Antidepressant-Induced Sexual Dysfunction and Its Management - Treatment of SRI-Induced Sexual Dysfunction With Sildenafil

Written by Steffany J. Fredman, MA Jerrold F. Rosenbaum, MD

New Research on the Treatment of SRI-Induced Sexual Dysfunction With Sildenafil

Sildenafil (Viagra) for SRI-Induced Male Sexual Dysfunction During Continuation Treatment for Major Depressive Disorder

George Nurnberg, MD,^[16] of the University of New Mexico School of Medicine, Albuquerque, presented new research on the use of sildenafil (Viagra) for SRI-induced sexual dysfunction. Participants were male patients with remitted major depression who were receiving a stable dose of continuation SRI antidepressants and also suffered from treatment-emergent SRI-induced sexual dysfunction (n = 90). They were then randomized to placebo or sildenafil (50 mg, which could be increased to 100 mg) for 6 weeks. Sildenafil is a phosphodiesterase type-5 inhibitor that is FDA-approved for the treatment of erectile dysfunction. The main results, summarized in a study by Nurnberg and colleagues,^[17] were that sildenafil-treated patients showed significantly greater improvements in sexual functioning relative to patients receiving placebo, as measured using the International Index of Erectile Function (IIEF).

Responders from the initial trial were discontinued from sildenafil for 3 weeks. Once it was determined that sexual dysfunction occurred in the absence of sildenafil (which suggests that previously observed improvements were, as hypothesized, due to sildenafil treatment rather than the passage of time per se), these patients then received 8 weeks of additional open-label sildenafil. They continued to show improvement in sexual functioning, and there were no relapses or recurrences of major depressive disorder.

Patients from the double-blind study who had shown a partial response or no response (defined as scoring higher than 2 on the CGI; n = 43) repeated the initial 6 weeks of sildenafil treatment and then received 8 additional weeks of open-label sildenafil, just as the original responders had. This group of patients, some of whom had originally received placebo, showed improvement with continued treatment that was comparable to that achieved by responders in the sildenafil double-blind group.

Sildenafil for SRI-Induced Erectile Dysfunction in Men With Remitted Depression

Maurizio Fava, MD,^[18] Director of the Depression Clinical and Research Program, Massachusetts General Hospital, and Professor of Psychiatry, Harvard Medical School, Boston, Massachusetts, presented results from a prospective, multicenter, randomized, double-blind, placebo-controlled study of sildenafil for SRI-induced erectile dysfunction. Participants were males with remitted depression (HAMD

Ninety-four percent of patients in the sildenafil group and 90% of those in the placebo group completed treatment. No patient discontinued in the study due to the study drug. At the end of treatment, sildenafil-treated patients reported significantly higher rates of frequency of penetration and maintenance of erection after penetration, as measured using the International Index of Erectile Function (IIEF), compared with patients receiving placebo. Patients in the sildenafil group also reported significantly higher levels of quality of life with respect to sexual functioning compared with those receiving placebo. The most frequently reported adverse events during treatment were headache (9% sildenafil vs 9% placebo), dyspepsia (9% vs 1%), and facial flushing (9% vs 0%).

Sildenafil for SRI-Induced Female Sexual Dysfunction

Nurnberg and colleagues presented results from an open-label extension phase of a double-blind, placebo-controlled trial of sildenafil treatment for SRI-induced female sexual dysfunction.^[19] Women with remitted major depression and SRI-induced sexual dysfunction were randomly assigned to receive sildenafil (50 mg, which could be increased to 100 mg) or placebo for 8 weeks (n = 150). Sexual dysfunction was characterized by arousal dysfunction or orgasmic dysfunction that interfered with sexual functioning for 4 or more weeks. The double-blind phase of the study was followed by 8 weeks of single-blind sildenafil. Results were presented for the first 42 patients who completed the extension phase of the study.

At baseline, the women in this subgroup of patients were taking fluoxetine (42%), sertraline (28%), paroxetine (10%), citalopram (10%), venlafaxine (5%), nefazodone (5%), and clomipramine (1%), and the most commonly reported aspects of sexual dysfunction were decreased libido (95%), orgasm delay (70%), decreased satisfaction (68%), and difficulties achieving lubrication (55%). At the end of the double-blind phase of the study, 39% of the 42 women were considered responders, defined as

Conclusions

Sexual dysfunction commonly occurs in the context of major depressive disorder. Although sexual dysfunction is not a symptom of major depressive disorder per se, decreased sexual desire and arousal may be characteristics associated with depression-related anhedonia. Sexual dysfunction is also a common side effect of treatment with serotonergic antidepressants and may be a reason that patients on SSRIs and other serotonergic medications discontinue treatment prematurely.

Given the importance of continuation and maintenance treatment for major depression, researchers are devoting increasing attention to understanding which treatments may be helpful or, alternatively, unhelpful with respect to sexual functioning so that compliance may be maintained and treatment optimized. Clinically, this suggests that as additional data regarding the differential impact of certain medications on sexual functioning in the context of depression become available, clinicians may be able to make more empirically informed decisions regarding which antidepressants might be effective for a given patient at the beginning of treatment. They may also have an empirically informed selection of "next-step" strategies to employ in the event that treatment-emergent sexual dysfunction develops over the course of pharmacotherapy.

References

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