A 24-week, multicenter, open-label, randomized study to compare changes in glucose metabolism in patients with schizophrenia receiving treatment with olanzapine, quetiapine, or risperidone
Date
2009
Authors
Newcomer J.W.
Ratner R.E.
Eriksson J.W.
Emsley R.
Meulien D.
Miller F.
Leonova-Edlund J.
Leong R.W.
Brecher M.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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. © Copyright 2009 Physicians Postgraduate Press, Inc.
Description
Keywords
lipid, olanzapine, quetiapine, risperidone, adult, akathisia, article, cholesterol blood level, clinical trial, controlled clinical trial, controlled study, delusion, dizziness, drug withdrawal, dyspnea, dystonia, extrapyramidal syndrome, female, glucose blood level, glucose metabolism, glucose tolerance, hallucination, headache, human, hypertension, insomnia, insulin blood level, insulin sensitivity, lipid blood level, major clinical study, male, multicenter study, neutrophil count, open study, oral glucose tolerance test, panic, priority journal, psychosis, randomized controlled trial, restlessness, schizophrenia, sedation, side effect, somnolence, thorax pain, treatment duration, triacylglycerol blood level, upper abdominal pain, weight gain, Adolescent, Adult, Aged, Antipsychotic Agents, Benzodiazepines, Cholesterol, HDL, Cholesterol, LDL, Dibenzothiazepines, Female, Glucose, Humans, Insulin, Male, Middle Aged, Risperidone, Schizophrenia, Triglycerides, Young Adult
Citation
Journal of Clinical Psychiatry
70
4
70
4