Lack of Association Between 5α-Reductase Inhibitors and Depression (04/2020)



Depressed mood and suicidality reported with 5α-reductase inhibitors (5-ARIs; 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 aimed to further evaluate 5-ARI exposure and depression risk using sequence symmetry analysis.


National Veterans Health Administration administrative data were used to identify 53,848 male patients initiating 5-ARI therapy during fiscal year 2014. Incident depression events were assessed separately using two measures: antidepressant prescription and depression diagnosis. Symmetry ratios (SR) were calculated as the ratio of patients with an incident depression event in the year following 5-ARI initiation to the year preceding initiation. An identical exposure counterfactual analysis was conducted among veterans initiating α-1-adrenergic receptor antagonists (α1-ARAs).


Incident antidepressant prescribing was observed in 2,563 patients following 5-ARI initiation and 3,051 patients preceding 5-ARI 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, 5-ARI agent, antidepressant class, prior α1-ARA exposure, and depression diagnosis type failed to demonstrate any positive association between 5-ARI and depression. Nearly identical results were observed in the α1-ARA analysis (SR: 0.87; 95% CI: 0.84-0.90).


Initiation of a 5-ARI 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 5-ARI exposure.

Does the study provide an age range? It just says veterans

That was my question too. It does say “stratification by age group…failed to demonstrate any positive association” but I would like to see the data.

I’ve emailed the lead author asking for a preprint. No response yet.

Another issue is that they do not look at post-discontinuation, and only look at the first year after being prescribed ARI, compared to the year before that. This is a limitation of many studies that find null results for hypothesized PFS symptoms.

It’s also not clear whether the post-5-ARI group took finasteride for the entire year after getting a prescription for it.