Gender differences in the response to antipsychotic medication in patients with schizophrenia: An individual patient data meta-analysis of placebo-controlled studies.

OBJECTIVE: To determine whether gender and menopausal status moderate the response to antipsychotic medication in patients with schizophrenia. METHODS: We analyzed data of 22 short-term placebo-controlled registration trials of antipsychotic medications, which included 5,231 patients with schizophrenia. We applied two-step individual patient data meta-regression analyses to establish the influence of gender and menopausal status on treatment response in mean difference in symptom severity and difference in response (>30% symptom reduction). Analyses were performed both with and without correction for baseline (negative) symptom severity. RESULTS: Antipsychotic treatment is associated with larger mean symptom reduction in women than in men with schizophrenia. The number needed to treat (NNT) for a response in women was 6.9, in men 9.4. Although, we found an age by gender effect, the gender by treatment effect was independent of premenopausal status and baseline (negative) symptom severity. CONCLUSION: In the treatment of schizophrenia we found evidence of a higher response to antipsychotic medication in women relative to men. We found no evidence that this effect was driven by menopausal status, or baseline (negative) symptom severity. Despite the impact of gender and age on effect size in acute antipsychotic treatment, efficacy was clinically relevant in all subgroups.

The effect of Ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT) gene.

There is ample evidence for decreased verbal memory in heavy Ecstasy users. However, findings on the presence of a dose-response relation are inconsistent, possibly due to individual differences in genetic vulnerability. Catechol-O-methyltransferase (COMT) is involved in the catabolism of Ecstasy. Therefore, COMT gene polymorphisms may moderate this vulnerability. We prospectively assessed verbal memory in subjects with a high risk for future Ecstasy use, and compared 59 subjects after first Ecstasy use with 60 subjects that remained Ecstasy-naive. In addition, we tested the interaction effect of Ecstasy and the functional val (158)met polymorphism on verbal memory. Met-allele carriers were somewhat more sensitive to the effects of Ecstasy on verbal learning than homozygous val-subjects. After correction for the use of other substances this effect was no longer statistically significant. The findings suggest that the COMT gene moderates the negative effect of Ecstasy on memory, but also other drug use seems to play a role.