Meta-analysis: Beta-blockers not linked to depression or adverse mental health events

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A meta-analysis of large-scale data from double-blind, randomised controlled trials does not support an association between β-blocker therapy and depression or other adverse mental health events, with the possible exceptions of sleep-related disorders.

Beta-blockers are a class of medications that reduce the heart rate, the heart's workload and the heart's output of blood, which, together, lower blood pressure. They are a common treatment for cardiovascular diseases, including heart failure, arrhythmias, chest pains and high blood pressure. Researchers have suspected beta-blockers of having 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," says Dr Reinhold Kreutz, a professor at the Berlin Institute of Health, Institute of Clinical Pharmacology and Toxicology and the study's supervising and corresponding author. "So, our results showing beta-blockers are not the cause of so many of these negative side effects are quite consequential."

The study is the first of its kind to examine the entire spectrum of mental health side effects in relation to beta-blockers. The researchers analysed data for more than 50,000 individuals from 258 studies including beta-blockers in double-blind, randomised controlled trials. Nearly 70% of the studies were clinical trials focused on high blood pressure treatment, and 31 assessed depression in placebo-controlled trials.

Results from the comprehensive analysis revealed:
Despite being the most frequently reported mental health side effect, depression did not occur more frequently during beta-blocker treatment compared to placebo treatment.
The rate of discontinuing medication use due to depression was not any different for those taking beta-blockers compared to those on other treatments.

Unusual dreams, insomnia and sleep disorders may be linked to beta-blockers.
Among the mental health events analysed, the most common reason for discontinuing beta-blockers was fatigue/tiredness.

"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," said Kreutz. "We found no indication of an association between beta-blocker use and depression. The same was true for most of the other mental health symptoms, as reported in the studies that were included in our analyses. However, sleep-related symptoms such as unusual dreams or insomnia did emerge during beta blocker therapy for some patients."

Kreutz added, "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."

The original studies did not include individual patient data, so for this analysis, researchers were unable to investigate whether sleep-related symptoms were persistent for those taking beta-blockers. Additional research is needed to address this question.

The researchers report there an important limitation to consider when interpreting the results of their analysis: most beta-blocker trials were conducted more than 20 years ago, before a uniform language to describe adverse events was established. Additionally, the authors only considered randomised, double-blind trials for their analysis, which left out some studies that might provide more data on long-term beta-blocker treatment.

 

Study details
Do β-Blockers Cause Depression?

Thomas G. Riemer, Linda E Villagomez Fuentes, Engi AE Algharably, Marie S Schäfer, Eva Mangelsen, Marc-Alexander Fürtig, Nadine Bittner, Annalena Bär, Laila Zaidi Touis, Kristian Wachtell, Tomislav Majic, Martin . Dinges, Reinhold Kreutz

Published in Hypertension on 15 March 2021

Abstract
β-Blockers are important drugs in the treatment of cardiovascular diseases. They are suspected of inducing various psychiatric adverse events (PAEs), particularly depression, affecting cardiovascular morbidity and mortality. We performed a systematic search for double-blind, randomized controlled trials investigating β-blockers to analyze the risk of PAEs or withdrawal of therapy due to PAEs. We extracted the frequencies of PAEs and rates of withdrawals and reviewed them to the number of exposed patients. For β-blockers versus placebo or other active treatment, we calculated odds ratios for individual PAEs and withdrawal rates. We retrieved overall 285 eligible studies encompassing 53 533 patients. The risk of bias was judged to be high in 79% of the studies. Despite being the most frequently reported PAE with a total of 1600 cases, depression did not occur more commonly during β-blockers than during placebo (odds ratio, 1.02 [95% CI, 0.83–1.25]). β-Blocker use was also not associated with withdrawal for depression (odds ratio, 0.97 [95% CI, 0.51–1.84]). Similar results were obtained for comparisons against active agents. Among other PAEs, only unusual dreams, insomnia, and sleep disorder were possibly related to β-blocker therapy. In conclusion, this analysis of large-scale data from double-blind, randomized controlled trials does not support an association between β-blocker therapy and depression. Similarly, no effect for β-blockers was found for other PAEs, with the possible exceptions of sleep-related disorders. Consequently, concerns about β-blockers’ impact on psychological health should not affect their use in clinical practice.

 

American Heart Association material

 

Hypertension study (Restricted access)

 

See also MedicalBrief archives:

Researchers look for links between prescription drugs and depression

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