Remission Rates Following Antidepressant Therapy With Bupropion or Selective Serotonin Reuptake Inhibitors: A Meta-Analysis of Original Data From 7 Randomized Controlled Trials

Michael E. Thase, M.D.; Barbara R. Haight, Pharm.D.; Nathalie Richard, M.S.; Carol B. Rockett, Pharm.D.; Melinda Mitton, Pharm.D.; Jack G. Modell, M.D.; Susan VanMeter, M.D.; April E. Harriett, M.A.; and Younghua Wang, Ph.D.

Background: Although it is widely believed that the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine).

Method: Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512). Response and remission rates were compared at week 8 or endpoint in both the intent-to-treat sample, using the last-observation-carried-forward (LOCF) method to account for attrition, and the observed cases. Tolerability data, including incidence of sexual side effects, were also compared.

Results: The LOCF response and remission rates for the bupropion (62% and 47%) and SSRI (63% and 47%) groups were similar; both active therapies were superior to placebo (51% and 36%; all comparisons, p < .001). The same pattern of results was demonstrated on the observed cases analyses. Although bupropion and SSRIs were generally well tolerated, SSRI therapy resulted in significantly higher rates of sexual side effects as compared to both bupropion and placebo. SSRIs were also associated with more somnolence and diarrhea, and bupropion was associated with more dry mouth.

Conclusion: Bupropion and the SSRIs were equivalently effective and, overall, both treatments were well tolerated. The principal difference between these treatments was that sexual dysfunction commonly complicated SSRI therapy, whereas treatment with bupropion caused no more sexual dysfunction than placebo.

(J Clin Psychiatry 2005;66:974-981)

Received April 13, 2004; accepted Jan. 20, 2005. From the Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, Pa. (Dr. Thase); and GlaxoSmithKline, Research Triangle Park, N.C. (Drs. Haight, Rockett, Mitton, Modell, VanMeter, and Wang and Mss. Richard and Harriett).

Drs. Haight, Rockett, Mitton, Modell, VanMeter, and Wang and Mss. Richard and Harriett are employees of GlaxoSmithKline. Dr. Thase's efforts are supported in part by National Institute of Mental Health grant MH-30915 (Mental Health Intervention Research Center, David J. Kupfer, M.D., principal investigator).

Dr. Thase discloses the following significant financial interests with GlaxoSmithKline (the manufacturer of bupropion and paroxetine): consultant, advisory board member, member of various speakers bureaus, and (in the past) recipient of research funding. He has had similar relationships with the manufacturers of 2 other drugs included in this report: Pfizer (sertraline) and Eli Lilly and Company (fluoxetine).

The medical writing assistance of Geoffrey Banks, Ph.D., and Charles Lineberry, Ph.D., of Lineberry Research Associates, L.L.C., is greatly appreciated.

Corresponding author and reprints: Michael E. Thase, M.D., Department of Psychiatry, University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213-2593 (e-mail: thaseme@upmc.edu).