (n =81),risperidone (n =63),olanzapine (n =58),quetiapine (n =44),aripiprazole (n =48) and eight antipsychotics drugs maintenance treatment,the self-made questionnaire and the positive and negative symptoms scale (PANSS) were used to observe their relapse rate and drug compliance within 2 years.Results:The total relapse rate of 425 patients was 64.06% within 2 years; the relapse rate from high to low in turn is chlorpromazine,perphenazine,sulpiride,aripiprazole,quetiapine,risperidone,clozapine,olanzapine.Olanzapine group relapse rate significantly lower than chlorpromazine,perphenazine and sulpiride group (x2 =5

  6. Antipsychotic treatment and the Rorschach Perceptual Thinking Index (PTI) in psychotic disorder patients: Effects of treatment.

    Science.gov (United States)

    Biagiarelli, Mario; Curto, Martina; Di Pomponio, Ileana; Comparelli, Anna; Baldessarini, Ross J; Ferracuti, Stefano

    2017-02-16

    The Rorschach-based Perceptual Thinking Index (PTI) is used to identify and rate features of psychotic disorders, but effects of antipsychotic treatment on such ratings is not clear. Accordingly, we examined potential effects of antipsychotic drugs on PTI measures in 114 patients with a psychotic or bipolar-I disorder. Use and doses of antipsychotic drugs (as chlorpromazine-equivalent [CPZ-eq] mg/day) were unrelated to PTI total or subscale scores in any diagnostic group. PTI scores were independently and significantly associated with psychotic symptomatic severity (PANSS score) and less with female sex. These findings support the validity and value of the PTI in identifying features of psychosis even in the presence of antipsychotic treatment.

  7. Determinants of physical health parameters in individuals with intellectual disability who use long-term antipsychotics

    NARCIS (Netherlands)

    de Kuijper, Gerda; Mulder, Hans; Evenhuis, Heleen; Scholte, Frans; Visser, Frank; Hoekstra, Pieter J.

    2013-01-01

    Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which

  8. Potential adverse effects of discontinuing psychotropic drugs. Part 3: Antipsychotic, dopaminergic, and mood-stabilizing drugs.

    Science.gov (United States)

    Howland, Robert H

    2010-08-01

    Abrupt discontinuation of antipsychotic drugs in patients with schizophrenia is associated with earlier, and often more severe, illness episodes than are seen with gradual discontinuation. Antipsychotic drugs can cause various abnormal motor syndromes, but abruptly stopping them has been associated with the seemingly paradoxical development of similar motor syndromes, such as withdrawal dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome. Dopamine-releasing and dopamine-agonist drugs are used to treat some of the motor syndromes caused by antipsychotic drugs, but their abrupt discontinuation can also be associated with abnormal syndromes. When antipsychotic drugs, lithium, or certain anticonvulsant drugs are used for treatment of bipolar disorder, rapid versus gradual discontinuation is more likely to lead to greater mood instability and manic relapse. If necessary, these medications should be gradually tapered to minimize all types of adverse discontinuation effects. Patients should be educated about the possible adverse effects of abrupt medication discontinuation.

  9. Prevalence of the metabolic syndrome in Danish psychiatric outpatients treated with antipsychotics

    DEFF Research Database (Denmark)

    Krane-Gartiser, Karoline; Breum, Leif; Glümrr, Charlotte

    2011-01-01

    The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment.......The incidence of the metabolic syndrome, a major risk factor for diabetes and cardiovascular disease, is increasing worldwide and is suggested to be higher among psychiatric patients, especially those on antipsychotic treatment....

  10. Role of 5-HT2C receptor gene variants in antipsychotic-induced weight gain

    Directory of Open Access Journals (Sweden)

    Brandl EJ

    2011-08-01

    Full Text Available Tessa JM Wallace, Clement C Zai, Eva J Brandl, Daniel J MüllerNeurogenetics Section, Center for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, CanadaAbstract: Antipsychotic-induced weight gain is a serious side effect of antipsychotic medication that can lead to increased morbidity, mortality, and non-compliance in patients. Numerous single nucleotide polymorphisms have been studied for association with antipsychotic-induced weight gain in an attempt to find genetic predictors of this side effect. An ability to predict this side effect could lead to personalized treatment plans for predisposed individuals, which could significantly decrease the prevalence and severity of weight gain. Variations in the serotonin receptor 2c gene (HTR2C have emerged as promising candidates for prediction of antipsychotic-induced weight gain. Specifically, the well-studied -759C/T promoter polymorphism has been associated with weight gain in diverse populations, although some studies have reported no association. This discrepancy is likely due to heterogeneity in study design with respect to ethnicity, treatment duration, and other variables. Notably, the association between HTR2C and antipsychotic-induced weight gain appears strongest in short-term studies on patients with limited or no previous antipsychotic treatment. Other, less extensively studied promoter polymorphisms (-697C/G, -997G/A, and -1165A/G have also emerged as potential predictors of antipsychotic-induced weight gain. Conversely, the well-studied intronic polymorphism Cys23Ser does not appear to be associated. With further research on both HTR2C and other genetic and environmental predictors of antipsychotic-induced weight gain, a predictive test could one day be created to screen patients and provide preventative or alternative treatment for those who are predisposed to this serious side effect.Keywords: HTR2C, pharmacogenomics, promoter polymorphism

  11. Berberine Alleviates Olanzapine-Induced Adipogenesis via the AMPKα–SREBP Pathway in 3T3-L1 Cells

    OpenAIRE

    Yanjie Li; Xiaomin Zhao; Xiyu Feng; Xuemei Liu; Chao Deng; Chang-Hua Hu

    2016-01-01

    The aim of this study was to investigate the mechanisms underlying the inhibitory effects of berberine (BBR) on olanzapine (OLZ)-induced adipogenesis in a well-replicated 3T3-L1 cell model. Oil-Red-O (ORO) staining showed that BBR significantly decreased OLZ-induced adipogenesis. Co-treatment with OLZ and BBR decreased the accumulation of triglyceride (TG) and total cholesterol (TC) by 55.58% ± 3.65% and 49.84% ± 8.31%, respectively, in 3T3-L1 adipocytes accompanied by reduced expression of S...

  12. Doubtful association of antipsychotic polypharmacy and high dosage with cognition in chronic schizophrenia.

    Science.gov (United States)

    Kontis, Dimitrios; Theochari, Eirini; Kleisas, Spyridon; Kalogerakou, Stamatina; Andreopoulou, Angeliki; Psaras, Rafael; Makris, Yannis; Karouzos, Charalambos; Tsaltas, Eleftheria

    2010-10-01

    Despite consistent recommendations for antipsychotic monotherapy, antipsychotic polypharmacy (the use of two or more antipsychotic agents) and the administration of excessive doses (higher than 1000 mgr/day of chloropromazine equivalents) is a common practice in schizophrenia. The therapeutic and adverse effects of this practice are poorly studied, in particular with regards to the cognitive symptoms of the disease. In this cross-sectional study we investigated the cognitive effects of antipsychotic polypharmacy and excessive doses in 53 patients with chronic schizophrenia using non-verbal cognitive tasks involving speed of movement, memory and executive functions. No significant difference in performance scores was found between the groups under polypharmacy and monotherapy, or the groups receiving either excessive or normal doses of antipsychotics. Since these groups did not also differ in demographic, clinical, other pharmacologic parameters, in the relative anticholinergic potency of antipsychotics, or in intelligence scores, we raise doubts about the association of polypharmacy and excessive doses with non-verbal cognitive performance in chronic schizophrenia.

  13. Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

    Science.gov (United States)

    Hu, Kai-Fang; Chou, Yu-Hsiang; Wen, Yen-Hsia; Hsieh, Kun-Pin; Tsai, Jui-Hsiu; Yang, Pinchen; Yang, Yi-Hsin; Lin, Chun-Hung Richard

    2016-11-30

    We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients.

  14. Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

    Directory of Open Access Journals (Sweden)

    Ishioka M

    2015-02-01

    Full Text Available Masamichi Ishioka, Norio Yasui-Furukori, Norio Sugawara, Hanako Furukori, Shuhei Kudo, Kazuhiko Nakamura Department of Neuropsychiatry, Graduate School of Medicine, Hirosaki University, Hirosaki, Japan Objective: The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation.Method: The participants included 182 patients with schizophrenia (male =89, female =93 who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex and serum prolactin concentrations were measured.Results: Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002 and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026 but not of the thrombin–antithrombin complex level (r=0.117, ns among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion: The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE. Keywords: prolactin, antipsychotics, venous thromboembolism

  15. Antipsychotics and Associated Risk of Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Weeke, Peter; Jensen, Aksel; Folke, Fredrik

    2014-01-01

    use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of event. Overall treatment with any antipsychotic was associated with OHCA (odds ratio [OR]= 1.53, 95......% confidence interval [CI]:1.23-1.89) as was use with typical antipsychotics (OR= 1.66, CI: 1.27-2.17). By contrast, overall atypical antipsychotics drug use was not (OR= 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs were associated with OHCA, haloperidol (OR= 2.43, CI: 1.......20-4.93) and levomepromazine (OR= 2.05, CI: 1.18-3.56) as was one atypical antipsychotic, quetiapine (OR= 3.64, CI: 1.59-8.30).Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 24 June 2014; doi:10.1038/clpt.2014.139....

  16. Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties.

    Science.gov (United States)

    Rudrangi, Shashi Ravi Suman; Trivedi, Vivek; Mitchell, John C; Wicks, Stephen Richard; Alexander, Bruce David

    2015-10-15

    The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of olanzapine-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of olanzapine. The complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analysed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of olanzapine with methyl-β-cyclodextrin. All the binary mixtures of olanzapine with methyl-β-cyclodextrin, except physical mixture, exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. The characterisation by different analytical techniques suggests complete complexation or amorphisation of olanzapine and methyl-β-cyclodextrin complexes prepared by supercritical carbon dioxide processing method. Therefore, organic solvent-free supercritical carbon dioxide processing method proved to be novel and efficient for the preparation of solid inclusion complexes of olanzapine with methyl-β-cyclodextrin. The preliminary data also suggests that the complexes of olanzapine with methyl-β-cyclodextrin will lead to better therapeutic efficacy due to better solubility and dissolution properties.

  17. A comparison of six kinds of antipsychotic drugs′effects on the cognitive function in patients with first-episode schizophrenia%6种抗精神病药对精神分裂症首次发病患者认知功能影响的比较

    Institute of Scientific and Technical Information of China (English)

    储文革; 陈燕; 赵宜生; 赵兵; 许志平; 邱睿; 梁涛; 程利民; 王卫民

    2015-01-01

    目的:比较利培酮、奥氮平、奎硫平、阿立哌唑、齐拉西酮、氨磺必利6种抗精神病药对急性期首发精神分裂症患者认知功能的影响。方法:120例精神分裂症首发患者分为6个药物组,每组各20例,分别给予6种抗精神病药治疗,观察12周。采用阳性和阴性症状量表( PANSS)、韦氏成人智力测验( WAIS-RC)、威斯康星卡片分类测验( WCST)、临床记忆量表( CMS)在治疗前后评估疗效及认知功能。结果:与治疗前相比,各药物组PANSS阳性症状、阴性症状及总分在治疗后各时点均明显下降(P0.05)。结论:6种新型抗精神病药均能改善首发精神分裂症患者的认知功能。%Objective:To make a comparison of the effects of the acute treatment with six kinds of antip-sychotic drugs,risperidone,olanzapine,quetiapine,aripiprazole,ziprasidone and amisulprid,on the cognitive function in patients with first-episode schizophrenia. Method:One hundred and twenty schizophrenic patients were divided into 6 groups,each group made up of 20 cases. Cases from each group receive medical treatment with one of the six antipsychotic drugs respectively and undergo the medical observation for 12 weeks. Positive and negative syndrome scale( PANSS),Wechsler adult intelligence scale-revised-China( WAIS-RC),Wisconsin card sort test(WCST)and clinical memory scale(CMS)were applied to make an assessment of the patients′therapeutic effectiveness and the improvement of cognitive function before and after the treatment. Resuits:After the treatment with different kinds of antipsychotic drugs,the PANSS positive,negative and total treatment scale scores of schizophrenia patients on each group at all time points declined obviously( P 0. 05). Conciusion:The six kinds of newly-developed antipsychotic drugs can improve the cognitive function of first-episode schizophrenia patients.

  18. Survey of antipsychotic druGs usinG status in patients with schizophrenia in Suzhou%苏州市精神分裂症患者抗精神病药物使用现况调查

    Institute of Scientific and Technical Information of China (English)

    杨勇; 盖海军; 王秀艳; 丁若水; 杨忠; 王新达; 杜向东; 梅其一; 吴爱勤

    2015-01-01

    Objective:To infestigate the status quo of antipsychotic drugs using in patients with schizo-phrenia in Suzhou. Method:The drugs using questionnaire was used to infestigate the drug using situation in 544 schizophrenic patients( including inpatients and outpatients)from 3 mental disease hospitals in Suzhou. Results:The first 6 drugs used frequently were clozapine( 25. 6%),risperidone( 16. 5%),olanzapine (13. 9%),quetiapine(11. 4%),aripiprazole(9. 1%)and chlorpromazine(6. 8%). The usage frequency of an-tipsychotic was significantly different between inpatients and outpatients(χ2 =37. 361,P=0. 003). Compared with inpatients,the dose of clozapine,risperidone,olanzapine,quetiapine,aripiprazole and chlorpromazine in outpatients were significantly lower,sulpiride,ziprasidone and haloperidol were significantly higher( all P ﹤0. 01). The rate of using single antipsychotic drug(54. 4%,293 cases)was higher than combination(45. 6%, 246 cases). Among the patients treated with single antipsychotic drug,84. 2%(247 cases)used the second gen-eration antipsychotics(SGAs);and among the patients treated with combination therapy,97. 8%(241 cases) main drug and 65. 0%(160 cases)secondary drugs were SGAs. The most common combinatife drugs were sed-atife hypnotics( 20. 2%),then mood stabilizers( 12. 2%),anticholinergics( 12. 1%),antidepressants (7. 8%)andβ-blockers(4. 3%). Conclusion:The major treatment model of schizophrenia in Suzhou is u-sing single antipsychotic drug and choosing SGAs.%目的:调查苏州市精神分裂症患者抗精神病药物使用现况。方法:采用患者药物使用调查表,对苏州市3家精神疾病专科医院的544例住院和门诊精神分裂症患者进行抗精神病药物使用情况调查。结果:使用居前6位的抗精神病药物分别是氯氮平(25.6%)、利培酮(16.5%)、奥氮平(13.9%)、奎硫平(11.4%)、阿立哌唑(9.1%)、氯丙嗪(6.8%)。门诊和住院

  19. Hospitalization and cost after switching from atypical to typical antipsychotics in schizophrenia patients in Thailand

    Directory of Open Access Journals (Sweden)

    Boonlue T

    2016-04-01

    Full Text Available Tuanthon Boonlue,1,2 Suphat Subongkot,1,2 Piyameth Dilokthornsakul,3,4 Ronnachai Kongsakon,5 Oraluck Pattanaprateep,6 Orabhorn Suanchang,7 Nathorn Chaiyakunapruk3,8–10 1Clinical Pharmacy Division, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand; 2The College of Pharmacotherapy of Thailand, Nonthaburi, Thailand; 3Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 4Center for Pharmaceutical Outcomes Research, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA; 5Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Department of Health Informatics, Ramathibodi Hospital, Mahidol University, 7Department of Pharmacy, Somdet Chaopraya Institute of Psychiatry, Bangkok, Thailand; 8School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 9School of Population Health, University of Queensland, Brisbane, Australia; 10School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA Background: Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective: This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods: From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual

  20. 奥氮平配合行为矫正治疗及综合康复模式治疗救助精神分裂症患者的对照研究%A controled study of olanzapine medication, behavior modification therapy and comprehensive rehabilitation model which treatment for patients with schizophrenia

    Institute of Scientific and Technical Information of China (English)

    马振玉; 毕崇波; 孙红立

    2014-01-01

    Objective: To explore effective rehabilitation treatment of patients with schizophrenia. Methods: Divided 100 patients into control group and study group. The control group used conventional antipsychotics and traditional occupational recreational rehabilitation therapy, study group with olanzapine drug therapy, in conjunction with behavior modification therapy and comprehensive rehabilitation model. Compare scores of scales before treatment and 3 months after treatment. Results:The two groups assessed PANSS, ADL, SDSS, lPRO before treatment and 3 months after treatment separately , there was a significant difference (P <0.05) in each group, scores of PANSS, ADL, SDSS, lPRO showed significant differences (P <0.05) between the two groups. Conclusion: Olanzapine medication and behavior modification therapy, meanwhile use comprehensive rehabilitation model, which can effectively improve their living skils and social adaptability.%目的::探讨救助精神分裂症患者的有效治疗方法。方法:将100例救助精神分裂症病人随机分为对照组和研究组各50例。对照组应用常规抗精神病药物治疗及传统工娱疗康复模式,研究组采用奥氮平系统治疗,同时配合行为矫正治疗及综合康复模式,比较两组在治疗前、治疗后3个月末各量表的评分。结果:研究组或对照组治疗前与治疗后3个月末评定PANSS、ADL、SDSS、lPRO,评分有显著性差异(P<0.05),且治疗后3个月研究组与对照组PANSS、ADL、SDSS、lPRO评分亦有显著性差异(P<0.05)。结论:应用奥氮平药物配合行为矫正治疗的同时,采用综合康复模式,能有效提高精神分裂症患者的生活自理能力及社会适应能力。

  1. Effects of acute and chronic administration of olanzapine in comparison to clozapine and haloperidol on extracellular recordings of substantia nigra reticulata neurons in the rat brain

    NARCIS (Netherlands)

    Timmerman, W; Heijmen, M; Westerink, B.H.C.; Bruggeman, R; den Boer, J.A.

    1999-01-01

    Rationale : Previously, we have shown that the atypical antipsychotics clozapine and risperidone, unlike haloperidol, decreased the firing rate of substantia nigra reticulata (SNR) neurons. As the SNR receives substantial input from the striatum, an area where motoric side-effects of antipsychotics

  2. Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy

    Directory of Open Access Journals (Sweden)

    Stanković Žana

    2013-01-01

    Full Text Available Background/Aim. There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. Methods. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20 (ICD-10, 1992 clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19 were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation and the patients from the oral group (n = 37 were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale] and attitudes toward medication [Drug Attitude Inventory (DAI subscale] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's χ2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Results. Significant betweengroup differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found

  3. Effects of antipsychotics on bone mineral density and prolactin levels \\ud in patients with schizophrenia: a 12-month prospective study

    OpenAIRE

    2014-01-01

    Objective: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia.\\ud \\ud Methods: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole)\\ud was prescribed for 12 months as appropria...

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

    Institute of Scientific and Technical Information of China (English)

    Wei Cheng

    2016-01-01

    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.

  5. Antiemetic Therapy With or Without Olanzapine in Preventing Chemotherapy-Induced Nausea and Vomiting in Patients With Cancer Receiving Highly Emetogenic Chemotherapy | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies antiemetic therapy with olanzapine to see how well they work compared to antiemetic therapy alone in preventing chemotherapy-induced nausea and vomiting in patients with cancer receiving highly emetogenic (causes vomiting) chemotherapy. Antiemetic drugs, such as palonosetron hydrochloride, ondansetron, and granisetron hydrochloride, may help lessen or prevent nausea and vomiting in patients treated with chemotherapy. |

  6. Efficacy and safety of olanzapine/fluoxetine combination in the treatment of treatment-resistant depression: a meta-analysis of randomized controlled trials

    Science.gov (United States)

    Luan, Shuxin; Wan, Hongquan; Wang, Shijun; Li, He; Zhang, Baogang

    2017-01-01

    Background Whether olanzapine/fluoxetine combination (OFC) is superior to olanzapine or fluoxetine monotherapy in patients with treatment-resistant depression (TRD) remains controversial. Thus, we conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of OFC with olanzapine or fluoxetine monotherapy for patients with TRD. Materials and methods RCTs published in PubMed, Embase, Web of Science, and the ClinicalTrials.gov registry were systematically reviewed to assess the efficacy and safety of OFC. Outcomes included mean changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Hamilton Rating Scale for Anxiety (HAM-A), Brief Psychiatric Rating Scale (BPRS) scores, response rate, remission rate, and adverse events. Results were expressed with weighted mean difference (WMD) with 95% confidence intervals (CIs) and risk ratio (RR) with 95% CIs. Results A total of five RCTs with 3,020 patients met the inclusion criteria and were included in this meta-analysis. Compared with olanzapine or fluoxetine monotherapy, OFC was associated with greater changes from baseline in MADRS (WMD =−3.37, 95% CI: −4.76, −1.99; Pfluoxetine monotherapy in the treatment of patients with TRD. Our results provided supporting evidence for the use of OFC in TRD. However, considering the limitations in this study, more large-scale, well-designed RCTs are needed to confirm these findings. PMID:28280343

  7. Characterization of rheology and release profiles of olanzapine-loaded lipid-core nanocapsules in thermosensitive hydrogel.

    Science.gov (United States)

    Dimer, F A; Pohlmann, A R; Guterres, S S

    2013-12-01

    In this study we developed a new drug delivery system for olanzanpine comprised of drug-loaded lipid-core nanocapsules incorporated in a thermosensitive hydrogel, intended to sustain the drug release. Firstly, olanzapine, a hydrophobic drug, was loaded in poly(epsilon-caprolactone) lipid core nanocapsules prepared by interfacial deposition of preformed polymer. The effects of the presence of ethanol and the amounts of sorbitan monostearate and medium-chain triglycerides on the particle size, zeta potential, polydispersity index, presence of microparticles and encapsulation efficiency were investigated using a 2(3) factorial design. The optimized nanocapsules were incorporated into a hydrophilic polymer (Poloxamer 407) dispersion in order to obtain a thermosensitive gel. The formulation containing 0.077 g of sorbitan monostearate, 0.22 ml of medium-chain triglycerides, 3 ml of ethanol and 18% of the thermosensitive polymer was selected according to the physicochemical properties. The rheology and release profiles of the mixed hydrophobic and hydrophilic delivery system were successfully characterized and revealed its great potential for the administration of hydrophobic drugs such as olanzapine with sustained in situ drug release.

  8. Venous thromboembolism as an adverse effect of antipsychotic treatment

    Directory of Open Access Journals (Sweden)

    Bałkowiec-Iskra, Ewa

    2014-10-01

    Full Text Available Many studies suggest an association between the use of antipsychotics (APs and occurrence of venous thromboembolism (VTE. Thromboembolism is often related to a significant risk of disability or death. Despite many years of investigating the interrelations between use of APs and VTE, they have not been specified yet. This paper aims to summarize reports on the VTE risk factors in patients using APs. Based on the analyzed clinical studies, meta-analyses and data published by European Medicines Agency, it has been determined, that the main risk factors for VTE are duration of treatment and patient-related factors, such as gender, age, body mass, and physical activity. Current data do not allow to identify the prothrombotic potential for individual APs or indicate a higher risk for developing VTE in patients treated with newer atypical APs. Due to the complex pathogenesis of VTE it would be necessary to perform large, comparative studies, allowing to identify precisely differences in prothrombotic potential of individual APs. It is necessary to specify products with the lowest VTE risk, what would be useful in the treatment of high-risk patients. All patients treated with APs should be assessed with the risk of VTE and, if needed, appropriate prevention methods (including most of all the elimination of modifiable risk factors should be implemented. Moreover, patients should be educated in scope of VTE prodromal symptoms. All patients with the higher VTE risk should be diagnosed as soon as possible and adequate treatment should be implemented.

  9. [Antipsychotics for schizophrenia: the paradigm of psychiatric drugs].

    Science.gov (United States)

    Pol Yanguas, Emilio

    2015-03-01

    Antipsychotic drugs do not appear to reverse the causes of schizophrenia, and although they can relieve symptoms in the short to medium term, in the long term they may not be beneficial and could even be counterproductive. Their use should be limited to acute situations in which agitation and tension is disabling. The drugs have significant adverse effects, and given the refusal of a person to continue taking them, a harm reduction strategy to support and monitor the withdrawal may be preferable to coercion. There are alternatives to neuroleptics. Prescribers should be more vigilant and consider the assessments of users regarding the drugs' effects. Adherence to treatment guidelines is low, probably because the guidelines are based on clinical trials of deficient quality which consequently should be improved and extended over a greater period of time. The root of the problem is likely the tautology on the etiology and biological nature of what is known as schizophrenia, which in fact does not seem to be more than a commercial and ideological construct.

  10. Antipsychotics--history of development and field of indication, new wine--old glassess.

    Science.gov (United States)

    Jašović-Gašić, Miroslava; Vuković, Olivera; Pantović, Maja; Cvetić, Tijana; Marić-Bojović, Nadja

    2012-10-01

    More than half a century ago, Delay and colleagues have discovered, quite accidentally, that antihistamine (chlorpromazine) relieves psychotic symptoms. This discovery prompted further investigation through a series of performed experiments aimed to elucidate the antipsychotic mechanism of action. Initial results have shown that antipsychotic drugs in experimental animals lead to "neuroleptic effect" (indifference). However, not until the end of 1960s, it becomes clear that all previously known antipsychotics block dopamine receptors, particularly postsynaptic D2 receptors. The next three decades marked the development and application of these so-called classic neuroleptics in the treatment of psychotic patients. During the nineteen nineties, as a result of ongoing efforts to achieve greater efficiency and reduce the scope of side effects, novel antipsychotics were synthesized (second generation antipsychotics--SGA). As a result the notion of serotonin-dopamine antagonist (SDA) was formulated. According to one of the hypothesis, "new", so called atypical antipsychotic drugs strongly block the serotonin (5-HT2), and weakly block the dopamine (D2) receptors. Yet, there is still a debate as to the molecular basis of atypicality, whether it is in dopaminergic and serotonergic antagonism of neurotransmission or it lays exclusively in the modulation of dopaminergic system and dissociation rate at the level of D2 receptors in specific brain regions. Although the synthesis and use of antipsychotics in clinical practice have radically changed not only the basic approach to the patient, but also the quality of life of millions of people, the question remains whether this is just "old wine in new glasses".

  11. Would I take antipsychotics, if I had psychotic symptoms? Examining determinants of the decision to take antipsychotics.

    Science.gov (United States)

    Berna, Fabrice; Göritz, Anja S; Llorca, Pierre-Michel; Vidailhet, Pierre; Fond, Guillaume; Moritz, Steffen

    2017-03-22

    Poor adherence to treatment in schizophrenia is mainly associated to patients-related factors. However, social negative representations of schizophrenia and its treatment may also contribute to patients' decision to take or not to take antipsychotics. A web-based study on 1807 participants was conducted during which participants imagined that they had a particular chronic illness based on clinical vignettes (mental illnesses: schizophrenia, depression; somatic illnesses: multiple sclerosis, rheumatoid arthritis). Participants rated their subjective distress and perceived social stigma associated with each illness. They also rated the perceived treatability of the illness, their belief in the effectiveness of treatment, and their treatment preference regarding medication. Results show that schizophrenia was considered more distressful, less treatable and associated with higher social stigma than somatic illnesses. Medication was less preferred for treating schizophrenia compared to somatic illnesses. Perceived treatability of illness and belief in the effectiveness of pharmacological treatment were the factors driving preference for medication in schizophrenia and depression respectively; these factors had weaker influence on preference for medication in somatic illnesses. Our study points out more severe negative representations of mental illnesses in general, and their treatment, particularly schizophrenia. These attitudes are not confined to patients, and may influence patients' decisions to take psychotropic drugs.

  12. Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

    Science.gov (United States)

    Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

    2013-03-01

    Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats.

  13. How do we choose between atypical antipsychotics? The advantages of amisulpride.

    Science.gov (United States)

    Mortimer, Ann M

    2004-03-01

    Clinician choice of an atypical antipsychotic may depend on a number of factors such as perceived efficacy, tolerability and cost. It is also important that the choice of treatment takes into consideration the previous response to treatment, experience of side-effects and personal clinical characteristics. The receptor-affinity profiles of the atypical antipsychotics differ; with the exception of amisulpride, a selective D2/D3 antagonist, all the atypical antipsychotics exhibit a greater affinity for the serotonin-2A receptors than dopamine receptors. However, there is no evidence that the variation in receptor affinities is relevant to efficacy. Indeed, the crucial factor may be fast dissociation from low affinity for the D2 receptor. Tolerability also varies between the atypical antipsychotics and the side-effect profile may be related to the receptor-affinity profile of the individual drugs. Extrapyramidal side-effects are generally less of a problem with most atypical drugs than with conventional drugs, but weight gain, loss of glycaemic control, sedation and hyperprolactinaemia remain problematic in some patients. Amisulpride is effective for the treatment of both positive and negative symptoms, and is well tolerated with regard to weight gain, glucose tolerance and sedation. In two clinical trials, the AMIRIS and SOLIANOL studies, amisulpride demonstrated clear advantages over some other atypical antipsychotics with respect to negative symptoms, depressive symptoms and weight gain.

  14. Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

    Directory of Open Access Journals (Sweden)

    Williams Sylvain

    2006-03-01

    Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

  15. Systematic review of the economic aspects of nonadherence to antipsychotic medication in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Dilla T

    2013-04-01

    Full Text Available Tatiana Dilla, Antonio Ciudad, María ÁlvarezDepartment of Clinical Research and Development, Lilly, S.A. Alcobendas, SpainPurpose: There is strong evidence supporting the link between nonadherence to antipsychotic medication and relapse of schizophrenia. However, less obvious are the economic consequences of nonadherence. The systematic review reported here evaluated the economic aspects of nonadherence to antipsychotic medication.Methods: A systematic review of scientific papers in the PubMed MEDLINE, Embase, PsychINFO, BIOSIS, and Evidence-Based Medicine Reviews databases was undertaken. Studies that measured adherence to antipsychotic medication and that provided comparative information on health care costs were included.Results: Eight studies met the inclusion criteria. All were observational. Despite the differences between the studies in terms of design, adherence measures, and cost components analyzed, the results of this systematic review indicate that nonadherence to antipsychotic medication is associated with increased hospitalization rates and resource utilization, resulting in increased direct health care costs.Conclusion: Nonadherence to antipsychotic medication results in poor health and economic outcomes; therefore, the authors suggest endorsing interventions aimed at improving adherence because they can improve patient health without substantially increasing costs.Keywords: adherence, costs, observational study, hospitalization rates, resource utilization

  16. Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

    Directory of Open Access Journals (Sweden)

    Fabio Panariello

    2011-01-01

    Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

  17. Effectiveness of antipsychotics used in first-episode psychosis: a naturalistic cohort study

    Science.gov (United States)

    Whale, Richard; Harris, Michael; Kavanagh, Gail; Wickramasinghe, Vijitha; Jones, Christopher I.; Marwaha, Steven; Jethwa, Ketan; Ayadurai, Nirmalan; Thompson, Andrew

    2016-01-01

    Background One year of antipsychotic treatment from symptom remission is recommended following a first episode of psychosis (FEP). Aims To investigate the effectiveness of commonly used antipsychotic medications in FEP. Method A retrospective cohort study of naturalistic treatment of patients (N=460) accepted by FEP services across seven UK sites. Treatment initiation to all-cause discontinuation determined from case files. Results Risk of treatment discontinuation is greatest within 3 months of treatment initiation. Risperidone had longest median survival time. No significant differences were observed in time to discontinuation between commonly used antipsychotics on multivariable Cox regression analysis. Poor adherence and efficacy failure were the most common reasons for discontinuation. Conclusions Effectiveness differences appear not to be a current reason for antipsychotic choice in FEP. Adherence strategies and weighing up likely adverse effects should be the clinical focus. Declaration of interest R.W., A.T. and S.M. have received research grant, speaker honoraria and conference attendance funding from all companies marketing antipsychotics. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27733935

  18. New prospects for antipsychotic treatment - the role of the kynurenine pathway

    Directory of Open Access Journals (Sweden)

    Hanna Karakuła-Juchnowicz

    2014-12-01

    Full Text Available The mechanism of action of antipsychotic drugs is mainly associated with changes in dopaminergic system. The application of antipsychotic agents simultaneously produces changes in concentrations of metabolites (e.g. kynurenic acid – KYNA, 3-hydroxykynurenine – 3-OHKYN, kynurenine – KYN of the kynurenine pathway, the pathway engaged in glutamatergic transmission. The increase in KYNA levels in certain areas of the central nervous system results in inhibition of glutamatergic transmission. Pharmacologically induced elevation of KYNA levels produces effects similar to those observed after administering ketamine or phencyclidine (the noncompetitive NMDA receptor antagonist, concerning increased activity of mesolimbic dopamine neurons, as well as reduction in dopamine release from the prefrontal cortex. Recent research results confirm the predictive value of changes in concentrations of kynurenine pathway metabolites for assessment of effectiveness of antipsychotic treatment. Significant relationships were found 1 in schizophrenia between the reduction of psychopathological symptoms and variations in 3-OHKYN levels as well as changes in KYNA/3-OHKYN and KYN/KYNA ratios, 2 in mania between varying tryptophan concentrations and the reduction in manic symptoms achieved with antipsychotic treatment. The research as well presented the possibilities of kynurenine pathway modifications, raising high hopes for their future application as target points for the action of novel antipsychotic agents.

  19. Clinical observation of aripiprazole orally disintegrating tablets in the improvement of women's weight,prolactin increase caused by risperidone,sulpiride,olanzapine%阿立哌唑口腔崩解片改善利培酮、舒必利、奥氮平致女性体重、泌乳素增加的临床观察

    Institute of Scientific and Technical Information of China (English)

    卓子禄; 王群英; 熊英; 胡俊英

    2015-01-01

    目的:探讨阿立哌唑口腔崩解片改善利培酮、舒必利、奥氮平等精神类药物所致体重、泌乳素增加的临床效果。方法:收治因服用利培酮、舒必利、奥氮平等精神类药物后引起体重增加及高催乳素血症患者60例,所有患者均维持原抗精神类药物的治疗方案,根据随机数字表将患者分为阿立哌唑口腔崩解片组(观察组)30例和安慰剂组(对照组)30例,两组患者干预12周后测量患者体质指数(BMI)变化及催乳素(PRI)的水平,同时采用不良反应量表(TESS)评定阿立哌唑口腔崩解片治疗的不良反应。结果:与对照组相比,观察组治疗后 BMI 及PRL 显著下降,差异有统计学意义(P<0.01)。观察组总有效率93.33%,对照组总有效率76.67%,两组比较有统计学意义(P<0.05)。TESS 评分观察组(5.12±1.12)分,对照组(4.98±1.08)分,两组比较差异无统计学意义(P>0.05)。结论:阿立哌唑口腔崩解片能有效改善利培酮、舒必利、奥氮平等抗精神病药所致体重、泌乳素增加症状,且安全、可靠,值得临床应用和推广。%Objective:To explore the clinical effect of aripiprazole orally disintegrating tablets in the improvement of women's weight,prolactin increase caused by sulpiride,risperidone,olanzapine.Methods:60 cases of weight gain and hyperprolactinemic patients caused by sulpiride,risperidone,olanzapine were selected.All patients maintained antipsychotic drug treatment scheme of the original.According to the random number table,they were divided into the aripiprazole orally disintegrating tablets group(observation group) with 30 cases and the placebo group(control group) with 30 cases.After 12 weeks of treatment,we measured body mass index patients(BMI) changes and prolactin(PRI) level.At the same time,we evaluated the adverse reactions of aripiprazole orally disintegrating tablets treatment using side effects scale

  20. Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

    Institute of Scientific and Technical Information of China (English)

    Jaqueline Nascimento PICADA; Viviane Minuzzo PONTES; Patrícia PEREIRA; Bruna de Jesus Neto DOS SANTOS; Franciele CELSO; Jéssica Dias MONTEIRO; Kelly Morais DA ROSA; Leandro Rosa CAMACHO; Luciana Rodrigues VIEIRA; Taís Madelon FREITAS; Tatiana Grasiela DASILVA

    2011-01-01

    Aim:Aripiprazole is an antipsychotic agent to treat schizophrenia,which acts through dopamine D2 partial agonism,serotonin 5-HT1A partial agonism and 5-HT2A antagonism.This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent,as well as its effects on lipoperoxidation.Methods:Open field and inhibitory avoidance tasks were used.Thirty min before performing the behavioral tasks,adult male CF-1 mice were administered aripiprazole (1,3 or 10 mg/kg,ip) once for the acute treatment,or the same doses for 5 d for the subchronic treatment.Genotoxic effects were assessed using comet assay in the blood and brain tissues.Mutagenic effects were evaluated using bone marrow micronucleus test.Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS).Results:Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task.Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task.Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain.Mutagenic effect was not detected in the acute and subchronic treatments.Nor TBARS levels in the liver were affected.Conclusion:Aripiprazole improved memory,but could impair motor activities in mice.The drug increased DNA damage in blood,but did not show mutagenic effects,suggesting that it might affect long-term genomic stability.

  1. Evaluation of Paraoxonase, Arylesterase and Malondialdehyde Levels in Schizophrenia Patients Taking Typical, Atypical and Combined Antipsychotic Treatment

    Science.gov (United States)

    Güneş, Mehmet; Camkurt, Mehmet Akif; Bulut, Mahmut; Demir, Süleyman; İbiloğlu, Aslıhan Okan; Kaya, Mehmet Cemal; Atlı, Abdullah; Kaplan, İbrahim; Sir, Aytekin

    2016-01-01

    Objective Human serum paraoxonase (PON1) prevents lipids from peroxidation and functions as an antioxidant mechanism. Malonyldialdehyde (MDA) is the final product of lipid peroxidation and can be used as an indicator of oxidative stress. The aim of this study was to investigate PON1, MDA, and arylesterase (ARY) levels in schizophrenic patients who are taking typical, atypical, or combined (typical and atypical) antipsychotic drug treatment, with respect to those of healthy controls. Methods We evaluated 41 patients (11 taking typical antipsychotics, 19 taking atypical antipsychotics, 11 taking combined anti-psychotics) and 43 healthy controls. Results MDA levels were higher in schizophrenic patients taking typical antipsychotics compared with healthy controls (p=0.001). ARY levels were higher in patients taking atypical antipsychotics compared with healthy controls (p=0.005). PON1 activity was similar in all groups. Conclusion Our results indicate that treatment with typical antipsychotic drugs could be related to increased MDA levels; and antipsychotic medication may increase PON1 levels in schizophrenic patients. PMID:27776386

  2. Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

    NARCIS (Netherlands)

    Koning, Jeroen P; Vehof, Jelle; Burger, Huibert; Wilffert, Bob; Al Hadithy, Asmar; Alizadeh, Behrooz; van Harten, Peter N; Snieder, Harold

    2012-01-01

    RATIONALE: Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamin

  3. The association between HTR2C polymorphisms and obesity in psychiatric patients using antipsychotics: a cross-sectional study.

    NARCIS (Netherlands)

    Mulder, H.; Franke, B.; Beek, A.A. van der; Arends, J.; Wilmink, F.W.; Egberts, A.C.G.; Scheffer, H.

    2007-01-01

    The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were associa

  4. Association of two DRD2 gene polymorphisms with acute and tardive antipsychotic-induced movement disorders in young Caucasian patients

    NARCIS (Netherlands)

    Koning, Jeroen P.; Vehof, Jelle; Burger, Huibert; Wilffert, Bob; Al Hadithy, Asmar; Alizadeh, Behrooz; van Harten, Peter N.; Snieder, Harold

    2012-01-01

    Pharmacogenetic studies on antipsychotic-induced movement disorders (MD) in schizophrenia so far have focused mainly on tardive dyskinesia. Only a few examined the more acute antipsychotic-induced MD such as parkinsonism and akathisia. Notably, all MD relate to deregulation of the dopamine system. T

  5. Targeting Dopamine D3 and Serotonin 5-HT1A and 5-HT2A Receptors for Developing Effective Antipsychotics

    DEFF Research Database (Denmark)

    Brindisi, Margherita; Butini, Stefania; Franceschini, Silvia;

    2014-01-01

    Combination of dopamine D3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structure-activity relationships resulted in the identification of safe and effective antipsychotics devoid...

  6. Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder.

    Science.gov (United States)

    Elie, D; Poirier, M; Chianetta, Jm; Durand, M; Grégoire, Ca; Grignon, S

    2010-07-01

    Antipsychotic polypharmacy and high doses have been associated with poorer outcome, longer hospital stays, and increased side effects. The present naturalistic study assessed the cognitive effects of antipsychotics in 56 patients with a diagnosis of schizophrenia or schizoaffective disorder, using the Brief Assessment of Cognition in Schizophrenia (BACS). Antipsychotic daily dose (ADD) was expressed as mg risperidone equivalents/day (RIS eq), using a model based on drug doses from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) study for second generation antipsychotics (SGA) and chlorpromazine equivalents for first generation antipsychotics (FGA), with a 1/1 equivalence between haloperidol and risperidone. Increasing age was associated with polypharmacy, FGA prescription and decreasing BACS score. FGA prescription, in turn, predicted a poorer cognitive functioning, independently of age, PANSS subscores and ADD. ADD was associated with decreasing cognitive scores, an effect that remained significant after controlling for age, PANSS or polypharmacy. The detrimental cognitive effects of polypharmacy, in turn, appeared to be mediated by ADD. Different methods of data fitting suggested that ADD above 5-6 mg RIS eq/day were associated with lower BACS scores. Overall, these results show that increasing antipsychotic daily dose is associated with poorer cognitive functioning at doses lower than previously thought, independently of the number of antipsychotic drugs.

  7. Previous hospital admissions and disease severity predict the use of antipsychotic combination treatment in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Agartz Ingrid

    2011-08-01

    Full Text Available Abstract Background Although not recommended in treatment guidelines, previous studies have shown a frequent use of more than one antipsychotic agent among patients with schizophrenia. The main aims of the present study were to explore the antipsychotic treatment regimen among patients with schizophrenia in a catchment area-based sample and to investigate clinical characteristics associated with antipsychotic combination treatment. Methods The study included 329 patients diagnosed with schizophrenia using antipsychotic medication. Patients were recruited from all psychiatric hospitals in Oslo. Diagnoses were obtained by use of the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I. Additionally, Global Assessment of Functioning (GAF, Positive and Negative Syndrome Scale (PANSS and number of hospitalisations and pharmacological treatment were assessed. Results Multiple hospital admissions, low GAF scores and high PANSS scores, were significantly associated with the prescription of combination treatment with two or more antipsychotics. The use of combination treatment increased significantly from the second hospital admission. Combination therapy was not significantly associated with age or gender. Regression models confirmed that an increasing number of hospital admission was the strongest predictor of the use of two or more antipsychotics. Conclusions Previous hospital admissions and disease severity measured by high PANSS scores and low GAF scores, predict the use of antipsychotic combination treatment in patients with schizophrenia. Future studies should further explore the use of antipsychotic drug treatment in clinical practice and partly based on such data establish more robust treatment guidelines for patients with persistently high symptom load.

  8. Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

    DEFF Research Database (Denmark)

    Baandrup, Lone; Allerup, Peter; Lublin, H;

    2010-01-01

    OBJECTIVE: To evaluate the effect of a multifaceted educational intervention on the frequency of antipsychotic co-prescribing in adult schizophrenia out-patients. METHOD: Controlled quasi-experimental study performed in two Danish municipalities matched for baseline prevalence of antipsychotic...

  9. Phosphodiesterase 4B genetic variants are not associated with antipsychotic-induced tardive dyskinesia.

    Science.gov (United States)

    Souza, Renan P; Remington, Gary; Meltzer, Herbert Y; Lieberman, Jeffrey A; Kennedy, James L; Wong, Albert H C

    2010-09-01

    Phosphodiesterase 4B (PDE4B) has been evaluated as a genetic risk factor for schizophrenia. Selective PDE4 inhibitor drugs have antipsychotic-like effects and reduce tardive dyskinesia-like movements in animal models. We investigated whether PDE4B genetic variants are associated with antipsychotic-induced tardive dyskinesia incidence and severity in schizophrenia patients. Our sample consisted of 169 Caucasian patients taking typical antipsychotic medication for at least 1 year. We found two PDE4B gene variants to be nominally associated with tardive dyskinesia (rs1338719 and rs7528545) in the overall population and two other variants nominally associated with the presence of tardive dyskinesia and severity in female patients (rs1890196 and rs783036). None of these results survived correction for multiple testing. Overall, our results do not support a genetic association between tardive dyskinesia and PDE4B.

  10. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain

    DEFF Research Database (Denmark)

    Ebdrup, Bjørn H; Knop, Filip K; Ishøy, Pelle L;

    2012-01-01

    between schizophrenia and overweight patients. DISCUSSION: Current interventions against antipsychotic-induced weight gain do not facilitate a substantial and lasting weight loss. GLP-1 analogues used in the treatment of type 2 diabetes are associated with significant and sustained weight loss...... are already compromised in normal weight patients with schizophrenia. Here we outline the current strategies against antipsychotic-induced weight gain, and we describe peripheral and cerebral effects of the gut hormone glucagon-like peptide-1 (GLP-1). Moreover, we account for similarities in brain changes...... in overweight patients. Potential effects of treating schizophrenia patients with antipsychotic-induced weight gain with GLP-1 analogues are discussed. CONCLUSIONS: We propose that adjunctive treatment with GLP-1 analogues may constitute a new avenue to treat and prevent metabolic and cerebral deficiencies...

  11. Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia

    DEFF Research Database (Denmark)

    Rajkumar, Anto P; Horsdal, Henriette Thisted; Wimberley, Theresa

    2017-01-01

    treatment in people with schizophrenia. METHOD: The study followed all people born in Denmark on or after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data......-line treatment with either first-generation antipsychotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited...... to type 2 diabetes corroborated these results. CONCLUSIONS: Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics. Early detection and effective treatment of diabetes should be an integral part...

  12. Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia

    DEFF Research Database (Denmark)

    Zakarias, Johanne Købstrup; Jensen-Dahm, Christina; Nørgaard, Ane;

    2016-01-01

    of behavioral symptoms. OBJECTIVE: To investigate potential geographical variances in use of antipsychotic drugs in dementia care. METHODS: A registry-based cross-sectional study in the entire elderly population of Denmark (≥65 years) conducted in 2012. Data included place of residence, prescriptions filled......, and hospital discharge diagnoses. Antipsychotic drug use among elderly with (n = 34,536) and without (n = 931,203) a dementia diagnosis was compared across the five regions and 98 municipalities in Denmark, adjusted for age and sex. RESULTS: In 2012, the national prevalence of antipsychotic drug use was 20.......7% for elderly patients with dementia, with a national incidence of 3.9%. The prevalence ranged from 17.0% to 23.3% in the five regions and from 7.5% to 33.1% in the 98 municipalities, demonstrating an over four-fold difference. CONCLUSION: The observed geographical variation was more pronounced at municipal...

  13. Could Reward-disturbances caused by antipsychotic medication lead to weight gain?

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Nørbak-Emig, Henrik

    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...... response in right putamen (r=0.541, p=0.001). There was no relation between weight gain and treatment response or medication dose. DISCUSSION As expected, antipsychotic treatment on average caused a moderate weight gain in the patients. The highest weight gain was found in the patients with the most......, it seems reasonable to assume that it is related to changes in dopamine transmission. Thus our results suggest that by altering the dopaminergic transmission in putamen, antipsychotic medication might affect appetite regulation through its influence on the reward system and thereby, together with other...

  14. Could Reward-Disturbances Caused by Antipsychotic Medication Lead to Weight Gain?

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Nørbak, Henrik

    2014-01-01

    BACKGROUND Disturbances of the brain reward system are suggested to play an important role in the development of central psychopathological symptoms in schizophrenia, and antipsychotic medication partly acts by modulating the reward system. Further, the reward system is known to be central...... putamen (r=0.541, p=0.001). There was no relation between weight gain and treatment response or medication dose. DISCUSSION As expected, antipsychotic treatment on average caused a moderate weight gain in the patients. The highest weight gain was found in the patients with the most aberrant f...... to assume that it is related to changes in dopamine transmission. Thus our results suggest that by altering the dopaminergic transmission in putamen, antipsychotic medication might through the influence on reward system affect appetite regulation and thereby, together with other mechanisms, lead to weight...

  15. Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Douglas L Noordsy

    2010-07-01

    Full Text Available Douglas L Noordsy1, Glenn A Phillips2, Daniel E Ball2, Walter T Linde-Zwirble31Department of Psychiatry, Dartmouth Medical School, Lebanon, NH, USA; 2Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 3ZD Associates, Perkasie, PA, USAObjective: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to ­different treatments.Methods: Adults with schizophrenia in the California Medicaid (MediCal database who ­initiated treatment with index medications in 1998–2001, were classified as having: 1 ­abandoned antipsychotic medications; 2 switched to another medication; or 3 continued with the index antipsychotic, for up to 6 months after the index date.Results: Of 2300 patients meeting eligibility criteria, 1382 (60.1% continued index medications, 480 (20.9% switched, and 438 (19.0% abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications. These included using psychiatric (24.2% vs 14.5%; P < 0.001 or nonpsychiatric (31.5% vs 24.3%; P < 0.05 emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05; making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05 or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05; and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001 or nonpsychiatric (82.7% vs 74.6%; P < 0.001 services.Conclusions: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment.Keywords: antipsychotics, drug therapy, resource use, treatment adherence

  16. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia

    OpenAIRE

    Honey, Garry D; Edward T Bullmore; Soni, William; Varatheesan, Malini; Williams, Steve C.R.; Sharma, Tonmoy

    1999-01-01

    Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal...

  17. Expression of brain-derived neurotrophic factor mRNA in rat hippocampus after treatment with antipsychotic drugs.

    Science.gov (United States)

    Bai, Ou; Chlan-Fourney, Jennifer; Bowen, Rudy; Keegan, David; Li, Xin-Min

    2003-01-01

    Typical and atypical antipsychotic drugs, though both effective, act on different neurotransmitter receptors and are dissimilar in some clinical effects and side effects. The typical antipsychotic drug haloperidol has been shown to cause a decrease in the expression of brain-derived neurotrophic factor (BDNF), which plays an important role in neuronal cell survival, differentiation, and neuronal connectivity. However, it is still unknown whether atypical antipsychotic drugs similarly regulate BDNF expression. We examined the effects of chronic (28 days) administration of typical and atypical antipsychotic drugs on BDNF mRNA expression in the rat hippocampus using in situ hybridization. Quantitative analysis revealed that the typical antipsychotic drug haloperidol (1 mg/kg) down-regulated BDNF mRNA expression in both CA1 (P BDNF mRNA expression in CA1, CA3, and dentate gyrus regions of the rat hippocampus compared with their respective controls (P BDNF mRNA expression in rat hippocampus.

  18. Recommendations for switching antipsychotics. A position statement of the Spanish Society of Psychiatry and the Spanish Society of Biological Psychiatry.

    Science.gov (United States)

    Bernardo, Miquel; Vieta, Eduard; Saiz Ruiz, Jerónimo; Rico-Villademoros, Fernando; Alamo, Cecilio; Bobes, Julio

    2011-07-01

    Switching antipsychotics is common in the clinical practice setting and is associated with potential clinically relevant complications. An expert group selected by Spanish Society of Psychiatry and the Spanish Society of Biological Psychiatry has reviewed the evidence provided by randomized clinical trials and other relevant information to reach consensus recommendations for switching antipsychotics. In this article, we will review all the information that has led to those recommendations and which includes: indications and contraindications for switching antipsychotics, pharmacological issues, switching strategies, switching antipsychotics due to efficacy problems, switching antispychotics due to tolerability issues (including extrapyramidal symptoms and tardive dyskinesia, weight gain, metabolic disorders, hyperprolactinemia, sexual dysfunction, persistent sedation, and QT prolongation), switching antypsychotics due to lack of treatment compliance, and switching antipsychotics in patients with bipolar disorders.

  19. Prior Haloperidol, but not Olanzapine, Exposure Augments the Pursuit of Reward Cues: Implications for Substance Abuse in Schizophrenia

    OpenAIRE

    Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

    2012-01-01

    Drug abuse and addiction are excessively common in schizophrenia. Chronic antipsychotic treatment might contribute to this comorbidity by inducing supersensitivity within the brain’s dopamine system. Dopamine supersensitivity can enhance the incentive motivational properties of reward cues, and reward cues contribute to the maintenance and severity of drug addiction. We have shown previously that rats withdrawn from continuous haloperidol (HAL) treatment (via subcutaneous minipump) develop do...

  20. Metabolic syndrome in patients with severe mental illness undergoing psychiatric rehabilitation receiving high dose antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Bapu V Ravindranath

    2012-01-01

    Full Text Available Background: To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens. Materials and Methods: Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III (NCEP ATP III criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose. Results: Out of 24 patients, 10 patients (41.7% were receiving high dose antipsychotics (HDA and four were on maximum dosage limits of 100%. 8.3% (2/24 patients were receiving only one first generation antipsychotics (FGA, 37.5% (9/24 patients were receiving only one second generation antipsychotic (SGA, 45.8% patients (11/24 were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN ("as needed" therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%. Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20 had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11 were on HDA and 27.3% (3/11 were on maximum British National

  1. -Amphetamine and Antipsychotic Drug Effects on Latent Inhibition in Mice Lacking Dopamine D2 Receptors

    OpenAIRE

    Bay-Richter, C.; O'Callaghan, M J; N Mathur; O'Tuathaigh, C.M.P.; Heery, D M; Fone, K C F; Waddington, J. L.; Moran, P.M.

    2013-01-01

    Drugs that induce psychosis, such as -amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd 2 −/−), we first investigated whether D2 is required for AMP disruption ...

  2. Hunger and negative alliesthesia to aspartame and sucrose in patients treated with antipsychotic drugs and controls.

    Science.gov (United States)

    Khazaal, Y; Chatton, A; Claeys, F; Ribordy, F; Khan, R; Zullino, D

    2009-12-01

    The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight.

  3. Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior

    Science.gov (United States)

    Tang, Yan; Chang, Chung-Chou H.; Lave, Judith R.; Gellad, Walid F.; Huskamp, Haiden A.; Donohue, Julie M.

    2016-01-01

    Background Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. Aims of the Study To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Methods Using 2011 data from Pennsylvania’s Medicaid program, IMS Health’s HCOS™ database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to ≥10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. Results There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Discussion Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians

  4. Are depot as effective as oral antipsychotics on first-episode psychosis?

    Science.gov (United States)

    Orus, Cristián; Aceituno, David

    2016-05-23

    Depot antipsychotics have been generally used in patients with chronic schizophrenia with adherence problems to oral therapy. However, it has been suggested they can be a good alternative in earlier stages too. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including two pertinent randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether there are differences between depot and oral antipsychotics in first-episode psychosis because the certainty of the available evidence is very low.

  5. 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

    ABSTRACT: BACKGROUND: This analysis of pooled data evaluates maintenance 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...

  6. S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1] benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), a preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent: III. Actions in models of therapeutic activity and induction of side effects.

    Science.gov (United States)

    Millan, Mark J; Loiseau, Florence; Dekeyne, Anne; Gobert, Alain; Flik, Gunnar; Cremers, Thomas I; Rivet, Jean-Michel; Sicard, Dorothée; Billiras, Rodolphe; Brocco, Mauricette

    2008-03-01

    In contrast to clinically available antipsychotics, the novel benzopyranopyrrolidine derivative, S33138 (N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenyl-acetamide), behaves as a preferential antagonist of D(3) versus D(2) receptors and does not interact with histamine H(1) and muscarinic receptors. In contrast to haloperidol, clozapine, olanzapine, and risperidone, S33138 (0.16-2.5 mg/kg s.c.) did not disrupt performance in passive-avoidance and five-choice serial reaction time procedures. Furthermore, upon either systemic administration (0.04-2.5 mg/kg s.c.) or introduction into the frontal cortex (0.04-0.63 mug/side), S33138 potently attenuated the perturbation of social recognition by scopolamine or a prolonged intersession delay. Over a comparable and low-dose range, S33138 (0.04-0.63 mg/kg s.c.) elevated dialysis levels of acetylcholine in the frontal cortex of freely moving rats. At higher doses (2.5-10.0 mg/kg s.c.), S33138 also increased frontocortical levels of histamine, whereas monoamines, glutamate, glycine, and GABA were unaffected. By analogy to the other antipsychotics, S33138 (0.63-10.0 mg/kg s.c.) inhibited conditioned avoidance responses in rats, apomorphine-induced climbing in mice, and hyperlocomotion elicited by amphetamine, cocaine, dizocilpine, ketamine, and phencyclidine in rats. S33138 (0.16-2.5 mg/kg s.c.) also blocked the reduction of prepulse inhibition elicited by apomorphine. In comparison with the above actions, only "high" doses of S33138 (10.0-40.0 mg/kg s.c.) elicited catalepsy. To summarize, reflecting preferential blockade of D(3) versus D(2) receptors, S33138 preserves and/or enhances cognitive function, increases frontocortical cholinergic transmission, and is active in models of antipsychotic properties at doses well below those inducing catalepsy. In comparison with clinically available agents, S33138 displays, thus, a distinctive and promising profile of potential

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

    DEFF Research Database (Denmark)

    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...

  8. Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics Revisão da eficácia do placebo nos ensaios clínicos que comparam antipsicóticos típicos e atípicos

    Directory of Open Access Journals (Sweden)

    Irismar Reis de Oliveira

    2009-03-01

    Full Text Available OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.OBJETIVO: Revisar a eficácia do placebo em comparação com a dos antipsicóticos atípicos e típicos no tratamento da esquizofrenia e do transtorno

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

    Directory of Open Access Journals (Sweden)

    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.

  10. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ): preliminary evidence for reliability and validity.

    Science.gov (United States)

    de Boer, Marrit K; Castelein, Stynke; Bous, Johan; van den Heuvel, Edwin R; Wiersma, Durk; Schoevers, Robert A; Knegtering, Henderikus

    2013-11-01

    The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia or a schizophrenia spectrum disorder using antipsychotics. The ASFQ is a semistructured interview, with good face validity and content validity, that takes on average about 10min to complete. The ASFQ has good internal reliability (Cronbach's alpha 0.84) and good test-retest reliability (mean Spearman's rho=.76). The inter-rater reliability is good for questions about libido, orgasm, erection and ejaculation. Correlation coefficients for calculating convergent validity were modest to good when comparing the ASFQ with the corresponding items on the Subject's Response to Antipsychotics (SRA) questionnaire and the Arizona Sexual Experience Scale (ASEX). Based on preliminary evidence, it can be concluded that the Antipsychotics and Sexual Functioning Questionnaire has reasonable reliability and is available for clinical use and research.

  11. The Antipsychotics and Sexual Functioning Questionnaire (ASFQ) : Preliminary evidence for reliability and validity

    NARCIS (Netherlands)

    de Boer, M.K.; Castelein, Stynke; Bous, Johan; van den Heuvel, Edwin R.; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

    2013-01-01

    The aim of this study is to describe the psychometric properties of the Antipsychotics and Sexual Functioning Questionnaire (ASFQ). Internal reliability, test-retest reliability, inter-rater reliability, validity and sensitivity to change were calculated in a sample of 30 patients with schizophrenia

  12. Treatment with the antipsychotic agent, risperidone, reduces disease severity in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    O'Sullivan, David; Green, Laura; Stone, Sarrabeth; Zareie, Pirooz; Kharkrang, Marie; Fong, Dahna; Connor, Bronwen; La Flamme, Anne Camille

    2014-01-01

    Recent studies have demonstrated that atypical antipsychotic agents, which are known to antagonize dopamine D2 and serotonin 5-HT2a receptors, have immunomodulatory properties. Given the potential of these drugs to modulate the immune system both peripherally and within the central nervous system, we investigated the ability of the atypical anti-psychotic agent, risperidone, to modify disease in the animal model of multiple sclerosis (MS)4, experimental autoimune encephalomyelitis (EAE). We found that chronic oral administration of risperidone dose-dependently reduced the severity of disease and decreased both the size and number of spinal cord lesions. Furthermore, risperidone treatment substantially reduced antigen-specific interleukin (IL)-17a, IL-2, and IL-4 but not interferon (IFN)-γ production by splenocytes at peak disease and using an in vitro model, we show that treatment of macrophages with risperidone alters their ability to bias naïve T cells. Another atypical antipsychotic agent, clozapine, showed a similar ability to modify macrophages in vitro and to reduce disease in the EAE model but this effect was not due to antagonism of the type 1 or type 2 dopamine receptors alone. Finally, we found that while risperidone treatment had little effect on the in vivo activation of splenic macrophages during EAE, it significantly reduced the activation of microglia and macrophages in the central nervous system. Together these studies indicate that atypical antipsychotic agents like risperidone are effective immunomodulatory agents with the potential to treat immune-mediated diseases such as MS.

  13. Quality of Life of Elderly Patients With Antipsychotic-Induced Parkinsonism : A Cross-Sectional Study

    NARCIS (Netherlands)

    Schouten, Henrike J.; Knol, Wilma; Egberts, Toine C. G.; Schobben, Alfred F. A. M.; Jansen, Paul A. F.; van Marum, Rob J.

    2012-01-01

    Objectives: Antipsychotic-induced parkinsonism (AIP) is one of the most common adverse effects of haloperidol. The purpose of this study was to investigate the association between AIP and quality of life of elderly patients treated with haloperidol. Design: Cross-sectional study design. Setting: Ele