Beta-Blockers Could Cause Sleep Disturbances, But Not Linked to Depression

Reinhold Kreutz, MD, PhD

Despite notions derived from previous data, new research from an international team of investigators indicate use of beta-blockers was not linked to depression but could contribute to sleep disturbances.

Published in the American Heart Association’s Hypertension journal, results of the systematic review and meta-analysis, which included data from more than 280 trials, found beta-blockers were not associated with an increased risk for psychiatric adverse events and concern over their impact on psychological health should not dissuade from use in clinical practice.

"The possible mental health side effects of beta-blockers have been the subject of discussion in the scientific community for many decades," said Reinhold Kreutz, MD, PhD, a lead investigator and professor at the Berlin Institute of Health, Institute of Clinical Pharmacology and Toxicology, in a statement. "So, our results showing beta-blockers are not the cause of so many of these negative side effects are quite consequential."

Used in the treatment of multiple forms of cardiovascular disease, Kreutz and a team of colleagues from the Berlin Institute of Health and Freie Universität Berlin sought to draw a more clear determination on the effects of beta-blockers on the psychological health of patients using data from randomized trials. To do so, the team designed their study as a systematic review and meta-analysis of double-blind, randomized controlled trials within the PubMed, Embase, and WebofScience databases from inception to September 11, 2020.

Investigators also searched ClinicalTrials.gov, EU Clinical Trials Register, Clinical Study DataRequest, the YODA PROJECT, and study registers from Allergan and GlaxoSmithKline for information on unpublished clinical trials.

After their initial search returned nearly 48,000 records, the application of inclusion criteria resulted in 2264 records being assessed for eligibility in full text. After further application of inclusion criteria, investigators identified 285 studies for inclusion in a qualitative analysis and 151 studies for inclusion in quantitative analysis. Within the 285 studies included in the analyses, investigators obtained data related to 53,533 patients and 24 different beta-blockers.

Upon analysis, investigators found 1600 cases of depression were reported within the 285 trials deemed eligible for inclusion in qualitative analysis. However, investigators noted depression did not occur more commonly among patients receiving beta-blockers than those receiving placebo (OR, 1.02; 95% CI, 0.83-1.25).

Results also indicated beta-blocker use was not associated with withdrawal for depression when compared to placebo (OR, 0.97; 95% CI, 0.51-1.84) and similar results were observed in trials that compared beta-blockers to other active comparators. Investigators pointed out the only psychiatric adverse events possibly related to beta-blocker therapy based on the results of their analyses were unusual dreams, insomnia, and sleep disorders.

"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,” added Kreutz.

Investigators cautioned against overinterpretation of their results—pointing out many of trials were conducted more than 20 years ago and including only randomized controlled trials limited the amount of long-term data included in their analyses.

This study, "Do β-Blockers Cause Depression?,” was published in Hypertension.