The atypical antipsychotics and sexual dysfunction: a pharmacovigilance-pharmacodynamic study

Area of Science:

• Pharmacovigilance
• Neuroscience
• Clinical Pharmacology

Background:

• Sexual dysfunction (SD) is a common, yet often underestimated, side effect of atypical antipsychotics (AAPs).
• Limited research exists on the specific associations between different AAPs and SD.
• Understanding these associations is crucial for effective clinical management.

Purpose of the Study:

• To quantify the association strength between various AAPs and SD using real-world data.
• To explore potential receptor mechanisms underlying AAP-induced SD.

Main Methods:

• Analysis of 4839 reports from the FDA Adverse Event Reporting System (FAERS) database (Q1 2004–Q3 2023).
• Disproportionality analysis using Reporting Odds Ratio (ROR) and Information Component (IC) methods.
• Linear regression to assess the relationship between ROR and estimated receptor occupancy (D2, D3, 5-HT1A).

Main Results:

• Statistical associations found between 12 AAPs and SD.
• Iloperidone showed the highest association with retrograde ejaculation (ROR=832.09).
• Aripiprazole was associated with compulsive sexual behavior (ROR=533.02) and psychosexual disorder (ROR=145.80).
• Regression analysis suggested potential roles for D2, D3, and 5-HT1A receptor occupancy, though not sustained in sensitivity analyses.

Conclusions:

• This is the first study to investigate AAP-SD associations using FAERS data.
• A significant association between aripiprazole and SD was identified using real-world evidence.
• Findings suggest varying SD risks among AAPs and potential receptor involvement, requiring further validation and clinical causality assessment.