Treatment of Antidepressant-Associated Sexual Dysfunction With Sildenafil

Abstract

Context Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance.Objective To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants.Design, Setting, and Patients Prospective, parallel-group, randomized, doubleblind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment.Intervention Patients were randomly assigned to take sildenafil (n=45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks. Main Outcome MeasuresThe primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D).Results Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 endpoint assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (PϽ.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score Յ10) in both groups for the study duration. ConclusionIn our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.

Antidepressant-induced sexual dysfunction

“…The evidence for bupropion augmentation is the most compelling. 31 Finally, there is firm evidence that remedial drug therapy with sildenafil, the selective and competitive inhibitor of phosphodiesterase type 5 (PDE-5), has proved effective in men for antidepressant-induced erectile dysfunction, 32 and more recently -although not licensed for this group -in women with SSRI-and SNRI-induced sexual adverse effects. 33 Its characteristics of peripheral site of action, high efficacy, good tolerability, relatively short duration of action and administration only if and when required make this agent in some ways the ideal antidote.…”

Do vardenafil and tadalafil have advantages over sildenafil in the treatment of erectile dysfunction?

“…96 These results have been confirmed in double-blind studies of males with major depression in remission and sexual dysfunction associated with SSRIs. 97,98 Erectile function, arousal, ejaculation, orgasm and overall satisfaction improved with sildenafil, compared to placebo, and depression remained in remission. 97,98 ED is also associated with the use of the antipsychotic drugs olanzapine and risperidone, and sildenafil is also effective in this (olanzapine, 99 resperidone 100 ).…”

“…97,98 Erectile function, arousal, ejaculation, orgasm and overall satisfaction improved with sildenafil, compared to placebo, and depression remained in remission. 97,98 ED is also associated with the use of the antipsychotic drugs olanzapine and risperidone, and sildenafil is also effective in this (olanzapine, 99 resperidone 100 ). Sildenafil was also safe and effective in the treatment of another 31 subjects with antipsychotic-induced ED (risperidone, n ¼ 15: olanzapine, 12).…”

Open-label sildenafil treatment of partial and non-responders to double-blind treatment in men with antidepressant-associated sexual dysfunction

“…12 At enrollment, eligible men with MDD-R and aged 18-55 years had taken an SRI antidepressant for at least 12 weeks, were on a stable dose for at least 6 weeks, had Hamilton Depression and Anxiety Rating Scale scores p10 and had SRI-AASD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Participants had some form of regular sexual activity that was to be continued for the study period, were in good general physical health and reported satisfactory sexual function before the current onset of depression and/or antidepressant treatment.…”

“…11 Sildenafil is the first treatment to demonstrate significant and meaningful efficacy for SRI-AASD in a prospective, randomized, parallel-group, double-blind, placebo-controlled study in men with MDD in remission (MDD-R); we reported that 55% of men assigned to sildenafil (50 mg adjustable to 100 mg taken 1-2 h before sexual activity) compared with 4% of men assigned to placebo were full responders (Po0.001), defined as 'much/very much improved' (score of p2 on a Clinical Global Impression Scale adapted for Sexual Function (CGI-SF)). 12 Erectile function, ejaculation, orgasm, sexual interest and overall satisfaction domain measures also improved significantly in patients receiving sildenafil compared with patients receiving placebo. All patients remained on their SRI antidepressant at full effective dose and maintained 17-item Hamilton Depression Rating Scale (HAM-D17) scores consistent with remission.…”