Sexual problems are highly prevalent in both men and women and are affected by, among other factors, mood state, interpersonal functioning, and psychotropic medications. The incidence of antidepressant-induced sexual dysfunction is difficult to estimate because of the potentially confounding effects of the illness itself, social and interpersonal comorbidities, medication effects, and design and assessment problems in most studies. Estimates of sexual dysfunction vary from a small percentage to more than 80%. This article reviews current evidence regarding sexual side effects of selective serotonin reuptake inhibitors (SSRIs). Among the sexual side effects most commonly associated with SSRIs are delayed ejaculation and absent or delayed orgasm. Sexual desire (libido) and arousal difficulties are also frequently reported, although the specific association of these disorders to SSRI use has not been consistently shown. The effects of SSRIs on sexual functioning seem strongly dose-related and may vary among the group according to serotonin and dopamine reuptake mechanisms, induction of prolactin release, anticholinergic effects, inhibition of nitric oxide synthetase, and propensity for accumulation over time. A variety of strategies have been reported in the management of SSRI-induced sexual dysfunction, including waiting for tolerance to develop, dosage reduction, drug holidays, substitution of another antidepressant drug, and various augmentation strategies with 5-hydroxytryptamine-2 (5-HT2), 5-HT3, and alpha2 adrenergic receptor antagonists, 5-HT1A and dopamine receptor agonists, and phosphodiesterase (PDE5) enzyme inhibitors. Sexual side effects of SSRIs should not be viewed as entirely negative; some studies have shown improved control of premature ejaculation in men. The impacts of sexual side effects of SSRIs on treatment compliance and on patients' quality of life are important clinical considerations.

Effects of SSRIs on sexual function: a critical review.

The Neurobiological Approach to Premature Ejaculation

https://www.geneqol-consortium.org/wp-content/uploads/sites/9/2013/07/Munafo_DRD4-and-personality_Biol-Psychiatry-2008.pdf

Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: meta-analysis and new data.

The aim of this systematic review and meta-analysis is to evaluate whether the design and methodology of drug-treatment studies of premature ejaculation affect the efficacy outcome differently. Therefore, methodological, design and efficacy data from 79 studies (3034 males), published between 1943 and 2003, are reviewed. A meta-analysis is performed on 43 selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003; these studies were pooled to provide a summary variance-weighted effect size. The antidepressant-induced percentage increase of the intravaginal ejaculation latency time (IELT) was calculated and examined against various methodological items. A significant difference in efficacy between SSRIs was observed. Using daily treatment, paroxetine appeared more effective than the other SSRIs. Retrospective use of a questionnaire, subjective reports, single-blind and open study designs generate far greater variability of ejaculation time both at baseline and during active drug treatment than real time assessment by stopwatch. In conclusion, at daily treatment, the overall efficacy of paroxetine, clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the strongest ejaculation delay. Only eight (18.5%) studies on antidepressant treatment fulfilled all criteria used in evidence-based medicine, for example, randomised, double-blind studies with prospective real time (stopwatch) assessment of the IELT at each intercourse. Single-blind studies, open designs, retrospective reporting, or the use of a questionnaire to assess ejaculation time should be avoided.

Relevance of methodological design for the interpretation of efficacy of drug treatment of premature ejaculation: a systematic review and meta-analysis.

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

An association study of catechol-O-methyltransferase and monoamine oxidase A polymorphisms and personality traits in Koreans.

There have been an increased number of recent reports on orgasm-related sexual dysfunction coincident with selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, it has also been reported that SSRIs improve sexual dysfunction. Low doses of clomipramine and paroxetine, potent 5-hydroxytryptamine reuptake blockers, have been found to retard ejaculation time. We hypothesized that the SSRI fluoxetine might be effective in treating premature ejaculation. In an 8-week open-label clinical study, 11 male patients with premature ejaculation were treated with fluoxetine. After a washout period of 2 weeks, each patient was assigned to receive fluoxetine, 20 mg/day for 2 weeks, and then titrated to 60 mg/day, depending on the patient's tolerability and clinical response. A within-subjects comparison of pre- and posttreatment intravaginal ejaculation latency time revealed a significant improvement. Fluoxetine treatment produced significant improvements in self-visual analogue scale scores for sexual desire, anxiety for rapid ejaculation, and partner's satisfaction with ejaculation and overall sexual function. These data suggest that serotonergic antidepressants may be effective in treating rapid ejaculation in men and underline the need to carry out a double-blind, placebo-controlled trial to confirm these results.

An open clinical trial of fluoxetine in the treatment of premature ejaculation

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.

/pdf/lack-of-association-between-polymorphisms-of-the-dopamine-1pd13o7vbv.pdf

Hong Shick Lee

Papers

An association study of catechol-O-methyltransferase and monoamine oxidase A polymorphisms and personality traits in Koreans.

An open clinical trial of fluoxetine in the treatment of premature ejaculation

Lack of Association between Polymorphisms of the Dopamine Receptor D4 and Dopamine Transporter Genes and Personality Traits in a Korean Population