A Comparison Study of Quetiapine and Risperidone's Effectiveness and Safety on Treating Alcohol-induced Mental Disorder.

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Lv, Bei; Duan, Haishui

2016-08-25

Compared with Risperidone, Quetiapine's effectiveness and safety on treating alcohol-induced mental disorder is still unclear. To investigate the clinical effectiveness and safety of Quetiapine on treating alcohol-induced mental disorder. One hundred and forty-eight patients with alcohol-induced mental disorder were divided into the experimental group (75 patients) and the control group (73 patients) by the treatments they received. The patients in the experimental group were treated with Quetiapine by taking it three times per day orally. The mean (sd) maintenance dose was 151.2(27.3) mg/d, and the treatment cycle was 6 weeks. Patients in the control group received Risperidone once per day orally with a mean (sd) maintenance dose being 2.3(0.9) mg/d, and the treatment cycle was 6 weeks as well. The PANSS scale was used to assess patients' before and after treatment. The researchers also observed any adverse reactions in both treatment strategies and evaluated the effectiveness and safety of both treatment strategies. The mean (sd) PANSS scale score of the experimental group after two weeks of treatment was 71.9 (10.2), which was clearly better than the mean (sd) score before treatment (82.6 [11.4]), and was significantly better than the control group's mean (sd) score after two weeks (76.5[12.8]). Also, the experimental group's scores after 4 weeks of treatment and 6 weeks of treatment were significantly better than the control group. The experimental group's efficacy rate (94.7%) was higher than the control group's (90.4%); the cure rate of the experimental group (33.3%) was higher than that of the control group (24.7%), and the difference was statistically significant. The rates of adverse reactions in the experimental and control groups were 13.3% and 19.2% respectively, and they were significantly different from each other. Treating alcohol-induced mental disorder with Quetiapine is more effective than treating it with Risperidone. Quetiapine can improve

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

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

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

2008-08-01

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

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

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Ascher-Svanum H

2012-05-01

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

Olanzapine induced Q-Tc shortening.

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Shoja Shafti, Saeed; Fallah Jahromi, Parisa

2014-12-01

Prolongation of Q-Tc interval is commonly accepted as a surrogate marker for the ability of a drug to cause torsade de pointes. In the present study, safety of olanzapine versus risperidone was compared among a group of patients with schizophrenia to see the frequency of the electrocardiographic alterations induced by those atypical antipsychotics. Two hundred and sixty-eight female inpatients with schizophrenia entered in one of the two parallel groups to participate in an open study for random assignment to olanzapine (n = 148) or risperidone (n = 120). Standard 12-lead surface electrocardiogram (ECG) was taken from each patient at baseline, before initiation of treatment, and then at the end of management, just before discharge. The parameters that were assessed included heart rate (HR), P-R interval, QRS interval, Q-T interval (corrected = Q-Tc), ventricular activation time (VAT), ST segment, T wave, axis of QRS, and finally, interventricular conduction process. A total of 37.83% of cases in the olanzapine group and 30% in the risperidone group showed some Q-Tc changes; 13.51% and 24.32% of the patients in the olanzapine group showed prolongation and shortening of the Q-Tc, respectively, while changes in the risperidone group were restricted to only prolongation of Q-Tc. Comparison of means showed a significant increment in Q-Tc by risperidone (p = 0.02). Also, comparison of proportions in the olanzapine group showed significantly more cases with shortening of Q-Tc versus its prolongation (p = 0.01). No significant alterations with respect to other variables were evident. Olanzapine and risperidone had comparable potentiality for induction of Q-Tc changes, while production of further miscellaneous alterations in ECG was more observable in the olanzapine group compared with the risperidone group. Also shortening of Q-Tc was specific to olanzapine.

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

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

1999-01-01

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

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

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

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P N Suresh Kumar

2016-01-01

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

Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder.

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Houthoofd, Sofie A M K; Morrens, Manuel; Sabbe, Bernard G C

2008-09-01

functioning), although the results for verbal fluency, verbal learning and memory, and reasoning and problem solving were not unanimous, and no comparative data on social cognition were available. Similar cognitive effects were found with risperidone, olanzapine, and quetiapine on the domains of verbal working memory and reasoning and problem solving, as well as verbal fluency. More research is needed on the domains in which study results were contradictory. For olanzapine versus risperidone, these were verbal and visual learning and memory and psychomotor functioning. No comparative data for olanzapine and risperidone were available for the social cognition domain. For quetiapine versus risperidone, the domains in which no unanimity was found were processing speed, attention/vigilance, nonverbal working memory, and verbal learning and memory. The limited available reports on risperidone versus clozapine suggest that: risperidone was associated with improved, and clozapine with worsened, performance on the nonverbal working memory domain; risperidone improved and clozapine did not improve reasoning and problem-solving performance; clozapine improved, and risperidone did not improve, social cognition performance. Use of long-acting injectable risperidone seemed to be associated with improved performance in the domains of attention/vigilance, verbal learning and memory, and reasoning and problem solving, as well as psychomotor functioning. The results for the nonverbal working memory domain were indeterminate, and no clear improvement was seen in the social cognition domain. The domains of processing speed, verbal working memory, and visual learning and memory, as well as verbal fluency, were not assessed. The results of this review of within-group comparisons of oral risperidone suggest that the agent appeared to be associated with improved functioning in the cognitive domains of processing speed, attention/vigilance, verbal and visual learning and memory, and reasoning and

Risperidone-induced enuresis in two children with autistic disorder.

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Hergüner, Sabri; Mukaddes, Nahit Motavalli

2007-08-01

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

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

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

2014-11-01

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

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

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Uguz, Faruk

2017-11-01

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

Risperidone-induced reversible neutropenia.

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

2017-01-01

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

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

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

2002-01-01

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

Edema associated with quetiapine

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Koleva, Hristina K.; Erickson, Mark A.; Vanderlip, Erik R.; Tansey, Janeta; Mac, Joseph; Fiedorowicz, Jess G.

2010-01-01

Background Edema associated with quetiapine has been described in only one case report to date and represents a potentially serious adverse reaction. Methods We present a case series of three patients who developed bilateral leg edema following initiation of quetiapine. Results One of these patients had a recurrence of edema with subsequent rechallenge. Another patient developed quetiapine-induced edema following a prior episode of olanzapine-induced edema. All the cases present a compelling temporal relationship between the drug challenge and the adverse event. Conclusions Prompt recognition and intervention with discontinuation of the offending agent is important for this potentially serious, seemingly idiosyncratic, vascular complication. PMID:19439156

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

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.

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

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

2005-01-01

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

[Prescription of olanzapine in children and adolescent psychiatric patients].

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Frémaux, T; Reymann, J-M; Chevreuil, C; Bentué-Ferrer, D

2007-01-01

A review of the literature from 1996-2004 on the indications and adverse reactions concerning the use of olanzapine, a second generation antipsychotic agent, in children and adolescents with psychiatric illness is made in this article. Studies lasted for 2 to 3 months and a few had a follow up period up to a year. Olanzapine, dosed from 2.5 to 20 mg/day, is shown to be a useful drug in the treatment of child and adolescent onset schizophrenia, bipolar disorder, anorexia nervosa with delusions, pervasive developmental disorder, tic disorders, and aggression. OPEN AND DOUBLE-BLIND STUDIES: In 4 open labeled studies (26, 34, 39, 43) and 2 case reports (25), 53 patients, aged from 6-18 years old, afflicted by child onset schizophrenia, were treated with olanzapine for 1 1/2 weeks to one year; 19 had treatment resistant childhood schizophrenia and 34 a first episode. In the first group 13/19 showed improvement whereas, in the second group 27/34 were considered responders. Four patients in the first group who had responded to clozapine (stopped because of adverse events) did less well on olanzapine. In 5 studies, 4 open labeled (15, 20, 44) and 1 double blind (27), 59 adolescent onset schizophrenic patients were treated by olanzapine from 8 to 26 weeks; 50/59 patients were considered responders. In the open label study (20) comparing 43 adolescents treated by olanzapine (19 patients), risperidone (17 patients), or haloperidol (7 patients), improvement was significant in the three groups after 4 weeks of treatment and continued after 8 weeks. It is most interesting to mention that 2 months after the end of the study 71% (12/17) of the olanzapine group that had completed the study, 10/15 (67%) of the risperidone group, and 43% (3/7) of the haloperidol group had continued their treatment. Dropouts were for inefficacy and non-compliance in the olanzapine and risperidone groups whereas they were also for adverse events in the haloperidol group (2/4). A final double blind

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

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Chiappini, Stefania; Schifano, Fabrizio

2018-02-01

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

Quetiapine monotherapy for bipolar depression

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Michael E Thase

2008-03-01

Full Text Available Michael E ThaseDepartments of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; the Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; and the University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: Bipolar depression is more common, disabling, and difficult-to-treat than the manic and hypomanic phases that define bipolar disorder. Unlike the treatment of so-called “unipolar” depressions, antidepressants generally are not indicated as monotherapies for bipolar depressions and recent studies suggest that - even when used in combination with traditional mood stabilizers – antidepressants may have questionable value for bipolar depression. The current practice is that mood stabilizers are initiated first as monotherapies; however, the antidepressant efficacy of lithium and valproate is modest at best. Within this context the role of atypical antipsychotics is being evaluated. The combination of olanzapine and the antidepressant fluoxetine was the first treatment to receive regulatory approval in the US specifically for bipolar I depression. Quetiapine was the second medication to be approved for this indication, largely as the result of two pivotal trials known by the acronyms of BOLDER (BipOLar DEpRession I and II. Both studies demonstrated that two doses of quetiapine (300 mg and 600 mg given once daily at bedtime were significantly more effective than placebo, with no increased risk of patients switching into mania. Pooling the two studies, quetiapine was effective for both bipolar I and bipolar II depressions and for patients with (and without a history of rapid cycling. The two doses were comparably effective in both studies. Although the efficacy of quetiapine monotherapy has been established, much additional research is necessary. Further studies are needed to more fully investigate dose-response relationships and comparing quetiapine monotherapy to other mood stabilizers

Use of psychotropic drugs during pregnancy and breast-feeding

DEFF Research Database (Denmark)

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

2015-01-01

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

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

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

2014-01-01

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

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...

Second-generation antipsychotics for major depressive disorder and dysthymia.

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

2010-12-08

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

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

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

2015-12-01

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

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

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mitra safa

2008-10-01

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

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

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

2009-01-01

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

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

African Journals Online (AJOL)

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

[Atypical antipsychotics and sexual dysfunction: five case-reports associated with risperidone].

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Haefliger, T; Bonsack, C

2006-01-01

Sexual and reproductive function side effects of atypical antipsychotics are frequent, often underestimated and badly tolerated. They contribute to the 50% rate of non-compliance reported for treated patients. Prevalence of sexual dysfunction associated with atypical antipsychotic treatment is high, varying from 18 to 96%. Atypical antipsychotics aren't, as a group, much better than typical antipsychotics, and among them, risperidone seems to induce more and quetiapine less sexual dysfunction. Most atypicals are non-selective, and have actions on multiple central and peripheral receptors. Among these, dopaminergic blockade could have a direct - altering motivation (desire) and reward (orgasm) - and an indirect negative influence on sexuality. Actually, the secondary hyperprolactinemia induced by some antipsychotics (typical antipsychotics, risperidone and amisulpiride), is dose-dependent, more pronounced for female patients, and may have a detrimental effect on sexual function. It also may result in hypogonadism, particularly for female patients. The long-term consequences of this secondary hypogonadism are subject to debate but potentially severe. Furthermore, the blocking and/or modulating actions of atypical antipsychotics on adrenaline, serotonine, histamine or acetyl-choline receptors all have the potential to contribute to secondary sexual problems. The pharmacological profile of risperidone, characterized by a strong affinity for D2 and alpha1 receptors, correlates with his tendency to significantly elevate prolactin levels and to produce ejaculatory disturbances. FIVE CASE-REPORTS: We describe five case-reports of sexual or hormonal disturbances associated with risperidone treatment: two cases of ejaculatory disturbance, one case of galactorrhea and two cases of amenorrhea. Alberto and David are two young male schizophrenic patients, treated with risperidone, and complaining of a total absence of ejaculation despite a preserved orgasm. Many recent case

Long-acting injectable antipsychotics: focus on olanzapine pamoate

Directory of Open Access Journals (Sweden)

JP Lindenmayer

2010-05-01

Full Text Available JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

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 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.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.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.In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

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

OpenAIRE

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

2013-01-01

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

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

Science.gov (United States)

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

2008-08-28

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

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

Directory of Open Access Journals (Sweden)

Papanicolaou Sotiria

2008-08-01

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

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

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

2018-05-01

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

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...

Study on effects of an atypical antipsychotic agent, quetiapine, on regional cerebral blood flow with 99mTc-ECD SPECT in drug-naive or unmedicated schizophrenic patients

International Nuclear Information System (INIS)

Monkawa, Akikazu

2007-01-01

The objective of this study was to investigate the underlying mechanisms of intracerebral actions or clinical efficacies of quetiapine, an atypical antipsychotic agent and a multi-action receptor targeting agent (MARTA), and the influences of quetiapine on absolute regional cerebral blood flows (rCBFs) of schizophrenic patients. Correlations between rCBFs and psychotic symptoms were also examined. Subjects comprised 12 patients who met the ICD-10 criteria for schizophrenia. All patients were drug-naive or unmedicated. Using single photon emission computed tomography (SPECT) with 99m Tc-ethyl cysteinate dimer (ECD), rCBFs were measured. Psychotic symptoms were evaluated with positive and negative syndrome scale (PANSS). The evaluations of SPECT and PANSS were repeated before and after oral 2-week administration of quetiapine 300 mg/day in all patients and after subsequent 2-week administration of quetiapine 600 mg/day in 6 patients. Administration of quetiapine yielded no significant changes in rCBFs at any dose. And there were no significant correlations between the scores of PANSS and the values of rCBFs in any region, though the scores of PANSS decreased after qutiapine administration. It has been reported that, a typical antipsychotic agent, haloperidol, and an atypical antipsychotic agent, risperidone, decrease rCBFs in the cerebral cortex in dose-dependently in drug-naive or unmedicated schizophrenic patients. This phenomenon is considered to be attributable to a secondary inactivation of the cerebral cortex due to D2 receptor blockade of haloperidol or risperidone in the striatum through the cortico-striatal-thalamic pathway. In the frame of this hypothesis, results of this study may relate to the lower degree of D2 blockade induced by quetiapine than that produced by haloperidol and risperidone. (author)

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

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

2016-01-01

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

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

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Maher, Alicia R; Theodore, George

2012-06-01

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

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

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

Science.gov (United States)

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

2013-12-01

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

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

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Correll Christoph

2005-05-01

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

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

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

1999-08-01

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

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

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

1999-08-01

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

The psychopharmacology algorithm project at the Harvard South Shore Program: an algorithm for acute mania.

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Mohammad, Othman; Osser, David N

2014-01-01

This new algorithm for the pharmacotherapy of acute mania was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. The authors conducted a literature search in PubMed and reviewed key studies, other algorithms and guidelines, and their references. Treatments were prioritized considering three main considerations: (1) effectiveness in treating the current episode, (2) preventing potential relapses to depression, and (3) minimizing side effects over the short and long term. The algorithm presupposes that clinicians have made an accurate diagnosis, decided how to manage contributing medical causes (including substance misuse), discontinued antidepressants, and considered the patient's childbearing potential. We propose different algorithms for mixed and nonmixed mania. Patients with mixed mania may be treated first with a second-generation antipsychotic, of which the first choice is quetiapine because of its greater efficacy for depressive symptoms and episodes in bipolar disorder. Valproate and then either lithium or carbamazepine may be added. For nonmixed mania, lithium is the first-line recommendation. A second-generation antipsychotic can be added. Again, quetiapine is favored, but if quetiapine is unacceptable, risperidone is the next choice. Olanzapine is not considered a first-line treatment due to its long-term side effects, but it could be second-line. If the patient, whether mixed or nonmixed, is still refractory to the above medications, then depending on what has already been tried, consider carbamazepine, haloperidol, olanzapine, risperidone, and valproate first tier; aripiprazole, asenapine, and ziprasidone second tier; and clozapine third tier (because of its weaker evidence base and greater side effects). Electroconvulsive therapy may be considered at any point in the algorithm if the patient has a history of positive response or is intolerant of medications.

Olanzapine-induced ischemic colitis

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Esteban Sáez-González

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

Amisulpride versus other atypical antipsychotics for schizophrenia

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

2014-01-01

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

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

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

2007-02-01

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

Treatment of anorexia nervosa with long-term risperidone in an outpatient setting: case study.

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Kracke, Elsa J; Tosh, Aneesh K

2014-01-01

There are currently few studies focusing on the efficacy of long-term atypical antipsychotics to treat anorexia nervosa in the pediatric population. This case report follows the treatment of a 17 year-old female with anorexia nervosa over her four-year undergraduate career. After two years of multidisciplinary treatment, low-dose risperidone was initiated due to persistence of her disease. She expressed decreased rigidity around meal times, her weight improved and she had resumption of menses. She was compliant with treatment through graduation and maintained her weight gain. Atypical antipsychotics are a treatment option in the management of anorexia nervosa. Risperidone has not been studied as frequently as olanzapine for eating disorders. Risperidone was chosen for its more favorable side effect profile and decreased cost to the patient. Previous studies on anorexia nervosa treatment have occurred during inpatient treatment and have limited follow-up due to patients' refusal to initiate or maintain medication compliance. This case presents 17 months of outpatient data. The efficacy of risperidone therapy was evaluated with frequent weight checks, subjective decrease in rigidity, serial complete metabolic panels, and restoration of menses. In this case report, an adolescent female treated with low-dose risperidone had decreased rigid thinking, weight gain and resolution of secondary amenorrhea without medication side effects. Therefore, the atypical antipsychotic risperidone may be an effective long-term outpatient treatment option for patients with anorexia nervosa.

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

Neurological Adverse Effects of Antipsychotics in Children and Adolescents.

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Garcia-Amador, Margarita; Merchán-Naranjo, Jessica; Tapia, Cecilia; Moreno, Carmen; Castro-Fornieles, Josefina; Baeza, Inmaculada; de la Serna, Elena; Alda, José A; Muñoz, Daniel; Andrés Nestares, Patricia; Cantarero, Carmen Martínez; Arango, Celso

2015-12-01

The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and

New Modified UPLC/Tandem Mass Spectrometry Method for Determination of Risperidone and Its Active Metabolite 9-Hydroxyrisperidone in Plasma: Application to Dose-Dependent Pharmacokinetic Study in Sprague-Dawley Rats

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Essam Ezzeldin

2017-01-01

Full Text Available Sensitive and specific liquid-chromatography tandem mass spectrometry (UPLC-MS/MS assay has been developed and validated for simultaneous quantification of risperidone (RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS in rat plasma using olanzapine (OLA as internal standard (IS. Pharmacokinetics of risperidone and its active metabolite 9-hydroxyrisperidone was compared across different doses (0.3, 1.0, and 6.0 mg/kg. Serial blood sample was collected over a time of 48 hours and analyzed for risperidone and its active metabolite 9-hydroxyrisperidone. The pharmacokinetics parameters including Cmax, tmax, and AUC were determined for risperidone and its active ingredient. The method was linear in the concentration range of 0.2–500 ng/mL for risperidone and 9-OH-risperidone, with coefficients of determination greater than 0.998 and lower limit of quantitation of 0.2 ng/mL. Blood levels of risperidone and its active metabolite were roughly dose-proportional. The method developed herein is simple and rapid and was successfully applied for dose-dependent pharmacokinetic study.

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

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

2014-10-01

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

Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost.

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Mortimer, A; Williams, P; Meddis, D

2003-01-01

Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.

Update on quetiapine in the treatment of bipolar disorder: results from the BOLDER studies

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Prashant Gajwani

2007-01-01

Full Text Available Prashant Gajwani1, David J Muzina2, David E Kemp3, Keming Gao1, Joseph R Calabrese11Case Western Reserve University (CWRU School of Medicine, 2Cleveland Clinic Lerner College of Medicine of CWRU, 3Case Western Reserve University, Cleveland OH, USAAbstract: The essential features of bipolar affective disorder involve the cyclical occurrence of high (manic or hypomanic episodes and low mood states. Depressive episodes in both bipolar I and II disorder are more numerous and last for longer duration than either manic or hypomanic episodes. In addition depressive episodes are associated with higher morbidity and mortality. While multiple agents, including all 5 atypical antipsychotics, have demonstrated efficacy and earned US FDA indication for manic phase of bipolar illness, the acute treatment of bipolar depression is less well-studied. The first treatment approved by the US FDA for acute bipolar depression was the combination of the atypical antipsychotic olanzapine and the antidepressant fluoxetine. Recently, quetiapine monotherapy has demonstrated efficacy in the treatment of depressive episodes associated with both bipolar I and II disorder and has earned US FDA indication for the same.Keywords: bipolar disorder, quetiapine, BOLDER studies

Weight change during long-term treatment with lurasidone: pooled analysis of studies in patients with schizophrenia.

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Meyer, Jonathan M; Mao, Yongcai; Pikalov, Andrei; Cucchiaro, Josephine; Loebel, Antony

2015-11-01

The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40-160 mg/day lurasidone; two studies included active comparators (2-6 mg/day risperidone or 200-800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N = 89 risperidone, N = 33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was -0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months.

Atypical antipsychotics in the treatment of early-onset schizophrenia

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Hrdlicka M

2015-04-01

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

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.

Change in Prolactin Levels in Pediatric Patients Given Antipsychotics for Schizophrenia and Schizophrenia Spectrum Disorders: A Network Meta-Analysis

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Chakrapani Balijepalli

2018-01-01

Full Text Available Background. Treatment of schizophrenia with first- and second-generation antipsychotics has been associated with elevated prolactin levels, which may increase the risk for prolactin-related adverse events. Methods. Randomized controlled trials (RCTs included in a recent systematic review were considered for this analysis. A Bayesian network meta-analysis was used to compare changes in prolactin levels in pediatric patients diagnosed with schizophrenia or schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs. Results. Five RCTs, including 989 patients combined, have evaluated the changes in prolactin for pediatric patients after 6 weeks of treatment with risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone. In the overall study population, treatment with risperidone was associated with the highest increase in mean prolactin levels compared to other SGAs. Patients treated with risperidone 4–6 mg/day were found to experience the greatest increases (55.06 ng/ml [95% CrI: 40.53–69.58] in prolactin levels, followed by risperidone 1–3 mg/day, paliperidone 3–6 mg/day, and paliperidone 6–12 mg/day. Conclusions. This study shows that there are differences in SGAs ability to cause hyperprolactinemia. Further, there is clear evidence of safety concerns with risperidone and paliperidone treatment in adolescent schizophrenia patients. Registration. PROSPERO CRD42014009506.

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

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Fresno David

2007-10-01

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

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

Aripiprazole versus other atypical antipsychotics for schizophrenia

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

2014-01-01

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

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

Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

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DuMouchel, William; Fram, David; Yang, Xionghu; Mahmoud, Ramy A; Grogg, Amy L; Engelhart, Luella; Ramaswamy, Krishnan

2008-01-01

This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. There are consistent and substantial differences between atypical antipsychotic drugs in the

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

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I. P. Remezova

2014-01-01

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

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

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

2014-03-01

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

The Safety of Second-Generation Antipsychotics During Pregnancy

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Damkier, Per; Videbech, Poul

2018-01-01

The issue of antipsychotic treatment during pregnancy is subject to substantial uncertainty and some controversy among healthcare providers, specifically pertaining to second-generation antipsychotics (SGAs) that are subject to a large gap in safety data during pregnancy compared...... with antidepressants. The amount of safety data for the use of SGAs during pregnancy is rapidly increasing, thus constantly changing the level of evidence. We performed a clinically focused review on the safety of SGA during pregnancy. Twenty-three studies provided various pregnancy outcomes for 14,382 pregnant women...... exposed to an SGA during pregnancy. In utero exposure to aripiprazole, olanzapine, and quetiapine is not associated with increased risks of major congenital malformations, whereas risperidone and paliperidone may be associated with a very minor increased risk of congenital malformations. Safety data...

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

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Swartz Marvin

2006-02-01

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

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

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Giorgio D’Allio

2005-12-01

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

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

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

2012-06-01

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

The management of schizophrenia: focus on extended-release quetiapine fumarate

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Peuskens J

2011-09-01

Full Text Available Joseph Peuskens Universitair Psychiatrisch Centrum KU Leuven, Campus St Jozef Kortenberg, Kortenberg, Belgium Abstract: Effective management of schizophrenia remains a significant clinical challenge. While antipsychotic medications have proven efficacy in this disease, there remains an opportunity to further improve symptom control and long-term relapse prevention. Also, a number of factors, including tolerability and complex dosing regimens, can result in nonadherence to medication. Quetiapine is an atypical antipsychotic with proven efficacy and an established tolerability profile in schizophrenia. The once-daily extended-release formulation (quetiapine XR offers a simplified dosing regimen and titration schedule. Short-term clinical studies have shown that quetiapine XR (400–800 mg/d is efficacious in the acute treatment of schizophrenia, while a long-term study has shown that quetiapine XR was significantly more effective than placebo at preventing relapse. Furthermore, an investigation in which stable patients switched from the immediate-release formulation (quetiapine IR to quetiapine XR showed that quetiapine XR is generally well tolerated and has no loss of efficacy compared with quetiapine IR. In patients who experienced insufficient efficacy or poor tolerability on their previous antipsychotic, switching to quetiapine XR significantly improved efficacy compared with the previous treatment. In conclusion, quetiapine XR is an effective and generally well tolerated treatment for schizophrenia. Furthermore, once-daily dosing may improve patient adherence, which may impact positively on patient outcomes. Keywords: adherence, atypical antipsychotics, adverse events

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

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

2013-08-01

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

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

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

2014-01-01

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

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

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

2014-12-01

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

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

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

2000-05-01

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

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

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

2017-09-01

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

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

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Joseph F Hayes

2016-08-01

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

Effects of Green Tea Extracts on the Pharmacokinetics of Quetiapine in Rats

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Essam Ezzeldin

2015-01-01

Full Text Available Quetiapine is an atypical antipsychotic, used clinically in the treatment of schizophrenia, acute mania in bipolar disorders, and bipolar depression in adults. In this study, the effect of green tea extracts (GTE on the pharmacokinetics of quetiapine (substrate of CYP3A4 was investigated in rats. Male Wistar albino rats received GTE (175 mg/kg or saline (control by oral gavage for 7 days before a single intragastric administration of 25 mg/kg quetiapine. Plasma concentrations of quetiapine were measured up to 12 h after its administration by a validated ultraperformance liquid chromatography-tandem mass spectroscopy. Pretreatment with GTE produced significant reductions in the maximum plasma concentration and area under the curve of quetiapine by 45% and 35%, respectively, compared to quetiapine alone. However, GTE did not produce significant change in elimination half-life and oral clearance of quetiapine. This study concluded that GTE may decrease the bioavailability of quetiapine when coadministered.

Safety and efficacy of quetiapine in bipolar depression.

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Bogart, Gregory T; Chavez, Benjamin

2009-11-01

To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression. Searches of MEDLINE and PubMed (1977-July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials. Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion. There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapine's efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%. Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.

[Eating disorders in psychiatric patients during treatment with second generation antipsychotics].

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Vasilenko, L M; Gorobets, L N; Bulanov, V S; Litvinov, A V; Ivanova, G P; Tsarenko, M A; Polyakovskaya, T P

2015-01-01

To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMIobesity grade 2-3 in 38 patients (BMI>30 kg/m²). Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these we developed recommendations for management of patients treated with second generation antipsychotics.

Update on extended release quetiapine fumarate in schizophrenia and bipolar disorders

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El-Khalili N

2012-11-01

Full Text Available Nizar El-KhaliliAlpine Clinic, Lafayette, IN, USAAbstract: The atypical antipsychotic quetiapine fumarate is available both as an immediate release (IR and as an extended release (XR formulation allowing flexibility of dosing for individual patients. Approved uses of quetiapine XR include the treatment of schizophrenia (including maintenance therapy for prevention of relapse, the treatment of bipolar disorder (manic and depressive episodes, and the prevention of recurrence in patients with bipolar disorder who respond to quetiapine XR. This narrative review provides an update on quetiapine XR in these indications. The pharmacological profile of quetiapine, including a moderate affinity for dopamine D2 receptors and higher affinity for serotonin 5-hydroxytryptophan (5-HT2A receptors, may explain its broad efficacy and low propensity for extrapyramidal symptoms (EPS. The XR formulation has similar bioavailability but prolonged plasma levels compared with the IR formulation, allowing for less frequent (once-daily dosing. Clinical studies have confirmed the efficacy of quetiapine XR in relieving the acute symptoms of schizophrenia during short-term trials, and reducing the risk for relapse in long-term studies. Direct switching from the IR formulation to the same dose of the XR formulation did not reveal any loss of efficacy or tolerability issues, and switching patients to quetiapine XR from conventional or other atypical antipsychotics (for reasons of insufficient efficacy or tolerability also proved to be beneficial and generally well tolerated. In bipolar disorder, quetiapine XR has also proven effective in relieving acute depressive and manic symptoms. Adverse events with quetiapine XR in patients with either schizophrenia or bipolar disorder are similar to those associated with the IR formulation, the most common being sedation, dry mouth, somnolence, dizziness, and headache. The low propensity for EPS is maintained with the XR formulation

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

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Sandip Shah

2011-01-01

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

Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children

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Eiji Kirino

2014-01-01

Full Text Available Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.

Serum prolactin level in patients taking olanzapine

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Diganta Das

2015-01-01

Full Text Available Introduction: Olanzapine is a commonly used antipsychotic. Prolactin elevation is a common adverse effect of anstipsychotics, and serum prolactin elevation is seen in about 30% patients treated with olanzapine. There are confounding results about dose dependency of olanzapine and prolactin elevation, and also the duration of treatment. Method: Fifty six patients, 36 male and 20 female, who were taking olanzapine for any condition for more than a month at a constant dose were enrolled in the study. Patients’ age, weight, body mass index (BMI, serum prolactin levels, and some biochemical values were recorded. Patients were taken from the review outpatient department (OPD after due consent. Results: Five each in male and female groups showed elevation of serum prolactin (estimated to be high if >20 ng/dl for males, and >25 ng/dl for females. In females, the elevation was found at lesser dose of olanzapine (13 mg/day, in males 18 mg/day and early in the treatment (2.4 months vs. 9.7 months in males. Males tended to show raised prolactin with higher doses of olanzapine (mean 18 mg/day. Females (26.31% also showed higher prevalence of prolactin elevation compared to males (13.51%. No other parameter was found to modify the prolactin levels. Conclusion: Olanzapine causes elevation of serum prolactin, though lesser degree than some other antipsychotics. Females are more prone to have raised serum prolactin with olanzapine compared to males. However, the elevation seems to be transient. Higher doses of olanzapine tend to cause elevation of serum prolactin. Serum prolactin estimation in patients taking olanzapine may be undertaken to maintain quality life, particularly in females.

Olanzapine

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Olanzapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual ... help control your symptoms, but it will not cure your condition. It may take several weeks or ...

Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms.

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Rock, Philippa L; Goodwin, Guy M; Wulff, Katharina; McTavish, Sarah F B; Harmer, Catherine J

2016-03-01

Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers. Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks. Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times. These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action. © The Author(s) 2016.

Postmortem Quetiapine Reference Concentrations in Brain and Blood

DEFF Research Database (Denmark)

Skov, Louise; Johansen, Sys Stybe; Linnet, Kristian

2015-01-01

and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N 5 36), the 10–90 percentiles for quetiapine concentrations in brain tissue were 0.030 – 1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10 –90 percentile values were 0.......007 – 0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain –blood ratio 10 –90 percentiles of 2.31 – 6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N 5 5), the median value......Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue...

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

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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...

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

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

2016-06-01

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

Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

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Miroshnichenko, Igor I; Baymeeva, Natalia V

2018-04-07

A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

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Goto, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Moriya, Junji; Hori, Hikaru; Hayashi, Kenji; Ikenouchi-Sugita, Atsuko; Nakano-Umene, Wakako; Katsuki, Asuka; Nishimura, Joji; Korogi, Yukunori; Nakamura, Jun

2010-12-01

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

First Episode Schizophrenia Regional Cerebral Blood Flow Assessment after Atypical Antipsychotics

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Rimbu, A.; Mititelu, R.; Marinescu, G.; Ghita, S.; Mazilu, C.; Codorean, I.; Gheorghe, M.

2006-01-01

Full text: Aim: Since regional cerebral blood flow (rCBF) findings in schizophrenic patients are inconsistent, the aim of our study was to evaluate and compare rCBF in the first episode of schizophrenia, before and after atypical antipsychotic treatment. Method: 21 patients who met criteria for schizophrenia were assessed PANSS score and tomographic brain perfusion (SPECT). The treatment was administered for 10-12 weeks and the dose was 4.8mg/day Risperidone, 11.6mg/day Olanzepine, 440mg/day Quetiapine. After finishing treatment all patients underwent a control SPECT study. Results: PANSS scores revealed two groups: group A-14 patients with predominant positive symptoms; 9 received Olanzapine and 5 Quetiapine. In group B -7 patients with predominant negative symptoms received Risperidone. Positive symptoms were associated with hypoperfusion in posterior parietal regions and superior temporal gyrus, bilaterally; for negative symptoms we found hypoperfusion in prefrontal cortex, predominantly in left side and a hyper perfusion in left basal ganglia. All patients that received atypical antipsychotic drugs had clinical improvement and decreases in PANSS scores; the control SPECT analysis revealed the same cortical changes as first studies in 15 patients and an increase of the rCBF in frontal lobes for 4 patients. 14 patients we noticed an increased rCBF at subcortical level, especially in left caudate nuclei. Conclusions: We found nonspecific features of rCBF in patients with first episode of schizophrenia, suggesting a perfusion dynamic balance rather than a fixed model. Those aspects are much more related to clinical symptoms, than to the therapeutical response. The rCBF changes in subcortical level after treatment (64.4% increase of rCBF; 35.6% not modified), can have a good prognostic value for therapeutic response. (author)

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

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Egidio Filippelli

2005-09-01

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

Pharmacology and clinical experience with risperidone.

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Love, R C; Nelson, M W

2000-12-01

Risperidone (Risperdal, Janssen Pharmaceutica) is a second generation antipsychotic (SGA) for the treatment of schizophrenia and other psychotic disorders. It is a potent antagonist of serotonin-2 (5-HT2) and dopamine-2 (D2) receptors in the brain. In comparison to conventional antipsychotics, risperidone demonstrates superior efficacy against the positive and negative symptoms of schizophrenia and a decreased occurrence of extrapyramidal side effects (EPS). Risperidone causes less weight gain than other marketed SGAs, but can increase prolactin levels and cause EPS in a dose-related manner. In a variety of pharmacoeconomic analyses, it has proven to be a cost-effective addition to the antipsychotic armamentarium. As the first SGA available for front line use, risperidone has established a new standard of care for the treatment of individuals with psychotic disorders.

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...

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

123I-IBZM SPECT in schizophrenic patients treated with quetiapine

International Nuclear Information System (INIS)

Pavics, L.; Szekeres, G.; Janka, Z.

2002-01-01

Full text: Quetiapine is a novel antipsychotic substance with relative short half-life and low affinity for D2 dopamine receptors. PET and SPECT studies demonstrated individually different D2 receptor occupancy during quetiapine monotherapy. In the present study D2 receptor occupancy was investigated in quetiapine treated schizophrenic patients for the detection of the relationship between the scintigraphic pattern and clinical sign and symptoms. In 10 schizophrenic patients (7 woman, 3 man, age ±SD: 34 ±7 PANSS: 72 ±20) IBZM SPECT (185 MBq, acquisition was started 90 min p.i.) were performed during introduction of quetiapine therapy (600-800 mg/day) and during a lower preservation dose (200-400 mg/day). All the patients were under quetiapine monotherapy. Simultaneously to the SPECT investigations visual contrast standardized rating scales determined sensitivity, clinical symptoms and extrapyramidal signs. For the evaluation of SPECT images visual interpretation and striatum/occipital lobe (S/O) activity ratio was calculated. The striatum/occipital lobe ratio at the first investigation was 1.7 ± 0.23 at the second 1.68 ± 0.12. The receptor occupancy was individually different but no significant difference was observed in relation to the quetiapine dose used. There was no significant difference in PANNSS and no patients had extrapyramidal signs. In 5 patients in clinical steady state decreasing the dose of quetiapine the S/O ratio increased by 1-35 % without long term relapse but in 5 with decreasing S/O ratio (9-29 %) clinical relapse of the disease were observed. The IBZM uptake changes correlated with the time interval until the relapse, but not with the PANNS changes. The initial striatum/occipital ratio was also significantly higher in the group of patients with relapse (over 1.8) compared to the other group. There were no relationship between the initial D2 receptor occupancy and the PANNS changes and the interval until the relapse. Endogen dopamin

A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: the PLATYPUS Study

NARCIS (Netherlands)

Karagianis, J.; Grossman, L.; Landry, J.; Reed, V. A.; de Haan, L.; Maguire, G. A.; Hoffmann, V. P.; Milev, R.

2009-01-01

BACKGROUND: Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine

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

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Kaneda, Yasuhiro; Kawamura, Ichiro; Ohmori, Tetsuro

2005-01-01

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

Risperidone as a treatment for childhood habitual behavior

Science.gov (United States)

Omranifard, Victoria; Najafi, Mostafa; Sharbafchi, Mohammad Reza; Emami, Parisa; Maracy, Mohammad

2013-01-01

Objective: The aim of this study was to investigate the effect of adding risperidone to the general behavioral treatment of masturbation in children 3-7 years old. Methods: A 4 week randomized clinical controlled trial was designed in year 2009. Samples have been chosen from children who have been referred to the Child and Adolescence Psychiatric Clinic of Isfahan University of Medical Sciences. Ninety children were recruited at the study and randomly allocated into the risperidone and control groups (44 and 46 respectively). The risperidone group was medicated simultaneously by behavioral treatments and 0.25-1 mg of risperidone daily while the controls only received the behavioral treatments. Findings: The mean ± SD age of the risperidone and control groups was 5.3 ± 1.1 and 4.9 ± 1.1 years, respectively. The mean ± SD of the period of suffering from masturbation was 3.4 ± 1.2 and 3.8 ± 1.7 months in the risperidone and the control groups, respectively. At the beginning of the study, the mean frequency of masturbation in control and the risperidone groups was 2.6 ± 0.9 and 2.7 ± 0.9 times/day, whereas after the 4th week, it decreased to 1.4 ± 0.6 and 1.1 ± 0.5 times/day, respectively. The results showed a more reduction in the mean frequency of masturbation in the risperidone group significantly. Conclusion: In comparison to the general behavioral treatment, risperidone in addition to the behavioral treatment will probably reduce the frequency of masturbation in children more effectively. PMID:24991601

Quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis

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Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers

2017-01-01

of quetiapine-extended release (quetiapine-ER) versus aripiprazole in children and adolescents with first-episode psychosis, to determine whether differences between the two treatments were sufficient to guide clinicians in their choice of one drug over the other. METHODS: In this multicentre, double-blind...... (47 [92%] vs 39 [71%]), orthostatic dizziness (42 [78%] vs 46 [81%]), depression (43 [80%] vs 44 [77%]), tension/inner unrest (37 [69%] vs 50 [88%]), failing memory (41 [76%] vs 44 [77%]), and weight gain (46 [87%] vs 38 [68%]). INTERPRETATION: This first head-to-head comparison of quetiapine...

Risperidone versus typical antipsychotic medication for schizophrenia.

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Hunter, R H; Joy, C B; Kennedy, E; Gilbody, S M; Song, F

2003-01-01

Risperidone is one of the 'new generation' antipsychotics. As well as its reputed tendency to cause fewer movement disorders than the older drugs such as chlorpromazine and haloperidol, it is claimed that risperidone may improve negative symptoms. To evaluate the effects of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. The original electronic searches of Biological Abstracts (1980-1997), Cochrane Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue 1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were updated with a new electronic search of the same databases in 2002. The search term used in the update was identical to that used in 1997. Any new studies or relevant references were added to the review. In addition, references of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were also contacted. All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for people with schizophrenia or other similar serious mental illnesses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Where possible, sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) were calculated on an intention-to-treat basis. In the short-term, risperidone was more likely to produce an improvement in the Positive and Negative Syndrome Scale (PANSS) when compared with haloperidol (n=2368, 9 RCTs, RR not 20% improved 0.72 CI 0.59 to 0.88 NNT 8). A similar, favourable outcome for risperidone was

A retrospective record review and assessment of cost of quetiapine ...

African Journals Online (AJOL)

Background: With the revision of the National Essential Medicines List in South Africa, quetiapine is only available at the discretion of individual institutions in the public health sector. However, quetiapine is effective in managing all aspects of bipolar disorder, including preventative treatment of depressive episodes, and ...

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

Risperidone-related reversal of primary enuresis: an unusual case report.

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Mendhekar, D N; Andrade, C

2010-03-01

Occasional reports have documented treatment-emergent enuresis with medication regimens that include risperidone. In contrast to these reports, we present a 12-year-old girl with mild mental retardation and primary nocturnal enuresis who received risperidone (0.5 mg/day) for the isolated symptom of inappropriate smiling. Surprisingly, in addition to reduction in inappropriate smiling, risperidone also substantially decreased the frequency of enuresis. These benefits with risperidone were confirmed in an on-off-on treatment sequence. To our knowledge, this is the first case in literature of primary enuresis responding to low-dose risperidone. Low-dose risperidone may merit study in children with enuresis. Clinical implications and possible mechanisms are discussed.

Olanzapine Overdose in a Pin Point Pupil with Altered Sensorium

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Naresh Midha

2017-09-01

Full Text Available Background:Olanzapine is a highly tolerable and easily affordable atypical antipsychotic drug which has been commonly prescribed in both inpatient and outpatient settings for several mental disorders. Olanzapine overdose is commonly seen in psychiatric patients, who attempt suicide by intoxicating themselves with their own prescribed medications. Increased olanzapine use is associated with increased incidence of overdosing. Case Presentation:We are reporting a case of olanzapine overdosage as a cause of pinpoint pupils and altered sensorium with exclusion of other differentials. The mainstay of managementof olanzapine overdose is general supportive and symptomatic measures. Discussion: Pinpoint pupils with altered sensorium and agitation are always an alarming situation for a clinician, because of differentials like organophosphorus poisoning, pontine hemorrhage and opium overdosing. Due to olanzapine overdosage, similar clinical picture can be confusing in the emergency department and early identification of such cases is helpful to decrease the risk of fatality. Conclusion: This case highlights the significance of olanzapine overdosing as a differential diagnosis for patients presented with altered sensorium and pinpoint pupils in the emergency department. Olanzapine overdosage is associated with high morbidity and mortality. Although there is no specific antidote for olanzapine overdose, appropriate history, assessment and early diagnosis are very useful for the better outcome.

Postmortem Femoral Blood Concentrations of Risperidone

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Linnet, Kristian; Johansen, Sys Stybe

2014-01-01

Postmortem femoral blood concentrations of the antipsychotic drug risperidone and the active metabolite 9-hydroxyrisperidone were determined by an achiral LC-MS/MS method in 38 cases. The cause of death was classified as unrelated to risperidone in 30 cases, in which the sum of the concentration ...

Olanzapine-induced weight gain: chronic infusion using osmotic minipumps does not result in stable plasma levels due to degradation of olanzapine in solution

NARCIS (Netherlands)

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

2008-01-01

The mechanisms underlying olanzapine-induced weight gain have not yet been fully elucidated. To examine the effects of long-term treatment with olanzapine on different aspects of energy balance, we administered olanzapine to male rats. Osmotic minipumps were chosen as preferred mode of

[Quetiapine and anticholinergic drugs induced ischaemic colitis: A case study].

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Cuny, P; Houot, M; Ginisty, S; Horowicz, S; Plassart, F; Mentec, H; Eftekhari, P

2017-02-01

The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects. A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction. On June 5th 2012, it was decided to administrate 600mg per day of quetiapine in combination with tropatepine consequent to an episode of agitation and aggressiveness. On June 14th 2012, while the patient was receiving diazepam and valproic acid, loxapine oral solution was introduced. On June 23th, the patient started mentioning digestive disorders, such as diffuse abdominal pain with constipation but continued to pass gaz. On June 25th, at 6:30 am, he declared abdominal pain, which worsened at 8:15 am despite administration of analgesics, followed by malaise and onset of vomiting. His laboratory tests showed leukocytosis 11.2G/L with neutrophils 7.7G/L. The abdomen's radiograph without preparation showed small bowel and colonic air-fluid levels. The result of the CT scan confirmed an occlusive syndrome affecting the whole small gut and colon. At 1 pm, the patient's condition worsened. He received an intramuscular injection of 100mg of loxapine and an opioid treatment, including tramadol and morphine. At 2:30 pm, the clinical condition further deteriorated with an onset of generalized abdominal contracture, the absence of abdominal breathing, sweating, tachycardia at 104 beats per minute, and hypothermia of 34.5°C. He was transferred to an intensive care unit. Laboratory tests showed metabolic acidosis, elevated liver enzymes and acute renal failure. He received volume expansion and was treated by renal replacement therapy and antibiotics. He was intubated and transferred to the

Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics.

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Li, Xiaohua; Rosborough, Kelley M; Friedman, Ari B; Zhu, Wawa; Roth, Kevin A

2007-02-01

Glycogen synthase kinase-3 (GSK3) has been recognized as an important enzyme that modulates many aspects of neuronal function. Accumulating evidence implicates abnormal activity of GSK3 in mood disorders and schizophrenia, and GSK3 is a potential protein kinase target for psychotropics used in these disorders. We previously reported that serotonin, a major neurotransmitter involved in mood disorders, regulates GSK3 by acutely increasing its N-terminal serine phosphorylation. The present study was undertaken to further determine if atypical antipsychotics, which have therapeutic effects in both mood disorders and schizophrenia, can regulate phospho-Ser-GSK3 and inhibit its activity. The results showed that acute treatment of mice with risperidone rapidly increased the level of brain phospho-Ser-GSK3 in the cortex, hippocampus, striatum, and cerebellum in a dose-dependent manner. Regulation of phospho-Ser-GSK3 was a shared effect among several atypical antipsychotics, including olanzapine, clozapine, quetiapine, and ziprasidone. In addition, combination treatment of mice with risperidone and a monoamine reuptake inhibitor antidepressant imipramine or fluoxetine elicited larger increases in brain phospho-Ser-GSK3 than each agent alone. Taken together, these results provide new information suggesting that atypical antipsychotics, in addition to mood stabilizers and antidepressants, can inhibit the activity of GSK3. These findings may support the pharmacological mechanisms of atypical antipsychotics in the treatment of mood disorders.

Quetiapine in overdosage : a clinical and pharmacokinetic analysis of 14 cases

NARCIS (Netherlands)

Hunfeld, N G M; Westerman, E M; Boswijk, D J; de Haas, J A M; van Putten, M J A M; Touw, D J

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported

Branch retinal vein occlusion associated with quetiapine fumarate

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Siang Lim

2011-08-01

Full Text Available Abstract Background To report a case of branch retinal vein occlusion in a young adult with bipolar mood disorder treated with quetiapine fumarate. Case Presentation A 29 years old gentleman who was taking quetiapine fumarate for 3 years for bipolar mood disorder, presented with sudden vision loss. He was found to have a superior temporal branch retinal vein occlusion associated with hypercholesterolemia. Conclusion Atypical antipsychotic drugs have metabolic side effects which require regular monitoring and prompt treatment.

Pancreatitis following Olanzapine Therapy: A Report of Three Cases

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Thomas A. Kerr

2007-06-01

Full Text Available Context: Atypical antipsychotic agents (clozapine, olanzapine have been linked to metabolic effects and acute pancreatitis. Case Report: We reviewed the inpatient and outpatient records of three patients who developed acute pancreatitis while being treated with olanzapine. The mean age of the patients was 37.7 years (range 18–54 years, 2 female, 1 male. No alternative cause of acute pancreatitis was found in two of the three patients. In the remaining patient, olanzapine may have contributed to acute pancreatitis in the setting of hypertriglyceridemia. Olanzapine was discontinued in all instances. Over a mean follow-up of 14 months, one patient has had a relapsing course, but the remaining two patients have been symptom free without recurrence of acute pancreatitis. Conclusions: Our case series adds further support to the potential link between olanzapine use and acute pancreatitis. Close monitoring of metabolic parameters is suggested in patients treated with olanzapine. Alternative antipsychotic agents should be considered in patients at high risk for pancreatitis.

Evaluation of the Reinforcing Effect of Quetiapine, Alone and in Combination with Cocaine, in Rhesus Monkeys.

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Brutcher, Robert E; Nader, Susan H; Nader, Michael A

2016-02-01

There are several case reports of nonmedicinal quetiapine abuse, yet there are very limited preclinical studies investigating quetiapine self-administration. The goal of this study was to investigate the reinforcing effects of quetiapine alone and in combination with intravenous cocaine in monkeys. In experiment 1, cocaine-experienced female monkeys (N = 4) responded under a fixed-ratio (FR) 30 schedule of food reinforcement (1.0-g banana-flavored pellets), and when responding was stable, quetiapine (0.003-0.1 mg/kg per injection) or saline was substituted for a minimum of five sessions; there was a return to food-maintained responding between doses. Next, monkeys were treated with quetiapine (25 mg, by mouth, twice a day) for approximately 30 days, and then the quetiapine self-administration dose-response curve was redetermined. In experiment 2, male monkeys (N = 6) self-administered cocaine under a concurrent FR schedule with food reinforcement (three food pellets) as the alternative to cocaine (0.003-0.3 mg/kg per injection) presentation. Once choice responding was stable, the effects of adding quetiapine (0.03 or 0.1 mg/kg per injection) to the cocaine solution were examined. In experiment 1, quetiapine did not function as a reinforcer, and chronic quetiapine treatment did not alter these effects. In experiment 2, cocaine choice increased in a dose-dependent fashion. The addition of quetiapine to cocaine resulted in increases in low-dose cocaine choice and number of cocaine injections in four monkeys, while not affecting high-dose cocaine preference. Thus, although quetiapine alone does not have abuse potential, there was evidence of enhancement of the reinforcing potency of cocaine. These results suggest that the use of quetiapine in cocaine-addicted patients should be monitored. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

A randomized, double-blind study of the efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder

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Wang G

2014-01-01

Full Text Available Gang Wang,1 Alexander McIntyre,2 Willie R Earley,3 Shane R Raines,3 Hans Eriksson4 1Beijing Anding Hospital, Capital Medical University, Beijing, People's Republic of China; 2Department of Psychiatry, Penticton Regional Hospital, Penticton, BC, Canada; 3AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 4AstraZeneca R&D, Södertälje, Sweden Objectives: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR monotherapy in patients with major depressive disorder (MDD. Patients and methods: This was a 10-week (8-week active treatment/2-week post-treatment randomized, double-blind, placebo- and active-controlled study (D1448C00004. Patients received quetiapine XR 150 mg/day, escitalopram 10 mg/day, or placebo; patients with an inadequate response (<20% improvement in Montgomery–Åsberg Depression Rating Scale [MADRS] total score at week two received double-dose treatment. The primary end point was week eight change from randomization in MADRS total score. Secondary end points included MADRS response (≥50% improvement and remission (score ≤8; Hamilton Rating Scale for Depression total and item 1; Hamilton Rating Scale for Anxiety total, psychic, and somatic; Clinical Global Impressions – Severity of Illness total; Pittsburgh Sleep Quality Index (PSQI global; and Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form percentage maximum total scores. Tolerability was assessed throughout. Results: A total of 471 patients was randomized. No significant improvements in MADRS total score were observed at week eight (last observation carried forward with either active treatment (quetiapine XR, -17.21 [P=0.174]; escitalopram, -16.73 [P=0.346] versus placebo (-15.61. There were no significant differences in secondary end points versus placebo, with the exception of week-eight change in PSQI global score (quetiapine XR, -4.96 [P<0.01] versus placebo, -3.37. Mixed-model repeated

Effects of quetiapine on sleep architecture in patients with unipolar or bipolar depression

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Laura Gedge

2010-08-01

Full Text Available Laura Gedge1, Lauren Lazowski1, David Murray2, Ruzica Jokic2,3, Roumen Milev2,31Centre for Neuroscience Studies, 2Department of Psychiatry, Queen’s University, Kingston, 3Providence Care-Mental Health Services, Kingston, Ontario, CanadaObjective: To determine the effect of adjunctive quetiapine therapy on the sleep architecture of patients with bipolar or unipolar depression.Methods: This is a prospective, single-blind, repeated measures polysomnographic study. Sleep architecture was analyzed by overnight polysomnography, and subjective sleep quality was measured using the Pittsburgh Sleep Quality Index. The Hamilton Rating Scale for Depression, Montgomery Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression-Severity Scale were employed to quantify changes in illness severity with adjunctive quetiapine treatment. Polysomnographs and clinical measures were administered at baseline, after 2–4 days of treatment, and after 21–28 days of quetiapine treatment. The average dose of quetiapine was 155 mg, ranging from 100–200 mg.Results: Adjunctive quetiapine therapy did not significantly alter sleep efficiency, sleep continuity, or Pittsburgh Sleep Quality Index scores. Respiratory Disturbance Index and percentage of total time in rapid eye movement (REM sleep significantly decreased and the percentage of total time in non-REM sleep, and duration of Stage 2 and non-REM sleep significantly increased after 2–4 days of quetiapine treatment. Illness severity significantly decreased over time.Conclusions: Adjunctive quetiapine treatment alters sleep architecture in patients with major depressive disorder or bipolar disorder, which may partially explain its early antidepressant properties. Changes in sleep architecture are more robust and significant within two to four days of starting treatment.Keywords: quetiapine, sleep architecture, depression, bipolar disorder

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

Science.gov (United States)

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

2018-05-23

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

Role of extended release quetiapine in the management of bipolar disorders

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Rayan K Al Jurdi

2010-02-01

Full Text Available Rayan K Al Jurdi1,2, Lena A Dixit1, Martha Sajatovic3 1Baylor College of Medicine, Department of Psychiatry, Houston, Texas, USA; 2South Central Mental Illness Research and Clinical Core, Department of Veterans Affairs, Houston, Texas; 3Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAAbstract: Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder.Keywords: quetiapine XR, bipolar disorder

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

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Tommaso Federico

2005-12-01

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

Metformin and berberine prevent olanzapine-induced weight gain in rats.

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Yueshan Hu

Full Text Available Olanzapine is a first line medication for the treatment of schizophrenia, but it is also one of the atypical antipsychotics carrying the highest risk of weight gain. Metformin was reported to produce significant attenuation of antipsychotic-induced weight gain in patients, while the study of preventing olanzapine-induced weight gain in an animal model is absent. Berberine, an herbal alkaloid, was shown in our previous studies to prevent fat accumulation in vitro and in vivo. Utilizing a well-replicated rat model of olanzapine-induced weight gain, here we demonstrated that two weeks of metformin or berberine treatment significantly prevented the olanzapine-induced weight gain and white fat accumulation. Neither metformin nor berberine treatment demonstrated a significant inhibition of olanzapine-increased food intake. But interestingly, a significant loss of brown adipose tissue caused by olanzapine treatment was prevented by the addition of metformin or berberine. Our gene expression analysis also demonstrated that the weight gain prevention efficacy of metformin or berberine treatment was associated with changes in the expression of multiple key genes controlling energy expenditure. This study not only demonstrates a significant preventive efficacy of metformin and berberine treatment on olanzapine-induced weight gain in rats, but also suggests a potential mechanism of action for preventing olanzapine-reduced energy expenditure.

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

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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....

Quetiapine-induced sleep-related eating disorder-like behavior: a case series

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Tamanna Sadeka

2012-11-01

Full Text Available Abstract Introduction Somnambulism or sleepwalking is a disorder of arousal from non-rapid eye movement sleep. The prevalence of sleep-related eating disorder has been found to be approximately between 1% and 5% among adults. Many cases of medication-related somnambulism and sleep-related eating disorder-like behavior have been reported in the literature. Quetiapine, an atypical antipsychotic medication, has been associated with somnambulism but has not yet been reported to be associated with sleep-related eating disorder. Case presentation Case 1 is a 51-year-old obese African American male veteran with a body mass index of 34.11kg/m2 and severe sleep apnea who has taken 150mg of quetiapine at bedtime for more than one year for depression. He developed sleepwalking three to four nights per week which resolved after stopping quetiapine while being compliant with bi-level positive pressure ventilation therapy. At one year follow-up, his body mass index was 32.57kg/m2. Case 2 is a 50-year-old African American female veteran with a body mass index of 30.5kg/m2 and mild sleep apnea who has taken 200mg of quetiapine daily for more than one year for depression. She was witnessed to sleepwalk three nights per week which resolved after discontinuing quetiapine while being treated with continuous positive airway pressure. At three months follow-up, her body mass index was 29.1kg/m2. Conclusion These cases illustrate that quetiapine may precipitate complex motor behavior including sleep-related eating disorder and somnambulism in susceptible patients. Atypical antipsychotics are commonly used in psychiatric and primary care practice, which means the population at risk of developing parasomnia may often go unrecognized. It is important to recognize this potential adverse effect of quetiapine and, to prevent injury and worsening obesity, discuss this with the patients who are prescribed these medications.

Olanzapine for chemotherapy-induced nausea and vomiting: systematic review and meta-analysis

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Chelkeba L

2017-03-01

Full Text Available Background: Chemotherapy induced nausea and vomiting (CINV remains the most distressing event in patients receiving highly emetogenic chemotherapy (HEC or moderately emetogenic chemotherapy (MEC. Objective: Therefore, this meta-analysis was conducted to evaluate the efficacy of olanzapine containing regimen in preventing acute, delayed and overall phases of CINV. Methods: PubMed, EBSCO, and Cochrane central register of controlled trials electronic databases were searched to identify RCTs that compared the effects of olanzapine with non-olanzapine regimen in preventing CINV. Randomized clinical trials (RCTs that compared olanzapine containing regimen with non-olanzapine regimen were included. The primary outcomes were the percentage of patients achieving no vomiting or no nausea in acute, delayed and overall phases. Results: 13 RCTs that enrolled 1686 participants were included in this meta-analysis. 852 patients were assigned to olanzapine and 834 patients were assigned to non-olanzapine regimen (other standard antiemetic regimen. The percentages of no emesis achieved were 87.5%, 76.2%, 73.6% in olanzapine versus 76.7%, 61.8%, and 56.4% in non-olanzapine regimen in acute, delayed and overall phases, respectively. The percentages of no nausea were 82%, 64.3%, 61.6% in olanzapine group versus 71.3%, 41.8%, and 40.6% in non-olanzapine group in acute, delayed and overall phases, respectively. In general, olanzapine containing regimen achieved statistical superiority to non-olanzapine regimen in no vomiting endpoint in acute phase (OR 2.16; 95%CI 1.60 to 2.91, p<0.00001; I-square=5%; p=0.40, delayed phase (OR 2.28; 95%CI 1.1.46 to 3.54, p=0.0003; I-square=65%; p=0.001 and overall phase (OR 2.48; 95%CI 1.59 to 3.86, p<0.0001; I-square=69%; p< 0.0001. Conclusion: The current meta-analysis showed that olanzapine was statistically and clinically superior to non-olanzapine regimen in preventing CINV in most domains of the parameters.

Oral glucose tolerance test performance in olanzapine-treated schizophrenia-spectrum patients is predicted by BMI and triglycerides but not olanzapine dose or duration.

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Guina, Jeffrey; Roy, Sayon; Gupta, Ankur; Langleben, Daniel D; Elman, Igor

2017-07-01

Olanzapine, an atypical antipsychotic, is associated with glucoregulatory abnormalities, but the nature of this link is not fully elucidated. This is the first olanzapine oral glucose tolerance test (oGTT) study to consider treatment dose and duration, and to compare complementary indices respectively assessing insulin sensitivity (Matsuda index) and resistance (homeostasis model assessment). Body mass index (BMI), body composition, plasma lipids, and oGTT were measured in olanzapine-treated nondiabetic patients with DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder (n = 35). While only one previously undiagnosed participant met diabetes criteria based on fasting plasma glucose alone (≥126 mg/dL), seven were diagnosed with oGTT (2-hr plasma glucose ≥200 mg/dL). Multiple regression analyses revealed that the Matsuda index correlated with BMI (p triglycerides (p = 0.01), but not with age, olanzapine dose, olanzapine treatment duration, or plasma cholesterol. Homeostasis model assessment and fasting plasma glucose correlated with triglycerides only (p triglycerides may be implicated in olanzapine-related glucoregulatory abnormalities. The lack of correlation between glucoregulatory abnormalities and olanzapine dose or treatment duration suggests preexisting metabolic disturbances and/or disturbances arising early in the course of treatment. Clinicians prescribing antipsychotics should consider oGTT, especially in patients with obesity and/or hypertriglyceridemia. Copyright © 2017 John Wiley & Sons, Ltd.

Reversible global aphasia as a side effect of quetiapine: a case report and literature review

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Chien CF

2017-08-01

Full Text Available Ching-Fang Chien,1 Poyin Huang,1,2 Sun-Wung Hsieh1,2 1Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 2Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan Abstract: Quetiapine is an atypical antipsychotic agent which is also prescribed for delirium due to its anti-dopaminergic effects; aphasia is an unusual side effect associated with the drug. Here, we report the case of an 83-year-old woman who was prescribed quetiapine (50 mg per day for delirium. Unexpected, global aphasia occurred 3 days after treatment began. Complete recovery occurred following discontinuation of the drug. A brain computed tomography scan excluded intracranial hemorrhage and the laboratory results confirmed that no exacerbation of infection or electrolyte imbalances were present. During the aphasic episode, the patient’s condition did not deteriorate and no new neurological symptoms occurred. We suspect that the occurrence of aphasia was directly due to an adverse reaction to quetiapine. To our knowledge, this is the first case report of reversible, global aphasia as a side effect of quetiapine. We propose that this occurrence of aphasia may be due to the action of quetiapine as a dopamine receptor antagonist. Clinicians should use quetiapine with caution, especially in elderly patients. On observation of aphasia, a review of the patient’s medical history is required to assess for the usage of quetiapine. Keywords: aphasia, quetiapine, insomnia, delirium

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.

Weight loss during therapy with olanzapine orally disintegrating tablets: two case reports.

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Kozumplik, Oliver; Uzun, Suzana; Jakovljević, Miro

2009-03-01

The aim of this article is to report weight loss in patients with schizophrenia after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In the first case report, the patient was switched to olanzapine ODT in daily dosage of 20 mg, while in the second case report, the patient was switched to olanzapine ODT in daily dosage of 15 mg, and weight loss was similar (14 kg vs. 15 kg). Switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained during 12 months in both case reports. Further controlled clinical investigations are necessary to evaluate change in weight during treatment with olanzapine ODT, and to improve our understanding of this change.

Quetiapine modulates functional connectivity in brain aggression networks.

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Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

2013-07-15

Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Triiodothyronine accelerates and enhances the antipsychotic effect of risperidone in acute schizophrenia.

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Steibliene, Vesta; Bunevicius, Adomas; Savickas, Arunas; Prange, Arthur J; Nemeroff, Charles B; Bunevicius, Robertas

2016-02-01

In acute psychotic schizophrenia patients we investigated if the combination of triiodothyronine (T3) plus risperidone was more effective when compared to risperidone monotherapy. Thirty-two in-patients meeting the DSM-IV-TR diagnostic criteria for schizophrenia and without thyroid disease received risperidone (flexibly adjusted dose for tolerability) and were randomized to additionally receive either T3 (25 μg daily; risperidone plus T3 group) or placebo (risperidone plus placebo group). Treatment lasted until meeting the response to treatment criteria defined as score of ≤ 3 on the Clinical Global Impression Severity and Improvement scales. Acute psychotic episode symptom severity was evaluated using the Brief Psychiatric Rating Scale (BPRS) at treatment initiation and at the final study assessment. Fourteen patients were randomized to receive risperidone plus T3 and eighteen to receive risperidone plus placebo. The time until treatment response was shorter in the risperidone plus T3 group relative to the risperidone plus placebo group (25.5 ± 4.4 days vs 32.2 ± 8.2 days, respectively; p = 0.001). Moreover, there was a greater reduction of BPRS-total score (p = 0.01) in the risperidone plus T3 group relative to the risperidone plus placebo group. Treatment with T3 was associated with shorter time to treatment response (β = -0.440, p = 0.022) and with greater improvement in BPRS score (β = 0.240, p = 0.053), independent of patients' gender, age, baseline BPRS score and mean risperidone dose. The study confirms that addition of T3 to risperidone was associated with accelerated and enhanced treatment response in acutely psychotic schizophrenic patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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

2005-01-01

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

Olanzapine monotherapy and olanzapine combination therapy in the treatment of mania: 12-week results from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) observational study.

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Vieta, Eduard; Panicali, Francesco; Goetz, Iris; Reed, Catherine; Comes, Merce; Tohen, Mauricio

2008-02-01

To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints. Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (pEMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

Convulsive syncope related to a small dose of quetiapine in an adolescent with bipolar disorder

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Lai J

2017-07-01

Full Text Available Jianbo Lai,1,2 Qiaoqiao Lu,3 Tingting Huang,3 Shaohua Hu,1,2 Yi Xu1,2 1Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, 2Key Laboratory of Mental Disorder Management in Zhejiang Province, 3Department of Internal Medicine, Zhejiang University School of Medicine, Hangzhou, China Abstract: Quetiapine, an atypical antipsychotic, has been extensively used in patients with bipolar disorder. Overdose of quetiapine can result in severe complications, such as coma, seizure, respiratory depression, arrhythmia, and even death. However, the paucity of toxicological evaluation in adolescence causes more potential risks in this population. Herein, we present a case of hypotension and convulsive syncope after exposure to a small dose of quetiapine in a 16-year-old who was diagnosed with bipolar disorder. After cessation of quetiapine, no additional convulsive movements were reported. This case indicates that even in young patients without predisposing factors, close monitoring of adverse effects should be warranted for safety concerns, especially at the initiation of quetiapine treatment. Keywords: quetiapine, bipolar disorder, hypotension, convulsive syncope

Use of psychotropic drugs during pregnancy and breast-feeding.

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Larsen, E R; Damkier, P; Pedersen, L H; Fenger-Gron, J; Mikkelsen, R L; Nielsen, R E; Linde, V J; Knudsen, H E D; Skaarup, L; Videbech, P

2015-01-01

To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics. As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted. Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia. It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risperidone treatment increases CB1 receptor binding in rat brain

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Secher, Anna; Husum, Henriette; Holst, Birgitte

2010-01-01

, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

Glucagon receptor knockout mice are protected against acute olanzapine-induced hyperglycemia.

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Castellani, Laura N; Peppler, Willem T; Sutton, Charles D; Whitfield, Jamie; Charron, Maureen J; Wright, David C

2017-08-01

To determine if glucagon is involved in mediating the increase in blood glucose levels caused by the second-generation antipsychotic drug olanzapine. Whole body glucagon receptor deficient mice (Gcgr -/- ) or WT littermate controls were injected with olanzapine (5mg/kg BW IP) and changes in blood glucose measured over the following 120min. Separate cohorts of mice were treated with olanzapine and changes in pyruvate tolerance, insulin tolerance and whole body substrate oxidation were determined. Olanzapine treatment increased serum glucagon and lead to rapid increases in blood glucose concentrations in WT mice. Gcgr -/- mice were protected against olanzapine-induced increases in blood glucose but this was not explained by differences in terminal serum insulin concentrations, enhanced AKT phosphorylation in skeletal muscle, adipose tissue or liver or differences in RER. In both genotypes olanzapine induced an equivalent degree of insulin resistance as measured using an insulin tolerance test. Olanzapine treatment led to an exaggerated glucose response to a pyruvate challenge in WT but not Gcgr -/- mice and this was paralleled by reductions in the protein content of PEPCK and G6Pase in livers from Gcgr -/- mice. Gcgr -/- mice are protected against olanzapine-induced increases in blood glucose. This is likely a result of reductions in liver glucose output, perhaps secondary to decreases in PEPCK and G6Pase protein content. Our findings highlight the central role of the liver in mediating olanzapine-induced disturbances in glucose homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments

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Ejsing, Thomas B.; Pedersen, Anne D.; Linnet, Kristian

2005-01-01

P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice......P-glycoprotein, risperidone, nortriptyline, cyclosporine A, drug-drug interaction, blood-brain barrier, knock-out mice...

Risperidone-induced enuresis in a 12-year-old child

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Reetika Dikshit

2017-01-01

Full Text Available Risperidone has been documented to be effective in the management of behavior problems, aggression, and conduct disorder in children. While metabolic side effects like weight gain and obesity have been attributed to Risperidone use in children, side effects of the drug related to the urinary bladder are rare. We present a case of Risperidone-induced enuresis in a 12-year-old boy with conduct disorder that resolved completely after stopping the medication.

[The lipid metabolism abnormality in patients administered with olanzapine].

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Amano, Taku; Hosaka, Shigetoshi; Takami, Hiroshi; Sugiyama, Chie; Oda, Kazue; Morikawa, Ryuichi

2012-11-01

The atypical antipsychotic medication olanzapine is a useful agent in acute and maintenance treatment of schizophrenia and related disorders. It has beneficial effects on both positive and negative symptoms, an early onset of antipsychotic action and a favourable side effect profile. On the other hand, olanzapine has many reports of causing weight gain, glucose metabolism disturbances and lipidosis. We carried out blood tests (leptin, adiponectin, remnant-like lipoprotein cholesterol (RLP-C), total cholesterol, HbA1C, 75-OGTT and etc.) on patients with schizophrenia who had taken olanzapine. As a result, leptin, neutral lipid and RLP-C were significantly correlated by BMI. (The average blood test data and BMI revealed a normal range). Most analysis results of the lipoprotein fraction by a polyacrylamide-gel-electrophoresis method were normal patterns. Furthermore, the serum insulin concentrations from 75 g glucose tolerance (75 g-OGTT) 30 minutes later, in one third of patients receiving olanzapine, registered more than 100 microU/ml. The mechanism of the insulin secretion rise by olannzapine is unknown. Olanzapine may impair glucose tolerance due in part to increased insulin resistance. These findings do not necessarily imply that olanzapine is directly associated with a risk of impairment of weight gain, glucose metabolism disturbances and lipidosis. These results suggest that it is useful to promote diet cure and exercise therapy with patients with high BMI levels.

Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptors

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Alireza Abed

2017-11-01

Full Text Available Objective(s: Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patient’s survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception. Materials and Methods: Paclitaxel (2 mg/kg IP was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia. Results: Early administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist. Conclusion: These results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.

Development of a Medication Monitoring System for an Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT Team

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Nicole B. Washington, DO, Assistant Professor

2012-01-01

Full Text Available Purpose: The primary goal was to improve medication management oversight for a severely mentally ill (SMI community-based population by developing a medication monitoring system based on current guidelines to optimize pharmacotherapy and minimize potential medication-related adverse effects. The secondary goal was improvement in coordination of care between healthcare providers. Methods: Guidelines for medication used for psychiatric indications were reviewed. A database of medication for psychiatric indications with monitoring recommendation was developed. Results: Medication regimens for 68 members of the Integrated Multidisciplinary Program of Assertive Community Treatment (IMPACT program qualified for review. Fourteen medications, carbamazepine, chlorpromazine, clozapine, fluphenazine and fluphenazine long-acting injections (LAI, haloperidol and haloperidol LAI, lithium, lurasidone, olanzapine, paliperidone and paliperidone LAI, perphenazine, quetiapine, risperidone and risperidone LAI, valproic acid/divalproex, and ziprasidone, were identified. In total, 111 medications are used on a monthly basis. Each member receives more than one medication qualifying for review. Additional monitoring parameters that were evaluated included changes in laboratory orders for members with insulin-dependent diabetes. Annual lipid panels were changed to every 6 months, if applicable. Conclusions and Future Directions: This medication monitoring program was developed to help ensure IMPACT members receive the most effective care and minimize potential medication-related adverse effects. The secondary goal was to improve coordination of care. Medication monitoring will be added as a continuous quality assurance measure. Lab results will be reviewed at least monthly. The medication monitoring program will be evaluated annually.

Cost-effectiveness of lurasidone vs quetiapine extended-release (XR) in patients with bipolar depression.

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Rajagopalan, Krithika; Meyer, Kellie; O'Day, Ken; Denno, Melissa; Loebel, Antony

2015-01-01

Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression. A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs. Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission. Lurasidone may be a cost-effective option when compared to

A randomized controlled trial of quetiapine for psychosis in Parkinson’s disease

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Paul Shotbolt

2009-05-01

Full Text Available Paul Shotbolt1, Michael Samuel2,3, Chris Fox3,4, Anthony S David11Section of Cognitive Neuropsychiatry, Institute of Psychiatry, King’s College, London, UK; 2Department of Neurology, King’s College hospital, London, UK; 3East Kent hospitals NHS Trust, William Harvey Hospital, Ashford, Kent, UK; 4Kent and Medway NHS and Social Care and Partnership Trust, Kent, UKIntroduction: Psychosis (delusions and/or hallucinations is a well-recognized complication of treatment of Parkinson’s disease (PD. Quetiapine is a currently favored treatment, but data on its efficacy are equivocal. This trial aimed to provide further evidence on the efficacy of quetiapine in PD psychosis.Methods: We conducted a 12 week double blind randomized placebo-controlled trial. Time to dropout due to lack of improvement of psychosis was the primary outcome measure. Other important secondary outcomes were evaluated using standard rating scales for PD and psychiatric symptoms.Results: Twenty-four eligible subjects gave consent. The primary outcome, time to dropout, was examined using survival analysis. It was shown that patients in the quetiapine group dropped out earlier than those in the placebo group, but this difference was not significant (p = 0.68. No significant changes were found for any of the secondary outcome measures in either group. Conclusions: In this study, quetiapine at doses of up to 150 mg/day failed to significantly improve psychosis compared to placebo, however the small sample size does not allow any conclusive interpretation of the results. Quetiapine did not appear to worsen PD motor functioning, but its use was limited by a faster drop out compared with placebo. Significant impediments were difficulty with recruitment and natural fluctuation in symptoms during the trial. Keywords: Parkinson’s disease, psychosis, antipsychotics, quetiapine

Theoretical study on the interaction of pregabalin and olanzapine with DNA

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ZibaHooshiarSodagar

2016-12-01

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

Treatment of delirium with risperidone in cancer patients.

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Kishi, Yasuhiro; Kato, Masashi; Okuyama, Toru; Thurber, Steven

2012-08-01

Antipsychotic medications have frequently been regarded as the treatment of choice for delirium. This study examined the clinical efficacy of risperidone for the treatment of delirium in cancer patients, combined with a repeated assessment of underlying medical severity levels. The study included consecutive referrals of 29 delirious cancer patients (mean age, 68.9 ± 12.5 years; male, 69%) to the psychiatric consultation service. Risperidone was given orally once per day (mean dosage, 1.4 ± 1.3 mg/day). Study participants were assessed using quantitative standardized scales of cognitive function, delirium, and physical impairment at baseline and at the end of the study (seventh day). Risperidone with routine clinical management was effective for the treatment of delirium: 48% of the patients responded and 38% achieved remission. The reduction of delirium severity occurred in 79% of the patients. Changes in delirium severity were unrelated to age, gender, general cognitive dysfunction, or to severity of attendant medical conditions. In addition to changes in agitation and perceptional disturbances, risperidone was also effective for other specific delirium symptoms. Risperidone with routine clinical management is effective in the treatment of delirium in advanced cancer patients, independent of changes in the underlying medical condition. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

Olanzapine-Induced Neuroleptic Malignant Syndrome

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Seyedhamze Hosseini

2017-05-01

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

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

[Conference report: Belgian consensus on metabolic problems associated with atypical antipsychotics].

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De Nayer, A; De Hert, M; Scheen, A; Van Gaal, L; Peuskens, J

2007-01-01

The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. As a consequence, there is a shift in attention toward physical health

Risperidone and Risk of Gynecomastia in Young Men.

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Etminan, Mahyar; Carleton, Bruce; Brophy, James M

2015-11-01

The purpose of this study was to quantify the risk of gynecomastia with risperidone in adolescent and young adult males. We created a cohort of males 15-25 years of age from the IMS LifeLink database, and conducted a case-control study within the cohort by identifying all new cases of gynecomastia. For each case, 10 controls were selected and matched to the cases by age, follow-up, and calendar times (cases and controls had the same follow up time and cohort entry date). Rate ratios (RR) for current use of risperidone were computed adjusting for potential confounding variables. First diagnosis of gynecomastia was made based on International Classification of Diseases, 9th revision (ICD-9) for gynecomastia. There were 401,924 males ages 15-25 in the primary cohort. There were 1556 cases of gynecomastia and 15,560 corresponding controls. Current users of risperidone had approximately four times the risk of developing gynecomastia than non-users (RR=3.91, 95% CI=2.01-7.62). When the analysis was stratified to children and adolescents (≤18 years of age) taking risperidone, the risk of gynecomastia was five times higher than for non-users (RR=5.44, 95% CI=1.50-19.74). Risperidone is associated with an increase with the risk of gynecomastia in adolescent and young adult males.

Effect of quetiapine vs. placebo on response to two virtual public speaking exposures in individuals with social phobia.

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Donahue, Christopher B; Kushner, Matt G; Thuras, Paul D; Murphy, Tom G; Van Demark, Joani B; Adson, David E

2009-04-01

Clinical practice and open-label studies suggest that quetiapine (an atypical anti-psychotic) might improve symptoms for individuals with social anxiety disorder (SAD). The purpose of this study was to provide a rigorous test of the acute impact of a single dose of quetiapine (25mg) on SAD symptoms. Individuals with SAD (N=20) were exposed to a 4-min virtual reality (VR) public speaking challenge after having received quetiapine or placebo (double-blind) 1h earlier. A parallel VR challenge occurred 1 week later using a counter-balanced cross-over (within subject) design for the medication-placebo order between the two sessions. There was no significant drug effect for quetiapine on the primary outcome measures. However, quetiapine was associated with significantly elevated heart rate and sleepiness compared with placebo. Study findings suggest that a single dose of 25mg quetiapine is not effective in alleviating SAD symptoms in individuals with fears of public speaking.

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

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Hwang, Wen-Juh

2012-12-01

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

Intoxication after Extreme Oral Overdose of Quetiapine to Attempt Suicide: Pharmacological Concerns of Side Effects

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C. Müller

2009-01-01

Full Text Available Quetiapine is an atypical antipsychotic approved for the treatment of patients with psychotic disorders. Since approvement several case reports about intoxication with quetiapine were linked mainly with tachycardia, QTc-prolongation, somnolence, and hyperglycemia. Here, we present the first case report of an intoxication with an extreme overdose of quetiapine (36 g, ingested by a 32-year-old female (62 kg bodyweight to attempt suicide. Symptoms associated with intoxication were coma without arterial hypotension, persistent tachycardia, hyperglycemia, and transient hypothyreoidism. QTc-interval was moderately extended. Management consisted of intubation for airway protection, gastric lavage, the use of activated charcoal, i.v. saline, and observation for 17 hours on an intensive care unit. Despite the extremely high dose of quetiapine, the patient recovered completely without residual symptoms.

Intramuscular Olanzapine – a UK case series of early cases

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Taylor Mark

2007-04-01

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

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

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Swapnajeet Sahoo

2016-01-01

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

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

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Giorgio Mariani

2006-06-01

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

A Lack of Systemic Absorption Following the Repeated Application of Topical Quetiapine in Healthy Adults.

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Kayhart, Bryce; Lapid, Maria I; Nelson, Sarah; Cunningham, Julie L; Thompson, Virginia H; Leung, Jonathan G

2018-01-01

In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.

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

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Katagiri H

2018-04-01

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

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

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Derya Arslan

2016-06-01

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

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

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Millán-González, Ricardo

2012-03-01

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

Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone.

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Aggarwal, Geeta; Dhawan, Sanju; Hari Kumar, S L

2013-01-01

The efficacy of oral risperidone treatment in prevention of schizophrenia is well known. However, oral side effects and patient compliance is always a problem for schizophrenics. In this study, risperidone was formulated into matrix transdermal patches to overcome these problems. The formulation factors for such patches, including eudragit RL 100 and eudragit RS 100 as matrix forming polymers, olive oil, groundnut oil and jojoba oil in different concentrations as enhancers and amount of drug loaded were investigated. The transdermal patches containing risperidone were prepared by solvent casting method and characterized for physicochemical and in vitro permeation studies through excised rat skin. Among the tested preparations, formulations with 20% risperidone, 3:2 ERL 100 and ERS 100 as polymers, mixture of olive oil and jojoba oil as enhancer, exhibited greatest cumulative amount of drug permeated (1.87 ± 0.09 mg/cm(2)) in 72 h, so batch ROJ was concluded as optimized formulation and assessed for pharmacokinetic, pharmacodynamic and skin irritation potential. The pharmacokinetic characteristics of the optimized risperidone patch were determined using rabbits, while orally administered risperidone in solution was used for comparison. The calculated relative bioavailability of risperidone transdermal patch was 115.20% with prolonged release of drug. Neuroleptic efficacy of transdermal formulation was assessed by rota-rod and grip test in comparison with control and marketed oral formulations with no skin irritation. This suggests the transdermal application of risperidone holds promise for improved bioavailability and better management of schizophrenia in long-term basis.

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

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

2011-01-01

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

Risperidone-associated urinary incontinence in patients with autistic disorder with mental retardation.

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Kumazaki, Hirokazu; Watanabe, Koichiro; Imasaka, Yasushi; Iwata, Kazuhiko; Tomoda, Akemi; Mimura, Masaru

2014-10-01

We report several cases in which patients with autistic disorder with mental retardation who received risperidone experienced urinary incontinence. We retrospectively investigated the medical records of patients housed in facilities for patients with autistic disorder with mental retardation. Those who had undergone a medical examination at a hospital in Tokyo from April 1999 to March 2009 were included in the study.Retrospective data were gathered including age, sex, IQ, birth weight, dosage of risperidone, urinary density, as well as existence of urinary and fecal incontinence. We divided the participants into those who did and did not experience urinary incontinence after taking risperidone and compared the 2 groups. Risperidone had been prescribed to 35 patients. In spite of the fact that no patient had a history of urinary incontinence, 14 patients experienced urinary incontinence after receiving risperidone. Moreover, 4 of these 14 patients also had fecal incontinence. Among the variables we examined, the only significant difference between groups was in sex, with significantly more women experiencing incontinence compared with men. When the dose of risperidone was reduced or the patients switched to other drugs, urinary incontinence of the patients improved.Hence, risperidone may have a casual relationship with urinary incontinence. Further research is needed to understand the pathophysiology of possible effect.

Emphysematous pancreatitis predisposed by Olanzapine

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Sukhen Samanta

2014-01-01

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

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

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

2016-01-01

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

Hyperprolactinemia in Thai children and adolescents with autism spectrum disorder treated with risperidone

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Hongkaew Y

2015-01-01

Full Text Available Yaowaluck Hongkaew,1,2 Nattawat Ngamsamut,3 Apichaya Puangpetch,1,2 Natchaya Vanwong,1,2 Pornpen Srisawasdi,4 Montri Chamnanphon,1,2 Bhunnada Chamkrachchangpada,3 Teerarat Tan-kam,3 Penkhae Limsila,3 Chonlaphat Sukasem1,2 1Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, 2Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC, Ramathibodi Hospital, Mahidol University, 3Yuwaprasart Waithayopathum Child and Adolescent Psychiatric Hospital, Department of Mental Health Services, Ministry of Public Health, 4Division of Clinical Chemistry, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: Hyperprolactinemia is a common adverse effect observed in children with autism spectrum disorder (ASD during pharmacotherapy with risperidone. The main aim of this study was to investigate important clinical factors influencing the prolactin response in risperidone-treated Thai ASD. A total of 147 children and adolescents (127 males and 20 females aged 3–19 years with ASD received risperidone treatment (0.10–6.00 mg/day for up to 158 weeks. Prolactin levels were measured by chemiluminescence immunoassay. The clinical data of patients collected from medical records – age, weight, height, body mass index, dose of risperidone, duration of treatment, and drug-use pattern – were recorded. Hyperprolactinemia was observed in 66 of 147 (44.90% subjects. Median prolactin level at the high doses (24.00, interquartile range [IQR] 14.30–29.20 of risperidone was significantly found to be higher than at the recommended (16.20, IQR 10.65–22.30 and low (11.70, IQR 7.51–16.50 doses of risperidone. There was no relationship between prolactin levels and duration of risperidone treatment. Dose-dependence is identified as a main factor associated with hyperprolactinemia in Thai children and adolescents with ASD treated with

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

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Spielmans, Glen I

2009-07-01

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

Olanzapine affects locomotor activity and meal size in male rats

NARCIS (Netherlands)

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

2010-01-01

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

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

NARCIS (Netherlands)

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

2015-01-01

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

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

NARCIS (Netherlands)

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

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

Evidence based administration of risperidone and paliperidone for the treating conduct disorder

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Ahmad Ghanizadeh

2013-01-01

Full Text Available Background: This study evaluates the evidence-based administration of risperidone and paliperidone for the treating children and adolescents with conduct disorder (CD. Materials and Methods: A review of the current literature from clinical trials that investigated the efficacy of risperidone and paliperidone on CD considering the inclusion criteria and search strategies was performed by a search of PubMed and Google Scholar databases. Results: Out of 53 titles, 31 were irrelevant. The abstract of 22 potentially related articles were studied. Only six articles reported the results of clinical trial. However, one of them reported the effect of risperidone on conduct behaviors in autistic disorders. One study was a re-analysis of two previous studies, one study reported the effects of maintenance versus withdrawal of risperidone treatment and two studies included children with sub-average intelligence. Headache, somnolence and increased appetite are among the most common reported adverse effects. No study examined the effect of paliperidone on CD was found. Conclusion: Current literature suggests that risperidone could be effective for treating some conduct behaviors in children and adolescents. The effect of risperidone on CD is not a well-researched area. There is no well-controlled evidence based reports about the safety and efficacy of risperidone for the treatment of CD. Further trials should examine the efficacy of these medications on CD rather than conduct behaviors or disruptive behavior disorders.

Olanzapine affects locomotor activity and meal size in male rats

NARCIS (Netherlands)

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

2010-01-01

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

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.

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.

Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial

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Maneeton B

2013-07-01

Full Text Available Benchalak Maneeton,1 Narong Maneeton,1 Manit Srisurapanont,1 Kaweesak Chittawatanarat2 1Department of Psychiatry, 2Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: Atypical antipsychotic drugs may have low propensity to induce extrapyramidal side effects in delirious patients. This study aimed to compare the efficacy and tolerability between quetiapine and haloperidol in controlling delirious behavior. Methods: A 7-day prospective, double-blind, randomized controlled trial was conducted from June 2009 to April 2011 in medically ill patients with delirium. Measures used for daily assessment included the Delirium Rating Scale-revised-98 (DRS-R-98 and total sleep time. The Clinical Global Impression, Improvement (CGI–I and the Modified (nine-item Simpson–Angus Scale were applied daily. The primary outcome was the DRS-R-98 severity scores. The data were analyzed on an intention-to-treat basis. Results: Fifty-two subjects (35 males and 17 females were randomized to receive 25–100 mg/day of quetiapine (n = 24 or 0.5–2.0 mg/day of haloperidol (n = 28. Mean (standard deviation doses of quetiapine and haloperidol were 67.6 (9.7 and 0.8 (0.3 mg/day, respectively. Over the trial period, means (standard deviation of the DRS-R-98 severity scores were not significantly different between the quetiapine and haloperidol groups (-22.9 [6.9] versus -21.7 [6.7]; P = 0.59. The DRS-R-98 noncognitive and cognitive subscale scores were not significantly different. At end point, the response and remission rates, the total sleep time, and the Modified (nine-item Simpson–Angus scores were also not significantly different between groups. Hypersomnia was common in the quetiapine-treated patients (33.3%, but not significantly higher than that in the haloperidol-treated group (21.4%. Limitations: Patients were excluded if they were not able to take oral medications, and the sample size was small. Conclusion: Low

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

DEFF Research Database (Denmark)

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

2014-01-01

BACKGROUND: A number of serious cardiovascular safety concerns related to the use of atypical antipsychotics, compared with no use, have emerged, but nearly all reports are from studies of older patients. We aimed to compare the risk of cardiovascular events between the three most commonly used...

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

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Sharma, Ravi C.; Aggarwal, Ashish

2010-01-01

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

Peripheral Edema Occurring during Treatment with Risperidone Combined with Citalopram

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Seyed Hamzeh Hosseini

2012-01-01

Full Text Available An 80-year-old female presented with symptoms of depression, worthlessness, hopelessness, loss of energy, insomnia, impatience, and forgetfulness associated with persecutory delusion that had begun about one year before her visit. She was diagnosed with major depression with psychotic signs and began treatment with risperidone (2 mg/night and citalopram (20 mg/day. After 20 days, she returned and reported partial improvement in her symptoms, although she had developed severe swelling of the hands and feet. The results of liver and renal function tests and rheumatologic tests were found to be within normal limits. Risperidone was discontinued for a week, and the swelling resolved completely. Risperidone was then administered again, and the swelling returned so that the patient had to discontinue taking the drug. The reappearance of edema on rechallenge is strong evidence implicating risperidone as the cause of the swelling.

Moderators, mediators, and other predictors of risperidone response in children with autistic disorder and irritability.

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Arnold, L Eugene; Farmer, Cristan; Kraemer, Helena Chmura; Davies, Mark; Witwer, Andrea; Chuang, Shirley; DiSilvestro, Robert; McDougle, Christopher J; McCracken, James; Vitiello, Benedetto; Aman, Michael G; Scahill, Lawrence; Posey, David J; Swiezy, Naomi B

2010-04-01

The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure in an 8-week double-blind, placebo-controlled trial for irritability in autistic disorder. This paper explores moderators and mediators of this effect. Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the evaluation of the results. Only baseline severity moderated treatment response: Higher severity showed greater improvement for risperidone but not for placebo. Weight gain mediated treatment response negatively: those who gained more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity negatively predicted outcome. Risperidone moderated the effect of change in 5'-nucleotidase, a marker of zinc status, for which decrease was associated with improvement only with risperidone, not with placebo. The benefit-risk ratio of risperidone is better with greater symptom severity. Risperidone can be individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and absence of co-morbid problems nonspecifically predict better outcome. Mineral interactions with risperidone deserve further study.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

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Olivares, J M; Rodriguez-Morales, A; Diels, J; Povey, M; Jacobs, A; Zhao, Z; Lam, A; Villalobos Vega, J C; Cuéllar, J Alonso; de Castro, F J Alberca; Quintero, C Morillo-Velarde; Martíin, J F Román; Domínguez, P Tabares; Ojeda, J L Prados; Cortés, S Sanz; Cala, F I Mata; Marín, C Gutiérrez; Castro, L Moyano; Duaso, M A Haza; Albarracín, J Requena; Vergara, G Narbona; Benítez, A Fernández; Cleries, F Mayoral; Pérez-Brian, J M García-Herrera; Aragón, A Bordallo; Navarro, J C Rodríguez; Biedma, J A Algarra; de Pedro, R Bravo; González, J F Delgado; López, M E Jaén; Moreno, H Díaz; López, J A Soto; Rodríguez, E Ojeda; de Hoyos, C Martínez; Sacristán, M Pardilla; Martín, M D Molina; Ballesteros, E Martín; Rodríguez, P A Sopelana; Menéndez, L Fernández; Rivas, R Santos; del Pino Cuadrado, P; Lauffer, J Correas; Solano, J J Rodríguez; Martínez, J M Fernández; Solano, F García; Rodríguez, P García-Lamberde; Rodríguez, J A Romero; Cano, T Rodríguez; Fortacin, M Ducaju; Lobeiras, J M Blanco; Sampedro, J M Piñeiro; Bravo, A Pérez; Pellicer, A Fernández; López, M D Alonso; Liste, J Fraga; Fernández, M Riobo; Losada, A Casas; Mendez, R Vazquez-Noguerol; Romero, S Agra; Blanco, J J Blanco; Bonaselt, I Tortajada; Mahia, M C García; del Valle, E Ferrer Gómez; Yañez, P Quiroga; Camarasa, M Gelabert; Alonso, J A Barbado; Mendez, G Florez; Feliz, F Doce; Lamela, M A López; Piñero, M Vega; Alvarado, P Fuentes; Gómez, I López; Martín, P Fadon; Gómez, J L Santos; López, A García; Jiménez, A Rodríguez; Nafs, A Escudero; Barquero, N Casas; Ortiz, R Fernández-Villamor; Noguera, J L Velez; Carrasco, P Ruiz; Muñoz, J Martín; Palma, M Masegoza; Hortelano, C Marín; Bonome, L Sánchez; Sevilla, J Sánchez; Juan, J M Mongil San; Ramos, J M García; Muñoz, J L Vallejo; Guisasola, J Elorza; Vazquez, L Santamaria; Guerras, F Campo; Nebot, F J Arrufat; Fernández, F J Baron; Nicolau, A L Palomo; Subirats, R Catala; Kidias, M Messays; Navarro, V Fabregat; García, B Frades; del Rosal, F Mejias; de Vicente Muñoz, T; Ballester, J Año; Lieb, P Malabia; Martel, A Delgado; Bea, E Roca; Joaquim, I Grau; Enjuanes, F Boatas; Piñol, M Bañuelos; Carbonell, E Fontova I; Muñoz, R Martín; Giribets, C Argila; Sans, L Albages; Blanco, A Serrano; Felipe, M Arcega; Muñoz, P González; Villanueva, A Pons; Arroyo, M Bernardo; Borri, R Coronas; Fallada, S Miret; Merola, M Celma; Rodon, E Parellada; Palmes, J R Pigem; Martínez, E Pérez; Catala, J Matarredona; Coca, A Sandoval; Ferrandiz, F Pascual; Paya, E Ferrandiz; Caballero, G Iturri; Bonet, A Franco; Figueras, J Fluvia; Pagador, P Moreno; Garibo, M Medina; Camo, V Pérez; Carrillo, C Sanz; Valero, C Pelegrin; Rebollo, F J Caro; García Campayo, J; Sala Ayma, J M Sala; Roig, M Martínez; de Uña Mateos, M A; Bertolin, R García; García, A Martín; Mazo, F Jiménez; Velasco, J L Galvez; Pérez, L Santa Maria; Casado, C Jiménez; Barba, J J Mancheño; Diaz, M Conde; Rubio, J P Alcon; Mandoli, A Soler; Herrero, A Uson; Martínez, A Rodríguez; Serrano, P Salgado; Rodríguez, E Nieto; Montesinos, J Segui; Macia, J Ferragud; Mateos Marcos, A Mateos; Soto, J V Pérez-Fuster; Dumont, M Verdaguer; Pagan, J Parra; Martínez, V Balanza; Santiuste de Pablos, M; Delgado, C Espinosa; Quiles, M D Martínez; López, F J Manzanera; Navarro, P Pozo; Torres, A Micol; Ingles, F J Martínez; Arias-Camison, J M Salmeron; Manzano, J C López; Peña, R Villanueva; Guitarte, G Petersen; Fontecilla, H Blasco; Romero, J Barjau; Gil, R Sanz; Lozano, J Marín; Adanez, L Donaire; Zarranz Herrera-Oria, I; Jiménez, J Pérez; Vaz, F Carrato; García, O Sanz; Anton, C Contreras; Casula, R Reixach; Hernandez, M C Natividad; Escabias, F Teba; Torresano, J Rodríguez; Pérez-Villamil, A Huidobro; Estevez, L; Figuero, M Aragües; Muñoz de Morales, A; Calvin, J L Rodríguez; Criado, M Delgado; Rodríguez, V Molina; Ambrosolio, E Balbo; Madera, P M Holgado; Alfaro, G Ponce; Vidal, M M Rojas; Valtuille, A García; Ruiz, O; Cabornero, G Lucas; Echevarria Martínez de Bujo, M; Mallen, M J Maicas; Puigros, J Santandreu; Martorell, A Liñana; Forteza, A Clar; Arrebola, E Rodríguez; Rodríguez de la Torre, M; Saiz, C G Anton; Bardolet I Casas, C; Linde, E Rodríguez; De Arce Cordon, R; Molina, E M Padial; Carazo, F J Ruiz; Romero, J J Muro; Cano, D Vico; Dorado, M Soria; Velazquez, S Campos; Sánchez, A J Rodríguez; Leon, S Ocio; Sánchez, K Pachas; Benitez, M Henry; Zugarramurai, A Intxausti; Contreras, M A; De la Varga González, M; Marín, P Barreiro; Robina, F Gómez; García, M Sánchez; Pérez, F J Otero; Bros, P Cubero; Gómez, A Carrillo; de Dios Molina Martín, J; Perera, J L Carrasco; Averbach, M C; Perera, J L Carrasco; Palancares, E Goenaga; Gallego de Dios, M T; Rojo, C Fernández; Iglesias, S Sánchez; Merino, M I Rubio; Mestre, N Prieto; Urdaniz, A Pérez; Sánchez, J M Martínez; Seco, R Gordo; Muñoz, J Franco; Agut, M Mateos; Lozano, M L Blanco; Herguedas, F Martín; Pena, A Torcal; García, J Vicente; Martínez, A Varona; Sanz Granado, O Sanz; Fernández, M A Medina; Canseco, J M Moran; López, P A Megia; Martín, M A Franco; Barrio, J A Espina; Ubago, J Giner; Bennassar, M Roca; Díez, J M Olivares; Fleta, J L Hernandez; Fortes, F Porras; López, C Arango; Medina, O; Alvarez, D Figuera; Roca, J M Peña; Valladolid, G Rubio; Tavera, J A Furquet; García-Castrillon Sales, J A; Llordes, I Batalla; Melgarejo, C Anchuistegui; Cañas de la Paz, F; Callol, V Vallés; García, M Bousoño; García, J Bobes; Leal, F J Vaz; Corrales, E Cáceres; Iglesias, E Sánchez; Gómez, M A Carreiras; Serrano, G García; Chillarón, E G Román; Aguado, F J Samino; Castillo, J J Molina; González, A González; Vázquez, J Gallardo; Peralvarez, M Bolivar; Diaz, M Rios; Mesa, M Ybarzabal; Artiles, F J Acosta; Chao, M Ajoy; Mesa, M Ybarzabal; del Rosario Santana, P; Escudero, M A García; Berenguer, M Molla; Llacer, J M Bonete; Berna, J A Juan; Ortiz, J Barragán; Pardell, L Tost; Hernández-Alvarez de Sotomayor, C; Méndez, M R Cejas; Garate, R Cabrera; Múgica, B Díaz; González, M Caballero; Domingo, J Pujol; Navarro, C Sáez; Vera, G Selva; Cuquerella, M A; Monzo, J Lonjedo; Boada, P Cervera; Pérez, M F Martín; Parrado, E Carrasco; Sánchez, J J Yañez; Fernández, J Calvo

2009-06-01

The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine

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Milin Robert

2009-02-01

Full Text Available Abstract Background The purpose of the study was to determine the effectiveness and tolerability of quetiapine as a maintenance treatment preventing against relapse or recurrence of acute mood episodes in adolescent patients diagnosed with bipolar disorder. Methods Consenting patients meeting DSM-IV lifetime criteria for a bipolar disorder and clinically appropriate for maintenance treatment were enrolled in a 48-week open prospective study. After being acutely stabilized (CGI-S ≤ 3 for 4 consecutive weeks, patients were started or continued on quetiapine and other medications were weaned off over an 8-week period. Quetiapine monotherapy was continued for 40-weeks and other mood stabilizers or antidepressants were added if clinically indicated. A neurocognitive test battery assessing the most reliable findings in adult patients was administered at fixed time points throughout the study to patients and matched controls. Results Of the 21 enrolled patients, 18 completed the 48-week study. Thirteen patients were able to be maintained without relapse or recurrence in good quality remission on quetiapine monotherapy, while 5 patients required additional medication to treat impairing residual depressive and/or anxiety symptoms. According to symptom ratings and global functioning scores, the quality of remission for all patients was very good. Neurocognitive test performance over treatment was equivalent to that of a matched control group of never ill adolescents. Quetiapine was generally well tolerated with no serious adverse effects. Conclusion This study suggests that a proportion of adolescent patients diagnosed with bipolar disorder can be successfully maintained on quetiapine monotherapy. The good quality of clinical remission and preserved neurocognitive functioning underscores the importance of early diagnosis and effective stabilization. Clinical Trials Registry D1441L00024

CYP2D6 polymorphisms and their influence on risperidone treatment

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Puangpetch A

2016-12-01

Full Text Available Apichaya Puangpetch,1 Natchaya Vanwong,1 Nopphadol Nuntamool,2 Yaowaluck Hongkaew,1 Monpat Chamnanphon,1 Chonlaphat Sukasem1 1Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, 2Molecular Medicine, Faculty of Science, Mahidol University, Bangkok, Thailand Abstract: Cytochrome P450 enzyme especially CYP2D6 plays a major role in biotransformation. The interindividual variations of treatment response and toxicity are influenced by the polymorphisms of this enzyme. This review emphasizes the effect of CYP2D6 polymorphisms in risperidone treatment in terms of basic knowledge, pharmacogenetics, effectiveness, adverse events, and clinical practice. Although the previous studies showed different results, the effective responses in risperidone treatment depend on the CYP2D6 polymorphisms. Several studies suggested that CYP2D6 polymorphisms were associated with plasma concentration of risperidone, 9-hydroxyrisperidone, and active moiety but did not impact on clinical outcomes. In addition, CYP2D6 poor metabolizer showed more serious adverse events such as weight gain and prolactin than other predicted phenotype groups. The knowledge of pharmacogenomics of CYP2D6 in risperidone treatment is increasing, and it can be used for the development of personalized medication in term of genetic-based dose recommendation. Moreover, the effects of many factors in risperidone treatment are still being investigated. Both the CYP2D6 genotyping and therapeutic drug monitoring are the important steps to complement the genetic-based risperidone treatment. Keywords: CYP2D6, risperidone, polymorphisms, adverse drug reaction, pharmacogenetics, pharmacokinetics, pharmacodynamics

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

Science.gov (United States)

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

2004-12-15

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

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

Science.gov (United States)

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

2012-04-01

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

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

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Svetlana Dzitoyeva

2013-01-01

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

Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials

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Maneeton N

2016-01-01

Full Text Available Narong Maneeton,1 Benchalak Maneeton,1 Pakapan Woottiluk,2 Surinporn Likhitsathian,1 Sirijit Suttajit,1 Vudhichai Boonyanaruthee,1 Manit Srisurapanont1 1Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Psychiatric Nursing Division, Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand Background: Some studies have indicated the efficacy of quetiapine in the treatment of generalized anxiety disorder (GAD.Objective: The purpose of this study was to systematically review the efficacy, acceptability, and tolerability of quetiapine in adult patients with GAD.Methods: The SCOPUS, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched in April 2015. All randomized controlled trials (RCTs of GAD were considered to be included in this meta-analysis. All RCTs of quetiapine in GAD patients providing endpoint outcomes relevant to severity of anxiety, response rate, remission rate, overall discontinuation rate, or discontinuation rate due to adverse events were included. The version reports from suitable clinical studies were explored, and the important data were extracted. Measurement for efficacy outcomes consisted of the mean-changed scores of the rating scales for anxiety, and response rate.Results: A total of 2,248 randomized participants in three RCTs were included. The pooled mean-changed score of the quetiapine-treated group was greater than that of the placebo-treated group and comparable to selective serotonin reuptake inhibitors (SSRIs. Unfortunately, the response and the remission rates in only 50 and 150 mg/day of quetiapine-XR (extended-release were better than those of the placebo. Their response and remission rates were comparable to SSRIs. The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo. Only the overall discontinuation rate of quetiapine-XR at 50 and

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

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Ascher-Svanum H

2014-06-01

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

Rhabdomyolysis following Acute Extended-Release Quetiapine Poisoning: A Case Report

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Antonios Liolios

2012-01-01

Full Text Available Background. During the past few years, there have been a number of case reports concerning rhabdomyolysis following quetiapine poisoning; however, there has been none concerning the medication in its extended-release form. Methods. We present the case report of a 48-year-old man presenting a major depressive disorder and borderline personality disorder, who after voluntary intoxication with 12000 mg of quetiapine extended-release developed signs of acute rhabdomyolysis. Results. The rhabdomyolysis was confirmed by the laboratory and the clinical findings, with elevated levels of creatinine, creatine phosphokinase, and CRP. Discussion. We would like to pinpoint the importance of this complication and our concern of prescribing it for psychiatric patients with chronic somatic comorbidities.

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

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

2016-09-01

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

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

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

2008-01-01

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

Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial

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Maneeton, Benchalak; Maneeton, Narong; Srisurapanont, Manit; Chittawatanarat, Kaweesak

2013-01-01

Background Atypical antipsychotic drugs may have low propensity to induce extrapyramidal side effects in delirious patients. This study aimed to compare the efficacy and tolerability between quetiapine and haloperidol in controlling delirious behavior. Methods A 7-day prospective, double-blind, randomized controlled trial was conducted from June 2009 to April 2011 in medically ill patients with delirium. Measures used for daily assessment included the Delirium Rating Scale-revised-98 (DRS-R-98) and total sleep time. The Clinical Global Impression, Improvement (CGI–I) and the Modified (nine-item) Simpson– Angus Scale were applied daily. The primary outcome was the DRS-R-98 severity scores. The data were analyzed on an intention-to-treat basis. Results Fifty-two subjects (35 males and 17 females) were randomized to receive 25–100 mg/day of quetiapine (n = 24) or 0.5–2.0 mg/day of haloperidol (n = 28). Mean (standard deviation) doses of quetiapine and haloperidol were 67.6 (9.7) and 0.8 (0.3) mg/day, respectively. Over the trial period, means (standard deviation) of the DRS-R-98 severity scores were not significantly different between the quetiapine and haloperidol groups (−22.9 [6.9] versus −21.7 [6.7]; P = 0.59). The DRS-R-98 noncognitive and cognitive subscale scores were not significantly different. At end point, the response and remission rates, the total sleep time, and the Modified (nine-item) Simpson–Angus scores were also not significantly different between groups. Hypersomnia was common in the quetiapine-treated patients (33.3%), but not significantly higher than that in the haloperidol-treated group (21.4%). Limitations Patients were excluded if they were not able to take oral medications, and the sample size was small. Conclusion Low-dose quetiapine and haloperidol may be equally effective and safe for controlling delirium symptoms. Clinical trials registration number clinicaltrials.gov NCT00954603. PMID:23926422

Focus on risperidone.

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Green, B

2000-01-01

Risperidone is a relatively new antipsychotic available world-wide since the early 1990s. It has been characterised as atypical, but shares some of the extrapyramidal side-effect profile of the earlier antipsychotics, when used at doses higher than those recommended by the manufacturer (4-6 mg/day). There is now adequate comparison with conventional antipsychotics to suggest its superiority, but a depot formulation is needed to complete the picture.

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

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Ratnayake Shiroma L

2011-05-01

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

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

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

2010-01-01

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

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

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

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

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

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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,

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

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Maneeton Narong

2012-09-01

Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

Double-blind, placebo-controlled pilot study of adjunctive quetiapine SR in the treatment of PMS/PMDD.

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Jackson, Christine; Pearson, Brenda; Girdler, Susan; Johnson, Jacqueline; Hamer, Robert M; Killenberg, Susan; Meltzer-Brody, Samantha

2015-11-01

Premenstrual dysphoric disorder (PMDD), a more severe form of premenstrual syndrome (PMS), afflicts 5-8% of reproductive age women and results in significant functional impairment. We conducted a double-blind, placebo-controlled trial of adjunctive quetiapine in patients with PMS/PMDD who had inadequate response to selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy for their symptoms. A PMS/PMDD diagnosis was confirmed by 2-month prospective diagnostic assessment of PMS/PMDD using the Prospective Record of the Impact and Severity of Premenstrual Symptoms (PRISM) calendar. Women were randomized equally to receive quetiapine sustained-release (SR) or placebo (25-mg starting dose) during the luteal phase for 3 months. Outcome variables included the Hamilton Depression and Anxiety Scales, Clinical Global Impression Scale, and PRISM. Twenty women were enrolled in the treatment phase. Although the study was underpowered, greater reductions in luteal phase mood ratings were observed in the quetiapine group on the 17-item Hamilton Depression Rating Scale, Clinical Global Impression improvement rating, and PRISM daily score. The quetiapine group showed most improvement in symptoms of mood lability, anxiety, and irritability. This small double-blind study suggests that adjunctive treatment with quetiapine SR may be a useful addition to selective serotonin reuptake inhibitor therapy in women with PMS/PMDD by reducing symptoms and improving quality of life. Copyright © 2015 John Wiley & Sons, Ltd.

Zinc salt enhances gastroprotective activity of risperidone in indomethacin-induced gastric ulcer.

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Oluwole, F S; Onwuchekwa, C

2016-09-01

Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways. The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5. There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology. These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

Neuroleptic malignant syndrome in an elderly with quetiapine: A case report and review of literature

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Devakshi Dua

2017-01-01

Full Text Available Over the years, there is an increase in the prescription of antipsychotics among elderly patients, and these are used for various clinical indications such as psychotic disorders, affective disorders, behavioral and psychological symptoms of dementia and delirium. Quetiapine is one of the preferred antipsychotics among elderly because of its safety profile. However, quetiapine has been rarely been associated with the development of neuroleptic malignant syndrome (NMS among elderly. In this report, we discuss a case of NMS in a 70-year-old female, who developed symptoms of NMS at the dose of 200 mg/day, while quetiapine was being used along with lithium. A review of literature suggests that there are 12 cases of NMS reported in subjects older than 55 years of age.

Change and dispersion of QT interval during treatment with quetiapine extended release versus aripiprazole in children and adolescents with first-episode psychosis

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Jensen, Karsten Gjessing; Gärtner, Stefan; Correll, Christoph U.

2018-01-01

was correlated to higher QTcH change in the quetiapine ER group. The HR increased significantly with quetiapine ER (+ 11.0 ± 14.2 bpm, p bpm, p = 0.643). QTd did not significantly change with quetiapine ER or aripiprazole. Conclusion: QTcH and HR increased...

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

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

2012-01-01

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

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

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Dinesh S. Patel

2012-10-01

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

Cognitive effects of six months of treatment with quetiapine in antipsychotic-naïve first-episode schizophrenia

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Andersen, Rune; Fagerlund, Birgitte; Rasmussen, Hans

2011-01-01

Effects of quetiapine on cognition were assessed in a group of first-episode antipsychotic-naïve patients with schizophrenia (N=24). A comprehensive battery of neuropsychological tests was administered at baseline and after 6months of treatment with quetiapine. In order to examine retest effects...

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

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Montgomery W

2012-02-01

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

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

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

2014-01-01

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

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

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Sárvári, Anitta K; Veréb, Zoltán; Uray, Iván P; Fésüs, László; Balajthy, Zoltán

2014-08-08

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 and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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

2016-01-01

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

The Effect of Ranitidine on Olanzapine-Induced Weight Gain

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Fatemeh Ranjbar

2013-01-01

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

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

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Alaa A.M. Osman

2018-05-01

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

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

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Cakir S

2016-09-01

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

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

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Katrina Weston-Green

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

Risperidone in psychotic combat-related posttraumatic stress disorder: an open trial.

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Kozarić-Kovacić, Dragica; Pivac, Nela; Mück-Seler, Dorotea; Rothbaum, Barbara Olasov

2005-07-01

Psychotic symptoms that frequently occur in combat-related posttraumatic stress disorder (PTSD) complicate its pharmacotherapy. We hypothesized that war veterans with psychotic PTSD, resistant to prior antidepressant treatment, would respond well to 6 weeks of treatment with the atypical antipsychotic risperidone, given as a monotherapy. Twenty-six male war veterans with psychotic PTSD (DSM-IV) completed the 6-week inpatient treatment with risperidone (2-4 mg/day) during the period from November 1999 through December 2002. The primary outcome measure was change from baseline to endpoint (6 weeks) in Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Secondary outcome measures were changes in PTSD Interview (PTSD-I) and Clinical Global Impressions-Severity of Illness scale (CGI-S) total and subscale scores. Clinical improvement was assessed by CGI-S, CGI-Improvement scale, and Patient Global Impression of Improvement scale, while adverse events were recorded by Drug-Induced Extrapyramidal Symptoms Scale. Treatment with risperidone for either 3 or 6 weeks in an open trial significantly reduced total and subscales scores on the PANSS and on the PTSD-I and CGI-S when compared to baseline scores in patients with psychotic PTSD. Our preliminary data from the open trial indicate that risperidone decreased most of the psychotic and PTSD symptoms. Psychotic PTSD patients, unresponsive to antidepressant treatment, improved significantly after treatment for either 3 or 6 weeks with risperidone.

Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

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Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

2017-10-05

Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

Sertindole versus other atypical antipsychotics for schizophrenia

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

2014-01-01

Background In many countries of the industrialised world second generation (atypical) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether and, if so, how much the effects of the various second generation antipsychotics differ is a matter of debate. Objectives To evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) and ClinicalTrials.gov (February 2009). Selection criteria We included all randomised trials comparing oral sertindole with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI −8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33

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

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

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

A case of neuroleptic malignant syndrome induced by risperidone in a schizophrenic woman.

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Gallelli, Luca; Spagnuolo, Vincenzo; Palleria, Caterina; De Sarro, Giovambattista; Ferraro, Maria

2009-05-01

We report a case of neuroleptic malignant syndrome in a woman who assumed risperidone for schizoaffective disorders. A 45-year-old woman affected by schizoaffective disorders was admitted to Infectious Disease unit of Crotone Hospital because of a diagnosis of a fever of unknown origin. Clinical evaluation documented confusion and dysphoria, whereas chemical blood evaluation revealed acidosis and liver dysfunction. After few days she was transferred to the Operative Unit of Internal Medicine of San Giovanni in Fiore Hospital because of an increase in liver transaminases. Clinical evaluation showed the persistence of fever (38.8 degrees Celsius), with an increase in CPK, and liver enzymes. Pharmacological evaluation indicated a probable relationship between risperidone and NMS and led to a diagnosis of neuroleptic malignant syndrome associated with risperidone in a woman with schizophrenia. About seven days later, we recorded a complete resolution of her psychiatric symptoms. We postulate a possible interaction between risperidone and neuroleptic malignant syndrome and we suggest to use risperidone with caution in both young and middle aged people.

Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure

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Sarah M. Bahr

2015-11-01

Full Text Available Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism.

Adjunctive Treatment of Acute Mania with Risperidone versus Typical Antipsychotics: A Retrospective Study

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Jui-Hsiu Tsai

2005-12-01

Full Text Available Few studies have directly compared atypical antipsychotics (e.g. risperidone with typical antipsychotics as adjunctive therapy in patients hospitalized for acute mania, especially during a lengthy hospital stay. Our retrospective, case-controlled study is a chart review of 64 patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, defined bipolar I disorder (current episode, mania. Patients were divided into two groups according to the adjunctive medications used: the risperidone group (mood stabilizers plus risperidone and the control group (mood stabilizers plus typical antipsychotics. Outcome at discharge, medications, adverse drug effects, and length of hospital stay were compared between groups, controlling for gender, age, number of prior admissions, and duration of illness. Results indicated no statistically significant differences between groups in the controlled factors, Global Assessment of Functioning and Clinical Global Impression-Improvement scores, and adverse drug events. Patients in the risperidone group used significantly lower doses of trihexyphenidyl than those in the control group (p < 0.05. Patients treated with risperidone had a shorter hospital stay than those treated with typical antipsychotics (p < 0.01. In conclusion, antipsychotics are effective as adjunctive agents in the treatment of acute mania. The use of risperidone, in particular, decreases the need for anticholinergics and may lead to a shorter hospital stay compared with typical antipsychotics.

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

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Ahmad Fakhri

2016-12-01

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

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

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van der Zwaal, E.M.

2011-01-01

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

Atypical antipsychotic medications to control symptoms of delirium in children and adolescents.

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Turkel, Susan Beckwitt; Jacobson, Julienne; Munzig, Elizabeth; Tavaré, C Jane

2012-04-01

Atypical antipsychotics have been documented to be effective in the management of delirium in adults, but despite considerable need, their use has been less studied in pediatric patients. A retrospective chart review was done to describe the use of atypical antipsychotics in controlling symptoms of delirium in children and adolescents. Pharmacy records at Children's Hospital Los Angeles were reviewed to identify patients to whom antipsychotic agents were dispensed over a 24-month period. Psychiatric inpatient consultations during the same 24-month period were reviewed. Patients 1-18 years old diagnosed with delirium given antipsychotics constituted the study population. Delirium Rating Scale-Revised-98 (DRS-R98) scores were retrospectively calculated, when possible, at time antipsychotic was started to confirm the initial diagnosis of delirium and evaluate symptom severity, and again when antipsychotic was stopped, to assess symptom response. Olanzapine (n=78), risperidone (n=13), and quetiapine (n=19) were used during the 2 years of the study. Mean patient age, length of treatment, and response were comparable for the three medications. For patients with two DRS-R98 scores available (n=75/110), mean DRS-R98 scores decreased significantly (pdelirium symptoms in pediatric patients while underlying etiology was addressed.

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

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Manuel Monti

2018-02-01

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

Eosinophilic myocarditis during treatment with olanzapine

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

2016-01-01

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

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

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Rehmat Shah

2016-11-01

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

The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

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Kaminska, K; Rogoz, Z

2016-06-01

Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

Issues around the Prescription of Half Tablets in Northern Switzerland: The Irrational Case of Quetiapine

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Samuel S. Allemann

2015-01-01

Full Text Available Background. Prescription of fragmented tablets is useful for individualisation of dose but includes several drawbacks. Although without score lines, the antipsychotic drug quetiapine was in 2011 the most often prescribed 1/2 tablet in discharge prescriptions at the University Hospital in Basel (USB, 671 beds. We aimed at analysing the prescription patterns of split tablets in general and of quetiapine in particular in Switzerland. Methods. All orders of community pharmacies for unit-of-use soft pouch blisters placed at Medifilm AG, the leader company in Switzerland for repackaging into pouch blisters, were analysed. Results. Out of 4,784,999 tablets that were repacked in 2012 in unit-of-use pouch blisters, 8.5% were fragmented, mostly in half (87.6%, and were predominantly psycholeptics (pipamperone 15.8%. Prescription of half quetiapine appears to be a Basel specificity (highest rates of fragments and half quetiapine. Conclusions. Prescription of fragmented tablet is frequent. It represents a safety issue for the patient, and a pharmaceutical care issue for the pharmacist. In ambulatory care, the patient’s cognitive and physical capacities must be clarified, suitability of the splitting of the tablet must be checked, appropriate aids must be offered, like a pill-splitting device in order to improve accuracy, and safe use of the drug must be ensured.

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

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Detke Holland C

2012-05-01

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

Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents.

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Nuntamool, Nopphadol; Ngamsamut, Nattawat; Vanwong, Natchaya; Puangpetch, Apichaya; Chamnanphon, Monpat; Hongkaew, Yaowaluck; Limsila, Penkhae; Suthisisang, Chuthamanee; Wilffert, Bob; Sukasem, Chonlaphat

2017-10-01

The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcome in autistic children and adolescents who were treated with risperidone for long periods. Eighty-two autistic subjects diagnosed with DSM-IV and who were treated with risperidone for more than 1 year were recruited. Pharmacogenomics and clinical outcome (CGI-I, aggressive, overactivity and repetitive score) were evaluated. Almost all patients showed stable symptoms on aggressive behaviour (89.02%), overactivity (71.95%), repetitive (70.89%) behaviour and all clinical symptoms (81.71%). Only 4.48% of patients showed minimally worse CGI-I score. Patients in the non-stable symptom group had DRD2 Taq1A non-wild-type (TT and CT) frequencies higher than the clinically stable group (p = 0.04), whereas other gene polymorphisms showed no significant association. Haplotype ACCTCAT (rs6311, rs1045642, rs1128503, rs1800497, rs4436578, rs1799978, rs6280) showed a significant association with non-stable clinical outcome (χ 2  = 6.642, p = 0.010). Risperidone levels showed no association with any clinical outcome. On the other hand, risperidone dose, 9-OH risperidone levels and prolactin levels were significantly higher in the non-stable compared to the stable symptom group (p = 0.013, p = 0.044, p = 0.030). Increased appetite was the most common adverse drug reaction and associated with higher body-weight, whereas it was not significantly associated with genetic variations and non-genetic information. In conclusion, risperidone showed efficacy to control autism, especially aggressive symptoms in long-term treatment. However, Taq1A T - carrier of dopamine 2 receptor gene - is associated with non-stable response in risperidone-treated patients. This study supports pharmacogenomics testing for personalized therapy with risperidone in autistic children and adolescents. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Aripiprazole versus risperidone for treating children and adolescents with tic disorder: a randomized double blind clinical trial.

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Ghanizadeh, Ahmad; Haghighi, Alireza

2014-10-01

There are some uncontrolled studies about the efficacy and safety of both aripiprazole and risperidone for treating tic disorder. Moreover, the efficacy of these medications has never been compared. This is the first double blind randomized clinical trial comparing the safety and efficacy of aripiprazole and risperidone for treating patients with tic disorder. Sixty children and adolescents with tic disorder were randomly allocated into one of the two groups to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was the score of Yale Global Tic Severity Scale. In addition, health related quality of life and adverse events were assessed. Both aripiprazole and risperidone decreased the Yale Global Tic Severity Scale score during this trial. Moreover, both medications increased the health related quality of life score. Both aripiprazole and risperidone were tolerated well. Aripiprazole [3.22 (1.9) mg/day] decreased tic score as much as risperidone [0.6 (0.2) mg/day]. Their adverse effects and their effects on health related quality of life were comparable. However, risperidone increased the patients' social functioning more than aripiprazole in short term.

Quetiapine mitigates the ethanol-induced oxidative stress in brain tissue, but not in the liver, of the rat

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Han JH

2015-06-01

Full Text Available Jin-hong Han,1,2 Hong-zhao Tian,2 Yang-yang Lian,1 Yi Yu,1 Cheng-biao Lu,2 Xin-min Li,3 Rui-ling Zhang,1 Haiyun Xu4 1The Second Affiliated Hospital of Xinxiang Medical University, 2School of Basic Medicine, Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China; 3Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada; 4The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Quetiapine, an atypical antipsychotic, has been employed to treat alcoholic patients with comorbid psychopathology. It was shown to scavenge hydroxyl radicals and to protect cultured cells from noxious effects of oxidative stress, a pathophysiological mechanism involved in the toxicity of alcohol. This study compared the redox status of the liver and the brain regions of prefrontal cortex, hippocampus, and cerebellum of rats treated with or without ethanol and quetiapine. Ethanol administration for 1 week induced oxidative stress in the liver and decreased the activity of glutathione peroxidase and total antioxidant capacity (TAC there. Coadministration of quetiapine did not protect glutathione peroxidase and TAC in the liver against the noxious effect of ethanol, thus was unable to mitigate the ethanol-induced oxidative stress there. The ethanol-induced alteration in the redox status in the prefrontal cortex is mild, whereas the hippocampus and cerebellum are more susceptible to ethanol intoxication. For all the examined brain regions, coadministration of quetiapine exerted effective protection on the antioxidants catalase and total superoxide dismutase and on the TAC, thus completely blocking the ethanol-induced oxidative stress in these brain regions. These protective effects may explain the clinical observations that quetiapine reduced psychiatric symptoms intensity and maintained a good level of tolerability in chronic alcoholism with

Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN

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Margaret E. Mattson

2015-01-01

Full Text Available Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional. Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN for prevalence of emergency department (ED visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA.

[Differences in cerebral blood flow following risperidone treatment in children with autistic disorder].

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Ozdemir, Dilşad Foto; Karabacak, Neşe Ilgin; Akkaş, Burcu; Akdemir, Ozgür; Unal, Fatih; Senol, Selahattin

2009-01-01

Functional changes in the brains of autistic children due to risperidone treatment and theirs relationship to the symptom clusters are yet unknown. In this autistic disorder case series we aimed to comparatively evaluate the clinical findings before and after risperidone treatment, and regional cerebral blood flow (rCBF) findings with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. Eleven autistic patients (age range: 6-7 years; 4 girls, 7 boys) received risperidone therapy (1.5-2.5 mg d(-1)) and were followed-up for 3 months. All the patients underwent neurologic examinations, psychometric examinations, and SPECT imaging, both at the start of risperidone treatment and 3 months after the treatment started. Clinical observations, and the observations of parents and teachers were recorded. These results were compared with cerebral perfusion indices obtained from SPECT data. After 3 months of treatment changes in rCBF were observed in various regions and to varying degrees. We observed relationships between clinical symptoms and pre-therapy rCBF findings, and between clinical improvement and rCBF changes. Findings in the present case series are the first to demonstrate a relationship between clinical improvement and regional perfusion patterns after risperidone treatment. We think that these findings may contribute to the understanding of the neurofunctional mechanisms and hypothetical models of autism.

Maintenance therapy with second generation antipsychotics for bipolar disorder - A systematic review and meta-analysis.

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Lindström, Leif; Lindström, Eva; Nilsson, Mikael; Höistad, Malin

2017-04-15

patients stabilized on quetiapine during the acute phase. As monotherapy, olanzapine, quetiapine and risperidone were shown to be superior to placebo in reducing the overall risk of relapses. There were considerable limitations to the evidence base of maintenance treatment with SGA in bipolar disorder. Most studies used stabilized patients, i.e. enrichment design (selection bias), had considerable dropout levels (attrition bias), and variable degree of reporting bias. No long-term RCT data on efficacy is available beyond 2 years, and almost all studies are on bipolar disorder type I patients only. Despite these limitations, we elucidate quantitative findings from meta-analyses conducted on the randomized trials published on the topic. Copyright © 2017 Elsevier B.V. All rights reserved.

Postmortem Femoral Blood Reference Concentrations of Aripiprazole, Chlorprothixene, and Quetiapine

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Skov, Louise; Johansen, Sys Stybe; Linnet, Kristian

2015-01-01

no or only limited postmortem redistribution for aripiprazole, chlorprothixene with metabolite, and quetiapine in these cases. One fatality caused by chlorprothixene with a blood level of 0.90 mg/kg was recorded, and in six cases chlorprothixene was judged to be contributing to death with concentrations 0...

Quetiapine monotherapy in adolescents with bipolar disorder comorbid with conduct disorder.

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Masi, Gabriele; Pisano, Simone; Pfanner, Chiara; Milone, Annarita; Manfredi, Azzurra

2013-10-01

Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Children's Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (pdisorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

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

Science.gov (United States)

2006-09-01

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

A Randomized Open Label Comparison of the Effects ofRisperidone and Haloperidol on Sexual Function

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S. Jaber Mousavi

2009-12-01

Full Text Available "n Objective: "nSexual dysfunction in patients who take antipsychotics causes adecline in their quality of life and medication acceptance. Considering the restrictions in cross sectional design of many earlier researches, we used a clinical trial aimed at assessing sexual dysfunction by substituting Risperidone, an atypical antipsychotic drug, with Haloperidol, a typical one . "n "n "nMethod: This clinical trial was conducted on 51 patients who had been using Risperidone with a minimum dose of 2 mg/daily for at least 2 months. The patients were randomly divided into 2 groups. The first group continued taking Risperidone, whereas the second group was given Haloperidol. Sexual function prior to and after the drug substitution was assessed using a sexual questionnaire designed to assess four stages of sexual function . "nResults: Compared to those who changed their medication to Haloperidol, the patients who remained on Risperidone therapy suffered from more sexual dysfunction, especially in their tendency towards having sexual activities (P= 0.01, post menstrual sexual activity (P= 0.002, and reaching orgasm in their sexual activities (P= 0.04; however in the Haloperidol group, no significant difference was observed before and after the change in medication . "nConclusion: Although Risperidone and Haloperidol can both disturb patients'sexual function, the side effects of Risperidone are stronger. Hence toprevent the decline of medication acceptance or irregular consumption by patients which may lead to possible relapse, substitution of Risperidone withanother drug with fewer side effects on sexual activities is definitely to the advantage of the patients .

Adverse events in children and adolescents treated with quetiapine: an analysis of adverse drug reaction reports from the Danish Medicines Agency database

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Jakobsen, Klaus D.; Wallach-Kildemoes, Helle; Bruhn, Christina H.

2017-01-01

Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children...... and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported......, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns....

Recurrent Priapism from Therapeutic Quetiapine

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Omeed Saghafi

2014-02-01

Full Text Available Priapism is rarely related to use of non-erectile related medications. The objective was to educate about the multiple possible causes of priapism and to provide treatment recommendations for the different types of priapism. We present the case of a 43 year-old African American male with a history of schizoaffective disorder who presented to our emergency department multiple times over a three year period with priapism, each episode related to the ingestion of quetiapine. Following penile aspiration and intercavernosal injection of phenylephrine, this patient had resolution of his priapism. This case demonstrates an unusual case of recurrent priapism. [West J Emerg Med. 2014;15(1:114–116.

Review of risperidone for the treatment of pediatric and adolescent bipolar disorder and schizophrenia

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Jeffrey R Bishop

2008-03-01

Full Text Available Jeffrey R Bishop1,2, Mani N Pavuluri21Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL, USA; 2Department of Psychiatry, Pediatric Mood Disorders Program and Center for Cognitive Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USAAbstract: Risperidone is a commonly used medication for the treatment of bipolar disorder and schizophrenia in children and adolescents. It has been studied as a monotherapy treatment in early onset schizophrenia and as both monotherapy and combination therapy for pediatric bipolar disorder. Studies to date indicate that risperidone is an effective treatment for positive and negative symptoms of schizophrenia and mania symptoms of bipolar disorder. In young patient populations, side effects such as weight gain, extrapyramidal side effects, and prolactin elevation require consideration when evaluating the risk benefit ratio for individual patients. Here we review published studies of risperidone for the treatment of bipolar disorder and schizophrenia in children and adolescents to provide practitioners with an overview of published data on the efficacy and safety of risperidone in these patient populations.Keywords: risperidone, bipolar disorder, schizophrenia, children, adolescents

Risperidone – Solid-state characterization and pharmaceutical compatibility using thermal and non-thermal techniques

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Daniel, Josiane Souza Pereira; Veronez, Isabela Pianna; Rodrigues, Larissa Lopes [Laboratório de Análise e Caracterização de Fármacos – LACFar, Instituto de Química, Universidade Federal de Alfenas, Alfenas, Minas Gerais (Brazil); Trevisan, Marcello G. [Laboratório de Análise e Caracterização de Fármacos – LACFar, Instituto de Química, Universidade Federal de Alfenas, Alfenas, Minas Gerais (Brazil); National Institute of Bioanalytics Science and Technology – INCTBio, Institute of Chemistry – UNICAMP, 13084-653, Campinas, São Paulo (Brazil); Garcia, Jerusa Simone, E-mail: jerusa.garcia@unifal-mg.edu.br [Laboratório de Análise e Caracterização de Fármacos – LACFar, Instituto de Química, Universidade Federal de Alfenas, Alfenas, Minas Gerais (Brazil)

2013-09-20

Highlights: • DSC was used to characterize Risperidone and study its compatibility with excipients. • FT-IR associated with PCA was used to complement DSC data. • LC analyzes confirmed the DSC and FT-IR/PCA results. • Risperidone was incompatible with three among five excipients evaluated. - Abstract: A full solid-state characterization of risperidone was conducted using differential scanning calorimetry (DSC), thermogravimetry (TG), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM) to examine its physicochemical properties and polymorphism. The primary aim of this work was to study the compatibility of risperidone with pharmaceutical excipients using DSC to obtain and compare the curves of the active pharmaceutical ingredient (API) and the excipients with their 1:1 (w/w) binary mixtures. These same binary mixtures were turned to room temperature and analyzed by FT-IR combined with principal component analysis (PCA) to evaluate solid-state incompatibilities. The chemical incompatibilities of these samples were verified using a stability-indicating liquid chromatography (LC) method to assay for the API and evaluate the formation of degradation products. All of these methods showed incompatibilities between risperidone and the excipients magnesium stearate, lactose and cellulose microcrystalline.

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.

Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents

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Roberto Canitano

2008-09-01

Full Text Available Roberto Canitano, Valeria ScandurraDivision of Child Neuropsychiatry, University Hospital of Siena, Siena, ItalyAbstract: This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD. The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review.Keywords: autism, pervasive developmental disorders, risperidone

Combination treatment with risperidone long-acting injection and psychoeducational approaches for preventing relapse in schizophrenia

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Zhao Y

2013-10-01

Full Text Available Yueren Zhao,1–3 Taro Kishi,1 Nakao Iwata,1 Manabu Ikeda3,4 1Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan; 2Department of Psychiatry, Okehazama Hospital Fujita Kokoro Care Center, Toyoake, Aichi, Japan; 3Department of Neuropsychiatry, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan; 4Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto, Japan Abstract: A recent meta-analysis showed that long-acting injectable (LAI antipsychotics were not superior to oral antipsychotics for preventing relapse in patients with schizophrenia. We therefore designed a treatment strategy combining risperidone LAI and COMPASS (COMprehensive Psycho-educational Approach and Scheme Set, an original psychoeducational program supporting treatment with risperidone LAI and evaluating subjective treatment satisfaction, transition of symptoms, and effectiveness in preventing symptomatic relapse. The aim of this study was to examine whether addition of COMPASS to risperidone LAI was more effective in preventing relapse in schizophrenia patients than risperidone LAI alone, with the latter group consisting of patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients were followed up for 6 months, with COMPASS continuously implemented from the transition to the observation phase. The primary efficacy measurements were relapse rate (rates of rehospitalization and discontinuation due to inefficacy. Secondary efficacy measurements were the Brief Psychiatric Rating Scale (BPRS and Global Assessment of Functioning (GAF scores. Of the 96 patients originally enrolled, 19 (19.8% were discontinued from all causes. During the 6-month study period, ten of the 96 patients (10.4% relapsed, compared with a 12.2% relapse rate in patients enrolled in a Phase III trial of risperidone LAI in Japan. Patients showed significant improvements in BPRS total

Effects of short- and long-term risperidone treatment on prolactin levels in children with autism.

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Anderson, George M; Scahill, Lawrence; McCracken, James T; McDougle, Christopher J; Aman, Michael G; Tierney, Elaine; Arnold, L Eugene; Martin, Andrés; Katsovich, Liliya; Posey, David J; Shah, Bhavik; Vitiello, Benedetto

2007-02-15

The effects of short- and long-term risperidone treatment on serum prolactin were assessed in children and adolescents with autism. Patients with autism (N = 101, 5-17 years of age) were randomized to an 8-week trial of risperidone or placebo and 63 then took part in a 4-month open-label follow-up phase. Serum samples were obtained at Baseline and Week-8 (N = 78), and at 6-month (N = 43) and 22-month (N = 30) follow-up. Serum prolactin was determined by immunoradiometric assay; dopamine type-2 receptor (DRD2) polymorphisms were genotyped. Baseline prolactin levels were similar in the risperidone (N = 42) and placebo (N = 36) groups (9.3 +/- 7.5 and 9.3 +/- 7.6 ng/ml, respectively). After 8 weeks of risperidone, prolactin increased to 39.0 +/- 19.2 ng/ml, compared with 10.1 +/- 8.8 ng/ml for placebo (p autism. Although risperidone-induced increases tended to diminish with time, further research on the consequences of long-term prolactin elevations in children and adolescents is needed.

Quetiapine Induced Acute Dystonia in a patient with History of severe Head Injury

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Robert G. Bota

2010-01-01

Full Text Available A patient with a history of severe head injury 10 years ago regained ability to walk after years of being bound to a wheelchair. During the last psychiatric hospitalization, quetiapine was increased to therapeutic dose using a normal titration. As a result the patient developed dystonia of multiple muscle groups requiring 4 days of hospitalization for remittance of symptoms. In this paper, we take a close look at the literature concerning extrapiramidal symptoms (EPS in this context, and we suggest that in patients with a history of head injury, it is warranted to consider a slower titration of antipsychotic medications, including ones that are considered having a lower risk of EPS such as quetiapine.

Adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia

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Ranjbar F

2015-03-01

Full Text Available Fatemeh Ranjbar,1 Homayoun Sadeghi-Bazargani,2,3 Parisa Niari Khams,1 Asghar Arfaie,1 Azim Salari,4 Mostafa Farahbakhsh1 1Clinical Psychiatry Research Center, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran; 2Road Traffic Injury Research Center, Department of Statistics & Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran; 3World Health Organization Collaborating Center on Community Safety Promotion, Karolinska Institute, Stockholm, Sweden; 4Emam Khomeini Hospital, Naghadeh, West Azerbaijan, Iran Background: Antipsychotics have been used for more than 50 years in the treatment of schizophrenia and many other psychiatric disorders. Prolactin levels usually increase in patients treated with risperidone. Aripiprazole, which has a unique effect as an antipsychotic, is a D2 receptor partial agonist. It is an atypical antipsychotic with limited extrapyramidal symptoms. Since it acts as an antagonist in hyperdopaminergic conditions and as an agonist in hypodopaminergic conditions, it does not have adverse effects on serum prolactin levels. The present study aimed to investigate the effect of aripiprazole on risperidone-induced hyperprolactinemia. Methods: This before-and-after clinical trial was performed in 30 patients. Baseline prolactin levels were measured in all patients who were candidates for treatment with risperidone. In subjects with elevated serum prolactin, aripiprazole was added to their treatment. Serum prolactin levels were measured during the first week, second week, and monthly thereafter for at least 3 months or until prolactin levels became normal. The data were analyzed using Stata version 11 software. Survival analysis and McNemar’s test were also performed. Results: The mean age of the participants was 30.8 years. Prolactin levels normalized in 23 (77% participants during the study, and menstrual disturbances normalized in 25 (83.3%. Prolactin levels normalized in most patients between days 50

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

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Ajeet Sidana

2014-01-01

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

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

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

2012-03-01

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

Naturalistic study of olanzapine in treatment-resistaant ...

African Journals Online (AJOL)

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

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

Energy Technology Data Exchange (ETDEWEB)

Jasinska, A.; Nalewajko, E

2004-04-22

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

Double-blind, placebo-controlled trial of risperidone plus topiramate in children with autistic disorder.

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Rezaei, Vala; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Sahraian, Ali; Tabrizi, Mina; Rezazadeh, Shams-Ali; Akhondzadeh, Shahin

2010-10-01

Autism is a complex neurodevelopmental disorder that forms part of a spectrum of related disorders referred to as Autism Spectrum Disorders. The present study assessed the effects of topiramate plus risperidone in the treatment of autistic disorder. Forty children between the ages of 4 and 12 years with a DSM IV clinical diagnosis of autism who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to topiramate+risperidone (Group A) or placebo+risperidone (Group B) for an 8-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of topiramate was titrated up to 200 mg/day depending on weight (100 mg/day for 30 kg). Patients were assessed at baseline and after 2, 4, 6 and 8 weeks after starting medication. Measure of outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Difference between the two protocols was significant as the group that received topiramate had a greater reduction in ABC-C subscale scores for irritability, stereotypic behavior and hyperactivity/noncompliance. The results suggest that the combination of topiramate with risperidone may be superior to risperidone monotherapy for children with autistic disorder. However the results need to be further confirmed by a larger randomized controlled trial. Copyright © 2010 Elsevier Inc. All rights reserved.

Enhancement of the anti-immobility action of antidepressants by risperidone in the forced swimming test in mice.

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Rogóż, Zofia; Kabziński, Marcin

2011-01-01

The aim of the present study was to examine the effect of antidepressants (ADs) belonging to different pharmacological groups and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. The antidepressants: citalopram, fluvoxamine, sertraline, reboxetine, milnacipran (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Co-treatment with reboxetine or milnacipran (10 mg/kg) and risperidone in a lower dose of 0.05 mg/kg or with sertraline, reboxetine (5 and 10 mg/kg), citalopram, fluvoxamine, milnacipran (10 mg/kg) and risperidone in a higher dose of 0.1 mg/kg produced antidepressant-like effect in the forced swimming test. WAY100635 (a 5-HT(1A) receptor antagonist) inhibited the effects induced by co-administration of ADs and risperidone. Active behavior in the forced swimming test was not a consequence of an increased general activity, since the combined treatment with ADs and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that a low dose of risperidone enhances the activity of ADs in an animal model of depression, and that, among other mechanisms, 5-HT(1A) receptors may play a role in these effects.

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

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

2005-06-01

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

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

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Rustembegovic, Avdo; Sofic, Emin; Wichart, Ildiko

2006-01-01

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

Superior effects of quetiapine compared with aripiprazole and iloperidone on MK-801-induced olfactory memory impairment in female mice.

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Mutlu, Ahmet; Mutlu, Oguz; Ulak, Guner; Akar, Furuzan; Kaya, Havva; Erden, Faruk; Tanyeri, Pelin

2017-05-01

Cognitive dysfunction is commonly observed in schizophrenic patients and the administration of antipsychotic treatments results in different outcomes. Although the typical antipsychotic treatments, such as haloperidol, appear to be unable to improve cognition dysfunction, the atypical antipsychotic drugs (quetiapine, aripiprazole and iloperidone) exert a beneficial effect. The purpose of the current study was to investigate the effects of atypical antipsychotics on olfactory memory in mice, utilizing the social transmission of food preference (STFP) tests to evaluate the effects of drugs on MK-801-induced cognitive dysfunction. Female BALB/c mice were treated with quetiapine (5 and 10 mg/kg), aripiprazole (3 and 6 mg/kg), iloperidone (0.5 and 1 mg/kg) or MK-801 (0.1 mg/kg) alone or concurrently prior to retention sessions of STFP tests. In the STFP tests, quetiapine (10 mg/kg; P<0.05), aripiprazole (3 and 6 mg/kg; P<0.01 and P<0.001, respectively), iloperidone (0.5 and 1 mg/kg; P<0.01 and P<0.001, respectively) and MK-801 (P<0.001) significantly decreased cued/total food eaten (%). Quetiapine (5 mg/kg; P<0.05) significantly increased MK-801-induced decreases in cued/total food eaten (%), while aripiprazole and iloperidone demonstrated no significant effects. The results revealed that all of the drugs disturbed olfactory memory in the naive mice; however, only quetiapine reversed MK-801-induced memory impairment in the STFP test.

Naturalistic study of olanzapine in treatment-resistaant ...

African Journals Online (AJOL)

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

Risperidone treatment for ADHD in children and adolescents with bipolar disorder

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Joseph Biederman

2008-03-01

Full Text Available Joseph Biederman, Paul Hammerness, Robert Doyle, Gagan Joshi, Megan Aleardi, Eric MickPediatric Psychopharmacology Research Department, Massachusetts General Hospital, Boston, MA, USAObjective: Children and adolescents with bipolar disorder are also at high risk of having comorbid attention-deficit hyperactivity disorder (ADHD. The objective of this study was to estimate improvement in ADHD symptoms in children with bipolar disorder.Methods: This was an open-label, study of risperidone monotherapy for the treatment of pediatric bipolar disorder. Thirty-one children and adolescents 4–15 years of age (7.2 ± 2.8 years of both sexes (71%, N = 22 male with pediatric bipolar disorder (YMRS score = 32.9 ± 8.8 and ADHD (ADHD-RS score = 37.9 ± 8.9 were included in these analyses.Results: Improvement in ADHD symptoms was contingent on improvement in manic symptoms. Although both hyperactive/impulsive (−7.5 ± 5.5.6, p < 0.05 and inattentive (−6.8 ± 5.0, p < 0.05 ADHD symptoms were significantly improved with risperidone, improvement was modest, and only 29% of subjects (N = 6 showed a 30% reduction in ADHD rating scale scores and had a CGI-I ≤ 2.Conclusions: These results suggest that that treatment with risperidone is associated with tangible but generally modest improvement of symptoms of ADHD in children with bipolar disorder.Keywords: ADHD, bipolar disorder, children, risperidone

Pharmacogenomics and Efficacy of Risperidone Long-Term Treatment in Thai Autistic Children and Adolescents

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Nuntamool, Nopphadol; Ngamsamut, Nattawat; Vanwong, Natchaya; Puangpetch, Apichaya; Chamnanphon, Monpat; Hongkaew, Yaowaluck; Limsila, Penkhae; Suthisisang, Chuthamanee; Wilffert, Bob; Sukasem, Chonlaphat

2017-01-01

The purpose of this study was to evaluate the association of pharmacogenomic factors and clinical outcome in autistic children and adolescents who were treated with risperidone for long periods. Eighty-two autistic subjects diagnosed with DSM-IV and who were treated with risperidone for more than

The use of dried blood spots for quantification of 15 antipsychotics and 7 metabolites with ultra-high performance liquid chromatography - tandem mass spectrometry.

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Patteet, Lisbeth; Maudens, Kristof E; Stove, Christophe P; Lambert, Willy E; Morrens, Manuel; Sabbe, Bernard; Neels, Hugo

2015-06-01

Therapeutic drug monitoring of antipsychotics is important in optimizing individual therapy. In psychiatric populations, classical venous blood sampling is experienced as frightening. Interest in alternative techniques, like dried blood spots (DBS), has consequently increased. A fast and easy to perform DBS method for quantification of 16 antipsychotics (amisulpride, aripiprazole, asenapine, bromperidol, clozapine, haloperidol, iloperidone, levosulpiride, lurasidone, olanzapine, paliperidone, pipamperone, quetiapine, risperidone, sertindole and zuclopenthixol) and 8 metabolites was developed. DBS were prepared using 25 μL of whole blood and extraction of complete spots was performed using methanol: methyl-t-butyl-ether (4:1). After evaporation, the extract was reconstituted in the mobile phase and 10 μL were injected on an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Separation using a C18 column and gradient elution with a flow rate of 0.5 mL/min resulted in a 6-min run-time. Ionization was performed in positive mode and a dynamic MRM method was applied. Median recovery was 66.4 % (range 28.7-84.5%). Accuracy was within the acceptance criteria, except for pipamperone (LLOQ and low concentration) and lurasidone (low concentration). Imprecision was only aberrant for lurasidone at low and medium concentration. All compounds were stable during 1 month at room temperature, 4 °C and -18 °C. Lurasidone was unstable when the extract was stored for 12 h on the autosampler. Absolute matrix effects (ME) (median 66.1%) were compensated by the use of deuterated IS (median 98.8%). The DBS method was successfully applied on 25-μL capillary DBS from patients and proved to be a reliable alternative for quantification of all antipsychotics except for olanzapine and N-desmethylolanzapine. Copyright © 2014 John Wiley & Sons, Ltd.

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

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

2010-05-01

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

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

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Mohammad Zia Ul Haq Katshu

2018-01-01

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

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

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

2007-06-01

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

Comparing Efficacy and Side Effects of Memantine vs. Risperidone in the Treatment of Autistic Disorder.

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Nikvarz, Nikvarz; Alaghband-Rad, Javad; Tehrani-Doost, Mehdi; Alimadadi, Abbas; Ghaeli, Padideh

2017-01-01

Introduction: This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. Methods: 30 children, aged 4-17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions - Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Results: Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed "very much improvement" when assessed by CGI-I scale when compared with those on memantine. Discussion and conclusion: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

Continuation of Quetiapine Versus Switching to Placebo or Lithium for Maintenance Treatment of Bipolar I Disorder (Trial 144 : A Randomized Controlled Study)

NARCIS (Netherlands)

Weisler, Richard H.; Nolen, Willem A.; Neijber, Anders; Hellqvist, Asa; Paulsson, Bjorn

Objective: Quetiapine, combined with lithium or divalproex, demonstrates efficacy in the maintenance treatment of bipolar I disorder. This study investigated the efficacy and safety of quetiapine monotherapy as maintenance treatment in bipolar I disorder compared with switching to placebo or

A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers.

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Kim, Anhye; Lim, Kyoung Soo; Lee, Howard; Chung, Hyewon; Yoon, Seo Hyun; Yu, Kyung-Sang; Cho, Joo-Youn; Jang, In-Jin; Chung, Jae-Yong

2016-07-01

Prolongation of the QT interval on an ECG is a surrogate marker for predicting the proarrhythmic potential of a drug under development. The aim of this study was to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine immediate release (IR) and escitalopram, in healthy individuals. This was a randomized, open-label, 4×4 Williams crossover study, with four single-dose treatments [placebo, 400 mg moxifloxacin (positive control), 20 mg escitalopram, and 100 mg quetiapine IR], conducted in 40 healthy volunteers. Serial blood samples for pharmacokinetics and ECG were collected. Individually, RR-corrected QTc intervals (QTcI) and placebo-adjusted changes from baseline values of QTcI (ΔΔQTcI) were evaluated. Lower-bound values of the one-sided 95% confidence interval for ΔΔQTcI of moxifloxacin with more than 5 ms confirmed the sensitivity of the assay. The maximum upper bound 95% confidence interval for the ΔΔQTcI of quetiapine IR and escitalopram was 13.7 and 10.5 ms, with mean estimates of 10.2 and 6.9 ms, respectively. Peak effects of moxifloxacin and quetiapine IR on ΔΔQTcI were observed at approximately time to maximum concentration (Tmax), whereas that of escitalopram was observed 3 h after Tmax. The concentration-ΔΔQTcI relationships of quetiapine IR and escitalopram were relatively flat, as compared with that of moxifloxacin. The results demonstrated the validity of trial methodology and that quetiapine IR and escitalopram caused QT prolongation in healthy individuals. In addition, hysteresis of escitalopram-induced QTc prolongation. These results indicate that higher doses of these drugs could lead to greater QT prolongation in a dose-response manner.

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

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

2018-01-01

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

A Randomized, Placebo-Controlled Pilot Study of Quetiapine-XR Monotherapy or Adjunctive Therapy to Antidepressant in Acute Major Depressive Disorder with Current Generalized Anxiety Disorder.

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Li, Ranran; Wu, Renrong; Chen, Jun; Kemp, David E; Ren, Ming; Conroy, Carla; Chan, Philip; Serrano, Mary Beth; Ganocy, Stephen J; Calabrese, Joseph R; Gao, Keming

2016-03-01

To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings.

Fatal hypertriglyceridaemia, acute pancreatitis and diabetic ketoacidosis possibly induced by quetiapine

DEFF Research Database (Denmark)

Madsen, Kristian Roerbaek

2014-01-01

A 27-year-old man treated with quetiapine for anxiety disorder developed hypertriglyceridaemia-induced acute pancreatitis and diabetic ketoacidosis. He was otherwise physically healthy with no family history of hyperlipidaemia. Despite aggressive intensive therapy he died of multiorgan failure wi...... and possibly plasmapheresis in case of extreme hypertriglyceridaemia....

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

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Stefaniak Victoria J

2010-06-01

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

Can authorities appreciably enhance the prescribing of oral generic risperidone to conserve resources? Findings from across Europe and their implications.

Science.gov (United States)

Godman, Brian; Petzold, Max; Bennett, Kathleen; Bennie, Marion; Bucsics, Anna; Finlayson, Alexander E; Martin, Andrew; Persson, Marie; Piessnegger, Jutta; Raschi, Emanuel; Simoens, Steven; Zara, Corinne; Barbui, Corrado

2014-06-13

Generic atypical antipsychotic drugs offer health authorities opportunities for considerable savings. However, schizophrenia and bipolar disorders are complex diseases that require tailored treatments. Consequently, generally there have been limited demand-side measures by health authorities to encourage the preferential prescribing of generics. This is unlike the situation with hypertension, hypercholaesterolaemia or acid-related stomach disorders.The objectives of this study were to compare the effect of the limited demand-side measures in Western European countries and regions on the subsequent prescribing of risperidone following generics; to utilise the findings to provide future guidance to health authorities; and where possible, to investigate the utilisation of generic versus originator risperidone and the prices for generic risperidone. Principally, this was a segmented regression analysis of retrospective time-series data of the effect of the various initiatives in Belgium, Ireland, Scotland and Sweden following the introduction of generic risperidone. The study included patients prescribed at least one atypical antipsychotic drug up to 20 months before and up to 20 months after generic risperidone. In addition, retrospective observational studies were carried out in Austria and Spain (Catalonia) from 2005 to 2011 as well as one English primary care organisation (Bury Primary Care Trust (PCT)). There was a consistent steady reduction in risperidone as a percentage of total selected atypical antipsychotic utilisation following generics. A similar pattern was seen in Austria and Spain, with stable utilisation in one English PCT. However, there was considerable variation in the utilisation of generic risperidone, ranging from 98% of total risperidone in Scotland to only 14% in Ireland. Similarly, the price of generic risperidone varied considerably. In Scotland, generic risperidone was only 16% of pre-patent loss prices versus 72% in Ireland. Consistent

Case Report: Valproic Acid and Risperidone Treatment Leading to Development of Hyperammonemia and Mania

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Carlson, Teri; Reynolds, Charles A.; Caplan, Rochelle

2007-01-01

This case report describes two children who developed hyperammonemia together with frank manic behavior during treatment with a combination of valproic acid and risperidone. One child had been maintained on valproic acid for years and risperidone was added. In the second case, valproic acid was introduced to a child who had been treated with…

Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents.

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Canitano, Roberto; Scandurra, Valeria

2008-08-01

This is a review of the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autistic spectrum disorders (ASD). The main clinical characteristics are impairment in social skills, communication difficulties, repetitive movements and behaviors, including stereotypies. Pharmacotherapy is mainly directed at the so-called target symptoms, ie, behavioral disorders and the various kinds of repetitions associated with ASD. According to the available data, risperidone seems to be moderately efficacious and safe for treating behavioral disorders. 4 double blind controlled trial. 3 reanalysis studies, and 12 open studies have documented the role of risperidone in children with ASD. Controlled studies have been thoroughly considered in this review.

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

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

2009-07-01

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

Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

DEFF Research Database (Denmark)

Johansen, Sys Stybe

2017-01-01

A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she......-three hours after the suspected drug-facilitated sexual assault (DFSA), blood and urine samples were collected and the initial toxicological screening detected quetiapine. Confirmation and quantification by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) revealed...... a concentration of 0.007mg/kg quetiapine in blood and 0.19mg/l in urine. Six months after the DFSA, a hair sample was collected and segmental hair analysis was performed on four washed segments (0-3cm, 3-5cm, 5-7cm, and 7-9cm). The last segment contained 0.011ng/mg of quetiapine, whereas the other segments were...

The prognostic value of dopamine receptor occupancy by [123I]IBZM-SPECT in schizophrenic patients treated with quetiapine

International Nuclear Information System (INIS)

Pavics, L.; Ambrus, E.; Argyelan, M.; Kanyo, B.; Csernay, L.; Szekeres, G.; Kovacs, Z.; Keri, S.; Janka, Z.

2004-01-01

In the present study D2 receptor occupancy was investigated in quetiapine treated schizophrenic patients for the detection of a relationship between the scintigraphic pattern and clinical signs and symptoms. In 10 schizophrenic patients [ 123I ]IBZM-SPECTs were performed during the introduction of quetiapine therapy (600 - 800 mg/day) and during a lower maintenance dose (200 - 400 mg/day). The patients clinical follow-up was continued for 1 year. For the evaluation of SPECT images, visual interpretation was performed and striatum/occipital lobe (S/O) activity ratio was calculated. The initial striatum/occipital ratio was significantly higher in patients with relapse compared to the others (1.86 ± 0.17, 1.53 ± 0.15, p nd SPECT was a predictive factor for the relapse. D2 receptor occupancy and its changes during quetiapine therapy were related to the prognosis of the treatment efficacy. (author)

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

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

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

2010-01-01

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

Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study.

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Fervaha, Gagan; Agid, Ofer; Takeuchi, Hiroyoshi; Foussias, George; Remington, Gary

2014-07-01

The field of schizophrenia is redefining optimal outcome, moving beyond clinical remission to a more comprehensive model including functional recovery and improved subjective well-being. Although numerous studies have evaluated subjective outcomes within the domain of subjective quality of life in patients with schizophrenia, less is known about global evaluations of subjective well-being. This study examined the effects of antipsychotic medication on overall life satisfaction in patients with chronic schizophrenia. Data were drawn from the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, where participants with a DSM-IV diagnosis of schizophrenia were randomized to receive olanzapine, perphenazine, quetiapine, risperidone or ziprasidone under double-blind conditions (N=753). The primary outcome measure was prospective change in subjectively evaluated overall life satisfaction scores following 12 months of antipsychotic treatment. Psychopathology, medication side effects and functional status were also evaluated, among other variables. Patients experienced modest improvements in overall life satisfaction (d=0.22, p0.05). Change in severity of positive, negative, and depressive symptoms as well as functional status each demonstrated a small, albeit statistically significant, association with change in life satisfaction (r=0.10-0.21, p׳slife satisfaction scores (explained variance satisfaction with life. Clinicians should be aware that these two domains are not inextricably linked. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Do We Really Know How to Treat a Child with Bipolar Disorder or One with Severe Mood Dysregulation? Is There a Magic Bullet?

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Rajeev Jairam

2012-01-01

Full Text Available Background. Despite controversy, bipolar disorder (BD is being increasingly diagnosed in under 18s. There is scant information regarding its treatment and uncertainty regarding the status of “severe mood dysregulation (SMD” and how it overlaps with BD. This article collates available research on treatment of BD in under 18s and explores the status of SMD. Methods. Literature on treatment of BD in under 18s and on SMD were identified using major search engines; these were then collated and reviewed. Results. Some markers have been proposed to differentiate BD from disruptive behaviour disorders (DBD in children. Pharmacotherapy restricted to short-term trials of mood-stabilizers and atypical-antipsychotics show mixed results. Data on maintenance treatment and non-pharmacological interventions are scant. It is unclear whether SMD is an independent disorder or an early manifestation of another disorder. Conclusions. Valproate, lithium, risperidone, olanzapine, aripiprazole and quetiapine remain first line treatments for acute episodes in the under 18s with BD. Their efficacy in maintenance treatment remains unclear. There is no validated treatment for SMD. It is likely that some children who are currently diagnosed with BD and DBD and possibly most children currently diagnosed with SMD will be subsumed under the proposed category in the DSM V of disruptive mood dysregulation disorder with dysphoria.

Dementia.

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Butler, Rob; Radhakrishnan, Raghavakurup

2012-09-10

Dementia is characterised by chronic, global, non-reversible deterioration in memory, executive function, and personality. Speech and motor function may also be impaired. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments on cognitive symptoms of dementia (Alzheimer's, Lewy body, or vascular)? What are the effects of treatments on behavioural and psychological symptoms of dementia (Alzheimer's, Lewy body, or vascular)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 49 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine), antidepressants (clomipramine, fluoxetine, imipramine, sertraline), antipsychotics (haloperidol, olanzapine, quetiapine, risperidone), aromatherapy, benzodiazepines (diazepam, lorazepam), cognitive behavioural therapy (CBT), cognitive stimulation, exercise, ginkgo biloba, memantine, mood stabilisers (carbamazepine, sodium valproate/valproic acid), music therapy, non-steroidal anti-inflammatory drugs (NSAIDs), omega 3 (fish oil), reminiscence therapy, and statins.

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

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Christopher J Lynch

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

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

African Journals Online (AJOL)

Arun Kumar Agnihotri

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

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

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

2015-01-01

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

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

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

2005-07-01

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

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

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KANAKAPURA BASAVAIAH

2009-05-01

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

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

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Nielsen, Marie Katrine Klose; Johansen, Sys Stybe

2009-01-01

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

Development of Risperidone PLGA Microspheres

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Susan D’Souza

2014-01-01

Full Text Available The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25 were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug.

Double-blind comparison of ziprasidone and risperidone in the treatment of Chinese patients with acute exacerbation of schizophrenia

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Hongyan Zhang

2011-03-01

Full Text Available Hongyan Zhang1, Huafang Li2, Liang Shu1, Niufan Gu2, Gang Wang3, Yongzhen Weng3, Shiping Xie4, Xinbao Zhang4, Ting Li5, Cui Ma5, Wei Yu6, Bruce Parsons7, Manjula Schou81Institute of Mental Health, Peking University, Beijing, China; 2Shanghai Mental Health Center, Shanghai, China; 3Capital Medical University, Beijing An Ding Hospital, Beijing, China; 4Nanjing Brain Hospital, Nanjing, China; 5Guangzhou Brain Hospital, Guangzhou, China; 6Pfizer China, Beijing, China; 7Pfizer Inc, New York, NY, USA; 8Pfizer Australia, Sydney, AustraliaBackground: The aim of the study was to evaluate the efficacy and safety of ziprasidone versus risperidone in Chinese subjects with acute exacerbation of schizophrenia.Methods: In patients meeting the Chinese Classification of Mental Disorders criteria for schizophrenia and with a Positive and Negative Syndrome Scale (PANSS total score ≥60 were randomly assigned to six weeks of double-blind treatment with ziprasidone 40–80 mg twice daily or risperidone 1–3 mg bid, flexibly dosed. Noninferiority was demonstrated if the upper limit of the two-sided 95% confidence interval (CI for the difference in PANSS total score improvement from baseline in the evaluable population was smaller than the prespecified noninferiority margin of 10 units.Results: The intent-to-treat population comprised 118 ziprasidone-treated and 121 risperidone-treated subjects. Improvement (reduction from baseline to week 6 in PANSS total score was (-35.6 [95% CI: -38.6, -32.6] for ziprasidone and (-37.1 [95% CI: -39.9, -34.4] for risperidone. Noninferiority was demonstrated in the evaluable population with a difference score of 1.5 [95% CI: -2.5, 5.5]. Mean prolactin levels decreased at week 6 compared with baseline for ziprasidone (-3.5 ng/mL, but significantly increased for risperidone (61.1 ng/mL; P < 0.001. More risperidone-treated subjects (14.9% than ziprasidone-treated subjects (4.2% reported weight gain ≥7%. Akathisia and somnolence in

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

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

2017-01-05

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

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

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Chawla, Bharat; Luxton-Andrew, Heather

2008-04-01

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

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

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

2012-01-01

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

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

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Fiorenzo Mignini

2013-03-01

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

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

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

2011-11-01

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

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

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

2012-04-01

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

Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response-a prospective open-label study.

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Hashimoto, Naoki; Toyomaki, Atsuhito; Honda, Minoru; Miyano, Satoru; Nitta, Nobuyuki; Sawayama, Hiroyuki; Sugawara, Yasufumi; Uemura, Keiichi; Tsukamoto, Noriko; Koyama, Tsukasa; Kusumi, Ichiro

2015-01-01

While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the Schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and

On-Line Organic Solvent Field Enhanced Sample Injection in Capillary Zone Electrophoresis for Analysis of Quetiapine in Beagle Dog Plasma

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Yuqing Cao

2016-01-01

Full Text Available A rapid and sensitive capillary zone electrophoresis (CZE method with field enhanced sample injection (FESI was developed and validated for the determination of quetiapine fumarate in beagle dog plasma, with a sample pretreatment by LLE in 96-well deep format plate. The optimum separation was carried out in an uncoated 31.2 cm × 75 μm fused-silica capillary with an applied voltage of 13 kV. The electrophoretic analysis was performed by 50 mM phosphate at pH 2.5. The detection wavelength was 210 nm. Under these optimized conditions, FESI with acetonitrile enhanced the sensitivity of quetiapine about 40–50 folds in total. The method was suitably validated with respect to stability, specificity, linearity, lower limit of quantitation, accuracy, precision and extraction recovery. Using mirtazapine as an internal standard (100 ng/mL, the response of quetiapine was linear over the range of 1–1000 ng/mL. The lower limit of quantification was 1 ng/mL. The intra- and inter-day precisions for the assay were within 4.8% and 12.7%, respectively. The method represents the first application of FESI-CZE to the analysis of quetiapine fumarate in beagle dog plasma after oral administration.

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

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Mong-Liang Lu

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

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

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

2018-02-01

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

Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.

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Srisawasdi, Pornpen; Vanwong, Natchaya; Hongkaew, Yaowaluck; Puangpetch, Apichaya; Vanavanan, Somlak; Intachak, Boontarika; Ngamsamut, Nattawat; Limsila, Penkhae; Sukasem, Chonlaphat; Kroll, Martin H

2017-08-01

To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein. The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses. Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.

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McDougle, C J; Holmes, J P; Carlson, D C; Pelton, G H; Cohen, D J; Price, L H

1998-07-01

Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (Pautism (Pautism in adults.

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

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Ciudad A

2013-11-01

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

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

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Stickelmeyer Mary

2010-06-01

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

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

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Haeberle Anne

2012-09-01

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

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

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

2001-01-01

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

Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder

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Klok, Rogier M; Al Hadithy, Asmar Fy; van Schayk, Nathalie Pjt; Antonisse, Ad Jj; Caro, Jaime J; Brouwers, Jacobus Rbj; Postma, Maarten J

2007-01-01

Bipolar disorder (or manic depression) is a lifelong, severe and complex psychiatric illness characterized by recurrent episodes of depression and mania. The aim of this study is to explore the cost-effectiveness of quetiapine compared with other alternatives for the treatment of acute manic

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

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Okazaki K

2017-11-01

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

Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation.

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Đorđević, Sanela M; Cekić, Nebojša D; Savić, Miroslav M; Isailović, Tanja M; Ranđelović, Danijela V; Marković, Bojan D; Savić, Saša R; Timić Stamenić, Tamara; Daniels, Rolf; Savić, Snežana D

2015-09-30

This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters--co-emulsifier type, aqueous phase type, homogenization temperature--on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution Solutol(®) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics

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El-Say Khalid M.

2015-12-01

Full Text Available This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1, swelling pressure of the superdisintegrant (X2, and the surface area of Aerosil as a glidant (X3. Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for preand post-compression characteristics. The prepared ODmini- tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2 and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics.

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El-Say, Khalid M; Ahmed, Tarek A; Abdelbary, Maged F; Ali, Bahaa E; Aljaeid, Bader M; Zidan, Ahmed S

2015-12-01

This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for pre- and post-compression characteristics. The prepared OD-mini-tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

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

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

2010-01-01

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

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

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

2009-07-15

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

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

2017-07-01

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

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

African Journals Online (AJOL)

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

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

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

2011-03-01

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

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

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Silvia Duong

2015-01-01

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

Dopamine transporter density assessed with [123]IPT SPECT before and after risperidone treatment in children with tourette's disorder

International Nuclear Information System (INIS)

Ryu, Young Hoon; Kim, Tae Hoon; Ryu, Won Gee

2004-01-01

Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled N-(3-iodopropen-2-yl)-2β-carbomethoxy-3beta-(4-chlorophenyl)tropane ([ 123 I]IPT) single photon emission computed tomography (SPECT). [ 123I ]IPT SPECT imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of [ 123 I]IPT. Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system

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

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

2016-05-01

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

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

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Sparkman, Nathan L.; Li, Ming

2016-01-01

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

Patient perspectives on antipsychotic treatments and their association with clinical outcomes

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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

Insight and Treatment Outcomes in Schizophrenia: Post-hoc Analysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR.

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Harvey, Philip D; Siu, Cynthia O; Loebel, Antony D

2017-12-01

Objective: The objective of this post-hoc analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition ( p =0.014), functional capacity (p=0.006, UPSA-B), quality of well-being ( p =0.033, QWB), and depressive symptoms ( p =0.05, Montgomery-Åsberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this post-hoc analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time.

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.

Analysis of risperidone and 9-hydroxyrisperidone in human plasma, urine and saliva by MEPS-LC-UV.

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Mandrioli, Roberto; Mercolini, Laura; Lateana, Domenico; Boncompagni, Giancarlo; Raggi, Maria Augusta

2011-01-15

Risperidone is currently one of the most frequently prescribed atypical antipsychotic drugs; its main active metabolite 9-hydroxyrisperidone contributes significantly to the therapeutic effects observed. An original analytical method is presented for the simultaneous analysis of risperidone and the metabolite in plasma, urine and saliva by high-performance liquid chromatography coupled to an original sample pre-treatment procedure based on micro-extraction by packed sorbent (MEPS). The assays were carried out using a C8 reversed-phase column and a mobile phase composed of 73% (v/v) acidic phosphate buffer (30 mM, pH 3.0) containing 0.23% triethylamine and 27% (v/v) acetonitrile. The UV detector was set at 238 nm and diphenhydramine was used as the internal standard. The sample pre-treatment by MEPS was carried out on a C8 sorbent. The extraction yields values were higher than 92% for risperidone and 90% for 9-hydroxyrisperidone, with RSD for precision always lower than 7.9% for both analytes. Limit of quantification values in the different matrices were 4 ng/mL or lower for risperidone and 6 ng/mL or lower for the metabolite. The method was successfully applied to plasma, urine and saliva samples from psychotic patients undergoing therapy with risperidone, with satisfactory accuracy results (recovery>89%) and no interference from other drugs. Thus, the method seems to be suitable for the therapeutic drug monitoring of schizophrenic patients using the three different biological matrices plasma, urine and saliva. Copyright © 2010 Elsevier B.V. All rights reserved.

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

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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

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

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Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

2014-01-01

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

Dilemma of prescribing aripiprazole under the Taiwan health insurance program: a descriptive study

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Hsu YC

2015-01-01

Full Text Available Yi-Chien Hsu,1,2 Yu-Ching Chou,3 Hsin-An Chang,1,2,4 Yu-Chen Kao,1,2,5 San-Yuan Huang,1,2 Nian-Sheng Tzeng1,2,4 1Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan; 2School of Medicine, 3School of Public Health, 4Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 5Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, Taipei, Taiwan Objectives: Refractory major depressive disorder (MDD is a serious problem leading to a heavy economic burden. Antipsychotic augmentation treatment with aripiprazole and quetiapine is approved for MDD patients and can achieve a high remission rate. This study aimed to examine how psychiatrists in Taiwan choose medications and how that choice is influenced by health insurance payments and administrative policy.Design: Descriptive study.Outcome measures: Eight questions about the choice of treatment strategy and atypical antipsychotics, and the reason to choose aripiprazole.Intervention: We designed an augmentation strategy questionnaire for psychiatrists whose patients had a poor response to antidepressants, and handed it out during the annual meeting of the Taiwanese Society of Psychiatry in October 2012. It included eight questions addressing the choice of treatment strategy and atypical antipsychotics, and the reason whether or not to choose aripiprazole as the augmentation antipsychotic.Results: Choosing antipsychotic augmentation therapy or switching to other antidepressant strategies for MDD patients with an inadequate response to antidepressants was common with a similar probability (76.1% vs 76.4%. The most frequently used antipsychotics were aripiprazole and quetiapine, however a substantial number of psychiatrists chose olanzapine, risperidone, and sulpiride. The major reason for not choosing aripiprazole was cost (52.1%, followed by insurance official policy audit and deletion in the claims review system (30.1%.Conclusion: The prescribing

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

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Kittipeerachon, Mantana; Chaichan, Warawat

2016-10-01

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

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

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

2018-01-01

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

An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

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Pandina Gahan

2012-06-01

Full Text Available Abstract Background Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. Methods This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children’s Global Assessment Scale, adverse event (AE monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. Results A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7% subjects completed this study: 209 of the 279 subjects (75% in the 6-month group and 55 of the 111 subjects (50% in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs (≥10% of subjects were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs were reported by 36 (9% subjects. The AE profile in this study was

METABOLIC SIDE EFFECTS OF HALOPERIDOL AND RISPERIDONE- A SIX MONTHS FOLLOWUP STUDY

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Kalaimathi B

2017-03-01

Full Text Available BACKGROUND To compare and analyse the metabolic side effects of Risperidone and Haloperidol in newly diagnosed drug-naive schizophrenic disorder patients attending Govt. Stanley Medical College Hospital during initial 6 months of therapy. MATERIALS AND METHODS Newly diagnosed drug-naïve Schizophrenic Patients (n = 60 aged between 18 - 45 years are recruited and randomly allocated into Group A (Risperidone 4 - 6 mg daily and Group B (Haloperidol 5 - 10 mg daily after getting informed consent from the patient’s family members. Patients are followed up monthly for the occurrence of metabolic abnormalities like weight gain, rise in blood pressure, elevated fasting, post-prandial blood sugar level, dyslipidaemia for a period of 6 months. RESULTS Risperidone group showed the mean body weight increase from 64.40 to 69.27, SBP/DBP increase from 123.80/79 to 129.90/83.13; FBS/PPBS increase from 100.20/129.30 to 135.40/185.00; TC increase from 177.23 to 206.23; LDL from 124.30 to 158.30; HDL 48.83 to 50.07; TG 133.47 to 197.83: Haloperidol group showed the mean body weight increase from 64.07 to 68.48, SBP/DBP increase from 123.80/79.00 to 124.27/81.67; FBS/PPBS increase from 100.20/129.30 to 119.87/167.10; TC increase from 177.23 to 197.40; LDL from 119.77 to 139.00; HDL remained 48.83; TG 133.47 to 171.40. CONCLUSION This study showed that patients in both the groups had weight gain, rise in blood sugar, LDL cholesterol and Triglycerides level, but the rise was significant in patients on Risperidone when compared to those on Haloperidol during the 6-month followup.

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

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Zhao J

2014-02-01

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

Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.

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Moreno, Carmen; Merchán-Naranjo, Jessica; Alvarez, Mar; Baeza, Inmaculada; Alda, Jose A; Martínez-Cantarero, Carmen; Parellada, Mara; Sánchez, Bernardo; de la Serna, Elena; Giráldez, Marisa; Arango, Celso

2010-03-01

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p or = 1 obesity-related complication at follow-up. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

The Facts About Sexual (Dys)function in Schizophrenia: An Overview of Clinically Relevant Findings

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de Boer, Marrit K.; Castelein, Stynke; Wiersma, Durk; Schoevers, Robert A.; Knegtering, Henderikus

2015-01-01

A limited number of studies have evaluated sexual functioning in patients with schizophrenia. Most patients show an interest in sex that differs little from the general population. By contrast, psychiatric symptoms, institutionalization, and psychotropic medication contribute to frequently occurring impairments in sexual functioning. Women with schizophrenia have a better social outcome, longer lasting (sexual) relationships, and more offspring than men with schizophrenia. Still, in both sexes social and interpersonal impairments limit the development of stable sexual relationships. Although patients consider sexual problems to be highly relevant, patients and clinicians not easily discuss these spontaneously, leading to an underestimation of their prevalence and contributing to decreased adherence to treatment. Studies using structured interviews or questionnaires result in many more patients reporting sexual dysfunctions. Although sexual functioning can be impaired by different factors, the use of antipsychotic medication seems to be an important factor. A comparison of different antipsychotics showed high frequencies of sexual dysfunction for risperidone and classical antipsychotics, and lower frequencies for clozapine, olanzapine, quetiapine, and aripiprazole. Postsynaptic dopamine antagonism, prolactin elevation, and α1-receptor blockade may be the most relevant factors in the pathogenesis of antipsychotic-induced sexual dysfunction. Psychosocial strategies to treat antipsychotic-induced sexual dysfunction include psychoeducation and relationship counseling. Pharmacological strategies include lowering the dose or switching to a prolactin sparing antipsychotic. Also, the addition of a dopamine agonist, aripiprazole, or a phosphodiesterase-5 inhibitor has shown some promising results, but evidence is currently scarce. PMID:25721311

Pharmacokinetic-pharmacodynamic analysis of antipsychotics-induced extrapyramidal symptoms based on receptor occupancy theory incorporating endogenous dopamine release.

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Matsui-Sakata, Akiko; Ohtani, Hisakazu; Sawada, Yasufumi

2005-06-01

We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

[Lithium and anticonvulsants in the treatment of mania and in the prophylaxis of recurrences].

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Salvi, Virginio; Cat Berro, Alberto; Bechon, Elisa; Bogetto, Filippo; Maina, Giuseppe

2011-01-01

A mood stabilizer is an agent effective in treating both poles of the illness and at the same time being able to prevent both manic and depressive episodes in bipolar disorder. According to a broader definition, a mood stabilizer should be effective in decreasing the frequency or severity of any type of episode in bipolar disorder, without worsening the frequency or severity of episodes of opposite polarity. According to this, anticonvulsants and atypical antipsychotics can be considered as mood stabilizers. In this paper we review the use of lithium and other anticonvulsants that have proved effective in randomized controlled trials of the treatment of manic episodes and prevention of recurrences of bipolar disorder. Lithium and valproate are considered as first-line treatment options for acute mania while evidence regarding carbamazepine is insufficient to consider it as a first-line agent. Patients who fail to respond to first-line treatments may benefit from the adjunct of an atypical antipsychotic such as olanzapine, quetiapine, risperidone or aripiprazole. Lithium retains the strongest evidence of efficacy in the prophylaxis of manic episodes, lamotrigine in the prevention of depressive episodes. Valproate and carbamazepine have no indication for long-term treatment of bipolar disorder. Lithium can still be considered a gold standard in the treatment of manic episodes as well as in the prophylaxis of recurrences. Other anticonvulsants should be employed in particular situations, such as valproic acid in the treatment of mania and lamotrigine in the prevention of depressive recurrences.

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

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van der Zwaal, E.M.

2011-01-01

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

Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

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Singh, K P; Tripathi, Nidhi

2015-05-01

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier

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

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

2012-03-01

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

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

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

2017-07-15

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

Effects of co-treatment with mirtazapine and low doses of risperidone on immobility time in the forced swimming test in mice.

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Rogóż, Zofia

2010-01-01

The aim of the present study was to examine the effect of mirtazapine (MIR) and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J mice. Fluoxetine (FLU) was used as a reference drug. MIR (2.5, 5 and 10 mg/kg) and FLU (5 and 10 mg/kg), or risperidone in low doses (0.05 and 0.1 mg/kg) given alone did not change the immobility time of mice in the forced swimming test. Joint administration of MIR (5 and 10 mg/kg) or FLU (10 mg/kg) and risperidone (0.1 mg/kg) produced antidepressant-like activity in the forced swimming test. WAY100636 (a 5-HT(1A) receptor antagonist) inhibited, while yohimbine (an α(2)-adrenergic receptor antagonist) potentiated the antidepressant-like effect induced by co-administration of MIR and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined administration of antidepressants and risperidone failed to enhance the locomotor activity of mice. The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of MIR and that, among other mechanisms, 5-HT(1A)-, and α(2)-adrenergic receptors may play a role in this effect.

Comparative study on clinically latent aggressiveness inoutpatients with schizophrenia treated with classical antipsychotics and with risperidone

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Konstantinos Tsirigotis

2014-03-01

Full Text Available Objective: The use of neuroleptics causes not only regression of psychotic symptoms; neuroleptics affect also the patients’ mental state which is changing not only due to medications effects but also secondarily, as a result of regression of psychotic symptoms. The aim of this study was evaluation of subjectively felt “silent” (clinically latent hostility and aggressiveness in patients with paranoid schizophrenia treated with typical neuroleptics and risperidone. Material and methods: Sixty patients (30 patients treated with typical neuroleptics and the other 30 – with risperidone were examined with the Polish version of the following tools: Minnesota Multiphasic Personality Inventory (MMPI, Adjective Check List (ACL and Stern Activities Index (SAI. Results: The statistical analysis of the obtained results yielded many statistically significant differences within the intensity of hostility and aggressiveness in the examined groups. Conclusions: The results of this study showed a higher severity of psychological and personality problems in patients treated with typical neuroleptics, as compared to those treated with risperidone. In patients with paranoid schizophrenia treated with risperidone a lower severity of psychopathological, especially schizophrenic and paranoid, symptoms and lower hostility and aggressiveness were found. Considering that risperidone improves verbal functions, it can be assumed that this entails an improvement in the patients’ communicative competences, thereby improving also their interpersonal relationships. The results of this study indicate a higher susceptibility of people in this group to social influences and less hostility and negativity experienced by them.

How can lipid nanocarriers improve transdermal delivery of olanzapine?

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

2017-06-01

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

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

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Ye W

2012-01-01

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

Successful treatment with risperidone increases 5-HT 3A receptor gene expression in patients with paranoid schizophrenia - data from a prospective study.

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Chen, Hongying; Fan, Yong; Zhao, Lei; Hao, Yong; Zhou, Xiajun; Guan, Yangtai; Li, Zezhi

2017-09-01

The relationship between peripheral 5-HT3A receptor mRNA level and risperidone efficiency in paranoid schizophrenia patients is still unknown. A total 52 first-episode and drug-naive paranoid schizophrenia patients who were treated with risperidone and 53 matched healthy controls were enrolled. Patients were naturalistically followed up for 8 weeks. Positive and Negative Syndrome Scale (PANSS) was applied to assess symptom severity of the patients at baseline and at the end of 8th week. There was no difference in 5-HT3A receptor mRNA level between paranoid schizophrenia patients and healthy controls at baseline ( p  = .24). Among 47 patients who completed 8-week naturalistic follow-up, 37 were responders to risperidone treatment. 5-HT3A receptor mRNA level of paranoid schizophrenia patients did not change in overall patients after 8-week treatment with risperidone ( p  = .29). However, 5-HT3A receptor mRNA level in responders increased significantly ( p  = .04), but not in nonresponders ( p  = .81). Successful treatment with risperidone increases 5-HT3A receptor gene expression in patients with paranoid schizophrenia, indicating that 5-HT3A receptor may be involved in the mechanism of risperidone effect.

Acute anxiolytic effects of quetiapine during virtual reality exposure--a double-blind placebo-controlled trial in patients with specific phobia.

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Diemer, Julia; Domschke, Katharina; Mühlberger, Andreas; Winter, Bernward; Zavorotnyy, Maxim; Notzon, Swantje; Silling, Karen; Arolt, Volker; Zwanzger, Peter

2013-11-01

Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies. Increasing evidence points towards anxiety-reducing properties of atypical antipsychotics, particularly quetiapine. Therefore, we aimed to evaluate the putative acute anxiolytic effects of this compound, choosing the induction of acute anxiety in patients with specific phobia as a model for the evaluation of ad-hoc anxiolytic properties in a proof-of-concept approach. In a randomized, double-blind, placebo-controlled study, 58 patients with arachnophobia were treated with a single dose of quetiapine XR or placebo prior to a virtual reality spider challenge procedure. Treatment effects were monitored using rating scales for acute anxiety as well as measurements of heart rate and skin conductance. Overall, quetiapine showed significant anxiolytic effects compared to placebo. However, effects were not seen on the primary outcome measure (VAS Anxiety), but were limited to somatic anxiety symptoms. Additionally, a significant reduction of skin conductance was observed. Further exploratory analyses hint towards a mediating role of the (COMT) val158met genotype on treatment response. The present results thus suggest a possible suitability of quetiapine in the acute treatment of anxiety, particularly with regard to somatic symptoms. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: relationship with stearoyl-CoA desaturase activity.

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McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W

2011-06-01

Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6mg/kg/d), paliperidone (1.5, 3, and 6mg/kg/d), olanzapine (2.5, 5, and 10mg/kg/d), quetiapine (5, 10, and 20mg/kg/d), haloperidol (1, and 3mg/kg/d) or vehicle through their drinking water for 40days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, 'desaturation index') were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n=122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects. Copyright © 2011 Elsevier B.V. All rights reserved.

Non-medical use of psychoactive prescription drugs is associated with fatal poisoning.

Science.gov (United States)

Haukka, Jari; Kriikku, Pirkko; Mariottini, Claudia; Partonen, Timo; Ojanperä, Ilkka

2018-03-01

The aims of this study were to estimate the prevalence and predictors of non-medical substance use, and to assess the association between non-medical substance use and fatal poisoning or history of drug abuse in Finland. Retrospective cohort study of all medico-legally investigated death cases in Finland. The postmortem toxicology database was linked together with the register on reimbursed prescription medicines. All postmortem cases between 2011 and 2013 positive for one or more of the following drugs: oxycodone, fentanyl, tramadol, clonazepam, gabapentin, pregabalin, tizanidine, olanzapine, quetiapine, risperidone, alprazolam, zolpidem, mirtazapine and bupropion, n = 2974. Non-medical use of substance was the outcome variable. Predictors were the following: gender, residence at the time of death, place of death, blood alcohol concentration, age, drug abuse, number of prescriptions of any psychoactive drugs in last year and proportion of prescriptions issued by psychiatrist in last year. In 50.4% of the studied cases, at least one drug was detected without a prescription. Clonazepam, alprazolam and tramadol were the most prevalent non-medical findings in these cases (6.6, 6.1 and 5.6%, respectively). The risk of non-medical use of prescription drugs was especially high in cases with history of drug abuse (88.5%) and in fatal poisonings (71.0%). The proportion of non-medical use of the studied substances varied between 5.9% [95% confidence interval (CI) = 3.1-10.1%)] for risperidone and 55.7% for fentanyl (95% CI = 44.1-66.9%). Valid prescription for one or more of any psychoactive drug was associated with lower odds for non-medical use of the studied substances. Additionally, the higher the proportion of psychoactive drugs prescribed by a psychiatrist, the lower the probability of non-medical use. Non-prescribed psychoactive drugs are found commonly at postmortem in drug poisoning deaths in Finland, with history of drug abuse being a major contributing

Impact of pharmaceutical policy interventions on utilization of antipsychotic medicines in Finland and Portugal in times of economic recession: interrupted time series analyses.

Science.gov (United States)

Leopold, Christine; Zhang, Fang; Mantel-Teeuwisse, Aukje K; Vogler, Sabine; Valkova, Silvia; Ross-Degnan, Dennis; Wagner, Anita K

2014-07-25

To analyze the impacts of pharmaceutical sector policies implemented to contain country spending during the economic recession--a reference price system in Finland and a mix of policies including changes in reimbursement rates, a generic promotion campaign and discounts granted to the public payer in Portugal - on utilization of, as a proxy for access to, antipsychotic medicines. We obtained monthly IMS Health sales data in standard units of antipsychotic medicines in Portugal and Finland for the period January 2007 to December 2011. We used an interrupted time series design to estimate changes in overall use and generic market shares by comparing pre-policy and post-policy levels and trends. Both countries' policy approaches were associated with slight, likely unintended, decreases in overall use of antipsychotic medicines and with increases in generic market shares of major antipsychotic products. In Finland, quetiapine and risperidone generic market shares increased substantially (estimates one year post-policy compared to before, quetiapine: 6.80% [3.92%, 9.68%]; risperidone: 11.13% [6.79%, 15.48%]. The policy interventions in Portugal resulted in a substantially increased generic market share for amisulpride (estimate one year post-policy compared to before: 22.95% [21.01%, 24.90%]; generic risperidone already dominated the market prior to the policy interventions. Different policy approaches to contain pharmaceutical expenditures in times of the economic recession in Finland and Portugal had intended--increased use of generics--and likely unintended--slightly decreased overall sales, possibly consistent with decreased access to needed medicines--impacts. These findings highlight the importance of monitoring and evaluating the effects of pharmaceutical policy interventions on use of medicines and health outcomes.

A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

Directory of Open Access Journals (Sweden)

Galynker Igor I

2009-05-01

Full Text Available Abstract Background Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks. Methods Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS, the Hamilton Anxiety Scale (Ham-A, the Hamilton Depression Rating Scale (Ham-D, the Sheehan Panic Anxiety Scale-Patient (SPAS-P, and the Clinical Global Impression scale (CGI. Results All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine. Conclusion We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component. Trial Registration ClinicalTrials.gov Identifier: NCT100457106

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

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Zhang, Chen; Li, Ming

2011-01-01

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

Olanzapine-Induced 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.

Synthesis of 11-14C-quetiapine, 11-14C-isoclotiapine and 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine[10-14C

International Nuclear Information System (INIS)

Naghi Saadatjoo; Mohsen Javaheri; Nuclear Science and Technology Research Institute, Tehran; Nader Saemian; Mohsen Amini

2016-01-01

Quetiapine is one of the most widely used antipsychotic drug which acts as an antagonist for multiple neurotransmitter receptor sites. 2-[2-(4-(Dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)ethoxy]ethanol (quetiapine) labeled with carbon-14 in 11-position has been synthesized as part of a 5-step sequence from anthranilic acid-[carboxy- 14 C]. We have presented a convenient synthetic pathway for labeling of quetiapine with carbon-14 by using one-pot procedures from a key thiazepin-11(10H)-one-[11- 14 C] by good radiochemical yield. And also isoclotiapine[11- 14 C], and 10-(4-methylpiperazin-1-yl)pyrido[4,3-b][1,4]benzothiazepine[10- 14 C], synthesized according to this route. (author)

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

Science.gov (United States)

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

2016-08-01

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

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

Science.gov (United States)

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

2011-05-01

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

Preparation and Biological Evaluation of Radioiodinated Risperidone and Lamotrigine as Models for Brain Imaging

International Nuclear Information System (INIS)

Saddar, E.; El-Tawoosy, M.; Motaleb, H.A.

2014-01-01

Brain imaging technology is becoming an important tool in both research and clinical care. Due to the sensitivity of brain imaging technology, neuroscientists are able to visualize brain structure and function from the level of individual molecules to the whole brain, recognize and diagnose neurological disorders, develop new strategies for treatment and determine how therapies work. The study aimed to take advantages from drugs that are able to cross the brain barrier for the development of potential radiopharmaceuticals for non-invasive brain imaging. Risperidone and lamotrigine were successfully labeled with 125 I via direct electrophilic substitution reaction at 80 degree C. The reaction parameters affecting the preparation process were studied. 125 I-risperidone and 125 I-lamotrigine gave maximum labeling yield of 89 % ± 3.75 and 97.5 % ± 1.0 %, respectively and their stability were up to 6 and 24 h, respectively. Biodistribution studies showed that maximum uptake of 125 I-risperidone and 125 I-lamotrigine in the brain of mice were 4.27 % ± 0.38 and 2.45 % ± 0.18 of the injected activity/g tissue organ, at 10

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

OpenAIRE

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

2013-01-01

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

Effect of co-treatment with fluoxetine or mirtazapine and risperidone on the active behaviors and plasma corticosterone concentration in rats subjected to the forced swim test.

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Rogóż, Zofia; Kabziński, Marcin; Sadaj, Witold; Rachwalska, Paulina; Gądek-Michalska, Anna

2012-01-01

Several clinical reports have postulated a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants in treatment-resistant depression. The present study aimed to examine the effect of treatment with fluoxetine or mirtazapine, given separately or jointly with risperidone, on active behavior and plasma corticosterone level in male Wistar rats subjected to the forced swim test (FST). The obtained results showed that fluoxetine (5 mg/kg), mirtazapine (5 and 10 mg/kg) or risperidone (0.05 and 0.1 mg/kg) did not change the active behavior of rats in the FST. However, co-treatment with fluoxetine (10 mg/kg) and risperidone (0.1 mg/kg) induced an antidepressant-like effect in that test because it significantly increased the swimming time and decreased the immobility time, while combined treatment with mirtazapine at 5 and 10 mg/kg and risperidone at 0.05 and 0.1 mg/kg evoked a significant increase in the swimming time and also climbing, and decreased the immobility time. WAY 100635 (a 5-HT(1A) receptor antagonist) at a dose of 0.1 mg/kg inhibited the antidepressant-like effect induced by co-administration of fluoxetine or mirtazapine and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined treatment with fluoxetine or mirtazapine and risperidone failed to enhance the exploratory activity of rats. Co-treatment with fluoxetine or mirtazapine and risperidone did not reduce the stress-induced increase in plasma corticosterone concentration in animals subjected to the FST. The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of fluoxetine and mirtazapine in the FST (but does not normalize the stress-induced increase in corticosterone level in these rats), and that 5-HT(1A) receptors may play some role in these effects.

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

DEFF Research Database (Denmark)

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

2009-01-01

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

Effect of switching to risperidone after unsuccessful treatment with aripiprazole on plasma monoamine metabolites level in the treatment of acute schizophrenia.

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Miura, Itaru; Takeuchi, Satoshi; Katsumi, Akihiko; Kanno, Keiko; Watanabe, Kenya; Mashiko, Hirobumi; Niwa, Shin-Ichi

2012-09-01

In the treatment of acute schizophrenia, risperidone and aripiprazole are both placed the first line antipsychotics. These two antipsychotics have different pharmacological effects. We investigated the effects of risperidone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol after unsuccessful aripiprazole treatment in acute schizophrenia. Ten Japanese patients with acute schizophrenia were enrolled to this study. Plasma levels of monoamine metabolites were analyzed with high-performance liquid chromatography with electrochemical detection. Risperidone improved the symptoms and 4 of 10 patients were responders. Risperidone showed a tendency to decrease plasma HVA (pHVA) levels in responders (p = 0.068), but not in non-responders (p = 1.0). At baseline, pHVA levels of responders were significantly higher than that of non-responders (p = 0.033). A trend for negative correlation was found between pHVA at baseline and the changes in Positive and Negative Syndrome Scale-Total (p = 0.061, r = -0.61). Our results suggest that high pHVA level before switching may predict good response to the second line antipsychotics after unsuccessful first antipsychotic treatment. If aripiprazole is not effective in acute schizophrenia, switching to risperidone may be effective and reasonable strategy for improving symptoms. Copyright © 2012 John Wiley & Sons, Ltd.

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.

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

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

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

2005-07-01

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

Impact of haloperidol and quetiapine on the expression of genes encoding antioxidant enzymes in human neuroblastoma SH-SY5Y cells.

Science.gov (United States)

Schmidt, Andreas Johannes; Hemmeter, Ulrich Michael; Krieg, Jürgen-Christian; Vedder, Helmut; Heiser, Philip

2009-05-01

Antipsychotics are known to alter antioxidant activities in vivo. Therefore, the aim of the present study was to examine in the human neuroblastoma SH-SY5Y cell line the impact of a typical (haloperidol) and an atypical (quetiapine) antipsychotic on the expression of genes encoding the key enzymes of the antioxidant metabolism (Cu, Zn superoxide dismutase; Mn superoxide dismutase; glutathione peroxidase; catalase) and enzymes of the glutathione metabolism (gamma-glutamyl cysteine synthetase, glutathione-S-transferase, gamma-glutamyltranspeptidase, glutathione reductase). The cells were incubated for 24h with 0.3, 3, 30 and 300microM haloperidol and quetiapine, respectively; mRNA levels were measured by polymerase chain reaction. In the present study, we observed mostly significant decreases of mRNA contents. With respect to the key pathways, we detected mainly effects on the mRNA levels of the hydrogen peroxide detoxifying enzymes. Among the enzymes of the glutathione metabolism, glutathione-S-transferase- and gamma-glutamyltranspeptidase-mRNA levels showed the most prominent effects. Taken together, our results demonstrate a significantly reduced expression of genes encoding for antioxidant enzymes after treatment with the antipsychotics, haloperidol and quetiapine.

Dopamine transporter density assessed with [{sup 123}]IPT SPECT before and after risperidone treatment in children with tourette's disorder

Energy Technology Data Exchange (ETDEWEB)

Ryu, Young Hoon; Kim, Tae Hoon; Ryu, Won Gee [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)] [and others

2004-02-01

Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled N-(3-iodopropen-2-yl)-2{beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane ([{sup 123}I]IPT) single photon emission computed tomography (SPECT). [{sup 123I}]IPT SPECT imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of [{sup 123}I]IPT. Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

Quetiapine: recent developments in preclinical research

Directory of Open Access Journals (Sweden)

Marco Orsetti

2010-03-01

Full Text Available Quetiapine (QTP is an atypical antipsychotic labelled for the treatment of patients with schizophrenia, bipolar mania and bipolar depression. Nevertheless, QTP has been tried across multiple diagnosis categories and seems to be used, among other atypical antipsychotics, in clinical practice for an expanding range of disorders such as major depression, substance abuse disorders, anxiety disorders, and borderline personality disorders. The present review focuses on papers which investigated the molecular mechanism(s of QTP antidepressant effect. In particular, preclinical studies performed by coupling the chronic mild stress, an animal model of human depression with Affymetrix microarray technology, revealed that chronic QTP administration prevented the stress-induced up- or down-regulation of 42 genes involved in the central nervous system development or having a crucial role for viability of neural cells, like regulation of signal transduction, inorganic ion transport, membrane organisation, and neurite morphogenesis. Among these, Ptgs2, Hes5, Plcb1, Senp2, Gad1, and Marcks are presumably the effectors of the QTP clinical efficacy.

Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

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Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

2012-01-01

Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

Achieving symptomatic remission in out-patients with schizophrenia--a naturalistic study with quetiapine.

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Wobrock, T; Köhler, J; Klein, P; Falkai, P

2009-08-01

Symptomatic remission was defined as a score of mild or less on each of eight key schizophrenia symptoms on the Positive and Negative Syndrome Scale (PANSS-8). To evaluate the symptomatic remission criterion in clinical practice and to determine predictors for achieving symptomatic remission, a 12-week non-interventional study (NIS) with quetiapine was conducted in Germany. For the comparison of patients with and without symptomatic remission, sociodemographic and clinical variables of 693 patients were analyzed by logistic regression for their predictive value to achieve remission. Four hundred and four patients (58.3%) achieved symptomatic remission after 12 weeks' treatment with quetiapine. Remission was significantly predicted by a low degree of PANSS-8 total score, PANSS single items blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), mannerism and posturing (G5), and low disease severity (CGI-S) at baseline. Predictors of non-remission were older age, diagnosis of schizophrenic residuum, multiple previous episodes, longer duration of current episode, presence of concomitant diseases, and alcohol abuse. This study demonstrated that the majority of schizophrenia out-patients achieved symptomatic remission after 12 weeks treatment and confirms the importance of managing negative symptoms in order to achieve disease remission.

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

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

2010-12-08

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

The influence of risperidone on attentional functions in children and adolescents with attention-deficit/hyperactivity disorder and co-morbid disruptive behavior disorder.

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Günther, Thomas; Herpertz-Dahlmann, Beate; Jolles, Jellemer; Konrad, Kerstin

2006-12-01

This study aims to examine the influence of risperidone on various attentional functions, including intensity and selectivity aspects of attention plus inhibitory control in children with attention deficit/hyperactivity disorder (ADHD) with co-morbid Disruptive Behavior Disorders (DBD) and normal IQ. Children with ADHD and DBD, aged 8-15 years, were treated with risperidone (mean daily dose: 1.5 mg; n = 23) and examined with three attentional paradigms before and after a 4-week treatment period. Age- and IQ-matched normal controls (n = 23) were also tested without medication on the same two occasions. No influence of the medication could be detected for any neuropsychological variable, neither as a positive enhancement nor as adverse side effects. However, clinical symptoms of ADHD and DBD assessed on the IOWA Conners Scale significantly improved after the 4-week treatment period. Divergent behavioral and cognitive effects of risperidone on ADHD symptoms were observed, with a significant reduction in behavioral symptoms, whereas no positive treatment effects were found on laboratory tasks of impulsivity. Thus, the cognitive effects of risperidone seem to differ from the cognitive effects of stimulant treatments in children with ADHD + DBD. However, no negative impact of risperidone was observed on attentional functions either, i.e., there was no slowing of cognitive speed.

Different mechanisms of risperidone result in improved interpersonal trust, social engagement and cooperative behavior in patients with schizophrenia compared to trifluoperazine.

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Tse, Wai Shing; Wong, Ann Siu Wah; Chan, Fu; Pang, Alfred Hin Tat; Bond, Alyson Jane; Chan, Chau Kiu Raymond

2016-05-01

Atypical antipsychotic treatment (e.g. risperidone) has been found to improve social functioning more than standard antipsychotic treatment. However, it is unclear which specific social behaviors are implicated in this improvement. The current study employed an interactive puzzle game to examine how social behaviors contribute to the improvement of social functioning by comparing patients receiving risperidone with those receiving trifluoperazine. Scores on the Positive and Negative Syndrome Scale, executive functioning, and social functioning were obtained from 24 patients with schizophrenia receiving either risperidone (n = 12) or trifluoperazine (n = 12), before their social behavior was measured in the interactive Tangrams Game. Immediately after the Tangrams Game, participants filled in two questionnaires measuring their interpersonal trust and rejection toward their game partner. Patients receiving risperidone showed more social engagement, cooperative behavior and interpersonal trust toward their game partners than those receiving trifluoperazine. Additional multivariate analysis of variance revealed that lower affiliative behavior was a function of positive symptoms; interpersonal trust had an impact on social engagement but executive functioning did not explain lower interpersonal trust or social disengagement. Improvement of social competence by risperidone might be related to the enhancement of both social behaviors and interpersonal trust as well as better symptom resolution. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Clozapine usage increases the incidence of pneumonia compared with risperidone and the general population: a retrospective comparison of clozapine, risperidone, and the general population in a single hospital over 25 months.

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Stoecker, Zachary R; George, Wales T; O'Brien, Jeffrey B; Jancik, Jon; Colon, Eduardo; Rasimas, Joseph J

2017-05-01

The aim of this study was to determine whether the incidence of pneumonia in patients taking clozapine was more frequent compared with those taking risperidone or no atypical antipsychotics at all before admission to a tertiary care medical center. This was a retrospective, case-matched study of 465 general medicine patients over a 25 month period from 1 July 2010 to 31 July 2012. Detailed electronic medical records were analyzed to explore the association between the use of two atypical antipsychotics and incidence of pneumonia. Of the 155 patients in the clozapine group, 54 (34.8%) had documented pneumonia compared with 22 (14.2%) in the risperidone group and 18 (11.6%) in the general population group. Clozapine, when compared with the untreated general population, was associated with an increased risk of pneumonia (odds ratio=4.07; 95% confidence interval=2.25-7.36). There was, however, no significant increase in the risk of pneumonia associated with the use of risperidone (odds ratio=1.26; 95% confidence interval=0.65-2.45). Clozapine use is associated with increased risk of pneumonia that may be related to immunologic factors or side effects of sedation and drooling that make aspiration more likely, although causative mechanisms require further investigation. These findings suggest that providers should use added caution in choosing candidates for clozapine therapy.

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

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

2016-01-01

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

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

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

2011-06-01

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

Preparation of magnetic ODS-PAN thin-films for microextraction of quetiapine and clozapine in plasma and urine samples followed by HPLC-UV detection.

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Li, Dan; Zou, Juan; Cai, Pei-Shan; Xiong, Chao-Mei; Ruan, Jin-Lan

2016-06-05

In this study, conventional thin-film microextraction (TFME) was endowed with magnetic by introducing superparamagnetic SiO2@Fe3O4 nanoparticles in thin-films. Novel magnetic octadecylsilane (ODS)-polyacrylonitrile (PAN) thin-films were prepared by spraying, and used for the microextraction of quetiapine and clozapine in plasma and urine samples, followed by the detection of HPLC-UV. The influencing factors on the extraction efficiency of magnetic ODS-PAN TFME, including pH, extraction time, desorption solvent, desorption time, and ion strength were investigated systematically. Under the optimal conditions, both analytes showed good linearity over ranges of 0.070-9.000μgmL(-1) and 0.012-9.000μgmL(-1) in plasma and urine samples, respectively, with correlation coefficients (R(2)) above 0.9990. Limits of detection (LODs) for quetiapine in plasma and urine samples were 0.013 and 0.003μgmL(-1), respectively. LODs for clozapine in plasma and urine samples were 0.015 and 0.003μgmL(-1), respectively. The relative standard deviations (RSDs) for quetiapine and clozapine were less than 9.23%. After the validation, the protocol was successfully applied for the determination of quetiapine and clozapine in patients' plasma and urine samples with satisfactory recoveries between 99-110%. The proposed magnetic ODS-PAN TFME was very simple, fast and easy to handle. It showed high potential as a powerful pretreatment technology for routine therapeutic drug monitoring (TDM) in plasma and urine samples. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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Ye W

2011-12-01

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

Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology.

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Bhidayasiri, Roongroj; Fahn, Stanley; Weiner, William J; Gronseth, Gary S; Sullivan, Kelly L; Zesiewicz, Theresa A

2013-07-30

To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966-2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).

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.

Antipsychotics and amotivation.

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Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

2015-05-01

Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.

The association between weight change and symptom reduction in the CATIE schizophrenia trial.

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Hermes, Eric; Nasrallah, Henry; Davis, Vicki; Meyer, Jonathan; McEvoy, Joseph; Goff, Donald; Davis, Sonia; Stroup, T Scott; Swartz, Marvin; Lieberman, Jeffrey; Rosenheck, Robert

2011-05-01

Weight gain and changes in metabolic indicators associated with some antipsychotics may be related to symptom improvement and thus an unavoidable correlate of clinical benefit. Data from the CATIE schizophrenia trial comparing the effectiveness of perphenazine, olanzapine, risperidone, quetiapine and ziprasidone in a randomized, double-blind, trial over 18 months were used to evaluate the relationship between percent change in body mass index (BMI) and change in total serum cholesterol and triglycerides with the Positive and Negative Syndrome Scale (PANSS) score. Analysis of covariance for observations at 3 months and a mixed effects model for all observations up to 18 months adjusted for potentially confounding variables were used to examine these associations. In both models, there was a significant association (p = 0.001) between change in PANSS total score and percent change in BMI, equating to a 0.28 and 0.21 point decrease in PANSS total score (range 30-210) per 1% increase in BMI respectively. Change in BMI accounted for 3% or less of variance for change in PANSS scores. There was no evidence that the association of symptoms and weight gain differed across medications in spite of substantial differences in weight gain and other metabolic measures. Neither total serum cholesterol nor triglyceride levels displayed a significant association with change in PANSS. The magnitude of the relationship between change in BMI and PANSS was too small to be clinically important, indicating that switching medications to one with less metabolic risk is unlikely to result in meaningful loss of clinical benefit. Copyright © 2011 Elsevier B.V. All rights reserved.

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

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McDougle, Christopher J; Scahill, Lawrence; Aman, Michael G; McCracken, James T; Tierney, Elaine; Davies, Mark; Arnold, L Eugene; Posey, David J; Martin, Andrès; Ghuman, Jaswinder K; Shah, Bhavik; Chuang, Shirley Z; Swiezy, Naomi B; Gonzalez, Nilda M; Hollway, Jill; Koenig, Kathleen; McGough, James J; Ritz, Louise; Vitiello, Benedetto

2005-06-01

Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

Memantine as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

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Ghaleiha, Ali; Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Shahei, Maryam; Tabrizi, Mina; Hajiaghaee, Reza; Hassanzadeh, Elmira; Akhondzadeh, Shahin

2013-05-01

Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propose both hyper-and hypoglutamatergic ideologies for autism. The objective of this study was to assess the effects of memantine plus risperidone in the treatment of children with autism. Children with autism were randomly allocated to risperidone plus memantine or placebo plus risperidone for a 10-wk, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 3 mg/d and memantine was titrated to 20 mg/d. Children were assessed at baseline and after 2, 4, 6, 8 and 10 wk of starting medication protocol. The primary outcome measure was the irritability subscale of Aberrant Behavior Checklist-Community (ABC-C). Difference between the two treatment arms was significant as the group that received memantine had greater reduction in ABC-C subscale scores for irritability, stereotypic behaviour and hyperactivity. Eight side-effects were observed over the trial, out of the 25 side-effects that the checklist included. The difference between the two groups in the frequency of side-effects was not significant. The present study suggests that memantine may be a potential adjunctive treatment strategy for autism and it was generally well tolerated. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N10; www.irct.ir).

The use of olanzapine in Huntington disease accompanied by psychotic symptoms

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Cafer Alhan

2014-06-01

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

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

NARCIS (Netherlands)

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

2007-01-01

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

Quetiapine Induced Acute Dystonia in a patient with History of severe Head Injury

OpenAIRE

Robert G. Bota; Joanne W. Witkowski

2010-01-01

A patient with a history of severe head injury 10 years ago regained ability to walk after years of being bound to a wheelchair. During the last psychiatric hospitalization, quetiapine was increased to therapeutic dose using a normal titration. As a result the patient developed dystonia of multiple muscle groups requiring 4 days of hospitalization for remittance of symptoms. In this paper, we take a close look at the literature concerning extrapiramidal symptoms (EPS) in this context, and we ...

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

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

2015-01-01

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

Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

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Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Modabbernia, Amirhossein; Ashrafi, Mandana; Hassanzadeh, Elmira; Forghani, Saeedeh; Akhondzadeh, Shahin

2013-01-01

Autism is associated with activation of the inflammatory response system. This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autism In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C. Significant time × treatment interaction was observed for Irritability (F (1.658, 63.021) = 13.580, P autism. (Registration, www.irct.ir ; IRCT138711091556N2).

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

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

2016-04-01

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

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

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mozhgan Jariani

2009-03-01

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

Quetiapine for the continuation treatment of bipolar depression : naturalistic prospective case series from the Stanley Bipolar Treatment Network

NARCIS (Netherlands)

Suppes, Trisha; Kelly, Dorothy I.; Keck, Paul E.; McElroy, Susan L.; Altshuler, Lori L.; Mintz, Jim; Frye, Mark A.; Nolen, Willem A.; Luckenbaugh, David A.; Post, Robert M.; Leverich, Gabriele S.; Kupka, Ralph W.; Grunze, Heinz

Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic. Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression, but there are limited data for its use in continuation treatment. This study

No change of dopamine transporter density in basal ganglia after risperidone treatment in drug-naive children with Tourette's disorder

International Nuclear Information System (INIS)

Ryu, W. K.; Ryu, Y. H.; Yoon, M. J.; Chun, K. A.; Lee, J. D.; Zee, D. Y.; Choi, T. H.

2003-01-01

Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the DAT densities between drug-naive children with TD and normal children investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using lodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane(I-123 IPT) single photon emission computed tomography (SPECT). I-123 IPT SPECT imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in eight drug-naive children with TD. Eight normal children also underwent SPECT imaging 2 hours after an intravenous administration of I-123 IPT and carried out both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. The drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with riperidone in children with TD was not found, although tic symptoms were significantly improved with risperidone. These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system

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

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

2002-08-01

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

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

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Vance L Albaugh

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

Bioequivalence study of a generic Risperidone (Iperdal® in healthy Thai male volunteers

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Werawath Mahatthanatrakul

2008-05-01

Full Text Available The objective of this study was to compare the rate and extent of absorption of a generic risperidone (Iperdal® with a reference formulation (Risperdal® when given orally. The study was an open label, randomized, two-period, two-sequence,single dose cross-over design with a 2 weeks washout period in 16 healthy Thai male volunteers. Single oral dose of two 2-mg tablets of risperidone were administered and serial blood samples were collected from the antecubital vein before and at0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 24 and 48 hours post dose. Risperidone plasma concentrations were assayed using a validated High Performance Liquid Chromatographic (HPLC-UV method modified from Avenosoet al. (2000. Pharamcokinetic parameters i.e. Cmax, AUC0à48 and Tmax were analyzed by noncompartment analysis. Variations of the data were analyzed by “Two Way Analysis of Variance” (ANOVA. Statistics were tested as stated in USP 28 guidelinefor bioequivalence study. The maximum concentration (Cmax, ng/ml of risperidone for the innovator and the generic product were 31.11±17.24 (range 5.64-56.78 and 32.58±19.77 (range 5.29-84.56 ng/ml, respectively. The area under theplasma concentration-time curve (AUC0®48 of the innovator and the generic product were 160.64±152.89 (range 18.57- 550.32 and 144.03±127.37 (range 16.27-456.0 ng.hr/ml, respectively. The time to maximum concentration (Tmax of theinnovator and the generic product were 0.97±0.41(range 0.5-2 and 1.02±0.32 (range 0.5-1.5 hr, respectively. The 90% confidence interval of the ratio of the ln-transformed of Cmax and AUC0à48 of both preparations were 89.39-112.99% and80.02-107.28% respectively which were within the acceptance range of 80.00-125.00%. Therefore, it can be concluded that both preparations used in this study are bioequivalent in terms of both the rate and extent of absorption.

Risperidone in Children and Adolescents with Conduct Disorder: A Single-Center, Open-Label Study

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Ercan, Eyüp Sabri; Kutlu, Ayşe; Çıkoğlu, Sibel; Veznedaroğlu, Baybars; Erermiş, Serpil; Varan, Azmi

2003-01-01

Background: Risperidone is one of the most commonly used atypical antipsychotic drugs in the treatment of children and adolescents. However, the data about its use in children and adolescents with conduct disorder (CD) are limited.

A comparison of risperidone and haloperidol for the risk of ischemic stroke in the elderly: a propensity score-matched cohort analysis.

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Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo

2015-08-01

With an increase in antipsychotic use in the elderly, the safety profile of antipsychotics has been emphasized. Strong concerns have been raised about whether the risk of ischemic stroke differs between risperidone and haloperidol. This study compared the risk of ischemic stroke between elderly patients taking risperidone and haloperidol. We conducted a retrospective cohort study using the Korea Health Insurance Review and Assessment Service database, applying a propensity-matched analysis. The cohort consisted of elderly patients who were newly prescribed haloperidol or risperidone between January 1, 2006 and December 31, 2009. Patients with prior cerebrovascular diseases (ICD-10, I60-I69), transient ischemic attack (ICD-10, G45), or cerebral tumors (ICD-10, C31) during 365 days prior to the initiation date were excluded. The study subjects were selected by propensity score matching. The outcome was defined as the first hospitalization for ischemic stroke (ICD-10, I63). Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for ischemic stroke with haloperidol compared with risperidone use. A total of 14,103 patients were included in the propensity-matched cohort for each drug. Overall, the incidence rate was higher for haloperidol users compared to the risperidone users (6.43 per 1000 person-years vs. 2.88 per 1000 person-years). A substantially increased risk was observed in haloperidol users (adjusted HR = 2.02, 95% CI, 1.12-3.62). The evidence showed that haloperidol should be prescribed in the elderly with caution. © The Author(s) 2015.

The effect of combined treatment with risperidone and antidepressants on the MK-801-induced deficits in the social interaction test in rats.

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Kamińska, Katarzyna; Rogóż, Zofia

2015-12-01

Several clinical reports have suggested that augmentation of atypical antipsychotics' activity by antidepressants may efficiently improve the treatment of negative and some cognitive symptoms of schizophrenia. The aim of the present study was to investigate the effect of antidepressant mirtazapine or escitalopram and risperidone (an atypical antipsychotic), given separately or jointly, on the MK-801-induced deficits in the social interaction test in rats. Antidepressants and risperidone were given 60 and 30 min before the test, respectively. The social interaction of male Wistar rats was measured for 10 min, starting 4 h after MK-801 (0.1 mg/kg) administration. In the social interaction test, MK-801-induced deficits in the parameters studied, i.e. the number of episodes and the time of interactions. Risperidone at a higher dose (0.1 mg/kg) reversed that effect. Co-treatment with an ineffective dose of risperidone (0.01 mg/kg) and mirtazapine (2.5 or 5 mg/kg) or escitalopram only at a dose of 5 mg/kg (but not 2.5 and 10 mg/kg) abolished the deficits evoked by MK-801. The obtained results suggest that especially mirtazapine, and to a smaller degree escitalopram may enhance the antipsychotic-like effect of risperidone in the animal test modeling some negative symptoms of schizophrenia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Risperidone-induced type 2 diabetes presenting with diabetic ketoacidosis

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Clarissa Ern Hui Fang

2018-05-01

Full Text Available A 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM. On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2. Dipstick urinalysis showed ketonuria and glycosuria. Blood results were consistent with diabetic ketoacidosis (DKA, with hyperosmolar state. We initiated our DKA protocol, with intravenous insulin, fluids and potassium, and we discontinued risperidone. His obesity, family history of T2DM, acanthosis nigricans and hyperosmolar state prompted consideration of T2DM presenting with ‘ketosis-prone diabetes’ (KPD rather than T1DM. Antibody markers of beta-cell autoimmunity were subsequently negative. Four weeks later, he had modified his diet and lost weight, and his metabolic parameters had normalised. We reduced his total daily insulin dose from 35 to 18 units and introduced metformin. We stopped insulin completely by week 7. At 6 months, his glucometer readings and glycated haemoglobin (HbA1c level had normalised.

The effects of antipsychotics on weight gain, weight-related hormones and homocysteine in children and adolescents: a 1-year follow-up study.

Science.gov (United States)

Baeza, Inmaculada; Vigo, Laura; de la Serna, Elena; Calvo-Escalona, Rosa; Merchán-Naranjo, Jessica; Rodríguez-Latorre, Pamela; Arango, Celso; Castro-Fornieles, Josefina

2017-01-01

To analyze weight gain, metabolic hormones, and homocysteine (Hcys) levels in children and adolescents on antipsychotics (AP) during a year-long follow-up. 117 patients, AP-naïve or quasi-naïve (less than 30 days on AP), were included. Weight, body mass index (BMI), BMI z-score (z-BMI), and levels of leptin, insulin, insulin resistance (HOMA-IR), adiponectin, ghrelin, thyroid stimulating hormone (TSH), free thyroxine (FT4), and Hcys were measured at baseline, and at 3, 6, and 12 months, while patients remained on the same AP. Patients (mean age: 14.4 ± 3 years; 64.1 % male) were on risperidone (N = 84), olanzapine (N = 20) or quetiapine (N = 13) from baseline up to 1-year follow-up and significantly increased weight (5.8 ± 4.3 kg at 3-month, 8.1 ± 6.1 kg at 6-month, and 11.6 ± 7.0 kg at 1 year), BMI, and z-BMI. Leptin levels significantly increased from baseline to 3 and 6 months, as did TSH levels from baseline to 3 months, while FT4 levels decreased from baseline to 3 and 6 months. Patients with BMI >85th percentile at baseline (N = 16) significantly increased weight, BMI, and z-BMI, more than patients with normal BMI over time. Higher baseline levels of insulin, HOMA-IR, and leptin were associated with increased weight/BMI during follow-up, while higher baseline levels of FT4, adiponectin, and ghrelin were associated with lower weight/BMI during follow-up. All AP were associated with increased weight and BMI/z-BMI in all of the assessments; however, at 1-year assessment, this increase was significantly higher for patients on quetiapine. Both higher baseline levels of insulin, HOMA-IR, and leptin, as well as being overweight/obese at baseline were associated with increased weight/BMI during 1-year follow-up in children and adolescents on AP. Awareness of weight-related parameters in this population may help inform decisions regarding AP prescriptions.

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

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

2011-04-01

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

Effects of risperidone on core symptoms of autistic disorder based on childhood autism rating scale: an open label study.

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Ghaeli, Padideh; Nikvarz, Naemeh; Alaghband-Rad, Javad; Alimadadi, Abbas; Tehrani-Doost, Mehdi

2014-01-01

The aim of the present study was to evaluate the effect of risperidone in patients afflicted by autistic disorder especially with regards to its three core symptoms, including "relating to others", "communication skills", and "stereotyped behaviors" based on Childhood Autism Rating Scale (CARS). An 8-week open-label study of risperidone for treatment of autistic disorder in children 4-17 years old was designed. Risperidone dose titration was as follow: 0.02 mg/kg/day at the first week, 0.04 mg/kg/day at the second week, and 0.06 mg/kg/day at the third week and thereafter. The outcome measures were scores obtained by CARS, Aberrant Behavior Checklist (ABC), and Clinical Global Impression-Improvement (CGI-I) scale. Fifteen patients completed this study. After 8 weeks, CARS total score decreased significantly, (P=0.001). At the end of the study, social interactions and verbal communication skills of the patients were significantly improved (Pautistic disorder.

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

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Giordano F. Cittolin-Santos

2017-01-01

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

Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care: A Randomized Clinical Trial.

Science.gov (United States)

Agar, Meera R; Lawlor, Peter G; Quinn, Stephen; Draper, Brian; Caplan, Gideon A; Rowett, Debra; Sanderson, Christine; Hardy, Janet; Le, Brian; Eckermann, Simon; McCaffrey, Nicola; Devilee, Linda; Fazekas, Belinda; Hill, Mark; Currow, David C

2017-01-01

Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care. To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival. Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both

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

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

2015-05-01

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

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

Science.gov (United States)

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

2017-07-01

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

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

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Wei Cheng

2016-12-01

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

Sammenligning af sertindols og olanzapins effekt på kognition

DEFF Research Database (Denmark)

Nielsen, René Ernst

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

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Kokalj, Anja; Rijavec, Nikolina; Tavčar, Rok

2016-06-22

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

Gabapentin pharmacotherapy for antipsychotic-induced akathisia: single-patient experiment and case report.

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Sullivan, Maria A; Wilbur, Robert

2014-04-01

This clinical study reports upon the efficacy of gabapentin (Neurontin) for treating severe akathisia (3 on the Barnes Akathisia Rating Scale) in two patients receiving quetiapine (Seroquel), one of whom also received olanzapine (Zyprexa) for a short period. The first patient participated in an open-label experiment in which the bedtime dose of gabapentin was discontinued three times at intervals 1 week apart, resulting in severe akathisia which was quickly terminated by taking his usual 1200 mg gabapentin dose. This patient was also taking high doses of two benzodiazepines and a beta blocker, without therapeutic effect upon his akathisia; only gabapentin was efficacious. The second case is a report of a woman taking a high dose of quetiapine for anxiety who experienced severe akathisia which was relieved by taking 1200 mg of gabapentin. Possible mechanisms of action of gabapentin are discussed. Particular attention is drawn to the difference between neuroleptic-induced akathisia and the neurological condition of restless legs syndrome.

Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

DEFF Research Database (Denmark)

Ebdrup, Bjørn H; Skimminge, Arnold; Rasmussen, Hans

2011-01-01

. Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement of negative symptoms. Progressive regional volume loss in quetiapine-treated, first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying...... scarcely been investigated. Here we investigated structural brain changes in antipsychotic-naive, first-episode schizophrenia patients after 6 months treatment with the SGA, quetiapine. We have recently reported on baseline volume reductions in the caudate nucleus and hippocampus. Baseline and follow-up T1......-weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations...

Clinical and pharmacokinetic evaluation of risperidone for the management of autism spectrum disorder

NARCIS (Netherlands)

Dinnissen, Mariken; Dietrich, Andrea; van den Hoofdakker, Barbara J.; Hoekstra, Pieter J.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is often accompanied by psychiatric comorbidity. Although there is no medication currently available to treat the core symptoms of ASD, risperidone was the first drug to be approved for use in ASD and is still the

Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment

Science.gov (United States)

Chen, Guangdong; Lin, Xiaodong; Li, Gongying; Jiang, Diego; Lib, Zhiruo; Jiang, Ronghuan; Zhuo, Chuanjun

2017-01-01

The aim of the present study was to investigate the effects of a commonly-used atypical antipsychotic, risperidone, on alterations in spatial learning and in the hippocampal brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signalling system caused by acute dizocilpine maleate (MK-801) treatment. In experiment 1, adult male Sprague-Dawley rats subjected to acute treatment of either low-dose MK801 (0.1 mg/kg) or normal saline (vehicle) were tested for spatial object recognition and hippocampal expression levels of BDNF, TrkB and the phophorylation of TrkB (p-TrkB). We found that compared to the vehicle, MK-801 treatment impaired spatial object recognition of animals and downregulated the expression levels of p-TrkB. In experiment 2, MK-801- or vehicle-treated animals were further injected with risperidone (0.1 mg/kg) or vehicle before behavioural testing and sacrifice. Of note, we found that risperidone successfully reversed the deleterious effects of MK-801 on spatial object recognition and upregulated the hippocampal BDNF-TrkB signalling system. Collectively, the findings suggest that cognitive deficits from acute N-methyl-D-aspartate receptor blockade may be associated with the hypofunction of hippocampal BDNF-TrkB signalling system and that risperidone was able to reverse these alterations. PMID:28451387

Tic Reduction with Risperidone Versus Pimozide in a Randomized, Double-Blind, Crossover Trial

Science.gov (United States)

Gilbert, Donald L.; Batterson, J. Robert; Sethuraman, Gopalan; Sallee, Floyd R.

2004-01-01

Objective: To compare the tic suppression, electrocardiogram (ECG) changes, weight gain, and side effect profiles of pimozide versus risperidone in children and adolescents with tic disorders. Method: This was a randomized, double-blind, crossover (evaluable patient analysis) study. Nineteen children aged 7 to 17 years with Tourette's or chronic…

Severe ischemic colitis following olanzapine use: a Case Report

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Samuel Raimundo Fernandes

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

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

Science.gov (United States)

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

2017-02-01

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

Cost-effectiveness of an atypical conventional antipsychotic in South Africa: An economic evaluation of quetiapine versus haloperidol in the treatment of patients partially responsive to previous antipsychotics

Directory of Open Access Journals (Sweden)

Robin Emsley

2004-10-01

Full Text Available Background. The introduction of a new generation of atypical antipsychotic agents has raised difficult economic and ethical questions, particularly in lower-income countries. The reported tolerability and efficacy advantages of the atypical antipsy- chotics over their conventional predecessors have to be weighed against their higher acquisition costs. Pharmaco-eco- nomic studies conducted in Western countries consistently report cost advantages or cost neutrality for these new agents. However, considerable differences in health care service pro- vision make it difficult to generalise these findings to South Africa. Method. We compared the direct costs (private and public sector of treating schizophrenia with an atypical antipsychotic quetiapine, and with a conventional antipsychotic haloperidol, by adapting a decision-analytic pharmaco-economic model for South African circumstances. The sample comprised patients partially responsive to antipsychotics, who had partic- ipated in a multinational randomised controlled trial compar- ing the efficacy and safety of quetiapine versus haloperidol. Results. The estimated total direct cost for the treatment with quetiapine in South Africa was slightly less than for haloperidol for various models in both the private and the public sectors. Conclusions. Significant differences in health care provision make pharmaco-economic studies conducted in other coun- tries invalid for South African circumstances. Previously queti- apine treatment did not result in direct cost savings in South Africa. However, the recently introduced legislation to estab- lish single exit prices for medications has resulted in the cost of quetiapine treatment declining by 36.7% and that of haloperi- dol by 13%. This has translated into an overall direct cost sav- ing for quetiapine in both the private and public sector models. This, together with additional indirect advantages of the atypi- cal antipsychotics such as improved quality of

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

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Katagiri H

2018-01-01

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

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

Science.gov (United States)

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

2010-03-01

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

No change of dopamine transporter density in basal ganglia after risperidone treatment in drug-naive children with Tourette's disorder

Energy Technology Data Exchange (ETDEWEB)

Ryu, W. K.; Ryu, Y. H.; Yoon, M. J.; Chun, K. A.; Lee, J. D. [College of Medicine, Univ. of Yonsei, Seoul (Korea, Republic of); Zee, D. Y. [Univ. of Inhwa, Incheon (Korea, Republic of); Choi, T. H. [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

2003-07-01

Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the DAT densities between drug-naive children with TD and normal children investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using lodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane(I-123 IPT) single photon emission computed tomography (SPECT). I-123 IPT SPECT imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in eight drug-naive children with TD. Eight normal children also underwent SPECT imaging 2 hours after an intravenous administration of I-123 IPT and carried out both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. The drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with riperidone in children with TD was not found, although tic symptoms were significantly improved with risperidone. These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

Risperidone treatment for ADHD in children and adolescents with bipolar disorder

OpenAIRE

Biederman, Joseph

2008-01-01

Joseph Biederman, Paul Hammerness, Robert Doyle, Gagan Joshi, Megan Aleardi, Eric MickPediatric Psychopharmacology Research Department, Massachusetts General Hospital, Boston, MA, USAObjective: Children and adolescents with bipolar disorder are also at high risk of having comorbid attention-deficit hyperactivity disorder (ADHD). The objective of this study was to estimate improvement in ADHD symptoms in children with bipolar disorder.Methods: This was an open-label, study of risperidone monot...

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

Science.gov (United States)

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

2016-01-01

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

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

Weight changes and their associations with demographic and clinical characteristics in risperidone maintenance treatment for schizophrenia.

Science.gov (United States)

Xiang, Y-T; Wang, C-Y; Ungvari, G S; Kreyenbuhl, J A; Chiu, H F K; Lai, K Y C; Lee, E H M; Bo, Q-J; Dixon, L B

2011-06-01

This study aimed to characterize weight changes in schizophrenia patients taking risperidone as part of a randomized, controlled, open-label clinical trial. A total of 374 patients with schizophrenia who had been clinically stabilized following an acute episode were randomly assigned to a 'no-dose-reduction' group (initial optimal therapeutic doses continued throughout the study), a '4-week group' (initial optimal therapeutic doses continued for 4 weeks followed by a half dose reduction that was maintained until the end of the study) or a '26-week group' (initial optimal therapeutic doses continued for 26 weeks followed by a half dose reduction until the end of the study). Participants were assessed monthly using standardized assessment instruments during the first 6 months, and then every 2 months until the last recruited patient completed the 1-year follow-up. Weight gain was defined as gaining at least 7% of initial body weight, weight loss as losing at least 7% of initial body weight. A BMI weight loss compared to being normal weight. No correlation was found between weight change and dose reduction. Weight change is a common, long-term, but heterogeneous side effect in risperidone maintenance treatment for stable schizophrenia patients. Special attention should be paid to fluctuations in weight that may occur throughout the course of treatment with risperidone. © Georg Thieme Verlag KG Stuttgart · New York.

Different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia

OpenAIRE

Bei-Fang Fan; Ze-Hui Li; Shuo Yang; Cai-Hong Gao

2017-01-01

Objective: To explore the different effects of paliperidone and risperidone therapy on blood lipid and Hcy metabolism as well as endocrine hormones in patients with schizophrenia. Methods: A total of 118 patients with schizophrenia who were treated in the hospital between December 2014 and February 2017 were collected as the research subjects and divided into control group and study group by random number table, each group with 59 cases. Control group received risperidone thera...

Dopamine D2/D3 receptor binding of [123I]epidepride in risperidone-treatment chronic MK-801-induced rat schizophrenia model using nanoSPECT/CT neuroimaging

International Nuclear Information System (INIS)

Huang, Y.R.; Pai, C.W.; Cheng, K.H.; Kuo, W.I.; Chen, M.W.; Chang, K.W.

2014-01-01

Introduction: Epidepride is a compound with an affinity in picomolar range for D 2 /D 3 receptors. The aim of this work was designed to investigate the diagnostic possibility of [ 123 I]epidepride imaging platform for risperidone-treatment chronic MK-801-induced rat schizophrenia model. Methods: Rats received repeated administration of MK-801 (dissolved in saline, i.p., 0.3 mg/kg/day) or saline for 4 weeks. After 1-week administration of MK-801, rats in MK-801 + risperidone group received risperidone (0.5 mg/kg/day) intraperitoneally 15 min prior to MK-801 administration for the rest of 3-week treatment. We obtained serial [ 123 I]epidepride neuroimages from nanoSPECT/CT and evaluated the alteration of specific binding in striatum and midbrain. Results: Risperidone reversed chronic MK-801-induced decrease in social interaction duration. IHC and ELISA analysis showed consistent results that chronic MK-801 treatment significantly decreased striatal and midbrain D 2 R expression but repeated risperidone administration reversed the effect of MK-801 treatment. In addition, [ 123 I]epidepride nanoSPECT/CT neuroimaging revealed that low specific [ 123 I]epidepride binding ratios caused by MK-801 in striatum and midbrain were statistically alleviated after 1- and 2-week risperidone administration, respectively. Conclusions: We established a rat schizophrenia model by chronic MK-801 administration for 4 weeks. [ 123 I]Epidepride nanoSPECT neuroimaging can trace the progressive alteration of D 2 R expression in striatum and midbrain caused by long-lasting MK-801 treatment. Besides diagnosing illness stage of disease, [ 123 I]epidepride can be a useful tool to evaluate therapeutic effects of antipsychotic drug in chronic MK-801-induced rat schizophrenia model

Second generation antipsychotics in Asperger's Disorder and high functioning autism: a systematic review of the literature and effectiveness of meta-analysis.

Science.gov (United States)

Sochocky, Natalie; Milin, Robert

2013-11-01

Second generation antipsychotics (SGA) have gained increased evidence for the treatment of irritability and aggression in children and adolescents with lower functioning autistic disorder. Individuals with Asperger's Disorder (AD) and High Functioning Autism (HFA) experience significant emotional and behavioral problems and psychiatric comorbidity. There is a need to review the published literature on SGA treatment efficacy in the AD and HFA populations to provide more effective treatment choices for these subgroups. We conducted a systematic review and meta-analysis of the recent English literature on SGA use in children and adolescents (ages 0-24 years) with AD and HFA using the Medline/PubMed and PsychINFO computerized databases. Key search words were 'Asperger', 'high functioning autism', 'autism spectrum disorders (ASD)', and 'pervasive developmental disorder (PDD)' in combination with 'second generation antipsychotics', 'aripiprazole; 'olanzapine', 'quetiapine', 'risperidone', or 'ziprasidone'. Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with ≥25% of their subjects having an IQ≥71 were included in our review. Eleven original studies met our inclusion parameters for review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of the studies reported weight gain as a potentially concerning adverse effect. There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.

Comparison of outcomes for African Americans, Hispanics, and Non-Hispanic Whites in the CATIE study.

Science.gov (United States)

Arnold, Jodi Gonzalez; Miller, Alexander L; Cañive, José M; Rosenheck, Robert A; Swartz, Marvin S; Mintz, Jim

2013-06-01

Medication outcome literature in schizophrenia across racial-ethnic groups is sparse, with inconsistent findings. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study provided an opportunity for exploratory analyses of racial-ethnic outcomes. The study objective was to examine race-ethnicity outcomes for CATIE's main outcome (study discontinuation) and secondary outcomes. CATIE participants included whites (non-Hispanic) (N=722), African Americans (N=506), and Hispanics (N=170). Survival analyses and mixed-effects regression modeling were conducted, with adjustment for baseline sociodemographic differences and baseline scores of the secondary outcomes. Racial-ethnic groups had unique patterns of outcomes. Hispanics were much more likely to discontinue for lack of efficacy from perphenazine (64% versus 42% non-Hispanic whites and 24% African Americans) and ziprasidone (71% versus 40% non-Hispanic whites and 24% African Americans); Hispanics' quality of life also declined on these medications. Non-Hispanic whites were more likely to discontinue for lack of efficacy in general (averaging olanzapine, quetiapine, and risperidone discontinuation rates). African Americans were less likely to continue after the first phase (32% continuing versus 40% for non-Hispanic whites and 41% Hispanics). Discontinuations were driven by research burden, personal issues, and unspecified loss to follow-up. Non-Hispanic whites had higher depression scores during the follow-up period. African Americans had fewer side effects. CATIE results did not show disparities favoring non-Hispanic whites. CATIE may have provided state-of-the-art treatment and thus reduced disparate treatments observed in community clinics. African Americans discontinued even after consideration of socioeconomic differences. Why perphenazine and ziprasidone may be less effective with Hispanics should be explored.

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

Science.gov (United States)

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

2010-09-01

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

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

OpenAIRE

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

2011-01-01

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

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

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

2016-03-01

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

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

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

2011-01-01

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

Cost-effectiveness of pharmacological and psychosocial interventions for schizophrenia

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2011-01-01

Background Information on cost-effectiveness of interventions to treat schizophrenia can assist health policy decision making, particularly given the lack of health resources in developing countries like Thailand. This study aims to determine the optimal treatment package, including drug and non-drug interventions, for schizophrenia in Thailand. Methods A Markov model was used to evaluate the cost-effectiveness of typical antipsychotics, generic risperidone, olanzapine, clozapine and family interventions. Health outcomes were measured in disability adjusted life years. We evaluated intervention benefit by estimating a change in disease severity, taking into account potential side effects. Intervention costs included outpatient treatment costs, hospitalization costs as well as time and travel costs of patients and families. Uncertainty was evaluated using Monte Carlo simulation. A sensitivity analysis of the expected range cost of generic risperidone was undertaken. Results Generic risperidone is more cost-effective than typicals if it can be produced for less than 10 baht per 2 mg tablet. Risperidone was the cheapest treatment with higher drug costs offset by lower hospital costs in comparison to typicals. The most cost-effective combination of treatments was a combination of risperidone (dominant intervention). Adding family intervention has an incremental cost-effectiveness ratio of 1,900 baht/DALY with a 100% probability of a result less than a threshold for very cost-effective interventions of one times GDP or 110,000 baht per DALY. Treating the most severe one third of patients with clozapine instead of risperidone had an incremental cost-effectiveness ratio of 320,000 baht/DALY with just over 50% probability of a result below three times GDP per capita. Conclusions There are good economic arguments to recommend generic risperidone as first line treatment in combination with family intervention. As the uncertainty interval indicates the addition of clozapine

Cost-effectiveness of pharmacological and psychosocial interventions for schizophrenia

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Vos Theo

2011-05-01

Full Text Available Abstract Background Information on cost-effectiveness of interventions to treat schizophrenia can assist health policy decision making, particularly given the lack of health resources in developing countries like Thailand. This study aims to determine the optimal treatment package, including drug and non-drug interventions, for schizophrenia in Thailand. Methods A Markov model was used to evaluate the cost-effectiveness of typical antipsychotics, generic risperidone, olanzapine, clozapine and family interventions. Health outcomes were measured in disability adjusted life years. We evaluated intervention benefit by estimating a change in disease severity, taking into account potential side effects. Intervention costs included outpatient treatment costs, hospitalization costs as well as time and travel costs of patients and families. Uncertainty was evaluated using Monte Carlo simulation. A sensitivity analysis of the expected range cost of generic risperidone was undertaken. Results Generic risperidone is more cost-effective than typicals if it can be produced for less than 10 baht per 2 mg tablet. Risperidone was the cheapest treatment with higher drug costs offset by lower hospital costs in comparison to typicals. The most cost-effective combination of treatments was a combination of risperidone (dominant intervention. Adding family intervention has an incremental cost-effectiveness ratio of 1,900 baht/DALY with a 100% probability of a result less than a threshold for very cost-effective interventions of one times GDP or 110,000 baht per DALY. Treating the most severe one third of patients with clozapine instead of risperidone had an incremental cost-effectiveness ratio of 320,000 baht/DALY with just over 50% probability of a result below three times GDP per capita. Conclusions There are good economic arguments to recommend generic risperidone as first line treatment in combination with family intervention. As the uncertainty interval indicates

Cost-effectiveness of pharmacological and psychosocial interventions for schizophrenia.

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Phanthunane, Pudtan; Vos, Theo; Whiteford, Harvey; Bertram, Melanie

2011-05-13

Information on cost-effectiveness of interventions to treat schizophrenia can assist health policy decision making, particularly given the lack of health resources in developing countries like Thailand. This study aims to determine the optimal treatment package, including drug and non-drug interventions, for schizophrenia in Thailand. A Markov model was used to evaluate the cost-effectiveness of typical antipsychotics, generic risperidone, olanzapine, clozapine and family interventions. Health outcomes were measured in disability adjusted life years. We evaluated intervention benefit by estimating a change in disease severity, taking into account potential side effects. Intervention costs included outpatient treatment costs, hospitalization costs as well as time and travel costs of patients and families. Uncertainty was evaluated using Monte Carlo simulation. A sensitivity analysis of the expected range cost of generic risperidone was undertaken. Generic risperidone is more cost-effective than typicals if it can be produced for less than 10 baht per 2 mg tablet. Risperidone was the cheapest treatment with higher drug costs offset by lower hospital costs in comparison to typicals. The most cost-effective combination of treatments was a combination of risperidone (dominant intervention). Adding family intervention has an incremental cost-effectiveness ratio of 1,900 baht/DALY with a 100% probability of a result less than a threshold for very cost-effective interventions of one times GDP or 110,000 baht per DALY. Treating the most severe one third of patients with clozapine instead of risperidone had an incremental cost-effectiveness ratio of 320,000 baht/DALY with just over 50% probability of a result below three times GDP per capita. There are good economic arguments to recommend generic risperidone as first line treatment in combination with family intervention. As the uncertainty interval indicates the addition of clozapine may be dominated and there are serious

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

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Azarekhsh Mokri

2009-08-01

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

Synthesis, recognition and evaluation of molecularly imprinted polymer nanoparticle using miniemulsion polymerization for controlled release and analysis of risperidone in human plasma samples

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Asadi, Ebadullah; Azodi-Deilami, Saman; Abdouss, Majid; Kordestani, Davood; Rahimi, Alireza; Asadi, Somayeh

2014-01-01

We prepared high selective imprinted nanoparticle polymers by a miniemulsion polymerization technique, using risperidone as the template, MAA as the functional monomers, and TRIM as the cross-linker in acetonitrile as solvent. The morphology of the nanoparticles determined by scanning electron microscopy (SEM) images and drug release, binding properties and dynamic light scattering (DLS) of molecularly imprinted polymers (MIPs) were studied. Controlled release of risperidone from nanoparticles was investigated through in 1% wt sodium dodecyl sulfate aqueous solution and by measuring the absorbance by HPLC-UV. The results showed that the imprinted nanoparticles exhibited a higher binding level and slower release rate than non-imprinted nanoparticles, which contributed to interaction of risperidone with imprinted cavities within nanoparticles. Furthermore, the results from HPLC showed good precision (5% for 50.0 µg L -1 ) and recoveries (between 86-91) using MIP from human plasma samples

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

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Anand E

2016-10-01

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

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

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Brewerton, Timothy D; D'Agostino, Meredith

2017-12-01

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

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

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

2013-12-01

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

An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder.

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Kent, Justine M; Hough, David; Singh, Jaskaran; Karcher, Keith; Pandina, Gahan

2013-12-01

The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders. In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors. This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

Handwriting Movement Analyses for Monitoring Drug-Induced Motor Side Effects in Schizophrenia Patients Treated with Risperidone

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Caligiuri, Michael P.; Teulings, Hans-Leo; Dean, Charles E.; Niculescu, Alexander B.; Lohr, James

2009-01-01

Epidemiologic studies indicate that nearly 60% of schizophrenia (SZ) patients treated with conventional antipsychotic drugs develop extrapyramidal side effects (EPS) such as parkinsonism and tardive dyskinesia. Although the prevalence of EPS has decreased due to the newer antipsychotics, EPS continue to limit the effectiveness of these medicines. Ongoing monitoring of EPS is likely to improve treatment outcome or compliance and reduce the frequency of re-hospitalization. A quantitative analysis of handwriting kinematics was used to evaluate effects of antipsychotic medication type and dose in schizophrenia patients. Twenty-seven schizophrenia patients treated with risperidone, six schizophrenia patients who received no antipsychotic medication and 46 healthy comparison participants were enrolled. Participants performed a 20-minute handwriting task consisting of loops of various sizes and a sentence. Data were captured and analyzed using MovAlyzeR software. Results indicated that risperidone-treated participants exhibited significantly more dysfluent handwriting movements than either healthy or untreated SZ participants. Risperidone-treated participants exhibited lower movement velocities during production of simple loops compared to unmedicated patients. Handwriting dysfluency during sentence writing increased with dose. A 3-factor model consisting of kinematic variables derived from sentence writing accounted for 83% (r = .91) of the variability in medication dose. In contrast, we found no association between observer-based EPS severity ratings and medication dose. These findings support the importance of handwriting-based measures to monitor EPS in medicated schizophrenia patients. PMID:19692133

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

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Holzer, Barry; Lopes, Vasco; Lehman, Robert

2013-08-01

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

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

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

2005-03-01

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

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

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Watson Susan B

2011-02-01

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

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

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

2013-09-01

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

Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys.

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Banks, Matthew L; Blough, Bruce E

2015-08-01

Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food

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

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Novin Nikbakhsh

2016-01-01

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

Risperidone Versus Methylphenidate in Treatment of Preschool Children With Attention-Deficit Hyperactivity Disorder.

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Arabgol, Fariba; Panaghi, Leily; Nikzad, Vahid

2015-02-01

Attention Deficit Hyperactivity Disorder (ADHD) is a common psychiatric diagnosis among preschool children. The aim of this study was to examine the Risperidone treatment compared to Methylphenidate (MPH) in preschool children with ADHD. Thirty three outpatient preschool children, aged 3-6 years, diagnosed with ADHD (The diagnosis of ADHD was established by two child and adolescent psychiatrists according to the DSM-IV-TR criteria), participated in a 6-week, double-blind clinical trial with risperidone (0.5-1.5 mg/d) and methylphenidate (5-20 mg/d), in two divided doses. Treatment outcomes were assessed using the Parent ADHD Rating Scale and Conners Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks after the medication started. Side effects were also rated by side effects questionnaire. There were no significant differences between the two protocols on the Parent ADHD Rating Scale scores (P > 0.05) and Parent Conners Rating Scale scores (P > 0.05). Both groups showed a significant improvement in ADHD symptoms over the 6 weeks of treatment for parent ADHD Rating Scale (P benefits and adverse effects in long term use and comorbid conditions.

Comparative study of clozapine versus risperidone in treatment-naive, first-episode schizophrenia: A pilot study

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Sukhtej Sahni

2016-01-01

Interpretation & conclusions: The findings of this preliminary study showed clozapine as a better choice than risperidone in terms of efficacy, tolerability and better quality of life in treatment-naive, first-episode schizophrenia. However, further studies need to be done on a larger group of patients to confirm the findings.

Comparison between risperidone, an atypical antipsychotic agent and haloperidol, a conventional agent used to treat schizophrenia

International Nuclear Information System (INIS)

Rehman, A.; Jawed, M.; Maheshwari, M.P.

2012-01-01

An observational and comparative study was conducted to compare the functional outcome between the patients treated with conventional antipsychotic agent haloperidol and typical antipsychotic agent, Risperidone (Risperidal). A total of 32 patients were included in the study with established schizophrenia according to (DSM iv). The data was processed on SSPE 10th version. The primary outcome measure was the improvement of negative symptoms of schizophrenia and secondary outcome measure was to observe the superiority of the atypical drug Risperid one over conventional agent haloperidol regarding side effects. Patients were assessed at baseline, 2nd and 8th week, using four tools of assessment. For treatment group receiving haloperidol mean was 47.2+-11.50 at 8th week and for Risperidone treatment group mean was 43+-14.68. The P values for all the parameters in the Clozapine group were significant as compared to haloperidol. (author)

Worsening of myasthenia gravis after administration of injectable long-acting risperidone for treatment of schizophrenia; first case report and a call for caution.

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