Extended-Release Bupropion for Patients With Major Depressive Disorder Presenting With Symptoms of Reduced Energy, Pleasure, and Interest: Findings From a Randomized, Double-Blind, Placebo-Controlled Study 

James W. Jefferson, M.D.; A. John Rush, M.D.; J. Craig Nelson, M.D.; Susan A. VanMeter, M.D.; Alok Krishen, M.S.; Kenneth D. Hampton, B.S.; Donna S. Wightman, R.Ph.; and Jack G. Modell, M.D. 

Objective: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of extended-release bupropion (bupropion XL) in the treatment of major depressive disorder (MDD) with prominent symptoms of decreased energy, pleasure, and interest.

Method: Eligible adult outpatients meeting DSM-IV criteria for MDD were randomly assigned to bupropion XL 300 to 450 mg/day (N = 135) or placebo (N = 139) for 8 weeks. The primary efficacy measure, change from baseline on the 30-item Inventory of Depressive Symptomatology-Self Report (IDS-IVR-30) total score, was obtained using interactive voice response (IVR) technology. Secondary measures included change from baseline on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C-30) total score and change in domain subset scores for energy, pleasure, and interest; for insomnia; and for anxiety. Response and remission rates were also calculated. Safety was assessed by withdrawal rates, adverse events (AEs), body weight, and vital signs. The study was conducted from June 24, 2003, to June 30, 2004.

Results: Bupropion XL was superior to placebo at endpoint in reducing the IDS-IVR-30 total score (p = .018) and the energy, pleasure, and interest domain (p = .007) and the insomnia domain (p = .023) scores. IDS-C-30 outcomes were also significant (p < .001; p < .001, and p = .008, respectively). Clinician-rated remission rates were significantly higher with bupropion XL than placebo (32% vs. 18%, IDS-C-30; 41% vs. 27%, IDS-IVR-30), as were response rates (50% vs. 35%, IDS-C-30; 53% vs. 38%, Clinical Global Impressions-Improvement of Illness). Most AEs were mild or moderate. The incidence of a > = 7% body weight loss was 3.7% with bupropion XL and 1.4% with placebo.

Conclusion: Bupropion XL was effective and well tolerated in MDD patients with decreased energy, pleasure, and interest.

(J Clin Psychiatry 2006;67:865-873)

Received Jan. 13, 2006; accepted Feb. 14, 2006. From Madison Institute of Medicine, Madison, Wis. (Dr. Jefferson); the Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas(Dr. Rush); the Department of Psychiatry, University of California, San Francisco (Dr. Nelson); and the Neurosciences Medicine Development Center, GlaxoSmithKline, Research Triangle Park, N.C. (Drs. VanMeter and Modell, Messrs. Krishen and Hampton, and Ms. Wightman).

This research study was funded by GlaxoSmithKline, Research Triangle Park, N.C.

Financial disclosure appears at the end of the article.

The medical writing and editorial assistance of Marian S. Rhodes, Ph.D.; J. Neal Weakly, Ph.D.; and Charles G. Lineberry, Ph.D., of Lineberry Research Associates, L.L.C., are greatly appreciated.

Corresponding author and reprints: James W. Jefferson, M.D., Madison Institute of Medicine, 7617 Mineral Point Rd., Suite 300, Madison, WI 53717 (e-mail: jjefferson@healthtechsys.com).