Aripiprazole Augmentation of Antidepressants for the Treatment of Partially Responding and Nonresponding Patients With Major Depressive Disorder

Jeffrey S. Simon, M.D., and Charles B. Nemeroff, M.D., Ph.D.

Objective: To determine the efficacy and tolerability of aripiprazole, a dopamine D₂ and 5-HT_1A receptor partial agonist, as augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder.

Method: Fifteen patients with major depressive disorder (diagnosed with a site-generated form described in the text) and an incomplete response or no response to >= 8 weeks of antidepressant (selective serotonin reuptake inhibitor, venlafaxine, or bupropion) monotherapy were treated with aripiprazole augmentation in an 8-week, open-label study. Data were gathered from July 2003 to March 2004.

Results: The mean duration of antidepressant monotherapy at baseline was 43.1 weeks. At baseline, mean Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Depression (HAM-D) scores were 4.3 and 18.9, respectively. After initiation of aripiprazole augmentation, 6 of 15 patients achieved remission (HAM-D score <= 7) at week 1, and 9 of 15 patients remitted by week 2. All 8 completers achieved remission by study endpoint. Akathisia in 2 patients who withdrew prematurely prompted a reduction in the starting dose of aripiprazole from 10 mg/day to 2.5 mg/day, resulting in a 50% reduction in attrition due to akathisia (2/7 withdrew due to akathisia with the 10-mg starting dose, 1/8 withdrew due to akathisia with the 2.5-mg starting dose). Discontinuation rates after 4 weeks of treatment were lower for the 2.5-mg starting dose (1/8 patients) than for the 10-mg starting dose (3/7 patients). Overall discontinuation rates at endpoint were lower for the 2.5-mg dose (3/8 patients) than the 10-mg dose (4/7 patients). Response to aripiprazole augmentation did not appear to be related to the antidepressant used at study initiation.

Conclusion: Aripiprazole is an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical signal, a double-blind, placebo-controlled trial is warranted.

(J Clin Psychiatry 2005;66:1216-1220)

Received June 12, 2005; accepted Aug. 8, 2005. From the Northbrooke Research Center, Brown Deer, Wis. (Dr. Simon), and the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Ga. (Dr. Nemeroff).

Funding for this investigator-initiated study was provided by Bristol-Myers Squibb and Otsuka Pharmaceuticals, Inc.

These data were presented in poster form at the 43rd annual meeting of the American College of Neuropsychopharmacology, Dec. 12-16, 2004, San Juan, Puerto Rico.

Financial disclosure appears at the end of the article.

The content in this manuscript, expressed and unexpressed, is the sole representation of the investigators/authors. Collection, interpretation, and/or representation of this data have not been influenced by Otsuka Pharmaceuticals, Inc., or Bristol-Myers Squibb.

Corresponding author and reprints: Jeffrey S. Simon, M.D., Northbrooke Research Center, 9275 North 49th St., Suite 200, Brown Deer, WI 53223 (e-mail: jssimonmd@aol.com).