beta-Blockers and the Risk of Incident Depression in the Elderly

The hypothesis that beta-blockers cause depression has been both confirmed and refuted in previous studies. However, in hardly any of these studies, depression was systematically and adequately assessed. The aim of this cohort study was to examine whether beta-blockers, in general, highly lipid-soluble, nonselective, or serotonergic receptor-binding beta-blockers, are associated with incident depression. Between 1993 and 2005, 5104 elderly persons were followed for incident depressions. Depressions were identified by regular interview and continuous monitoring of medical records. Cases were categorized as clinically relevant depressive symptoms or as depressive syndromes, the latter including Diagnostic and Statistical Manual of Mental Disorders-IV-defined depressive disorders. Pharmacies provided information on filled beta-blockers. We used Cox regression with drug use as a time-dependent variable to analyze the data, adjusted for potential demographic covariates, activity of daily living, and (contra) indications for beta-blockers. We found that use of beta-blockers in general did not convey an increased risk of depressive symptoms (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.37-1.59) or depressive syndromes (HR, 0.99; 95% CI, 0.53-1.84). Highly lipid-soluble beta-blockers, mostly propranolol in our study, were associated with depressive symptoms during the first 3 months of use (HR, 3.31; 95% CI, 1.03-10.6), but not with depressive syndromes. Nonselective or serotonergic receptor affinity was not associated with an increased risk of depressive symptoms or syndromes independent of high lipid solubility. We conclude that beta-blockers in general do not convey an increased risk of depression. Lipophilic beta-blockers are associated with an increased risk of depressive symptoms.