Predicting antipsychotic-induced weight gain in first episode psychosis – A field-wide systematic review and meta-analysis of non-genetic prognostic factors

Background: Whether non-genetic prognostic factors significantly influence the variable prognosis of antipsychotic-induced weight gain (AIWG) has not yet been systematically explored. Methods: Searches for both randomised and non-randomised studies were undertaken by searching four electronic databases, two trial registers and via supplemental searching methods. Unadjusted and adjusted estimates were extracted. Meta-analyses were undertaken using a random-effects generic inverse model. Risk of bias and quality assessments were undertaken using QUIPS and GRADE, respectively. Results: Seventy-two prognostic factors were assessed across 27 studies involving 4426 participants. Only age, baseline BMI and sex were suitable for meta-analysis. Age (b= -0.044, 95%CI -0.157–0.069), sex (b=0.236, 95%CI -0.086-0.558) and baseline BMI (-0.013 95%CI - 0.225-0.200) were associated with non-significant effects on AIWG prognosis. The highest quality GRADE rating was moderate in support of age, trend of early BMI increase, response to antipsychotic treatment, unemployment, and antipsychotic plasma concentration. Trend of early BMI increase was identified as the most clinically significant prognostic factor influencing long-term AIWG prognosis. Conclusion: The strong prognostic information provided by BMI trend change within 8-12 weeks of antipsychotic initiation should be included as part of novel and risk stratified AIWG management guidance to highlight those at highest risk of worse long-term prognosis.