Depression Risk of 5-Alpha Reductase Inhibitors: A Systematic Review and Meta-Analysis with a Focus on Comparator Groups

    August 2025 in “ medRxiv (Cold Spring Harbor Laboratory) ”
    Minh Thien Nguyen, Tien Hoang Tran, J. Donovan
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    TLDR 5-alpha reductase inhibitors may increase depression risk by 31%, but results vary based on comparison groups.
    This systematic review and meta-analysis investigated the association between 5-alpha reductase inhibitors (5-ARIs) and depression, analyzing data from 5 longitudinal studies with a total of 2,517,859 patients. The study found that 5-ARI use was associated with a 31% increased risk of depression, although there was high heterogeneity in the results. The choice of comparator group significantly influenced the findings, with studies using non-drug controls showing a higher risk of depression, while those using alpha-blocker comparators showed a decreased risk. The results suggest that concerns about 5-ARIs may be overstated in studies with inappropriate control groups, highlighting the importance of comparator selection in pharmacoepidemiologic research.
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