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

J Sex Med. 2012 Aug;9(8):2009-16. doi: 10.1111/j.1743-6109.2012.02769.x. Epub 2012 May 21.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Cyclohexanols / administration & dosage
  • Cyclohexanols / adverse effects
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / psychology
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Sexual Dysfunction, Physiological / chemically induced
  • Sexual Dysfunction, Physiological / etiology*
  • Sexual Dysfunction, Physiological / genetics
  • Sexual Dysfunction, Physiological / psychology
  • Venlafaxine Hydrochloride
  • Young Adult

Substances

  • Antidepressive Agents
  • Cyclohexanols
  • Receptor, Serotonin, 5-HT2A
  • Serotonin Uptake Inhibitors
  • Venlafaxine Hydrochloride