Depression Risk of 5-Alpha Reductase Inhibitors: Impact of Active-Comparator Versus Non-Drug User Control Groups on Risk Measurement

This meta-analysis examined the risk of depression associated with 5-alpha reductase inhibitors (5-ARIs) across 5 longitudinal studies involving 2,517,859 patients. The findings indicate a 31% increased risk of depression with 5-ARI use, though this risk varies significantly depending on the control group used. Studies with non-drug controls reported a higher risk, while those with alpha-blocker comparators showed a decreased risk. The choice of comparator group was a major source of heterogeneity in the results. Overall, the risk of depression with 5-ARI use is likely minimal, with observational data suggesting a slight reduction in risk and randomized data indicating a potential slight increase. Previous reports of a much higher risk may have resulted from inappropriate control group selection.