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Safety, tolerability, and efficacy of quetiapine in youth with schizophrenia or bipolar I disorder: a 26-week, open-label, continuation study.

ABSTRACT: The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder.Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13-17 years) or a manic episode of bipolar I disorder (ages 10-17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine were potentially eligible to enroll in a 26-week, open-label study. During the open-label study, quetiapine was flexibly dosed at 400-800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability. Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs.Of 381 patients enrolled in the open-label study (n=176, schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. A total of 14.9% of patients experienced a shift to potentially clinically significant low levels of high-density lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially clinically significant high triglyceride levels. Weight gain ? 7% was reported in 35.6% of patients between open-label baseline and final visit. After adjustment for normal growth, 18.3% of study participants experienced clinically significant weight gain (i.e., increase in body mass index ? 0.5 standard deviations from baseline).In this 26-week study, quetiapine flexibly dosed at 400-800 mg/day, with options to reduce dosing based on tolerability, was generally safe and well tolerated in youth. Clinicians should monitor lipid profiles and weight gain in youth with schizophrenia or bipolar disorder during treatment with quetiapine.

SUBMITTER: Findling RL

PROVIDER: S-EPMC3778946 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Safety, tolerability, and efficacy of quetiapine in youth with schizophrenia or bipolar I disorder: a 26-week, open-label, continuation study.

Findling Robert L RL Pathak Sanjeev S Earley Willie R WR Liu Sherry S DelBello Melissa M

Journal of child and adolescent psychopharmacology 20130911 7

<h4>Objective</h4>The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder.<h4>Methods</h4>Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13-17 years) or a manic episode of bipolar I disorder (ages 10-17 years) who participated in one of two acute, double-blind ...[more]

PMID: 24024534

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Project description:The purpose of this study was to evaluate the safety and efficacy of asenapine in adolescents with schizophrenia.In an 8 week, randomized, double-blind placebo-controlled trial, subjects (12-17 years of age) meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria for schizophrenia were randomized 1:1:1 to placebo, asenapine 2.5?mg b.i.d., or asenapine 5?mg b.i.d. Subjects who completed the 8 week acute study could participate in a 26 week flexible-dose asenapine-only open-label extension (OLE).A similar percentage of subjects completed treatment on day 56 (2.5?mg b.i.d. (n=98): 83%; 5?mg b.i.d. [n=106]: 79%; placebo [n=102]: 79%). In the mixed model for repeated measures analysis of the primary end-point (with Hochberg correction for multiplicity), least squares (LS) mean differences between asenapine and placebo on the Positive and Negative Syndrome Scale (PANSS) total score at day 56 were not significant (-4.8 for 2.5?mg b.i.d., p=0.070; -5.6 for 5?mg b.i.d., p=0.064). Significant improvement in the Clinical Global Impressions-Severity score was observed in the 5?mg b.i.d. group versus placebo on day 56 (LS mean -0.3, p=0.024). In the acute phase, ?7% weight gain and the composite event of somnolence, sedation, and hypersomnia were more common in both asenapine groups than in the placebo group. Akathisia, fasting glucose elevation, and extrapyramidal syndrome were more common in the 5?mg b.i.d. group than in the placebo group. There were no unexpected adverse events in the OLE, and PANSS total scores decreased by -16.1 points in the group previously treated with placebo (n=62) and by -11.2 points in the continuous asenapine group (n=131) from OLE baseline to week 26.Although improvements in PANSS total score at day 56 of the acute phase were numerically greater for both asenapine 2.5 and 5?mg b.i.d. than for placebo and were maintained in the OLE, the primary end-point did not achieve statistical significance in the acute phase. No new or unexpected safety concerns were detected during the acute phase or after an additional 26 weeks of asenapine treatment in the adolescent population with schizophrenia.NCT01190254 and NCT1190267 at ClinicalTrials.gov.

Project description:OBJECTIVE:This randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with DSM-IV schizophrenia receiving initial exposure to olanzapine, quetiapine, or risperidone. METHOD:The hypothesized primary endpoint was change (baseline to week 24) in area under the curve (AUC) 0- to 2-hour plasma glucose values during an oral glucose tolerance test (OGTT); primary analysis: olanzapine versus quetiapine. Secondary endpoints included mean change in AUC 0- to 2-hour plasma insulin values, insulin sensitivity index, and fasting lipids. The first patient enrolled on April 29, 2004, and the last patient completed the study on October 24, 2005. RESULTS:Mean weight change (kg) over 24 weeks was +3.7 (quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (quetiapine, N = 115 [mean dose = 607.0 mg/day], olanzapine, N = 146 [mean dose = 15.2 mg/day], and risperidone, N = 134 [mean dose = 5.2 mg/day]), mean change in AUC 0- to 2-hour glucose value (mg/dL x h) at week 24 was significantly lower for quetiapine versus olanzapine (t = 1.98, df = 377, p = .048). Increases in AUC 0- to 2-hour glucose values were statistically significant with olanzapine (+21.9 mg/dL x h, 95% CI = 11.5 to 32.4 mg/dL x h) and risperidone (+18.8 mg/dL x h, 95% CI = 8.1 to 29.4 mg/dL x h), but not quetiapine (+9.1 mg/dL x h, 95% CI = -2.3 to 20.5 mg/dL x h). AUC 0- to 2-hour insulin values increased statistically significantly with olanzapine (+24.5%, 95% CI = 11.5% to 39.0%), but not with quetiapine or risperidone. Reductions in insulin sensitivity index were statistically significant with olanzapine (-19.1%, 95% CI = -27.9% to -9.3%) and risperidone (-15.8%, 95% CI = -25.1% to -5.4%), but not quetiapine. Total cholesterol and low-density lipoprotein levels increased statistically significantly with olanzapine (+21.1 mg/dL, 95% CI = 13.0 to 29.2 mg/dL, and +20.5 mg/dL, 95% CI = 13.8 to 27.1 mg/dL, respectively) and quetiapine (+13.1 mg/dL, 95% CI = 4.3 to 21.9 mg/dL, and +13.3 mg/dL, 95% CI = 6.1 to 20.5 mg/dL, respectively), but not risperidone. Statistically significant increases in triglycerides (+30.9 mg/dL, 95% CI = 10.9 to 51.0 mg/dL), total cholesterol/high-density lipoprotein (HDL) ratio (0.5, 95% CI = 0.2 to 0.8), and triglyceride/HDL ratio (0.3, 95% CI = 0.0 to 0.6) were observed with olanzapine only. CONCLUSION:The results indicate a significant difference in the change in glucose tolerance during 6 months' treatment with olanzapine versus quetiapine, with significant reductions on olanzapine and risperidone, but not quetiapine; these differential changes were largely explained by changes in insulin sensitivity. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00214578.

Project description:ObjectiveQuetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression.MethodsThis multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates.ResultsOf 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group.ConclusionsQuetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.

Project description:BACKGROUND:The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. METHODS:This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. RESULTS:Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (<?10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. CONCLUSION:AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Dataset Information

Safety, tolerability, and efficacy of quetiapine in youth with schizophrenia or bipolar I disorder: a 26-week, open-label, continuation study.

Publications

Safety, tolerability, and efficacy of quetiapine in youth with schizophrenia or bipolar I disorder: a 26-week, open-label, continuation study.

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