Risk of Incident Antidepressant-Treated Depression Associated with Use of 5α-Reductase Inhibitors Compared with Use of α-Blockers in Men with Benign Prostatic Hyperplasia: A Population-Based Study Using the Clinical Practice Research Datalink

STUDY OBJECTIVE To estimate the risk of incident antidepressant-treated depression in men with benign prostatic hyperplasia (BPH) who were prescribed 5 alpha-reductase inhibitors (5-ARIs) compared with those prescribed an active comparator, alpha-blockers (ABs). DESIGN Retrospective cohort study with a nested case-control analysis. DATA SOURCE United Kingdom's Clinical Practice Research Datalink. PATIENTS A total of 77,732 men with a diagnosis of BPH who received a prescription for a 5-ARI only and/or AB between January 1, 1992, and December 31, 2013. Of these men, 2842 had a first-time (incident) diagnosis of depression and received a prescription for an antidepressant within 90 days of the depression diagnosis date (cases); 11,333 controls without a diagnosis of depression were matched to the cases for the case-control analysis. MEASUREMENTS AND MAIN RESULTS Exposures were classified as 5-ARI only, 5ARI + AB, or AB only. We calculated incidence rates of antidepressant-treated depression and compared rates among users of 5-ARIs only and 5-ARIs + ABs with rates among users of ABs only (i.e., incidence rate ratios [IRRs]). We also calculated odds ratios (ORs) to estimate the risk of incident depression with use of 5-ARIs only and 5-ARIs + ABs compared with ABs only. In this population of men with BPH, the risk of depression was not increased with use of 5-ARIs only (IRR 0.94, 95% confidence interval [CI] 0.85-1.04) or 5-ARIs + ABs (IRR 1.04, 95% CI 0.89-1.21) compared with use of ABs only. In the case-control analysis, exposure to 5-ARIs only (adjusted OR 0.88, 95% CI 0.78-1.01) or 5-ARIs + ABs (adjusted OR 0.90, 95% CI 0.73-1.10) was not associated with the risk of treated depression compared with exposure to ABs only, and results remained null regardless of number of prescriptions or timing of exposure. The risk of incident antidepressant-treated depression increased with longer duration of BPH, independent of study drug exposure. CONCLUSION In this population of men with treated BPH, use of 5-ARIs, alone or in combination with ABs, did not increase the risk of incident antidepressant-treated depression compared with use of ABs only. Risk of treated depression increased with longer duration of BPH.