A Study of Aripiprazole in Patients With Major Depressive Disorder

The purpose of this 14 week, randomized, double-blind, placebo controlled study is to assess the safety and efficacy of aripiprazole to placebo as adjunctive treatment to an assigned open-label marketed antidepressant therapy (ADT) in patients with Major Depressive Disorder who demonstrate an incomplete response to a prospective eight week trial of the same assigned open-label marketed antidepressant therapy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 349
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • University of Alabama at Birmingham
  • California
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Center
  • Florida
    • Coral Springs, Florida, United States, 33065
      • CNS Clinical Research Group
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute, LLC
    • Edwardsville, Illinois, United States, 62025
      • Cunningham Clinical Research, Llc
    • Hoffman Estates, Illinois, United States, 60194
      • Comprehensive NeuroScience, Inc.
    • Springfield, Illinois, United States, 62711
      • Vine Street Clinical Research Center
  • Kansas
    • Witchita, Kansas, United States, 67211
      • Clinical Research Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • LSU Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Pharmasite Research, Inc.
  • Michigan
    • Farmington Hills, Michigan, United States, 48336
      • Summit Research Network
    • Flint, Michigan, United States, 48507
      • Summit Research Network
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89146
      • Radiant Research Las Vegas
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Behavioral Health Center
  • Ohio
    • Dayton, Ohio, United States, 45408
      • Midwest Clinical Research Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Phebe Tucker, Md
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Southeast Health Consultants
    • Columbia, South Carolina, United States, 29203
      • Usc School Of Medicine
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research, Inc.
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine
    • Salt Lake City, Utah, United States, 84107
      • Radiant Research, Slc
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Clinical Research Center
  • Wisconsin
    • Brown Deer, Wisconsin, United States, 53223
      • Northbrooke Research Center
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation For Health Research & Education

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women, 18-65 years old who have experienced single or recurrent, non-psychotic episodes of 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 adequate antidepressant trials.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1	Drug: Aripiprazole+ ADT; Tablets, Oral, 2 - 20 mg variable dose once daily, 14 weeks; Other Names: Abilify
Placebo Comparator: A2	Drug: Placebo+ ADT; Tablets, Oral, 2 - 20 mg variable dose once daily, 14 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in the Montgomery Åsberg Depression Rating Scale (MADRS)	Mean change from Week 8 (baseline) to Week 14 in MADRS total score, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.	Baseline (Week 8) and Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Sheehan Disability Scale (SDS) Mean Score	Mean change from Week 8 (baseline) to Week 14 in SDS Mean Score, a 3-item, ordinal scale (0=unimpaired; 30=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.	Baseline (Week 8) and Week 14
Mean Change in SDS Item Score (Social Life)	Mean change from Week 8 (baseline) to Week 14 in SDS Social Life Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.	Baseline (Week 8) and Week 14
Mean Change in SDS Item Score (Family Life)	Mean change from Week 8 (Baseline) to Week 14 in SDS Family Life Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.	Baseline (Week 8) and Week 14
Mean Change in SDS Item Score (Work/School)	Mean change from Week 8 (baseline) to Week 14 in SDS Work/School Item Score, 1 item from a 3-item, ordinal scale (0=unimpaired; 10=highly impaired). Change from baseline=postbaseline score - baseline score. A negative change score indicates improvement.	Baseline (Week 8) and Week 14

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MADRS Response	Number of subjects with a ≥50 percent reduction from Week 8 (baseline) in MADRS Total Score, a 10-item, ordinal rating scale to assess the severity of depressive symptoms (0=no symptoms; 60=most severe symptoms).	Baseline (Week 8) and Week 14
Clinical Global Impression (CGI)-Improvement Response	Number of subjects with response relative to Week 8 (baseline). Response defined as score of 1 (very much improved) or 2 (much improved) on a 7-point, ordinal scale (1=very much improved; 7=very much worse).	Baseline (Week 8) and Week 14
MADRS Remission	Number of subjects in remission. Remission defined as as MADRS Total Score of <10 at 14 weeks, and a reduction of ≥50 percent from Week 8 (baseline) in MADRS, a 10-item, ordinal rating scale (0=no symptoms; 60=most severe symptoms).	Baseline (Week 8) and Week 14

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Berman RM, Fava M, Thase ME, Trivedi MH, Swanink R, McQuade RD, Carson WH, Adson D, Taylor L, Hazel J, Marcus RN. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. CNS Spectr. 2009 Apr;14(4):197-206. doi: 10.1017/s1092852900020216.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: March 9, 2005
• First Submitted That Met QC Criteria: March 9, 2005
• First Posted (Estimate): March 10, 2005

Study Record Updates

• Last Update Posted (Estimate): December 2, 2013
• Last Update Submitted That Met QC Criteria: November 7, 2013
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Single or recurrent; non-psychotic episode of Major Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: CN138-165