BETA-BLOCKERS AND DEPRESSION - THE MORE THE MURKIER

OBJECTIVE: To review the literature regarding the purported associatio n between oral ingestion of beta-blocker drugs and depressed mood. DAT A SOURCE: MEDLINE was searched for published articles using the key wo rds propranolol, atenolol, metoprolol, nadolol, timolol, beta-blocker, beta-adrenergic antagonist, or beta-adrenergic blocker in combination with the key words depression, depressive symptomatology, major depre ssive disorder, or depressed mood from January 1966 through December 1 996. DATA SYNTHESIS: Findings regarding the association are equivocal. Plausible explanations include study design, case definition, and con founding disease states. Most of the evidence supporting an associatio n has used case series and case reports. Findings from cross-sectional observational studies and case-control studies are equivocal. Case de finition and measurement instruments may partially explain these incon sistencies. Studies using a diagnosis of depression generally do not s upport the relationship. Trials using depressive symptoms are about ev enly split, but they have generally enrolled a small number of patient s and have questionable statistical power. Studies defining antidepres sant prescriptions dispensed as a marker for depression generally supp ort the association. Evidence exists both for and against the hypothes is that lipophilic beta-blockers cause more depression than do hydroph ilic beta-blockers. CONCLUSIONS: beta-Blockers may have been unjustly associated with depression and their use avoided for that reason. Futu re studies into the association between depression and beta-blocker us e should evaluate whether the association is affected by case definiti on and study design characteristics, including disease, dose-response, bias, measurement error, or ability to precisely measure the length o f the exposure.