Do men and women respond differently to ketamine for depression? Review finds no clear answer

The question

Does ketamine work differently as a depression treatment for men and women? The authors reviewed the published research to see whether sex-based differences in effect, side effects or drug processing show up consistently.

What they did

The researchers systematically searched the literature and identified 22 studies that reported on ketamine treatment for depressive disorders and included information relevant to sex. Together these studies involved 1,155 people: 485 males and 670 females. The authors compared what each study reported about efficacy, side effects and levels of ketamine’s breakdown products (metabolites) in men versus women.

What they found

Some individual studies did report differences between men and women, including differences in metabolite levels, side effects and how well the treatment worked. But the results did not line up across studies. The authors concluded the overall evidence is limited, mainly because the studies had small sample sizes and were not designed to test sex differences in the first place. They stress that this inconsistency should be read as ‘we don’t know yet’, not as proof that sex makes no difference.

The fine print

This is a review of existing studies, not new data, and the included studies varied widely in design. Sex comparisons were generally not pre-planned, which makes any apparent difference more likely to be a chance finding. Factors that could drive differences, such as hormone levels, dose and baseline characteristics, were not consistently measured. This summary is based on the abstract only, which does not state how the studies were graded or whether results were statistically pooled.

What it means

At present there is not enough good-quality evidence to say whether ketamine treatment for depression works differently in men and women; larger studies designed to answer that question are needed.

Evidence grade: Low. A systematic review that pooled small, heterogeneous studies in which sex differences were mostly not planned analyses, so the findings are descriptive and inconclusive.

This summary is based on the study’s published abstract.