Drug Saf. 2026 Apr 14. doi: 10.1007/s40264-026-01673-7. Online ahead of print.
ABSTRACT
INTRODUCTION: Antipsychotic-associated sexual adverse drug reactions (ADRs) are well known in clinical practice, although efforts to understand differences between antipsychotics and distinct types of sexual ADRs are limited.
OBJECTIVE: The aim of this study was to assess and prioritize the profile of each antipsychotic regarding sexual ADRs reporting, and to account for potential confounders.
METHODS: We used VigiBase® to conduct a case/non-case study using a customized clinically guided search strategy of antipsychotic-related sexual ADRs. The reporting odds ratio (ROR) and Bayesian information component (IC) with relevant 95% confidence intervals (95% CIs) were used as disproportionality measures to identify signals of disproportionate reporting (SDRs). Antipsychotics were compared with all other drugs and with thiazides (positive control). Sensitivity analyses included non-serious reports, excluding patients with potentially confounding co-medication(s), excluding adolescent and elderly patients, and including cases with co-reported hyperprolactinemia. Analyses were stratified by sex. Antipsychotics were ranked in terms of clinical priority using qualitative and quantitative criteria.
RESULTS: We included 5195 cases of antipsychotic-related sexual ADRs (43.1% serious, median time to onset of 61 days, 36.1% physician-reported). Several SDRs emerged in males (erectile dysfunction [3487 reports; ROR 2.49, 95% CI 2.40-2.57]; priapism [2372 reports; ROR 15.55, 95% CI 14.82-16.32]) and females (decreased libido [373 reports; ROR 1.61, 95% CI 1.46-1.79]) for all antipsychotic classes, except for muscarinic antagonists in females (ROR 0.64, 95% CI 0.55-0.73; IC – 0.65, 95% CI – 0.86 to – 0.45). In both sexes, the highest number of reports were for risperidone, aripiprazole and olanzapine. The SDRs disappeared in the sensitivity analysis including only non-serious cases and cases with co-reported hyperprolactinemia. Sexual ADRs for all antipsychotics were classified as of moderate priority, with the exception of fluspirilene (low priority).
CONCLUSIONS: Notwithstanding limitations, including inability to infer causality, these findings raise the hypothesis that sexual ADRs could be a class effect of antipsychotics, yet possibly reversible, in both women and men.
REGISTRATION: The protocol is registered to the Open Science Framework: https://osf.io/96eq7 .
PMID:41979819 | DOI:10.1007/s40264-026-01673-7
