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Sildenafil Treatment of Women With Antidepressant-Associated Sexual Dysfunction

Authors: H. George Nurnberg, MD; Paula L. Hensley, MD; Julia R. Heiman, PhD; Harry A. Croft, MD; Charles Debattista, MD; Susan Paine, MPH

Source: JAMA. 2008;300(4):395-404.

Back ground: Many hopes and fantasies were related to Sildenefil since it emerged in 1998. Many of those regarded the feasibility to use Viagra as a medication for female sexual dysfunction. A pile of works with controversial results were published, but only few used these scientific tools, that should make those works considerable. This study is among those few. Antidepressant treatment–associated sexual dysfunction is estimated to occur in 30% to 70% of men and women treated for major depression with first- or second-generation agents, a principal reason for a 3-fold increased risk of nonadherence that approaches 70% in the first months of treatment and leads to increased relapse, recurrence, disability, and resource utilization by affected patients. Compared with men, women are prescribed antidepressants at rates of 2 to 1 and can be expected to represent a significant number of patients needing relief. In women, sexual dysfunction is associated with decreased sexual interest, genital sensitivity, and vaginal lubrication; delayed or absent orgasm; dyspareunia; reduced sexual activity; and overall dissatisfaction or loss of pleasure in sexual relations. Among the numerous strategies proposed for managing sexual dysfunction associated with SRI treatment, selective phosphodiesterase type 5 inhibitors, which have been limited to studies involving men, have demonstrated the best evidence-based data to support broad-based and clinically meaningful treatment efficacy. However, no randomized controlled trial (RCT) has demonstrated effectiveness for women experiencing sexual dysfunction associated with SRI treatment.

Objective To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women.

Methods An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction. Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity.

Main Outcome Measures The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed.

Results In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression–sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects.

Conclusion In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects.