Berlin, Germany—Questions have been raised for years about whether widely prescribed beta-blockers can cause depression. Now, a new international study provides some answers.

The report in Hypertension states that beta-blockers, used to treat various cardiovascular diseases (CVDs), were not more likely to cause depression compared with other similar treatments. Even when depression occurs during beta-blocker therapy, Berlin Institute of Health–led researchers suggest those medications are not the likely cause.

Beta-blockers, which lower blood pressure by reducing heart rate, workload, and output of blood, are a common treatment for cardiovascular diseases, including heart failure, arrhythmias, and chest pain, as well as hypertension.

Concerns have been raised about whether beta-blockers have negative psychological side effects, including depression, anxiety, drowsiness, insomnia, hallucinations, and nightmares.

“The possible mental health side effects of beta-blockers have been the subject of discussion in the scientific community for many decades,” explained supervising author Reinhold Kreutz, MD, PhD. “So, our results showing beta-blockers are not the cause of so many of these negative side effects are quite consequential.”

The study team performed a systematic search for double-blind, randomized, controlled trials investigating beta-blockers to analyze the risk of psychiatric adverse events (PAEs) or withdrawal of therapy due to PAEs. To do that, researchers extracted the frequencies of PAEs and rates of withdrawals and compared them with the number of exposed patients.

They then calculated odds ratios for individual PAEs and withdrawal rates for beta-blockers versus placebo or other active treatment.

Overall, 285 eligible studies involving 53,533 patients were retrieved. While the risk of bias was judged to be high in 79% of the studies and despite depression being the most frequently reported PAE with a total of 1,600 cases, it did not occur more commonly during beta-blocker treatment than placebo (odds ratio, 1.02 [95% CI, 0.83-1.25]), the authors report.

Furthermore, beta-blocker use also was not associated with withdrawal for depression (odds ratio, 0.97 [95% CI, 0.51-1.84]), with similar results obtained for comparisons with active agents.

“Among other PAEs, only unusual dreams, insomnia, and sleep disorder were possibly related to beta-blocker therapy,” the researchers note. “In conclusion, this analysis of large-scale data from double-blind, randomized controlled trials does not support an association between beta-blocker therapy and depression. Similarly, no effect for beta-blockers was found for other PAEs, with the possible exceptions of sleep-related disorders. Consequently, concerns about beta-blockers’ impact on psychological health should not affect their use in clinical practice.”

The study is touted as the first of its kind to examine the entire spectrum of mental-health side effects possibly linked to beta-blockers.

“Our results indicate that concerns about adverse mental health events, especially depression, should not affect the decision about beta blockers. Beta-blockers are mostly safe regarding psychological health,” Dr. Kreutz said, adding, “Patients with a history of cardiovascular events such as a heart attack or stroke were prone to develop psychological complications. Though we found beta-blockers were not causally linked, these patients should be monitored.”

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