Sex differences in the efficacy, acceptability, and tolerability of antipsychotics in people with acute schizophrenia: individual participant data pairwise, dose-response, and network meta-analyses.

In 30 seconds

This individual participant data pairwise, dose-response, and network meta-analysis examined sex differences in antipsychotic efficacy, acceptability, and tolerability in adults with acute schizophrenia. Main analyses included 18 fixed-dose trials and 7062 participants. Overall symptom effects did not differ between females and males (difference of standardised mean difference 0·04, 95% CI -0·09 to 0·18), and dose-response patterns were similar. Antipsychotics reduced all-cause dropout more in females, while prolactin increases were also greater in females; other tolerability outcomes showed no clear sex differences.

Key findings

• Overall symptom effects showed no evidence of a sex difference (difference of standardised mean difference 0·04, 95% CI -0·09 to 0·18).
• Antipsychotics reduced all-cause dropout more in females than males (ratio of odds ratios 0·74, 95% CI 0·56-0·98; moderate credibility).
• Prolactin increase was greater in females (difference of standardised mean difference 0·83, 0·67-0·99; high credibility).
• Dose-response curves were similar between sexes, plateauing at 3-5 mg risperidone equivalents.

Why it matters

The findings suggest that overall efficacy estimates from prior antipsychotic meta-analyses apply to both sexes for the drugs studied. At the same time, the sex differences in dropout and prolactin elevation highlight outcomes that may warrant attention when assessing treatment acceptability and adverse effects. Sex-stratified reporting can help clarify whether these patterns extend across treatments and populations.

What to keep in mind

Main analyses were restricted to fixed-dose trials and included five antipsychotics, limiting conclusions to the drugs and trial settings studied.