A Study of Adjunctive Aripiprazole in Participants With Major Depressive Disorder

A Study of Adjunctive Aripiprazole in Patients With Major Depressive Disorder

This trial is a 14 week, randomized, double-blind, placebo controlled study, to assess the safety and efficacy of aripiprazole as adjunctive treatment to an ongoing antidepressant treatment in patients with Major Depressive Disorder.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Antidepressant + Placebo; Drug: Antidepressant + Aripiprazole

• Study Type: Interventional
• Enrollment (Actual): 1151
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Beverly Hills, California, United States
      • Local Institution
    • Burbank, California, United States
      • Local Institution
    • National City, California, United States
      • Local Institution
    • Orange, California, United States
      • Local Institution
    • Pasadena, California, United States
      • Local Institution
  • Colorado
    • Denver, Colorado, United States
      • Local Institution
  • Connecticut
    • Farmington, Connecticut, United States
      • Local Institution
  • Florida
    • Jacksonville, Florida, United States
      • Local Institution
    • Orlando, Florida, United States
      • Local Institution
  • Georgia
    • Atlanta, Georgia, United States
      • Local Institution
  • Maryland
    • Rockville, Maryland, United States
      • Local Institution
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Local Institution
  • New York
    • Brooklyn, New York, United States
      • Local Institution
    • New York, New York, United States
      • Local Institution
  • Ohio
    • Cincinnati, Ohio, United States
      • Local Institution
    • Toledo, Ohio, United States
      • Local Institution
  • Oregon
    • Portland, Oregon, United States
      • Local Institution
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Local Institution
  • Tennessee
    • Memphis, Tennessee, United States
      • Local Institution
  • Texas
    • Dallas, Texas, United States
      • Local Institution
    • Houston, Texas, United States
      • Local Institution
  • Virginia
    • Arlington, Virginia, United States
      • Local Institution
    • Herndon, Virginia, United States
      • Local Institution
    • Richmond, Virginia, United States
      • Local Institution
  • Washington
    • Bellevue, Washington, United States
      • Local Institution
    • Seattle, Washington, United States
      • Local Institution
  • Wisconsin
    • Brown Deer, Wisconsin, United States
      • Local Institution
    • Middleton, Wisconsin, United States
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women, 18-65 years old
• Experienced a Major Depressive Disorder with the current episode of minimally 8 weeks in duration.
• Treatment history of an inadequate response to at least one and no more than three antidepressants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A2	Drug: Antidepressant + Aripiprazole; Antidepressant Caps/Tablets Aripiprazole Tablets, Oral, 2-20 mg Aripiprazole, once daily, 6 weeks following an 8 week Prospective Treatment (Baseline) Phase.; Other Names: Abilify
Placebo Comparator: A1	Drug: Antidepressant + Placebo; Antidepressant Caps/Tablets Placebo Tablets, Oral, 2-20 mg Placebo, once daily, 6 weeks following an 8 week Prospective Treatment (Baseline) Phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in a depression rating scale at endpoint	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in a disability scale and Clinical Global Impression scale at endpoint	Baseline, Week 8

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Collaborators: Otsuka America Pharmaceutical

Publications and helpful links

General Publications

• Boulton DW, Balch AH, Royzman K, Patel CG, Berman RM, Mallikaarjun S, Reeves RA. The pharmacokinetics of standard antidepressants with aripiprazole as adjunctive therapy: studies in healthy subjects and in patients with major depressive disorder. J Psychopharmacol. 2010 Apr;24(4):537-46. doi: 10.1177/0269881108096522. Epub 2008 Oct 2.
• Marcus RN, McQuade RD, Carson WH, Hennicken D, Fava M, Simon JS, Trivedi MH, Thase ME, Berman RM. The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a second multicenter, randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol. 2008 Apr;28(2):156-65. doi: 10.1097/JCP.0b013e31816774f9.
• Stewart TD, Hatch A, Largay K, Sheehan JJ, Marler SV, Berman RM, Nelson JC. Effect of symptom severity on efficacy and safety of aripiprazole adjunctive to antidepressant monotherapy in major depressive disorder: a pooled analysis. J Affect Disord. 2014 Jun;162:20-5. doi: 10.1016/j.jad.2014.03.017. Epub 2014 Mar 24.
• Casey DE, Laubmeier KK, Marler SV, Forbes RA, Baker RA. Efficacy of adjunctive aripiprazole in major depressive disorder: a pooled response quartile analysis and the predictive value of week 2 early response. Prim Care Companion CNS Disord. 2012;14(3):PCC.11m01251. doi: 10.4088/PCC.11m01251. Epub 2012 May 31.
• Fabian TJ, Cain ZJ, Ammerman D, Eudicone JM, Tang Y, Rollin LM, Forbes RA, Berman RM, Baker RA. Improvement in functional outcomes with adjunctive aripiprazole versus placebo in major depressive disorder: a pooled post hoc analysis of 3 short-term studies. Prim Care Companion CNS Disord. 2012;14(6):PCC.12m01394. doi: 10.4088/PCC.12m01394. Epub 2012 Dec 20.
• Dunner DL, Laubmeier KK, Manos G, Forbes RA, Baker RA, Berman RM. Beneficial effects of adjunctive aripiprazole in major depressive disorder are not dependent on antidepressant therapy history: a post hoc analysis of 3 randomized, double-blind, placebo-controlled trials. Prim Care Companion CNS Disord. 2012;14(6):PCC.12m01380. doi: 10.4088/PCC.12m01380. Epub 2012 Nov 22.
• Fava M, Dording CM, Baker RA, Mankoski R, Tran QV, Forbes RA, Eudicone JM, Owen R, Berman RM. Effects of adjunctive aripiprazole on sexual functioning in patients with major depressive disorder and an inadequate response to standard antidepressant monotherapy: a post hoc analysis of 3 randomized, double-blind, placebo-controlled studies. Prim Care Companion CNS Disord. 2011;13(1):PCC.10m00994. doi: 10.4088/PCC.10m00994gre.
• Trivedi MH, Thase ME, Fava M, Nelson CJ, Yang H, Qi Y, Tran QV, Pikalov A, Carlson BX, Marcus RN, Berman RM. Adjunctive aripiprazole in major depressive disorder: analysis of efficacy and safety in patients with anxious and atypical features. J Clin Psychiatry. 2008 Dec;69(12):1928-36. Epub 2008 Dec 2.
• Nelson JC, Thase ME, Trivedi MH, Fava M, Han J, Van Tran Q, Pikalov A, Qi Y, Carlson BX, Marcus RN, Berman RM. Safety and Tolerability of Adjunctive Aripiprazole in Major Depressive Disorder: A Pooled Post Hoc Analysis (studies CN138-139 and CN138-163). Prim Care Companion J Clin Psychiatry. 2009;11(6):344-52. doi: 10.4088/PCC.08m00744gre.
• Thase ME, Trivedi MH, Nelson JC, Fava M, Swanink R, Tran QV, Pikalov A, Yang H, Carlson BX, Marcus RN, Berman RM. Examining the efficacy of adjunctive aripiprazole in major depressive disorder: a pooled analysis of 2 studies. Prim Care Companion J Clin Psychiatry. 2008;10(6):440-7. doi: 10.4088/pcc.v10n0603.
• Fava M, Wisniewski SR, Thase ME, Baker RA, Tran QV, Pikalov A, Yang H, Marcus RN, Berman RM. Metabolic assessment of aripiprazole as adjunctive therapy in major depressive disorder: a pooled analysis of 2 studies. J Clin Psychopharmacol. 2009 Aug;29(4):362-7. doi: 10.1097/JCP.0b013e3181ac9b0b.
• Weisler RH, Khan A, Trivedi MH, Yang H, Eudicone JM, Pikalov A, Tran QV, Berman RM, Carlson BX. Analysis of suicidality in pooled data from 2 double-blind, placebo-controlled aripiprazole adjunctive therapy trials in major depressive disorder. J Clin Psychiatry. 2011 Apr;72(4):548-55. doi: 10.4088/JCP.09m05495gre. Epub 2010 Aug 24.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2004
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: November 9, 2004
• First Submitted That Met QC Criteria: November 8, 2004
• First Posted (Estimated): November 9, 2004

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Psychotropic Drugs; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Quinolones; Quinolines; Central Nervous System Agents; Piperazines; Aripiprazole; Antidepressive Agents
• Other Study ID Numbers: CN138-163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets or beginning 1-3 years following article publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF