Aripiprazole Augmentation of Selective Serotonin Reuptake Inhibitors for Treatment-Resistant Major Depressive Disorder

George I. Papakostas, M.D.; Timothy J. Petersen, Ph.D.; Gustavo Kinrys, M.D.; Alana M. Burns, B.A.; John J. Worthington III, M.D.; Jonathan E. Alpert, M.D., Ph.D.; Maurizio Fava, M.D.; and Andrew A. Nierenberg, M.D.

Background: Due to their favorable side effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Aripiprazole, an atypical antipsychotic agent with partial dopaminergic and serotonin 1_A receptor agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study was to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI).

Method: 12 patients (mean ± SD age = 46.6 ± 11.3 years, 66.7% female) with major depressive disorder (MDD) diagnosed by use of the Structured Clinical Interview for DSM-IV-Axis I Disorders, who had failed to experience a clinical response following an adequate trial of an SSRI, were treated with open-label aripiprazole in addition to their SSRI for 8 weeks. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline-endpoint) as measured by the 17-item Hamilton Rating Scale for Depression total score. Data were collected from August 2003 to July 2004.

Results: 9/12 (75.0%) patients completed the trial. Using a completer analysis, 5/9 (55.6%) patients were classified as responders. An intent-to-treat (ITT) analysis resulted in 7 responders (58.3%). The overall proportion of remitters was 3/9 (33.3%) using a completer analysis and 5/12 (41.7%) using the ITT analysis. Aripiprazole administration appeared safe, with no severe adverse events observed in any of the study participants.

Conclusions: These results suggest a possible augmentation role for aripiprazole when used in conjunction with SSRIs in SSRI-resistant MDD.

(J Clin Psychiatry 2005;66:1326-1330)

Received Jan. 13, 2005; accepted March 30, 2005. From the Depression Clinical and Research Program, Massachusetts General Hospital, Boston (Drs. Papakostas, Petersen, Worthington, Alpert, Fava, and Nierenberg and Ms. Burns) and the Anxiety Disorders Research Program, Cambridge Health Alliance, Cambridge (Dr. Kinrys), Mass.

Supported by an unrestricted grant from Bristol-Myers Squibb Pharmaceuticals (Dr. Nierenberg), New York, N.Y.

Financial disclosure appears at the end of this article.

Corresponding author and reprints: George I. Papakostas, M.D., Massachusetts General Hospital, Department of Psychiatry, Depression Clinical and Research Program, 15 Parkman St., WAC 812, Boston, MA 02114 (e-mail: gpapakostas@partners.org).