Practice changer
Tell women for whom you prescribe selective and nonselective serotonin reuptake inhibitors (SRIs) to let you know if they develop sexual dysfunction. Offer sildenafil (50 mg with the option to increase to 100 mg) to premenopausal women on stable, effective doses of SRIs who experience this common—and treatable—side effect.1
Strength of recommendation
B: One high-quality RCT that confirms smaller, open-label studies
Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S. Sildenafil treatment of women with antidepressant-associated sexual dysfunction: a randomized controlled trial. JAMA. 2008;300:395-404.
ILLUSTRATIVE CASE
A 34-year-old woman comes to your office and asks to be taken off the paroxetine you prescribed for her 4 months ago. The medication is working well; her depression has been in remission for at least 12 weeks. But she no longer enjoys sex. She used to have a healthy libido and satisfying arousal and orgasm, but since starting the antidepressant, her sexual interest and pleasure have been low.
Although she’s afraid of sinking back into a depression without the medication, she’s willing to take the risk. If she were your patient, what alternatives would you suggest?
Sexual dysfunction affects an estimated 30% to 50% of patients on selective and nonselective SRIs, and some studies report rates as high as 70% to 80%.2 Many patients stop taking these antidepressants prematurely, often because of sexual side effects.3,4
Phosphodiesterase type 5 (PDE-5) inhibitors are well established as an effective treatment for erectile dysfunction,5 and randomized controlled trials (RCTs) have shown sildenafil to be effective in treating male SRI-induced sexual impairment.6,7 For women, there has been no parallel evidence-based treatment.
Limited options, with little support
Typically, women who reported antidepressant-associated sexual disturbances have been offered options for which there was only weak evidence—dose changes or augmentation with another agent, switching to another antidepressant, or taking occasional drug holidays. A 2004 Cochrane review found that there were no RCTs involving dose changes or drug holidays.8 Among studies of the efficacy of switching to a different drug, nefazodone was the only agent whose use was supported by a double-blind RCT.9 Augmentation trials of a wide range of medications and supplements—including amantadine, bupropion, buspirone, granisetron, mirtazapine, olanzapine, ephedrine, ginkgo biloba, and yohimbine—yielded mixed results. Indeed, the research found that some were no better than placebo.
PDE-5 inhibitors for women? Inconclusive studies to date
Female sexual dysfunction is generally divided into 4 domains: disorders of desire, arousal, orgasm, or pain. Decreased desire and delayed or absent orgasm are the most common sexual side effects of SRI antidepressants in women.10 Several studies of PDE-5 inhibitors in this patient population have had positive results,11-15 so there has been good reason to think that they might help this subset of women. However, all the studies were small and nonblinded, and therefore inconclusive—until now.
STUDY SUMMARY: Finally, a well-done RCT provides some answers
Investigators enrolled 98 premenopausal women from 7 US research centers in a double-blind randomized trial. To qualify, participants had to be diagnosed with major depression in remission, be taking a selective or nonselective SRI for >8 weeks, and be on a stable dose for >4 weeks. They also had to meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for substance-induced sexual dysfunction lasting >4 weeks, but have no history of sexual impairment independent of antidepressants. Finally, participants had to engage in some form of regular sexual activity—intercourse, oral sex, and masturbation all qualified—at least twice a month, and be willing to continue efforts to have sex at least once a week during the study. Women with other medical, psychiatric, or sexual problems were excluded, as were those who were pregnant, breastfeeding, or able to become pregnant and not using reliable contraception.
Participants were randomized to receive 50 mg of sildenafil (n=49) or a matching placebo tablet (n=49), which they were instructed to take 1 to 2 hours before sexual activity. The dose could be adjusted to 2 tablets (100 mg sildenafil) based on investigator assessment of the patient’s response to the initial dose. Participants and all study personnel were blinded to group assignment.
