Comparing the Rapidity of Response During Treatment of Major Depressive Disorder With Bupropion and the SSRIs: A Pooled Survival Analysis of 7 Double-Blind, Randomized Clinical Trials

George I. Papakostas, M.D.; Stuart A. Montgomery, M.D.; Michael E. Thase, M.D.; Judith R. Katz, B.A.; Alok Krishen, M.Sc. (Hons. Sch.), M.S.; and Vivian L. Tucker, Pharm.D.

Objective: Several controlled studies, as well as a meta-analysis, suggest that the efficacy of bupropion, a norepinephrine-dopamine reuptake inhibitor, is comparable to that of the selective serotonin reuptake inhibitors (SSRIs). The current analysis was undertaken to determine if these antidepressants differ in rapidity of clinical effect.

Method: Individual patient data were obtained from 7 double-blind, randomized studies of 8 weeks' duration that compared bupropion (N = 836) and SSRIs (sertraline, paroxetine, fluoxetine, and escitalopram; N = 836). Time to first response and first remission were compared between treatment groups with the use of Cox proportional hazards regression models, stratified by trial number, with depression severity at baseline as a covariate. A secondary analysis compared outcomes in the 2 bupropion versus escitalopram studies. Random-effects meta-analyses were then conducted to confirm the survival-analysis findings.

Results: There was no statistically significant difference between bupropion and the SSRIs in time to first response (hazard ratio [HR] = 0.955; p = .43) and first remission (HR = 1.00; p = .97). Similarly, there was no statistically significant difference between bupropion and escitalopram in time to first response (HR = 0.897; p = .29), and first remission (HR = 0.999; p = .99). These results were confirmed with the use of random-effects meta-analyses (p > .05, all 4 analyses).

Conclusion: There does not appear to be any statistically detectable difference in the rapidity of antidepressant effect between bupropion and the SSRIs overall or escitalopram specifically.

(J Clin Psychiatry 2007;68:1907-1912)

Received Nov. 3, 2006; accepted March 12, 2007. From Massachusetts General Hospital, Harvard Medical School, Boston (Dr. Papakostas and Ms. Katz); Imperial College School of Medicine, London, U.K. (Dr. Montgomery); University of Pennsylvania, Philadelphia, and University of Pittsburgh Medical Center, Pittsburgh, Pa. (Dr. Thase); and GlaxoSmithKline, Research Triangle Park, Durham, N.C. (Mr. Krishen and Dr. Tucker).

This work was supported by National Institute of Mental Health grant K23 MH069629 to Dr. Papakostas/Massachusetts General Hospital.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: George I. Papakostas, M.D., Massachusetts General Hospital, Harvard Medical School, 15 Parkman St., WACC 812, Boston, MA 02114 (e-mail: gpapakostas@partners.org).