Sexual dysfunction during treatment with serotonergic and noradrenergic antidepressants: Clinical description and the role of the 5-HTTLPR

Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Mannheim, Germany.
The World Journal of Biological Psychiatry (Impact Factor: 4.18). 03/2011; 12(7):528-38. DOI: 10.3109/15622975.2011.559270
Source: PubMed


Sexual dysfunction (SD) is a frequently reported side-effect of antidepressant treatment, particularly of selective serotonin reuptake inhibitors (SSRIs). In the multicentre clinical and pharmacogenetic GENDEP study (Genome-based Therapeutic Drugs for Depression), the effect of the serotonin transporter gene promoter polymorphism 5-HTTLPR on sexual function was investigated during treatment with escitalopram (SSRI) and nortriptyline (tricyclic antidepressant).
A total of 494 subjects with an episode of DSM-IV major depression were randomly assigned to treatment with escitalopram or nortriptyline. Over 12 weeks, depressive symptoms and SD were measured weekly with the Montgomery-Asberg Depression Rating Scale, the Antidepressant Side-Effect Checklist, the UKU Side Effect Rating Scale, and the Sexual Functioning Questionnaire.
The incidence of reported SD after 12 weeks of treatment was relatively low, and did not differ significantly between antidepressants (14.9% escitalopram, 19.7% nortriptyline). There was no significant interaction between the 5-HTTLPR and antidepressant on SD. Improvement in depressive symptoms and younger age were both associated with lower SD. The effect of age on SD may have been moderated by the 5-HTTLPR.
In GENDEP, rates of reported SD during treatment were lower than those described in previous reports. There was no apparent effect of the 5-HTTLPR on the observed decline in SD.

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    • "Our results showed that there is an association between sexual dysfunction before and after treatment, i.e., worsening of sexual dysfunction items was more prevalent in patients with prior impairment in these items. The finding can be attributed to antidepressant effects on sexual dysfunction; however, decrease in sexual dysfunction during antidepressant therapy has been reported by Strohmaier et al. [28]. Finally, more impairment in sexual drive and decrease in interest in sexually explicit material were seen in patients who were not responders to treatment . "
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    ABSTRACT: Background: Selective serotonin reuptake inhibitors (SSRIs) are common treatments for patients with major depressive disorder (MDD). However, adverse effects of SSRIs on sexual function are common in the treatment of patients with MDD. There is a discrepancy in the reported frequency of SSRI-induced sexual dysfunction. On the other hand, there is also less evidence about sexual dysfunction with serotonin receptor antagonists and reuptake inhibitors (SARIs). Therefore, we aimed to assess sexual dysfunction in MDD patients who received fluoxetine, sertraline and trazodone. Method: In a single-blind, randomized, controlled trial in Kermanshah, Iran, during 2009-2010, 195 patients who met the DSMIV-IR criteria for MDD were enrolled. The patients completed the Hamilton Depression Rating Scale (HAM-D) and the sexual function questionnaire (SFQ). Eligible patients were allocated in three treatment groups (receiving fluoxetine, sertraline or trazodone) for 14 weeks randomly. Measurement of HAMD was repeated in 4-week interval. Analysis for comparing sexual dysfunction among three groups and men and women was performed. Results: There were 102 men and 93 women in the three groups receiving fluoxetine (n=64), sertraline (n=67) and trazodone (n=64). There was no significant difference in the sexual dysfunction of the patients in the three groups at baseline (P>.05). After treatment, both men and women who had received fluoxetine had the most impairment in desire/drive items (43%-51% and 44%-50%, respectively), while patients receiving trazodone had the least impairment in these items (12%-18% and 23%-24%, respectively). Trazodone was also induced with a lower rate of impairment in arousal/orgasm items in men (9%-15%) compared with the other two drugs. Compared with fluoxetine and trazodone, sertraline was associated with intermediate impairment in sexual function (39%-42% in desire/drive items and 32%-39% in arousal/orgasm items) that was lower than that with fluoxetine and more than that with trazodone. Conclusion: There were different rates of sexual dysfunction with different antidepressants drugs in under treated patients. Compared with fluoxetine, and sertraline, trazodone was associated with the fewest sexual dysfunction. Fluoxetine was also associated with more sexual dysfunction than sertraline. Further research to better identify the differences among antidepressant drugs is recommended.
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    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. Liang C-S, Ho P-S, Chiang K-T, and Su H-C. 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;9:2009–2016.
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