Lack of Association between 5α-Reductase Inhibitors and Depression

Depressed mood and suicidality reported with 5α-reductase inhibitors (finasteride and dutasteride) during post-marketing surveillance resulted in the addition of depression risk to finasteride labeling. As peer reviewed studies are limited and have reported mixed findings, we further evaluated 5α-reductase inhibitor exposure and depression risk using sequence symmetry analysis.

National Veterans Health Administration administrative data were used to identify 53,848 male patients initiating 5α-reductase inhibitor therapy during fiscal year 2014. Incident depression events were assessed separately using the 2 measures of antidepressant prescription and depression diagnosis. Symmetry ratios were calculated as the ratio of patients with an incident depression event in the year following 5α-reductase inhibitor initiation to the year preceding initiation. An identical exposure counterfactual analysis was conducted among veterans initiating α1-adrenergic receptor antagonists.

Incident antidepressant prescribing was observed in 2,563 patients following 5α-reductase inhibitor initiation and 3,051 patients preceding 5α-reductase inhibitor initiation (SR 0.84, 95% CI 0.80-0.89). Similar findings were observed for incident depression diagnosis (SR 0.83, 95% CI 0.79-0.86). Stratification by age group, 5α-reductase inhibitor agent, antidepressant class, prior α1-adrenergic receptor antagonist exposure and depression diagnosis type failed to demonstrate any positive association between 5α-reductase inhibitor and depression. Nearly identical results were observed in the α1-adrenergic receptor antagonist analysis (SR 0.87, 95% CI 0.84-0.90).

Initiation of a 5α-reductase inhibitor was not associated with increased risk of depression. Our findings support the hypothesis that depression is more likely attributable to underlying benign prostatic hyperplasia and associated lower urinary tract symptoms than 5α-reductase inhibitor exposure.