β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological-pharmacodynamic study

Aim: To compare different beta-adrenoceptor antagonists for the risk of reporting nightmare. Methods: The study involved two approaches: first, we investigated in VigiBase(R), the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each beta-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological-pharmacodynamic analysis, we assessed whether use of beta-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. Results: Of the 126,964 reports recorded with beta-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19-3.61), metoprolol (1.89, 1.66-2.16), and alprenolol (1.77, 1.06-2.97). Compared to use of low lipid solubility beta-adrenoceptor antagonists, use of moderate or high lipid solubility beta-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47-2.00 and aROR high vs. low 1.84, 95%CI 1.53-2.22). Use of moderate or high 5-HT1A affinity of beta-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of beta-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04-1.43 and aROR high vs. low 2.46, 95%CI 1.93-3.13). Conclusion: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among beta-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.