Gender differences in the response to antipsychotics or mood stabilizers in patients with acute mania: An individual patient data meta-analysis of placebo-controlled studies

Evidence suggests a worse clinical course in women compared to men with bipolar disorder. However, little research has explored gender differences in the efficacy of anti-manic medication. We sought to determine whether there are gender differences in efficacy of drug treatment in acute manic episodes of bipolar I disorder, and the influence of dichotomized age as a proxy for menopausal status and baseline severity on gender differences. We performed an individual patient data meta-analysis of 10 short term placebo controlled registration trials for treatment of acute mania (N = 2199) performed between 1996 and 2007 using the (Young) Mania Rating Scale ((Y)MRS)) as outcome. We observed a difference in effect size in mean change and responder status between men and women (NNT = 6.3 vs. 5.3), with a small but significant effect of gender on treatment response (β = 0.031). The effect size was larger in women older than 47 compared to women aged 47 and under (NNT = 4.2 vs. 7.5), and to a lesser extent, larger in men over 47 years compared those aged 47 and under (NNT = 3.8 vs. 6). Results were mainly driven by differences in response in the placebo group and independent of baseline severity. These findings suggest that men and premenopausal women might have a clinically modest advantage over their women and postmenopausal counterparts in treatment with anti-manic medication. Our results were limited by our sample not including antimanic agents registered after 2007 and by the absence of direct biological information regarding sex and menopausal state. Future research should aim to replicate current findings utilizing biological confirmation on the menopausal status and test whether findings are generalizable to newer antimanic agents.