Bupropion Extended Release Compared With Escitalopram: Effects on Sexual Functioning and Antidepressant Efficacy in 2 Randomized, Double-Blind, Placebo-Controlled Studies

Anita H. Clayton, M.D.; Harry A. Croft, M.D.; Joseph P. Horrigan, M.D.; Donna S. Wightman, R.Ph.; Alok Krishen, M.S.; Nathalie E. Richard, M.S.; and Jack G. Modell, M.D.

Objective: To compare the effects on sexual functioning and the antidepressant efficacy of once-daily bupropion extended release (XL) and escitalopram in adults with major depressive disorder (MDD).

Method: Adult outpatients with moderate to severe DSM-IV-defined MDD and normal sexual functioning were randomly assigned to receive bupropion XL (300-450 mg/day; N = 276), escitalopram (10-20 mg/day; N = 281), or placebo (N = 273) for up to 8 weeks in 2 identically designed, randomized, double-blind, parallel-group studies (study 1 conducted from February 6, 2003, to June 10, 2004; study 2 conducted from January 21, 2003, to June 15, 2004). Data were analyzed prospectively for each study individually, and pooled data were analyzed retrospectively.

Results: In both the individual studies and the pooled dataset, the incidence of orgasm dysfunction at week 8 (primary endpoint) and the incidence of worsened sexual functioning at the end of the treatment period were statistically significantly lower with bupropion XL than with escitalopram (p < .05), not statistically different between bupropion XL and placebo (p > = .067), and statistically significantly higher with escitalopram than with placebo (p < = .001). The percentages of patients with orgasm dysfunction at week 8 in study 1, study 2, and the pooled dataset, respectively, were 13%, 16%, and 15% with bupropion XL; 32%, 29%, and 30% with escitalopram; and 11%, 8%, and 9% with placebo. The respective percentages of patients with worsened sexual functioning at the end of the treatment period were 18%, 22%, and 20% with bupropion XL; 37%, 34%, and 36% with escitalopram; and 14%, 16%, and 15% with placebo. Mean changes in Changes in Sexual Functioning Questionnaire scores for all domains at week 8 were statistically significantly worse for escitalopram compared with bupropion XL (p < = .05). Separation from placebo could not be established at a statistical .05 level for bupropion on 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. However, escitalopram showed statistical superiority to placebo on HAM-D-17 total score in one of the 2 studies and in the pooled data. Bupropion XL did not statistically differ from escitalopram with respect to mean change in HAM-D-17 total score, HAM-D-17 response or remission rates, percentage of patients much or very much improved on Clinical Global Impressions-Improvement scale scores, or mean changes in the Hospital Anxiety and Depression (HAD) scale total score or Clinical Global Impressions-Severity of Illness scale score at week 8.

Conclusions: Bupropion XL had a sexual tolerability profile significantly better than that of escitalopram with similar HAM-D-17 remission rates and HAD total scores in patients with MDD.

(J Clin Psychiatry 2006;67:736-746)

Received Nov. 30, 2005; accepted April 10, 2006. From the Department of Psychiatric Medicine, University of Virginia Health System, Charlottesville (Dr. Clayton); Psychiatric Research Center, San Antonio, Tex. (Dr. Croft); and GlaxoSmithKline, Research Triangle Park, N.C. (Drs. Horrigan and Modell, Mss. Wightman and Richard, and Mr. Krishen).

Supported by GlaxoSmithKline, Research Triangle Park, N.C.

Dr. Clayton has received grants from Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Forest, GlaxoSmithKline, Neuronetics, Pfizer, and Wyeth; has been an advisory board member/consultant for Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Fabre-Kramer, GlaxoSmithKline, Pfizer, Vela, and Wyeth; and has been on the speakers bureau of/received honoraria from Eli Lilly, GlaxoSmithKline, Pfizer, and Wyeth. Dr. Croft has been a consultant for, received honoraria from, and participated in speakers/advisory boards of GlaxoSmithKline and has received grant/research support from GlaxoSmithKline and Wyeth. Drs. Horrigan and Modell, Mss. Wightman and Richard, and Mr. Krishen report no additional financial or other relationship relevant to the subject of the article.

Corresponding author and reprints: Anita H. Clayton, M.D., 2955 Ivy Rd., Northridge Suite 210, Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA 22903 (e-mail: ahc8v@virginia.edu).