Efficacy of Bupropion and the Selective Serotonin Reuptake Inhibitors in the Treatment of Major Depressive Disorder With High Levels of Anxiety (Anxious Depression): A Pooled Analysis of 10 Studies

George I. Papakostas, M.D.; Stephen M. Stahl, M.D.; Alok Krishen, M.Sc. (Hons. Sch.), M.S.; Cheryl A. Seifert, B.A.; Vivian L. Tucker, Pharm.D.; Elizabeth P. Goodale, Pharm.D.; and Maurizio Fava, M.D.

Objective: The goal of this work was to compare the efficacy of the norepinephrine and dopamine reuptake inhibitor bupropion with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder with high levels of anxiety (anxious depression).

Method: Ten double-blind, randomized studies from 1991 through 2006 were combined (N = 2122). Anxious depression was defined as a 17-item Hamilton Rating Scale for Depression (HAM-D-17) anxiety-somatization factor score >= 7.

Results: Among patients with anxious depression (N = 1275), response rates were greater following SSRI than bupropion treatment according to the HAM-D-17 (65.4% vs. 59.4%, p = .03) and the Hamilton Rating Scale for Anxiety (61.5% vs. 54.5%, p = .03). There was also a greater reduction in HAM-D-17 mean ± SD scores (-14.1 ± 7.6 vs. -13.2 ± 7.9, p = .03) and a trend toward statistical significance for a greater reduction in HAM-A mean ± SD scores (-10.5 ± 7.4 vs. -9.6 ± 7.6, p = .05) in favor of SSRI treatment among patients with anxious depression. There was no statistically significant difference in efficacy between bupropion and the SSRIs among patients with moderate/low levels of anxiety.

Conclusions: There appears to be a modest advantage for the SSRIs compared to bupropion in the treatment of anxious depression (6% difference in response rates). Using the number-needed-to-treat (NNT) statistic as 1 indicator of clinical significance, nearly 17 patients would need to be treated with an SSRI than with bupropion in order to obtain 1 additional responder. This difference falls well above the limit of NNT = 10, which was suggested by the United Kingdom's National Institute of Clinical Excellence. Nevertheless, the present work is of theoretical interest because it provides preliminary evidence suggesting a central role for serotonin in the regulation of symptoms of negative affect such as anxiety.

(J Clin Psychiatry 2008;69:1287-1292. Online Ahead of Print July 1, 2008.)

Received Sept. 21, 2007; accepted Nov. 28, 2007. From Massachusetts General Hospital, Harvard Medical School, Boston (Drs. Papakostas and Fava and Ms. Seifert); the Department of Psychiatry, University of California, San Diego (Dr. Stahl); and GlaxoSmithKline, Research Triangle Park, Durham, N.C. (Drs. Tucker and Goodale and Mr. Krishen).

This article was supported by National Institute of Mental Health grant K23 MH069629 (G.P.).

The authors would like to thank Sajida Chughtai, B.S., and Russel Hinkle, B.S., from GlaxoSmithKline, for their help with statistical programming. Messrs. Chughtai and Hinkle report no additional financial relationship relevant to the subject of this article.

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).