Weight Gain and Metabolic Changes in Patients With First-Episode Psychosis or Early-Phase Schizophrenia Treated With Olanzapine: A Meta-Analysis

Abstract

Abstract Background Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population. Methods PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5. Results Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42–8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05–12.65) vs 5.51 (4.73–6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration. Conclusions In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered.