Comparative Effects of 11 Antipsychotics on Weight Gain and Metabolic Function in Patients With Acute Schizophrenia

Objective: To investigate the association of metabolic side effects with antipsychotic dose, we conducted a dose-response meta-analysis of randomized controlled trials (RCTs) in which antipsychotics were administered to people with schizophrenia. The primary outcome was mean change in weight. The secondary outcomes were the mean changes in metabolic parameters.Data Sources: MEDLINE, Embase, PubMed, PsyARTICLES, PsycINFO, Cochrane Database of Systematic Reviews, and different trial registries were searched for articles published in English until February 2021.Study Selection: We identified fixed-dose RCTs with first- or second-generation antipsychotics. The quality of RCTs was measured with Cochrane's Risk of Bias tool.Data Extraction: We performed a dose-response meta-analysis.Results: We retained 52 RCTs including 22,588 participants. With the exception of aripiprazole long-acting injectable (LAI), all investigated antipsychotics presented significant dose-response associations with weight, from lurasidone with a quasi-parabolic shaped curve (9 studies, estimation of 95% effective dose [ED95; 59.93 mg/d] = 0.53 kg/6 wk) to olanzapine LAI with a curve that continued to increase with the dose (1 study, ED95 [15.05 mg/d] = 4.29 kg/8 wk). All curves could be ordered in 3 different classes of shapes-quasi-parabolic, plateau, and ascending.Conclusions: We found significant dose-response associations for weight and metabolic variables, with a unique signature for each antipsychotic. Weight gain can occur at a relatively low median effective dose, and increasing doses can be associated with greater weight gain for some drugs. Despite several limitations, including the limited number of available studies, our results may provide useful information for preventing weight gain and metabolic disturbance by adapting antipsychotic doses.Registration: PROSPERO ID number CRD42021176569.