Beta-blocker therapy and symptoms of depression,fatigue, and sexual dysfunction

Context  -Blocker therapy remains substantially underused in cardiac patientsdespite its proven mortality benefits. Reluctance to prescribe these agentsmay derive from concerns about their association with symptoms of depression,fatigue, and sexual dysfunction. Objective  To determine the association of -blockers with depressive symptoms,fatigue, and sexual dysfunction by performing a quantitative review of randomizedtrials that tested -blockers in myocardial infarction, heart failure,and hypertension. Data Sources  Randomized trials of -blockers used in the treatment of myocardialinfarction, heart failure, or hypertension were identified by searching theMEDLINE database for English-language articles (1966-2001). In addition, wesearched the reference lists of previously published trials and reviews of -blockersfor additional studies. Study Selection  Criteria for inclusion of trials in the review were: random allocationof study treatments, placebo control, noncrossover design, enrollment of atleast 100 patients, and a minimum of 6 months of follow-up. The initial searchproduced 475 articles, 42 of which met these criteria. Fifteen of these trialsreported on depressive symptoms, fatigue, or sexual dysfunction and were selectedfor inclusion. Data Extraction  For each trial, 1 author abstracted the frequency of adverse eventsin the -blocker and placebo groups and the numbers of patients randomizedto the treatment groups. Two other authors verified the counts of events,and all authors adjudicated any discrepancies. Two different types of informationon adverse events were abstracted: patient-reported symptoms and withdrawalof therapy due to a specified symptom. We categorized the tested -blockersby generation (early vs late) and lipid solubility (high vs low to moderate). Data Synthesis  The 15 trials involved more than 35 000 subjects. -Blockertherapy was not associated with a significant absolute annual increase inrisk of reported depressive symptoms (6 per 1000 patients; 95% confidenceinterval CI], –7 to 19). -Blockers were associated with a smallsignificant annual increase in risk of reported fatigue (18 per 1000 patients;95% CI, 5-30), equivalent to 1 additional report of fatigue for every 57 patientstreated per year with -blockers. -Blockers were also associatedwith a small, significant annual increase in risk of reported sexual dysfunction(5 per 1000 patients; 95% CI, 2-8), equivalent to one additional report forevery 199 patients treated per year. None of the risks of adverse effectsdiffered significantly by degree of -blocker lipid solubility. The riskassociated with reported fatigue was significantly higher for early-generationthan for late-generation -blockers (P = .04). Conclusion  The conventional wisdom that -blocker therapy is associated withsubstantial risks of depressive symptoms, fatigue, and sexual dysfunctionis not supported by data from clinical trials. There is no significant increasedrisk of depressive symptoms and only small increased risks of fatigue andsexual dysfunction. The risks of these adverse effects should be put in thecontext of the documented benefits of these medications.