Among Antihypertensives, Neuropsychiatric Events Seen in Beta-Blockers

While the increased rate of side effects such as hallucinations and nightmares shouldn’t significantly alter the use of beta-blockers in blood-pressure management, it could be more relevant to their off-label use for social anxiety disorder.

A study published in the Journal of Psychopharmacology that used the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) indicates that beta-blockers are linked to an elevated risk of neuropsychiatric adverse drug events (ADEs) compared with other blood-pressure medications.
“While case reports and older studies suggested that beta-blockers—especially those that cross into the brain—might cause problems like nightmares, insomnia, or hallucinations, many of these side effects have never been properly studied,” senior author Flory T. Muanda, M.D., Ph.D., an assistant professor of physiology and pharmacology at Western University in London, Ontario, said in an email to Psychiatric News.
A previously published systematic review and meta-analysis that Muanda had been a part of suggested beta-blockers—which block the effects of adrenaline on blood vessels—carry an increased risk of neuropsychiatric side effects, “but the evidence was uncertain and incomplete.”
Weighing the Potential Risks
To get more clarity, this study looked at all adverse events reported to the FDA from January 1, 2004, to December 31, 2023, that were linked to beta-blocker use and compared them with reports of ADEs linked to the antihypertensives lisinopril and losartan (which target a protein called angiotensin II rather than adrenaline). They adjusted for factors such as sex, age, weight, and cardiovascular conditions such as heart failure and atrial fibrillation.
Overall, beta-blockers were linked to increased reported odds of a nervous system–related event (such as dizziness) or a psychiatric event (such as hallucinations) compared with lisinopril (2.08 and 1.68 times more likely, respectively) or losartan (1.29 and 1.53 times more likely, respectively). Among individual side effects assessed, beta-blockers were associated with significantly elevated risks of nightmares, somnolence, and disorientation.
“Our study does not provide evidence to broadly replace beta-blockers (with other drugs) for hypertension,” Muanda said. “Our analysis of reported side effects in FAERS highlights potential safety signals, but it cannot measure how often these effects actually occur or prove that beta-blockers cause them. The main takeaway is that clinicians should be aware of these potential risks and weigh them when choosing a beta-blocker, particularly for patients who may be more vulnerable to neuropsychiatric effects.”
Muanda and colleagues also compared the impact of hydrophilic beta-blockers, such as propranolol, and lipophilic beta-blockers, such as atenolol, to determine if there was any difference in the frequency of neuropsychiatric ADEs with either type of beta-blocker.
“Lipophilic beta-blockers, specifically propranolol, were reported more often with neuropsychiatric side effects such as delirium, hallucinations, and disorientation, whereas hydrophilic beta-blockers like atenolol had fewer reports,” Muanda said. “This supports the idea that a drug’s ability to cross the blood-brain barrier may be linked to these central nervous system effects.”
These findings may suggest that hydrophilic beta-blockers may be a better option for minimizing the risk of neuropsychiatric adverse events. “The results, however, should be interpreted cautiously given the limitations of FAERS databases,” Muanda said, “and further studies are needed to confirm this relationship (between lipophilic beta-blockers and the risk of neuropsychiatric adverse events) with more comprehensive data.”
The Importance of Cooperation
Nina Kraguljac, M.D., M.A., chair of APA’s Council on Research and professor and executive vice chair of psychiatry and behavioral health at Ohio State University, commented that the study offered robustness because it used active comparators like lisinopril and losartan, which are used in a similar patient population as beta-blockers but have different mechanisms of action. “That was a real strength of the study,” Kraguljac said. “Most previous studies did not use active comparators. It also included data from almost 20 years of [reports].”
Kraguljac emphasized that the study does not suggest that other antihypertensives can be substituted for beta-blockers or that beta-blockers should be avoided. “There are benefits that beta-blockers offer that other medications that treat blood pressure do not,” she said. “It’s really the call of a cardiologist.”
Rather, the study’s findings reinforce the importance of cooperation across specialties. “Psychiatrists need to collaborate very closely with a cardiologist to decide together what the risk-benefit ratio is for their patients,” Kraguljac said.
For example, if a patient develops insomnia as a result of taking a beta-blocker, but their blood pressure is under control, offering an intervention like cognitive behavioral therapy for insomnia may be a better option than switching medications.
Off-Label Prescribing for Social Anxiety
Pierre Blier, M.D., Ph.D., a professor of psychiatry and cellular and molecular medicine at the University of Ottawa and endowed chair in mood disorders research at uOttawa’s Institute of Mental Health Research, said that the study findings should factor into clinical decision-making around the off-label prescription of some beta-blockers for social anxiety—notably propranolol.
“I hope [psychiatrists] would take the conclusions of this paper into consideration [if they are potentially choosing propranolol to treat social anxiety],” said Blier, one of the authors of the 2014 Canadian clinical practice guidelines on the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders, which are currently being updated.
“In our [2014] Canadian guidelines for the treatment of anxiety disorders, propranolol is not recommended, and that’s on the basis of controlled studies that had been published,” Blier said, adding that the Canadian guidelines also don’t recommend atenolol to manage social anxiety disorder. “People have looked at [propranolol to treat social anxiety] more recently in meta-analyses with more up-to-date reviews,” he said. “There is still no evidence for efficacy.”
As such, the forthcoming updated Canadian guidelines will continue to not recommend propranolol or atenolol as medications to manage social anxiety, Blier said. 
Resources
“Β-Blockers and Risk of Neuropsychiatric Adverse Events: An Active-Comparator Restricted Disproportionality on the FAERS”
“Canadian Clinical Practice Guidelines for the Management of Anxiety, Posttraumatic Stress and Obsessive-Compulsive Disorders”


https://psychiatryonline.org/doi/10.1176/appi.pn.2025.11.11.17