Efficacy and Safety of Sildenafil in Men With Serotonergic Antidepressant-Associated Erectile Dysfunction: Results From a Randomized, Double-Blind, Placebo-Controlled Trial

Maurizio Fava, M.D.; H. George Nurnberg, M.D.; Stuart N. Seidman, M.D.; Willis Holloway, M.D.; Susan Nicholas; Li-Jung Tseng, Ph.D.; and Vera J. Stecher, Ph.D.

Objective: To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED).

Method: Men (aged > = 18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity.

Results: Patients receiving sildenafil (N = 71) versus placebo (N = 71) reported significantly higher mean ± SE scores on Q3 (3.9 ± 0.2 vs. 3.1 ± 0.2, p = .003) and Q4 (3.7 ± 0.2 vs. 2.8 ± 0.2, p < .001) of the IIEF and significantly higher scores on all domains of the IIEF. Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS questionnaire (p < .02) and the GEQ (p < .0001) and an increased number of successful sexual intercourse attempts per week (p < .0001) compared with patients receiving placebo. All patients remained in MDD remission (score < = 10 on the Hamilton Rating Scale for Depression). Adverse events in patients taking sildenafil (vs. placebo) were headache (9% vs. 9%), dyspepsia (9% vs. 1%), anxiety (6% vs. 4%), and abnormal vision (3% vs. 0%).

Conclusions: Short-term (6-week) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD. Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy.

(J Clin Psychiatry 2006:67:240-246)

Received May 20, 2005; accepted Aug. 25, 2005. From the Depression Clinical and Research Program, the Department of Psychiatry, Massachusetts General Hospital, Boston (Dr. Fava); the Department of Psychiatry, University of New Mexico, Albuquerque (Dr. Nurnberg); the Department of Psychiatry, Columbia Presbyterian Medical Center, New York, N.Y. (Dr. Seidman); Cutting Edge Research, Oklahoma City, Okla. (Dr. Holloway); and Pfizer Inc, New York, N.Y. (Drs. Tseng and Stecher and Ms. Nicholas).

This study was supported by Pfizer Inc, New York, N.Y.

Data from this trial were presented at the 156th annual meeting of the American Psychiatric Association, May 17-22, 2003, in San Francisco, Calif.

Financial disclosure and acknowledgments appear at the end of the article.

Corresponding author and reprints: Maurizio Fava, M.D., the Depression Clinical and Research Program, the Department of Psychiatry, Massachusetts General Hospital, 15 Parkman St., ACC 812, Boston, MA 02114 (e-mail: mfava@partners.org).