5-HT2A receptor -1438 G/A polymorphism and serotonergic antidepressant-induced sexual dysfunction in male patients with major depressive disorder: a prospective exploratory study.

Introduction: To date, few studies have specifically investigated the genetic determinants of antidepressant-induced sexual dysfunction (SD).

Aim: The aim of this prospective study was to examine whether the 5-HT2A receptor -1438 G/A polymorphism has functional consequences on sexual well-being in young adult men presenting with their first episode of major depressive disorder (MDD) after serotonergic antidepressant treatment.

Methods: Between May 2010 and June 2011, a total of 56 drug-naïve patients presenting with their first episode of MDD were recruited from a psychiatric hospital and received either a selective serotonin reuptake inhibitor or venlafaxine monotherapy; the patients were then genotyped. Over the course of antidepressant treatment, the population was divided into a SD group (N=16) and a non-SD group (N=29) based on the Arizona Sexual Experience Scale (ASEX). Participants who did not achieve a significant improvement, as assessed by the Hamilton Depression Rating Scale (HAMD-17), were excluded from the final data analysis.

Main Outcome Measures: The primary outcome measures were the differences in the genotype distribution and allele frequencies between groups.

Results: In the SD group, the AA genotype was significantly overrepresented (P=0.004), and the mean baseline HAMD-17 score, the mean baseline ASEX score, and the mean end-point ASEX score were significantly higher than those in the non-SD group (P=0.026, P=0.004, and P<0.001, respectively). The mean end-point HAMD-17 score (P=0.115) did not differ significantly between the two groups.

Conclusion: These results suggest that the AA genotype may be a genetic trait offering an opportunity to strengthen early detection of serotonergic antidepressant-induced SD in young adult male patients with MDD, whereas the G allele is protective against SD in this population.