Does Sex Affect Antipsychotic-Induced Weight Gain in Patients Being Treated for Psychotic Disorders: A Systematic...

Antipsychotic-induced weight gain (AIWG) causes distress for patients, and contributes to cardiovascular morbidity and poor medication adherence. Narrative reviews suggest females may experience higher rates of AIWG due to pharmacokinetic and hormonal variations. We systematically evaluated whether patients' sex affects AIWG in patients with psychotic disorders.

This systematic review and meta-analysis (PROSPERO: CRD42023495785) followed PRISMA guidelines. We searched PubMed, EMBASE, and PsycINFO from inception to December 17, 2025, for observational studies and trials reporting sex-disaggregated AIWG data. Random-effects meta-analyses were conducted for change in weight (kg) and BMI (kg/m2), with subgroup analyses by drug and follow-up duration.

Of 8520 records screened, 27 studies (n = 5349) met inclusion criteria, with 15 contributing to meta-analyses. We found no statistically significant sex difference in weight change (SMD = 0.06, 95% CI, -0.14 to 0.27, I2 = 80%). However, females showed a small but significantly greater increase in BMI (SMD = 0.15, 95% CI, 0.02-0.28, I2 = 64%). Subgroup analyses revealed this BMI difference was more pronounced in studies with follow-up longer than 3 months (SMD = 0.30) and in observational studies (SMD = 0.24), but disappeared in RCTs and good-quality studies.

Females may experience a marginally greater increase in BMI due to antipsychotics relative to males, particularly over longer treatment durations. However, the profound scarcity of sex-disaggregated data-with only 3 RCTs identified-limits clinical recommendations. Future research must prioritize sex-disaggregated reporting. There is a need for well-designed, prospective studies that explicitly investigate sex differences in AIWG.