β-blockers and risk of neuropsychiatric adverse events: An active-comparator restricted disproportionality on the FAERS

Background: β-blockers (β-adrenoceptor antagonists), commonly used for cardiovascular conditions, may be linked to neuropsychiatric adverse events (AEs). However, many prevalent ones, including delirium and hallucinations, remain insufficiently studied. Aims: To compare the neuropsychiatric risks of β-blockers with other antihypertensive drugs using data from the FDA Adverse Event Reporting System (FAERS) and differences between lipophilic and hydrophilic β-blockers. Method: An active-comparator restricted disproportionality analysis was conducted using data from the FAERS (2004Q1–2023Q4). Neuropsychiatric AEs were analyzed using Preferred Terms and the System Organ Classes from the Medical Dictionary for Regulatory Activities for β-blockers compared to lisinopril and losartan. Adjusted Reporting Odds Ratios (aRORs) were calculated using logistic regression to account for potential confounders. Results: β-blockers were linked to a significantly higher risk of nervous and psychiatric disorders, compared to lisinopril and losartan. Among the nine types of neuropsychiatric events studied, six—dizziness, nightmares, insomnia, hallucinations, somnolence, and disorientation—showed higher aRORs with β-blockers. Propranolol, a lipophilic β-blocker, exhibited the highest aRORs for psychiatric disorders and six types of neuropsychiatric events, including nightmares, delirium, hallucinations, disorientation, altered mental status, and somnolence, compared to lisinopril and losartan. Compared to atenolol, propranolol remained significantly associated with delirium, hallucinations, and disorientation. Conclusion: β-blockers, especially propranolol, may be associated with a higher risk of neuropsychiatric AEs compared to lisinopril and losartan. These findings highlight the importance of considering the specific β-blocker prescribed, particularly in patients at risk for central nervous system side effects. Further population-based studies are warranted to confirm these results.