β-Blockers May Raise Depression Risk for Heart Attack Survivors Without Heart Failure

β-blockers, long trusted for survivors of heart attacks, may not be as essential or safe for all patients as once believed.

A recent study from Sweden suggests these drugs could increase depression risk in heart attack survivors who retained normal heart pumping function afterward.¹

“At the same time, beta blockers have no life-sustaining function for this group of patients,” Philip Leissner, lead study author and doctoral student in cardiac psychology at Uppsala University, said in a news release.²

As part of the REDUCE-AMI trial, the study published in the European Heart Journal sheds light on a decades-long practice in cardiology.¹ Historically, β-blockers have been prescribed to most patients that have heart attacks to reduce their chance of having another one, and these drugs are typically taken for life.³ However, for those without heart failure after a heart attack, long-term β-blocker use was linked to higher rates of depression.¹

“This effect may be especially pronounced among individuals with previous beta-blocker use,” the study authors wrote. “Given the remaining clinical controversy regarding the initiation and discontinuation of beta-blockers after AMI [acute myocardial infarction], a potential risk of slightly increased depressive symptoms found in our study should be considered.”

β-blockers have been long trusted for survivors of heart attacks. | Image credit: JU.STOCKER – stock.adobe.com

The study included more than 800 heart attack survivors without heart failure, with half prescribed β-blockers and half not. Patients in the β-blocker group were given either metoprolol or bisoprolol while hospitalized and were prescribed these medications to continue after being discharged. Physicians were advised to prescribe a daily dosage of at least 100 mg of metoprolol or 5 mg of bisoprolol. The study tracked psychological outcomes over 5 years using the Hospital Anxiety and Depression Scale.

The results showed an increase in depression symptoms among patients taking β-blockers, with 14% of enrolled patients having possible depression at baseline. At the first follow-up 6 to 10 weeks after hospitalization, these patients had more depressive symptoms with an effect size of 0.48 (95% CI, 0.09-0.86; P = .015). At the second follow-up conducted 12 to 14 months later, the depressive impact persisted, with an effect size of 0.41 (95% CI, 0.01-0.81; P = .047).

While the study also looked at treatment’s effect on anxiety, the researchers saw no clear change among the 27% of patients with anxiety symptoms at baseline.

One proposed explanation for the increase in depressive symptoms involves the treatment’s interaction with neurotransmitters, potentially affecting the autonomous nervous system based on characteristics like liposolubility and cardioselectivity. Additionally, β-blocker may reduce patients' engagement in pleasurable activities, leading to symptoms of anhedonia—a key depressive feature measured by the Hospital Anxiety and Depression Scale.

Previous studies have suggested a link between these drugs and mood disorders, including depression, insomnia, and nightmares. The new findings add weight to these concerns and suggest that the risk of depression may be dose dependent. Specifically, patients who had already been taking β-blocker before joining the study experienced even greater increases in depressive symptoms, pointing to a possible cumulative effect over time.

“Most doctors used to give beta blockers even to patients without heart failure, but as the evidence in favor of doing so is no longer so strong, this should be reconsidered,” Leissner added.² “We could see that some of these patients appear to be more at risk of depression. If the drug doesn’t make a difference to their heart, then they are taking it unnecessarily and at risk of becoming depressed.”

A major limitation of the study is the potential for baseline bias, as measurements were taken after treatment assignment.¹ Selection bias may have also occurred due to the exclusion of some eligible patients, and the sample was generally healthier than typical heart attack populations. The use of the Hospital Anxiety and Depression Scale also limited the assessment to specific depressive and anxiety symptoms, possibly missing broader psychological effects.

References

1. Leissner P, Mars K, Humphries S, et al. Short- and long-term effects of beta-blockers on symptoms of anxiety and depression in patients with myocardial infarction and preserved left ventricular function: a pre-specified quality of life sub-study from the REDUCE-AMI trial. Eur Heart J Acute Cardiovasc Care. Published online October 3, 2024. doi:10.1093/ehjacc/zuae112
2. Patients may become unnecessarily depressed by common heart medicine. News release. Uppsala University. November 11, 2024. Accessed November 12, 2024. https://www.uu.se/en/press/press-releases/2024/2024-11-11-patients-may-become-unnecessarily-depressed-by-common-heart-medicine
3. Watch: What are beta blockers and what do they do in your body? British Heart Foundation. Accessed November 12, 2024. https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/drug-cabinet/beta-blockers