Treating Sexual Dysfunction Related to Use of Antidepressants

Abstract & Commentary

By Frank W. Ling, MD, Clinical Professor, Department of Obstetrics and Gynecology, Vanderbilt University, School of Medicine, Nashville. Dr. Ling reports no financial relationship to this field of study. This article originally appeared in the December 2010 issue of OB/GYN Clinical Alerts. At that time it was peer reviewed by Catherine LeClair, MD, Associate Professor, Department of OB/GYN, Oregon Health & Science University, Portland. Dr. LeClair reports no financial relationship to this field of study.

Synopsis: In a prospective, randomized, double-blind, placebo-controlled trial of women taking SRI's, sildenafil treatment resulted in a reduction of sexual side effects.

Source: Nurnberg HG et al. Sildenafil treatment of women with antidepressant-associated sexual dysfunction. JAMA 2008;300:395-404.

A study group of 98 patients was enrolled through seven centers to evaluate the efficacy of sildenafil in the treatment of sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitors (SRIs). The patients had to be previously sexually functioning, premenopausal, and successfully treated for their depression with an SRI, but with sexual dysfunction at the time of enrollment. Several validated scales of sexual functioning were used to assess outcomes with the primary outcome being changes on the Clinical Global Impression sexual function scale (CGI). In the 8-week parallel group study, patients took either placebo or sildenafil (50-100 mg flexible dosing schedule) prior to activity. The CGI score of women treated with sildenafil was 1.9 (95% confidence interval [CI], 1.6-2.3), while those taking placebo scored on average 1.1 (95% CI, 0.8-1.5). Hormone levels were comparable and the rate of depression remission was also the same.

Commentary

How often has a patient asked you, "Why isn't there a Viagra for women?" Well, there is ... sort of. There was a minor blip on the radar screen of the medical news when this first came out in 2008, but the enthusiasm has somewhat died. The antidepressant-associated sexual dysfunction that we all encounter in our daily practices remains a challenge looking for an effective solution. As an editorial aside, I am particularly sensitive to this because of my skewed patient population that is heavy on chronic pelvic pain, antidepressant use, and sexual dysfunction. Particularly disconcerting is the repeated scenario in which patients prematurely discontinue their antidepressant therapy because of the sexual side effects. What are we to do?

We know that the phenomenon is common, i.e., the literature tells us that anywhere from 30% to 70% of patients on selective and nonselective serotonin reuptake inhibitors develop symptoms such as decrease in libido, vaginial lubrication, and sensitivity. In addition, women are also troubled by orgasmic dysfunction, dyspareunia, reduced sexual activity, and reduced satisfaction.

The relevance of the problem and the data in this article should be placed in proper perspective within the landscape of sexual dysfunction, which currently consists of four categories: sexual desire disorders (including hypoactive desire and aversion), sexual arousal disorders, sexual orgasmic disorders, and sexual pain disorders (dyspareunia and vaginismus). Whereas sildenafil is FDA-approved for arousal disorders in men, SRI-induced dysfunction is typically of the desire or orgasm type. To complicate the picture further, desire dysfunction (loss of libido) is the most common type of sexual dysfunction in females. If sildenafil works in women as it does in men, it should not directly affect libido, but should improve blood flow to the pelvic region. In men, this results in erection whereas in women, it would lead to more vasocongestion and vaginal lubrication, thereby simulating the normal physiologic response of arousal and reducing dyspareunia.

Even though the literature is not totally consistent in identifying a benefit for the use of sildenafil, it should be noted that this group of patients does show potential efficacy. Since we all see patients that might benefit from its use, knowing that there might be something available at least gives us another option to consider. As with men, the medication is used prior to sexual activity. This study started with 50 mg and allowed the patient to take up to 100 mg. In other studies involving male subjects, doses of up to 200 mg have been reported. When I offer this choice to patients, I typically start with the lowest dose, 25 mg, then increase from there.

Patient education is critical when considering applying these data. First, the clinician should recognize that depression itself can have a deleterious effect on sexual functioning. Also, an antidepressant, be it SRI or not, has the potential for adversely affecting libido and other aspects of sexual functioning. Sometimes, it becomes the proverbial "Which came first, the chicken or the egg?" quandary, trying to sort out what whether the sexual dysfunction antedated the use of the antidepressant or, more specifically, the SRI. The patient should be told specifically that the goal is not to increase libido directly. In men, it does not increase libido, but does increase blood flow to the penis, thereby generating the erection that allows the man to be sexually functional.

Other small series or case reports have suggested other approaches to these complaints, none of which has shown more than limited efficacy. The concept of a "drug holiday" in which the patient takes the SRI only on weekdays in order to be more sexually functional on the weekends has now been marginalized because of the tendency of the patient to be less compliant with taking the medication on a regular basis. Adding a non-SRI medication such as buproprion has shown limited success. Reports on yohimbine, urecholine, and periactin have been published. Any of you out there who has tried to deal with this problem has certainly found it frustrating and difficult.

Perhaps this report might allow some of us to step out and try it more often. We will continue to be asked by patients, so we might as well be open to new possibilities. As products are tested and new reports come out, we'll be watching. The testosterone patch has still not gotten here despite much anticipation. We know that women's sexual functioning is a different issue when compared to men. As I tell my patients, "Men use sex as stress relief, while women need to have stress relieved before they can have sex." Yes, it's different, not as simple, but certainly worth our continued efforts.