SNRIs lead the non-hormonal options for menopausal low mood

Low mood and anxiety are common during the menopausal transition and in the years after it, and hormone therapy is not an option or a preference for every woman. Non-hormonal medicines, including the SSRI and SNRI classes of antidepressant and the gabapentinoids, are widely prescribed instead. Yet the evidence comparing these classes has been fragmented, spread across studies that differ in design, population and outcome measures. This review set out to bring that scattered evidence together and ask which non-hormonal options actually have support for mood and anxiety symptoms in this stage of life.

The authors searched six databases and trial registries for randomised and non-randomised studies evaluating SSRIs, SNRIs, gabapentinoids and other pharmacotherapies for depressive and anxiety symptoms during the menopausal transition and postmenopause. Thirty-one studies covering 8,124 participants met the criteria. Because the studies varied so much in their methods and populations, the team could not combine results statistically; instead they used a structured approach for summarising evidence that is too different to pool, weighing the pattern of findings across studies and grading how certain each conclusion could be.

SNRIs showed positive effects on depressive symptoms more frequently than any other drug class examined. SSRIs demonstrated modest and variable effects on mood. Gabapentinoids consistently improved vasomotor symptoms, the hot flushes and related complaints of menopause, but their effects on mood were limited and backed by low-certainty evidence. For anxiety, the evidence was inconsistent across every class studied. Overall certainty ranged from very low to moderate, and no study compared the classes head to head.

This synthesis fills a practical gap, since clinicians and patients have long had to choose between non-hormonal options without comparative evidence. It complicates rather than settles the picture: the lean towards SNRIs is a pattern across separate studies, not the result of direct comparison, and the authors flag indirectness and inconsistency as central weaknesses. The clearest conclusion may be about what is missing, namely head-to-head trials and better evidence on anxiety outcomes in menopausal women specifically.

For women navigating mood changes around menopause who cannot or prefer not to use hormones, this is confirmation that pharmaceutical options exist and that the current evidence leans towards SNRIs for depressive symptoms. It is equally a reason for measured expectations: the anxiety evidence is inconsistent, and gabapentinoids appear better suited to hot flushes than to mood. Knowing where the evidence leans, and how thin it is, makes for a better-informed conversation with a prescriber.