Sildenafil May Improve Women's Antidepressant-Related Sexual Dysfunction
Sildenafil May Improve Women's Antidepressant-Related Sexual Dysfunction
July 23, 2008 — Premenopausal women with antidepressant-associated adverse sexual effects who receive sildenafil (Viagra, Pfizer Inc) and continued stable-dose antidepressant treatment have improved sexual function, according to a small, 8-week, prospective, randomized controlled trial.
The trial was designed to evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women.
The findings, by H. George Nurnberg, MD, at the University of New Mexico School of Medicine, in Albuquerque, and colleagues, are published in the July 23/30 issue of the Journal of the American Medical Association.
Clinicians need to alert patients about potential bothersome sexual adverse effects with SRI antidepressants, Dr. Nurnberg told Medscape Psychiatry. Patients should be informed that if any such effects occur, instead of prematurely discontinuing their SRI medication, they should discuss the adverse effects with their clinician to learn about available treatment options (such as sildenafil), he said. At the same time, patients need to be made aware of the dangers of self-medicating without a prescription; for example, combining nitroglycerin with Viagra could be lethal, he said.
It is also important to note that treating women with antidepressant-associated sexual dysfunction with sildenafil requires off-label prescribing, since the US Food and Drug Administration (FDA) has only approved this drug indication for men, and further research is needed, he added.
Patients Can Remain Antidepressant Adherent
"These findings are important not only because women experience major depressive disorder at nearly double the rate of men and because they experience greater resulting sexual dysfunction than men, but also because it establishes that selective phosphodiesterase type 5 inhibitors [such as sildenafil, vardenafil, and tadalafil] are effective for both sexes for this purpose," the study authors write.
"By treating this bothersome treatment-associated adverse effect in patients who have been effectively treated for depression, but need to continue on their medication to avoid relapse or recurrence, patients can remain antidepressant adherent, reduce the current high rates of premature medication discontinuation, and improve depression disease management outcomes," they note.
Antidepressant treatment–associated sexual dysfunction is estimated to occur in 30% to 70% of men and women treated for major depression with first-generation or second-generation agents, the group explains, adding that this is a major reason for treatment nonadherence. Sexual dysfunction associated with SRIs is dose related, usually occurs early in treatment, and rarely remits spontaneously, they note.
Selective phosphodiesterase type 5 inhibitors, which are effective and well tolerated for men with erectile dysfunction, including men who are also taking antidepressants such as SRIs, are not approved by the FDA for sexual dysfunction in women. However, case reports and open-label studies, but no randomized controlled trials, have suggested that these agents might be effective for women with sexual dysfunction associated with SRI treatment.
The objective of the current study was to assess the efficacy of sildenafil in women with major depression in remission who were taking a stable dose of an SRI and had sexual dysfunction (delay in orgasm or arousal [lubrication]) that had emerged from antidepressant treatment.
The study also aimed to determine whether sildenafil treatment was associated with change in severity of depression and to compare adverse events with sildenafil vs placebo.
The trial was conducted from 2003 to 2007. Premenopausal women aged 18 to 50 years who met the eligibility criteria including substantial impaired sexual dysfunction were enrolled at 7 outpatient clinic medical centers in the United States.
A total of 98 women were randomized to take a flexible dose of placebo (n = 49) or sildenafil (n = 49) approximately 1 to 2 hours before anticipated sexual activity, not more than once daily for 8 weeks. Participants were required to make at least 1 sexual attempt and try for 2 attempts per week. The dose could be adjusted from one 50-mg tablet to two 50-mg tablets, based on investigator judgment of efficacy and tolerability.
The primary outcome was the mean change from baseline to study end on the Clinical Global Impression sexual function scale, a clinician-rated severity improvement scale derived from a review of a patient's diary, and a discussion with the patient. To provide concurrent validity, other questionnaires on sexual function were also administered. The Hamilton Rating Scale for Depression was administered at baseline and at weeks 2, 4, and 8 to monitor depression severity. Hormone levels were determined from serum analyses.
The mean age of the women was 36.7 ± 7.1 years, and they had been taking antidepressant medication for 27.7 ± 34.6 months. The antidepressants taken in the sildenafil group were fluoxetine (24.5%), paroxetine (20.4%), sertraline (18.4%), escitalopram (14.3%), citalopram (12.2%), venlafaxine (8.2%), clomipramine (2.0%), and fluvoxamine (0.0%); the distribution was similar in the placebo group.
At baseline, the study subjects in the sildenafil group reported a mean number of 3.0 ± 0.7 sexual problems: orgasm delay (100%), decreased libido (87.8%), difficulty with arousal (lubrication) (83.7%), and anorgasmia (28.6%); the incidence of sexual problems in the placebo group was similar. The women self-reported a mean of 6 ± 5.2 sexual attempts per month, of which 1.4 ± 2.0 were considered successful.
Antidepressant treatment–associated sexual dysfunction is estimated to affect 30% to 70% of men and women treated for depression with first-generation or second-generation agents. This adverse effect leads to a 3-fold increase in nonadherence, approaching 70% in the first months of treatment, leading to relapse, recurrence, and disability. However, the prevalence is highly variable in women vs men. Sexual dysfunction in women consists of decreased interest, decreased genital sensitivity, decreased vaginal lubrication, and delayed or absent orgasm with subsequent loss of pleasure in sexual relations. Although sildenafil has been found to be useful for treatment-emergent sexual dysfunction in men, it is not FDA approved for use in women.
This is a prospective, parallel-group, randomized, double-blind, placebo-controlled, 8-week trial to test the efficacy of a flexible-dose regimen of sildenafil (50 - 100 mg) for women with treatment-associated sexual dysfunction conducted at 7 US outpatient clinics.
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