CNS Drugs

, Volume 25, Issue 2, pp 109–127 | Cite as

Aripiprazole as Adjunctive Therapy for Patients with Major Depressive Disorder

Overview and Implications of Clinical Trial Data
Review Article


Aripiprazole was initially approved to treat schizophrenia and later approved for bipolar mania, as a monotherapy and an adjunctive therapy (manic or mixed episodes), and for irritability associated with autism. Aripiprazole is a partial agonist at dopamine D2 and D3 and serotonin 5-HT1A receptors, and is an antagonist at 5-HT2a receptors. This profile, and convincing preliminary data from small-scale studies, provided the rationale for the large-scale exploration of aripiprazole for unipolar depression. Recently, three 6-week, large-scale, randomized, double-blind, placebo-controlled clinical trials demonstrated clinically meaningful efficacy for aripiprazole as an adjunctive therapy to antidepressants for treating major depressive disorder (MDD). In November 2007, aripiprazole was approved by the US FDA as an adjunctive therapy to antidepressants for treating MDD, with support from two of the above-mentioned trials. In the trials, aripiprazole was demonstrated to be safe and well tolerated, and showed a minimal trend for weight gain over the course of a 6-week treatment. The incidence of akathisia was higher than that reported in studies of patients with schizophrenia; however, most cases were mild to moderate and infrequently lead to discontinuation (5/1090 from all three trials).

This comprehensive review provides an overview of the data from all three 6-week studies (including a pooled analysis) and from an unpublished 52-week, open-label extension study, to inform physicians and facilitate reasonable treatment decisions. In addition, specific issues associated with the use of aripiprazole as an adjunctive therapy in patients with MDD, including possible early treatment effect, appropriate timing of therapy initiation, appropriate dosing and duration of treatment, possible differential effect on depressive subgroups and long-term tolerability, are also discussed.



This work was supported by a grant from the Medical Research Center, Korea Science and Engineering Foundation, Republic of Korea (R13-2002-005-04001-0). The authors did not receive any independent funding or payment from Otsuka Pharmaceuticals. Drs Pae and Patkar were involved in the commencement of the manuscript, data collection and review, and writing the draft and revised version of the manuscript. Dr Forbes reviewed the data accuracy and wrote specific parts of the manuscript (pharmacokinetics and pharmacodynamics).

Dr Pae has received research grants from GlaxoSmithKline Korea, GlaxoSmithKline, AstraZeneca Korea, Jansssen Pharmaceutcals Korea, Eli Lilly and Company Korea, Korea Science and Engineering Foundation, Korean Research Foundation, Otsuka Korea, Wyeth Korea and Korean Institute of Science and Technology Evaluation and Planning; has received honoraria and/or is on the speaker’s bureaux of GlaxoSmithKline Korea, GlaxoSmithKline Taiwan, Otsuka Taiwan, Lundbeck Korea, AstraZeneca Korea, Johnson & Johnson-Health Care Products & Pharmaceuticals, Janssen Pharmaceuticals Korea, Wyeth Korea, Abott Korea, Pfizer Korea, Eli Lilly and Company Korea, Norvatis Korea, McNeil Consumer and Specialty Inc., Otsuka Pharmaceutical Development & Commercialization and Otsuka Korea.

Dr Forbes is an employee of Otsuka Pharmaceutical Development & Commercialization.

Dr Patkar is a consultant for Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser; is on the speaker’s bureaux of Bristol-Myers Squibb, GlaxoSmithKline and Reckitt Benckiser; has received research support from National Institutes of Health, AstraZeneca, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Janssen, McNeil Consumer and Specialty Inc., Organon, Jazz Pharmaceuticals and Pfizer.


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Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  1. 1.Department of Psychiatry, Bucheon St. Mary’s HospitalThe Catholic University of Korea College of MedicineKyounggi-DoRepublic of Korea
  2. 2.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  3. 3.Otsuka Pharmaceutical Development & CommercializationPrincetonUSA

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