Drugs such as beta-adrenergic antagonists (beta blockers) have been linked to a range of adverse effects, including depression. But how reliable are these data, and which psychiatric side effects might indeed be caused by these drugs?

These questions have recently been addressed by a team of researchers from Charité-Universitätsmedizin Berlin, which published a meta-analysis, “Do β-blockers cause depression? Systematic review and meta-analysis of psychiatric adverse events during β-blocker therapy,” in the journal Hypertension. While treatment with beta blockers was not found to be associated with an increased incidence of depression, some studies recorded higher levels of sleep disturbance.

“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,” write the investigators.

“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.”

Beta-adrenergic antagonists such as metoprolol or propranolol are among the drugs most commonly prescribed for the treatment of cardiovascular disease. Their effect is to slow the heart rate and reduce blood pressure, which is why they are used in patients with heart failure, arrhythmias, and high blood pressure. Beta blockers have repeatedly been linked to an increased risk of depression, but also other side effects such as anxiety, sleep disturbance and hallucinations; these links had not previously been explored in a systematic manner.

“We found no evidence to suggest a link between the use of beta blockers and depression,” says Reinhold Kreutz, MD, PhD, director of Charité’s Institute of Clinical Pharmacology and Toxicology. “The same also goes for most of the other psychiatric symptoms described in the studies included in our analysis.”

Continuing his description of the meta-analysis conducted by his team—reportedly the first to study the full range of psychiatric side effects–he adds: “However, some patients developed sleep-related symptoms during treatment with beta blockers.”

The researchers analyzed data from more than 53,000 persons. These were taken from 285 individual studies and involved 24 different beta blockers. Only data from double-blind, randomized, controlled trials were included in the analysis. The majority of these related to high blood pressure and had been conducted more than 20 years ago.

Despite being the most commonly reported psychiatric side effect, depression did not occur more frequently during treatment with beta blockers than during treatment with a placebo. Kreutz, currently President of the European Society of Hypertension, explains that “Patients with a history of cardiovascular problems such as heart attack or stroke are per se prone to develop mental health complications. This means that, while we found no causal link for this problem with beta blockers, these patients should be anyway monitored in this regard in clinical practice.”

Patients treated with beta blockers were no more likely to discontinue their medications due to depression than patients undergoing different treatments. However, drowsiness and fatigue were the most commonly reported reasons for discontinuing treatment. Among the other side effects studied, such as anxiety and loss of appetite, memory, or libido, only sleep disturbance and abnormal dreams were found to be linked with beta blockers.

“Our results show that concerns regarding undesirable psychiatric effects, in particular depression, should not influence the decision-making process regarding the use of beta blockers,” says Kreutz. “For the most part, beta blockers have a good psychiatric safety profile,” and concerns about psychological health should not affect the clinical use of beta-blockers.

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