Drug or symptom-induced depression in men treated with alpha 1-blockers for benign prostatic hyperplasia? A nested case-control study.

Purpose: Regulatory authorities have raised concern that alpha 1-blockers, prescribed predominantly for benign prostatic hyperplasia (BPH), may be associated with an increased risk of depression. The aim was to assess the risk of depression with alpha 1-blockers independently of that associated with symptoms being treated and concurrent illness.

Methods: Using a study population registered on the UK General Practice Research Database, and taking a prescription for an antidepressant as a proxy for clinical depression, we performed: (a) cohort analyses comparing the incidence of depression in current users of alpha 1-blockers versus non-users, and in men with BPH versus those without. (b) A nested case-control analysis looking at the association between depression and alpha 1-blocker exposure, accounting for the presence of BPH and other illness.

Results: In the cohort analyses, risk of depression was significantly higher in men with BPH compared to those without (IRR 2.17, 2.12-2.22), but was not significantly different for men exposed to alpha 1-blockers versus those unexposed when adjusted for the presence of BPH. Cases of depression were more likely to have pre-existing BPH (crude OR 2.09, 2.02-2.15) than controls. After adjusting for concurrent illness (using number of GP visits as a proxy) and the presence of BPH (adjusted OR 1.38, 1.33-1.43), there was no association with depression for exposure to any alpha 1-blocker (adjusted OR 1.03, 0.90-1.18).

Conclusions: This study did not suggest that the prescribing of alpha 1-blockers increases the risk of being depressed. The association highlighted by spontaneous reporting systems appears to be explained by confounding by concurrent disease.