Do beta-blockers cause depressive symptoms?
||Response from Laura S. Lehman, PharmD
Clinical Pharmacy Coordinator, Carrol Hospital Center, Westminster, Maryland
Beta-blockers are used for various cardiac and noncardiac conditions. Certain beta-blockers decrease morbidity and mortality in myocardial infarction (MI) and heart failure (HF). Unfortunately, side effects limit their use in certain patients.
Depression is listed as an adverse reaction in the product labeling of many beta-blockers, and is based primarily on early case reports. The American Heart Association has stated that depression is a risk factor for poor outcomes in patients with acute coronary syndrome; thus, it is important to determine whether beta-blockers are associated with depressive symptoms.
A Long-Reported Adverse Effect
Initial reports of depression were with propranolol, whose lipophilic structure and central nervous system penetration could explain the development of mental depression. In a 1967 correspondence published in the British Medical Journal, Waal reported a case series of 89 hypertensive patients treated with propranolol for cardiac arrhythmias and noted a dose- and duration-related increase in incidence of depression. Subsequent studies evaluating an association between beta-blocker use and depression have demonstrated mixed results, prompting more recent investigations to attempt to set the record straight.
Why, after decades of widespread use of these drugs, has it been difficult to determine whether indeed beta-blockers cause depression? Earlier studies of depression and beta-blockers were noted to have differed in their study populations, study designs, and methods of assessing depression. Of note, Luijendijk and Koolman reviewed 22 studies assessing beta-blocker use and depression and found them to fit a pattern of publication bias. Positive studies (an association is seen) were published first, followed by negative studies (no association seen or inconclusive) using a similar study design. This implies that false-positive findings triggered studies that subsequently refuted them.
On the other hand, the authors noted that many of the negative studies were underpowered, with potential for false-negatives. They noted that most of the negative studies with inconclusive results did lean toward an association between propranolol and depression, yet the overall answer is still unclear. Publication bias has made it difficult to definitively rule in or rule out an association between beta-blockers and depression.