SSRI-associated Sexual Dysfunction Research Articles

Irisin ameliorates male sexual dysfunction in paroxetine-treated male rats

Sexual dysfunction is a common clinical condition due to different causes including the use of selective serotonin reuptake inhibitors (SSRI). Especially, SSRI paroxetine is known to cause numerous types of sexual dysfunction in men. There is growing interest in exercise as a non-pharmacological approach for the treatment of SSRI-induced sexual dysfunction. With these in mind, we investigated the effects of irisin, which is a recently detected exercise-linked hormone, on paroxetine-induced sexual dysfunction in male rats. Our findings showed that circulating irisin levels were lower in paroxetine-induced sexual dysfunction in male rats (20 mg/kg/day for 8 weeks by oral gavage than in vehicle-treated rats). In addition, results from sexual behavioral tests revealed that subcutaneous irisin perfusion (100 ng/kg/day via mini-osmotic pumps for 28 days) ameliorated sexual motivation and copulatory performance in sexually impaired male rats treated with paroxetine. The significantly reduced serum testosterone levels and α1-adrenoceptors (ADRA1A) and tyrosine hydroxylase gene (TH) expression levels in the nucleus accumbens (NAc) in paroxetine-induced sexually dysfunctioning male rats were markedly increased following irisin exposure. Similarly, the expression levels of ADRA1A and TH in the medial preoptic area (mPOA) significantly increased in male rats co-administered with paroxetine and irisin compared to the vehicle-treated male rats. These results demonstrate that irisin may be a therapeutic modality that mimics/supports the beneficial effects of exercise for improving SSRI-associated sexual dysfunction in men through increase in serum testosterone levels and increased expression of α1-adrenoceptors and TH in the NAc and mPOA associated with sexual motivation and copulatory behaviors.

Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: A narrative literature review.

Sexual dysfunction is an underdiscussed adverse effect to selective serotonin reuptake inhibitors (SSRIs) and may increase the risk for discontinuation and nonadherence to antidepressant pharmacotherapy. Given the prevalence of depression, health care providers should educate patients about SSRI-associated sexual dysfunction in order to promote patient awareness and medication adherence. This study evaluated primary literature from 1997 to 2015 to identify SSRI-related sexual side effects, therapeutic alternatives, and treatment strategies. The results indicate that paroxetine is associated with the greatest rate of sexual dysfunction among the SSRIs. Potential alternatives to SSRI treatment include bupropion, mirtazapine, vilazodone, vortioxetine, and serotonin-norepinephrine reuptake inhibitors. In the event that a subject responds solely to SSRIs but experiences unwanted sexual side effects, bupropion may be added as an adjunctive medication. Some limited evidence also suggests that saffron may reduce some aspects of sexual dysfunction, excluding ability to reach orgasm.

Pharmacogenetics of glutamate system genes and SSRI-associated sexual dysfunction

We examined whether polymorphisms in the GRIK2, GRIA3 and GRIA1 genes were associated with selective serotonin reuptake inhibitor (SSRI)-associated sexual dysfunction in 114 participants treated for depression. One polymorphism in GRIA1 (rs1994862) was associated with arousal dysfunction, providing further evidence for the role of GRIA1 in mechanisms underlying SSRI-associated sexual side effects.

ORIGINAL RESEARCH–EPIDEMIOLOGY: Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction

ABSTRACT Introduction Sexual dysfunctions are often present in subjects with mood disturbances; however. antidepressants can induce per se sexual dysfunctions. Aim To explore the relationship between the use of selective serotonin reuptake inhibitors (SSRIs), non-SSRIs antidepressants and benzodiazepines (BDZ), hormonal parameters, and reported sexual dysfunction (as assessed by the Structured Interview on Erectile Dysfunction [SIEDY]) in male subjects with comparable psychopathological symptoms (as assessed by the Middlesex Hospital Questionnaire [MHQ] a self-reported test for the screening of mental disorders in a non-psychiatric setting). Methods A consecutive series of 2,040 (mean age 51 ± 13 years) male patients with sexual dysfunction was studied. Main Outcome Measures Several hormonal and biochemical parameters were investigated, along with SIEDY and the MHQ. Results Higher prolactin was observed only in patients using SSRIs, whereas no other hormonal difference was found after adjustment for confounders. Use of SSRIs was associated with a twofold risk for patient hypoactive sexual desire and with a higher impairment of reported erectile function. However, no difference in penile blood flow was observed. A very high risk (sevenfold) for delayed ejaculation (DE) was observed in SSRI users. Interestingly, the association with the mild, but not severe, form of DE was observed also in subjects using non-SSRI antidepressants (3.35 [1.48–7.59]; P < 0.005). Different life stressors and relational parameters were also associated with SSRI use. SSRI users reported less enjoyment with masturbation and decreased partner desire and climax. Conversely, a lack of significant association was observed among BDZ or non-SSRI antidepressant users and all the aforementioned life-stressors and relational parameters. Conclusions SSRIs can negatively affect all the steps of the male sexual response cycle (desire–arousal–excitement–orgasm). SSRI-associated sexual dysfunction has a deleterious effect on both auto- and couple-erotic performances. Conversely, other antidepressants and BDZ are less often associated with sexual impairment.

SSRI-Associated Sexual Dysfunction

SSRI-Associated Sexual Dysfunction

Ejaculatory dysfunction and depression: pharmacological and psychobiological interactions

In recent years, increased attention has been focused on antidepressant-associated sexual dysfunction, largely because of the widespread use of serotonin-specific reuptake inhibitors (SSRIs) and the recognition that such side effects can have a negative impact on treatment compliance. Data suggest that serotonergic antidepressants are associated with delayed ejaculation and anorgasmia, although these sexual problems are also linked to depression and to age. In this review, we discuss central mediators of normal orgasmic functioning and dysfunction, the relationship between depression and sexual dysfunction, possible mechanisms for SSRI-associated sexual dysfunction, and evolving treatment strategies.

An open-label series using loratadine for the treatment of sexual dysfunction associated with selective serotonin reuptake inhibitors

Objective To assess the impact of loratadine as an add-on treatment of erectile dysfunctions associated with selective serotonin reuptake inhibitors (SSRIs). Methods Nine patients diagnosed as major depressive disorder (MDD), with erectile dysfunction associated with the administration of SSRIs, completed a 2-week trial of loratadine in the dose of 10 mg/day. The International Index of Erectile Function Five (IIEF-5) was used as an assessment measure for diagnosing the presence and severity of erectile dysfunction. The 17-item Hamilton Rating Scale for Depression (HAM-D) was administered for screening the potential impact of depressive symptoms. Results Baseline mean S.D. ± IIEF-5 scores were 10.33 ± 4.55 (range 5–20) and week 2 mean ± S.D. IIEF-5 was 14.44 ± 3.84 (range 10–22). Subjects had statistically significant improvement in their erectile functions on the IIEF-5 ( t = − 8.485; df = 8; p = 0.000) and 55% reported subjective improvement of the erectile function. No significant changes on HAM-D 17 scores were registered. Baseline mean S.D. scores were 13.66 ± 2.29 (range 10–17) and week 2 mean S.D. was 13.11 ± 1.96 (range 10–16) ( t = 1.47; df = 8; p = 0.179). Conclusion Our findings suggest the possible role of loratadine in the treatment of SSRI-associated sexual dysfunction. They are promising, but preliminary. Thus they should be replicated in a longer large-scale, double-blind, placebo-controlled trial.

Depression, antidepressants and sexual functioning in men

In recent years, increased attention has been focused on antidepressant-associated sexual dysfunction, largely because of the widespread use of serotonin specific reuptake inhibitors (SSRIs) and the recognition that their side-effects can have a negative impact on treatment compliance. Yet the relationship between the depressive illness, the antidepressant medication used to treat it and treatment of emergent sexual dysfunction is complicated and multifactorial. For example, when a depressed man treated with an antidepressant medication seeks treatment for a sexual dysfunction, the clinician is faced with the responsibility of deciphering whether the sexual dysfunction is the result of a pre-existing medical disorder, a symptom of depression or a treatment-emergent adverse effect of antidepressant medication. In order to do this, the clinician needs to be knowledgeable about the salient aspects of normal sexual functioning, and the influences of age, depression and antidepressant medications. In this review, we discuss normal sexual functioning and dysfunction in men, the relationship between depression and sexual functioning, possible mechanisms for SSRI-associated sexual dysfunction and evolving pharmacologic treatment strategies.

Strategies for Treatment of SSRI-Associated Sexual Dysfunction: A Survey of an Academic Psychopharmacology Practice

Strategies for Treatment of SSRI-Associated Sexual Dysfunction: A Survey of an Academic Psychopharmacology Practice

Strategies for Treatment of SSRI-Associated Sexual Dysfunction: A Survey of an Academic Psychopharmacology Practice

Strategies for Treatment of SSRI-Associated Sexual Dysfunction: A Survey of an Academic Psychopharmacology Practice

Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial

Background: Many agents have been proposed as potential treatments for SSRI-associated sexual dysfunction, but few placebo-controlled trials have been reported. Method: After a 1-month baseline evaluation, pre-menopausal women with moderate to severe sexual dysfunction associated with the institution of fluoxetine therapy were randomized to augmentation therapy with placebo ( N=39), mirtazapine ( N=36), yohimbine ( N=35) or olanzapine ( N=38) for a 6-week period. Outcomes were measured using a daily diary, a biweekly self-report assessment, and a computer assisted structured interview. Results: At baseline, orgasm was most severely impaired. After 6 weeks, there was statistically significant improvement on most measures for the overall group of patients, however there were few differences between treatment groups. Isolated treatment differences were observed for the patient self-report of overall sexual function (olanzapine superior to placebo) and the structured interview sexual satisfaction item (mirtazapine inferior to placebo). Conclusion: No drug assessed was consistently associated with differences from placebo. The results of the study do not support uncontrolled reports of efficacy for these agents in premenopausal women.

Bupropion Sustained Release as a Smoking Cessation Treatment in Remitted Depressed Patients Maintained on Treatment With Selective Serotonin Reuptake Inhibitor Antidepressants

Patients with depressive disorders smoke tobacco more often than the population at large and find quitting more difficult. Furthermore, when they quit smoking, they are more likely to suffer a relapse of depression. We evaluated the addition of bupropion sustained release (SR) for smoking cessation among patients with a history of depressive disorders being maintained in a euthymic state with selective serotonin reuptake inhibitor (SSRI) antidepressants. Twenty-five adults with DSM-IV major depressive disorder or depressive disorder NOS currently receiving SSRI maintenance treatment and smoking > or = 15 cigarettes per day participated in the 9-week study. Bupropion SR, 150 mg/day, was added to SSRI treatment and increased to 300 mg/day. Subjects were counseled on smoking cessation measures and chose a target quit date 2 or 4 weeks after the initiation of bupropion SR. Self-reported smoking status, expired carbon monoxide (CO) measurements, Hamilton Rating Scales for Depression and Anxiety scores, and weight were measured at each visit. Subjects were abstinent if they reported not smoking during the prior 7 days, confirmed with an expired-air CO value of < or = 10 ppm. Eight (32%) of 25 subjects were abstinent after 9 weeks. At 3-month follow-up, 3 subjects remained abstinent, 3 relapsed, and 2 were lost to follow-up. Eleven subjects (44%) were nonresponders, and 6 (24%) dropped out prior to 3 weeks of treatment due to side effects (N = 3) or were lost to follow-up (N = 3). Mean weight gain was approximately 0.5 lb (0.2 kg) for those completing 9 weeks of bupropion SR treatment. During the 9-week study and the 3-month follow-up, there was no evidence of emergent depression in any subject. Four subjects (16%) spontaneously reported an improvement in SSRI-associated sexual dysfunction. These open data suggest modest effectiveness for and the safety of bupropion SR as a smoking cessation agent in individuals with depression maintained on treatment with SSRIs. Minimal weight gain, lack of emergent depressive episodes, and improvement of SSRI-associated sexual dysfunction are added advantages.

Sildenafil citrate: A therapeutic update

Background: Since its approval by the US Food and Drug Administration in March 1998, sildenafil citrate has been used by millions of men for the treatment of erectile dysfunction. Recent studies and consensus reports have expanded our understanding of its efficacy, safety, contraindications, and drug interactions. Objective: This paper reviews recent studies of the efficacy of sildenafil, its adverse effects and drug interactions, and socioeconomic factors involved in its use, with a focus on specific patient populations (prostate cancer, diabetes mellitus, ischemic heart disease, spinal cord injuries, neurologic disorders). Methods: Clinical studies, case reports, and commentaries and editorials concerning sildenafil published in the international literature between January 1999 and August 2000 were identified through searches of MEDLINE®, PREMEDLINE®, and International Pharmaceutical Abstracts®, using the terms sildenafil, Viagra, and erectile dysfunction. Results: Sildenafil has demonstrated effectiveness in men with erectile dysfunction associated with prostatectomy, radiation therapy, diabetes mellitus, certain neurologic disorders, and drug therapy (eg, selective serotonin reuptake inhibitors [SSRIs]). It has not been as effective in women with sexual dysfunction, with the exception of SSRI-associated sexual dysfunction. Some disorders unrelated to sexual dysfunction (eg, esophageal motility dysfunction) may also respond to sildenafil. In the general population, sildenafil is considered to have an acceptable tolerability profile; however, patients with moderate to severe cardiovascular disease or those taking nitrate therapy are at increased risk for potentially serious cardiovascular adverse effects with sildenafil therapy. In addition, patients taking drugs that inhibit the cytochrome P450 3A4 isozyme, which metabolizes sildenafil, may experience increased drug concentrations and possible toxicity from normal doses of sildenafil. Conclusions: Sildenafil is an effective first-line therapy for erectile dysfunction in men. The decision to prescribe this agent should include such considerations as the cost-risk-benefit balance, patient access, drug distribution pathways, and prescription drug coverage.