Sexual Dysfunction with Antipsychotics: Emerging Clues from a Disproportionality Analysis of the World Health Organization VigiBase.
Description
Chiara Gastaldon and Georgios Schoretsanitis contributed equally.
Publisher DOI
PubMed ID
41979819
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 .
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 .
Date Issued
2026-04-14
Publication Type
Article
Language(s)
en
Author(s)
Pavlidis, Efstathios | |
Siafis, Spyridon | |
Arzenton, Elena | |
Crisafulli, Salvatore | |
Raschi, Emanuel | |
Moretti, Ugo | |
Isidori, Andrea M | |
Jannini, Emmanuele A | |
Trifirò, Gianluca | |
Seifritz, Erich | |
Barbui, Corrado | |
Journal
Drug Safety: The Official Journal of the International Society of Pharmacovigilance
Publisher
Springer
ISSN
1179-1942
0114-5916
Funding(s)
Access(Rights)
restricted