How gender affects the pharmacotherapeutic approach to treating psychosis – a systematic review

ABSTRACT

Introduction: The effectiveness, effective dosages and side effect profiles of antipsychotic medication differ significantly between the sexes.

Areas covered: We present a systematic review of gender-differences in the treatment of psychosis focusing on randomized, controlled trials and meta-analyses.

Expert opinion: Despite many years of research, the database on gender-differences affecting the pharmacotherapeutic approach to treating psychosis is insufficient. Currently, the US National Institute of Health encouraged the enrolment of female participants in federally supported phase III clinical trials to increase the data available of female patients. Emerging evidence points to a superior antipsychotic response in women, with men requiring higher dosages. In general, women metabolize drugs differently, resulting in side effects occuring more frequently when compared to men. In any case, women require electrocardiograms or bone density scans as well as diabetes and cardiovascular workups when treated with antipsychotics. Dose adjustments during the menstrual cycle (e.g. to raise antipsychotic doses premenstrually) should be considered. First-generation antipsychotics, drugs that are known to prolong QTc interval and increase prolactin levels should be avoided in postmenopausal female patients. Furthermore, the effects of antipsychotics during pregnancy and breastfeeding have been investigated insufficiently, and more research is urgently needed.

KEYWORDS:

• Schizophrenia
• adherence
• antipsychotic treatment
• treatment response
• side effects

Article highlights

• Most animal and human studies in this field show an unequal distribution between the sexes or neglect possible gender-related differences in mixed samples due to sample size, increasing costs or increased variability in the results, mainly because of the ‚hard to control’ phases of the estrous/menstrual cycle

• To overcome this limitation, the US National Institute of Health (NIH) encouraged the enrollment of female participants in federally supported phase III clinical trials

• Significant gender-differences in treating psychosis include differences regarding treatment response, effective dosage and side effects have been reported

• Data availability with respect to optimal treatment during adolescence, pregnancy, postpartum, breat feeding and postmenopausal is inadequate.

• Further clinical studies, focusing on gender-differences are urgently needed to better understand and to improve the gender-specific pharmacotherapeutic approach to treating psychosis

This box summarizes key points contained in the article.

Acknowledgment

We gratefully acknowledge the editing of this article by Ms. U. Schmid.

Declaration of interest

F M Leweke is a shareholder of curantis UG (ltd.) and received honoraria from Alexza, GlaxoSmithKline, Merz, Servier and has been a speaker and/or consultant for Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The authors have received intramural funding from the Central Institute of Mental Health, Mannheim.