Design: Individual participant data pairwise, dose-response and network meta-analyses
Population: 18 fixed-dose trials, 7,062 adults with acute schizophrenia (2,168 women)
Primary outcome: Overall symptoms on the PANSS at week 6
Effect: No sex difference (DoSMD 0.04, 95% CI -0.09 to 0.18); prolactin rise greater in women (DoSMD 0.83, 95% CI 0.67 to 0.99)

This individual participant data meta-analysis drew on 18 fixed-dose trials in acute schizophrenia, with 7,062 participants (2,168 women), covering haloperidol, olanzapine, paliperidone, risperidone and placebo. Using raw patient data allowed a direct test of whether sex changes the drug effect, rather than comparing trial averages.

There was no sex difference in the effect on overall symptoms at about six weeks (difference in standardised mean difference 0.04, 95% CI -0.09 to 0.18). Dose-response curves were alike in both sexes and plateaued at 3-5 mg risperidone equivalents. Antipsychotics reduced all-cause dropout more in women (ratio of odds ratios 0.74, 95% CI 0.56 to 0.98, moderate credibility), and raised prolactin more in women (difference 0.83, 95% CI 0.67 to 0.99, high credibility). Other tolerability outcomes showed no clear sex difference.

In practice: dose by response, not by sex, and do not push beyond the plateau expecting more benefit. The prolactin finding is the actionable one. Ask women directly about menstrual change, galactorrhoea and sexual dysfunction, which are often not volunteered, and think about the choice of agent when prolactin effects matter.

Dose antipsychotics by response and tolerability; the evidence does not support different doses for women and men.
Expect little extra benefit above about 3-5 mg risperidone equivalents in acute schizophrenia.
Ask women on prolactin-raising antipsychotics about missed periods, galactorrhoea and sexual side effects at each review.
Consider a prolactin-sparing agent when hyperprolactinaemia symptoms appear or fertility is a concern.
Remember that suppressed periods can mask pregnancy and that lowering prolactin by switching can restore fertility.

Why it matters

It answers a common question about sex-specific dosing with patient-level data, and shifts the attention to prolactin.

The statistics, in plain English

A difference in standardised mean difference of 0.04 with an interval from -0.09 to 0.18 means any sex difference in symptom response is too small to matter clinically. The prolactin difference of 0.83 is large and its interval stays far from zero. The dropout finding only just excludes no difference, so treat it as suggestive.