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

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. 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. 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). 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.