BackgroundWhether non-genetic prognostic factors significantly influence the variable prognosis of antipsychotic-induced weight gain (AIWG) has not yet been systematically explored.MethodsSearches for both randomized and non-randomized studies were undertaken using 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 Quality in Prognosis Studies (QUIPS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively.ResultsSeventy-two prognostic factors were assessed across 27 studies involving 4426 participants. Only age, baseline body mass index (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 (b=−0.013 95%CI −0.225–0.200) were associated with nonsignificant effects on AIWG prognosis. The highest quality GRADE rating was moderate in support of age, trend of early BMI increase, antipsychotic treatment response, unemployment, and antipsychotic plasma concentration. Trend of early BMI increase was identified as the most clinically significant prognostic factor influencing long-term AIWG prognosis.ConclusionsThe strong prognostic information provided by BMI trend change within 12 weeks of antipsychotic initiation should be included within AIWG management guidance to highlight those at highest risk of worse long-term prognosis. Antipsychotic switching and resource-intensive lifestyle interventions should be targeted toward this cohort. Our results challenge previous research that several clinical variables significantly influence AIWG prognosis. We provide the first mapping and statistical synthesis of studies examining non-genetic prognostic factors of AIWG and highlight practice, policy, and research implications.