Drug-drug Interaction Signals for Sexual Dysfunction with Antidepressants and Antipsychotics: A...

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.

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.

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-HT_1A receptor occupancy (β = 0.082, p = 0.008, R² = 0.782).

Brexpiprazole augmentation of SSRIs may be associated with desire-related sexual dysfunction. The findings also suggest a potential association between 5-HT_1A 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.