Serotonin 2A -1438 G/A and G-Protein Beta3 Subunit C825T Polymorphisms in Patients with Depression and SSRI-Associated Sexual Side-Effects

In 81 outpatients treated with citalopram, escitalopram, fluoxetine, paroxetine, or sertraline, sexual dysfunction was measured with the Changes in Sexual Function Questionnaire as a primary outcome. The HTR2A -1438 G/G genotype was associated with SSRI-associated sexual dysfunction both unadjusted and after controlling for age, gender, and anxiety/depression scores. In women, G/G carriers had significantly lower arousal and desire/frequency subscores; the association was not significant in men. A follow-up analysis by the same group suggested oral contraceptive use may mediate the HTR2A-sexual adverse reaction association. The authors propose that lower baseline 5-HT2A expression may heighten susceptibility to receptor saturation under SSRI exposure.