Author Affiliations: Section of Cardiovascular Medicine, Department of Medicine (Drs Ko, Hebert, Curtis, and Krumholz), and Section of Health Policy and Administration, Department of Epidemiology and Public Health (Drs Sedrakyan and Krumholz), Yale University School of Medicine, and Yale–New Haven Hospital Center for Outcomes Research and Evaluation (Dr Krumholz), New Haven, Conn; and Department of Biostatistics, University of Alabama at Birmingham (Dr Coffey).
Context β-Blocker therapy remains substantially underused in cardiac patients
despite its proven mortality benefits. Reluctance to prescribe these agents
may derive from concerns about their association with symptoms of depression,
fatigue, and sexual dysfunction.
Objective To determine the association of β-blockers with depressive symptoms,
fatigue, and sexual dysfunction by performing a quantitative review of randomized
trials that tested β-blockers in myocardial infarction, heart failure,
Data Sources Randomized trials of β-blockers used in the treatment of myocardial
infarction, heart failure, or hypertension were identified by searching the
MEDLINE database for English-language articles (1966-2001). In addition, we
searched the reference lists of previously published trials and reviews of β-blockers
for additional studies.
Study Selection Criteria for inclusion of trials in the review were: random allocation
of study treatments, placebo control, noncrossover design, enrollment of at
least 100 patients, and a minimum of 6 months of follow-up. The initial search
produced 475 articles, 42 of which met these criteria. Fifteen of these trials
reported on depressive symptoms, fatigue, or sexual dysfunction and were selected
Data Extraction For each trial, 1 author abstracted the frequency of adverse events
in the β-blocker and placebo groups and the numbers of patients randomized
to the treatment groups. Two other authors verified the counts of events,
and all authors adjudicated any discrepancies. Two different types of information
on adverse events were abstracted: patient-reported symptoms and withdrawal
of therapy due to a specified symptom. We categorized the tested β-blockers
by generation (early vs late) and lipid solubility (high vs low to moderate).
Data Synthesis The 15 trials involved more than 35 000 subjects. β-Blocker
therapy was not associated with a significant absolute annual increase in
risk of reported depressive symptoms (6 per 1000 patients; 95% confidence
interval [CI], –7 to 19). β-Blockers were associated with a small
significant 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 patients
treated per year with β-blockers. β-Blockers were also associated
with a small, significant annual increase in risk of reported sexual dysfunction
(5 per 1000 patients; 95% CI, 2-8), equivalent to one additional report for
every 199 patients treated per year. None of the risks of adverse effects
differed significantly by degree of β-blocker lipid solubility. The risk
associated with reported fatigue was significantly higher for early-generation
than for late-generation β-blockers (P = .04).
Conclusion The conventional wisdom that β-blocker therapy is associated with
substantial risks of depressive symptoms, fatigue, and sexual dysfunction
is not supported by data from clinical trials. There is no significant increased
risk of depressive symptoms and only small increased risks of fatigue and
sexual dysfunction. The risks of these adverse effects should be put in the
context of the documented benefits of these medications.
Ko DT, Hebert PR, Coffey CS, Sedrakyan A, Curtis JP, Krumholz HM. β-Blocker Therapy and Symptoms of Depression, Fatigue, and Sexual Dysfunction. JAMA. 2002;288(3):351-357. doi:10.1001/jama.288.3.351