Drug–drug Interaction Signals for Sexual Dysfunction with Antidepressants and Antipsychotics: A Pharmacovigilance–pharmacodynamic Study
- 1Department of Pharmacotherapeutics and Informatics, School of Medicine, Fujita Health University, Toyoake, Japan
Abstract
Objective: Sexual dysfunction is a common adverse event associated with antidepressants and antipsychotics, yet its risk during combination therapy remains unclear. This study evaluated sexual dysfunction signals associated with antidepressant–antipsychotic combinations using the FDA Adverse Event Reporting System (FAERS) and explored potential pharmacodynamic mechanisms.
Methods: A pharmacovigilance–pharmacodynamic analysis of the FAERS database covering the fourth quarter of 1997 through the first quarter of 2022 was conducted. Combinations of antidepressants (selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors) with seven antipsychotics (aripiprazole, brexpiprazole, cariprazine, olanzapine, quetiapine, risperidone, and ziprasidone) were evaluated. Drug–drug interaction signals were assessed using five frequency statistical models (Ω shrinkage, additive, multiplicative, combination risk ratio, and chi-square). The association between antipsychotic receptor occupancy and sexual dysfunction was analyzed using a linear regression model.
Results: In total, 15,808,026 reports were analyzed. Drug–drug interaction signals for desire-related sexual dysfunction were detected for the SSRI-brexpiprazole combination in four algorithms (Ω shrinkage, additive, multiplicative, and chi-square). Linear regression analysis showed that the desire-related sexual dysfunction signal values were positively associated with 5-HT1A receptor occupancy (β = 0.082, p = 0.008, R2 = 0.782).
Conclusion: Brexpiprazole augmentation of SSRIs may be associated with desire-related sexual dysfunction. The findings also suggest a potential association between 5-HT1A receptor occupancy and desire-related sexual dysfunction. As this study used a hypothesis-generating design based on spontaneous reporting data, further epidemiological studies are warranted.
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BibTeX
@article{horii2026drugdrug,
title = {{Drug–drug Interaction Signals for Sexual Dysfunction with Antidepressants and Antipsychotics: A Pharmacovigilance–pharmacodynamic Study}},
author = {Rina Horii and Masakazu Hatano and Shigeki Yamada},
journal = {Clinical Psychopharmacology and Neuroscience},
year = {2026},
month = jul,
doi = {10.9758/cpn.26.1443},
url = {https://doi.org/10.9758/cpn.26.1443},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Drug–drug Interaction Signals for Sexual Dysfunction with Antidepressants and Antipsychotics: A Pharmacovigilance–pharmacodynamic Study
AU - Rina Horii
AU - Masakazu Hatano
AU - Shigeki Yamada
PY - 2026
DA - 2026/07/23
JO - Clinical Psychopharmacology and Neuroscience
DO - 10.9758/cpn.26.1443
UR - https://doi.org/10.9758/cpn.26.1443
AB - Objective: Sexual dysfunction is a common adverse event associated with antidepressants and antipsychotics, yet its risk during combination therapy remains unclear. This study evaluated sexual dysfunction signals associated with antidepressant–antipsychotic combinations using the FDA Adverse Event Reporting System (FAERS) and explored potential pharmacodynamic mechanisms. Methods: A pharmacovigilance–pharmacodynamic analysis of the FAERS database covering the fourth quarter of 1997 through the first quarter of 2022 was conducted. Combinations of antidepressants (selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors) with seven antipsychotics (aripiprazole, brexpiprazole, cariprazine, olanzapine, quetiapine, risperidone, and ziprasidone) were evaluated. Drug–drug interaction signals were assessed using five frequency statistical models (Ω shrinkage, additive, multiplicative, combination risk ratio, and chi-square). The association between antipsychotic receptor occupancy and sexual dysfunction was analyzed using a linear regression model. Results: In total, 15,808,026 reports were analyzed. Drug–drug interaction signals for desire-related sexual dysfunction were detected for the SSRI-brexpiprazole combination in four algorithms (Ω shrinkage, additive, multiplicative, and chi-square). Linear regression analysis showed that the desire-related sexual dysfunction signal values were positively associated with 5-HT1A receptor occupancy (β = 0.082, p = 0.008, R2 = 0.782). Conclusion: Brexpiprazole augmentation of SSRIs may be associated with desire-related sexual dysfunction. The findings also suggest a potential association between 5-HT1A receptor occupancy and desire-related sexual dysfunction. As this study used a hypothesis-generating design based on spontaneous reporting data, further epidemiological studies are warranted.
SN - 1738-1088
SN - 2093-4327
ER -