Sex differences in ketamine treatment for depressive disorders: A systematic review

In recent years, ketamine has gained attention for its rapid onset and significant antidepressant effects, but research on its differential treatment effects between sexes is limited. This study systematically reviews 22 studies (n=1,155; 485 males, 670 females) to explore the sex differences in the effects of ketamine treatment for depression. The findings indicate that while some studies reported sex differences, such as variations in metabolite levels, side effects, and efficacy, the overall evidence is limited, with small sample sizes and inadequate study designs being major contributing factors. Additionally, sex differences may be influenced by hormone levels, drug dosage, and baseline characteristics, which have not been adequately considered. Accordingly, the current lack of consistent sex-specific findings should be interpreted as inconclusive, reflecting limited sample sizes, non-prespecified sex analyses, and heterogeneity of study designs, rather than as evidence of no sex differences. Future research should conduct in-depth analyses of the sex-specific mechanisms of ketamine treatment in larger, sex-balanced studies to advance the development of personalized medicine.