Combining Medications to Enhance Depression Outcomes (CO-MED)

April 21, 2014 updated by: National Institute of Mental Health (NIMH)
This study will compare whether a combination of antidepressant medications is better than one antidepressant medication alone when given as initial treatment for people with chronic or recurrent major depressive disorder.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The overall aim of Combining Medications to Enhance Depression Outcomes (CO-MED) is to enhance remission rates for outpatients with chronic or recurrent nonpsychotic major depressive disorder (MDD) as defined by DSM-IV TR, treated in primary or psychiatric care settings.

Current evidence indicates that remission, the goal of treatment, is found in only about one-third of representative depressed outpatients treated for up to 14 weeks with an initial SSRI. In addition, even for those who do respond or remit, over one-third relapse in the subsequent 12 months. Combinations of antidepressants are used in practice at the second or subsequent steps when relapse occurs in the longer term, or, in some cases, even acutely as a first step when speed of effect is a clinical priority. Whether such combinations could potentially offer higher remission rates, lower attrition, or greater longer-term benefit if used as initial treatments as compared to monotherapy remains to be examined.

CO-MED will test whether two different medications when given in combination as the first treatment step, compared to one medication, will enhance remission rates, increase speed of remission, be tolerable, and provide better sustained benefits in the longer term. Results of this study will inform practitioners in managing the treatment of patients with chronic or recurrent MDD.

Study Type

Interventional

Enrollment (Actual)

665

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Tuscaloosa, Alabama, United States, 35404
        • Tuscalossa VA Mental Health Clinic
    • California
      • Harbor City, California, United States, 90710
        • Harbor UCLA Family Health Care Center
      • Los Angeles, California, United States, 90024
        • UCLA Internal Medicine Clinic
      • San Diego, California, United States, 92161
        • Veterans Affairs Medical Center/FIRM Primary Care Clinic
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Psychiatric Outpatient Treatment Care Center
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Clinical Research Institute
    • Massachusetts
      • Salem, Massachusetts, United States, 01970
        • MGH/Northshore Medical Center (Salem Psychiatric Facility)
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • General Psychiatric Ambulatory Clinic
    • New York
      • New York, New York, United States, 11040
        • Irving Goldman Primary Care at North Shore Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7160
        • UNC Chapel Hill Adult Diagnostic & Treatment Clinic
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74135
        • Laureate Psychiatric Clinic and Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Bellefield Clinic of WPIC
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vine Hill Community Clinic
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Family Medicine Clinic
    • Virginia
      • Richmond, Virginia, United States, 23298
        • VCU Outpatient Psychiatry Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Seeking treatment at the primary or specialty care site, and be planning to continue living in the area of that clinic for the duration of the study
  • Meets clinical criteria for nonpsychotic MDD, recurrent (with the current episode being at least 2 months in duration), or chronic (current episode greater than 2 years) as defined by a clinical interview and confirmed by the MINI International Neuropsychiatric Interview (MINI)
  • Screening 17 item HRSD score of 16 or greater
  • Treatment with antidepressant medication combinations is clinically acceptable
  • Patient with and without current suicidal ideation may be included in the study as long as outpatient treatment is clinically appropriate

Exclusion Criteria:

  • Pregnant or breastfeeding
  • Plans to become pregnant over the ensuing 8 months following study entry or are sexually active and not using adequate birth control
  • History (lifetime) of psychotic depression, schizophrenia, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders
  • Current psychotic symptom(s)
  • History (within the last 2 years before study entry) of anorexia or bulimia
  • Current primary diagnosis of obsessive compulsive disorder
  • Current substance dependence that requires inpatient detoxification or inpatient treatment
  • Requiring immediate hospitalization for a psychiatric disorder
  • Definite history of intolerance or allergy (lifetime) to any protocol medication
  • History of clear nonresponse to an adequate trial of an FDA-approved monotherapy in the current MDE if recurrent, or during the last 2 years before study entry if chronic
  • History of clear nonresponse to an adequate trial of any study medication used as a monotherapy, or to one or more of the protocol combinations in the current or any prior MDE
  • Currently taking any of the study medications at any dose
  • Having taken Prozac (fluoxetine) or an MAOI in the 4 weeks before study entry
  • Presence of an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy less than 6 months after study entry)
  • Currently taking medications or have GMCs that contraindicate any study medications (e.g., seizure disorder)
  • Requiring medications for GMCs that contraindicate any study medication
  • Epilepsy or other conditions requiring an anticonvulsant
  • Lifetime history of having a seizure including febrile or withdrawal seizures
  • Receiving or have received vagus nerve stimulation (VNS), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), or other somatic antidepressant treatments
  • Currently taking or having taken within the 7 days before study entry any of the following exclusionary medications: antipsychotic medications, anticonvulsant medications, mood stabilizers, or central nervous system stimulants (antidepressant medication used for the treatment of depression or other purposes such as smoking cessation or pain are excluded since these agents may interfere with the testing of the major hypotheses under study)
  • Uncontrolled narrow angle glaucoma
  • Taking thyroid medication for hypothyroidism may be included only if stable on the medication for 3 months
  • Using agents within the 7 days before study entry that are potential augmenting agents (e.g., T3 in the absence of thyroid disease, SAMe, St. John's Wort, lithium, buspirone)
  • Therapy that is depression-specific

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: SSRI + placebo
Participants will take escitalopram plus placebo.
Drug: SSRI + placebo
Participants will take escitalopram (10 - 20 mg/day)+ placebo (1 to 3 pills per day). Medications taken orally. Participants will take escitalopram plus placebo for up to 28 weeks. Dosages were adjusted as need at each clinic visit.
Other Names:
  • placebo
  • escitalopram
Active Comparator: Escitalopram + Bupropion SR
Participants will take escitalopram + bupropion-SR.
Drug: Escitalopram + Bupropion SR
Participant will take Burpopion SR (150 to 450 mg/day) + Escitalopram (10 to 20 mg/day) for up to 28 weeks. Medications taken orally. Bupropion SR was blinded, and escitalopram was given open label. Dosages were adjusted as need at each clinic visit.
Other Names:
  • escitalopram
  • bupropion-SR
Active Comparator: Venlafaxine XR + Mirtazapine
Participants will take venlafaxine-XR + mirtazapine.
Drug: Venlafaxine XR + Mirtazapine
Participants will take Venlafaxine XR (75 to 225 mg/day) + Mirtazapine (15 to 45 mg/day) for up to 28 weeks. Medications taken orally. Venlafaxine XR was blinded, and mirtazapine was given open label. Dosages were adjusted as need at each clinic visit.
Other Names:
  • venlafaxine-XR
  • mirtazapine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quick Inventory of Depressive Symptoms
Time Frame: Measured at Month 7
Percentage of patients that achieve remission, as defined as QIDS total score below 6 for last 2 study visits. QIDS depression scores range from 0 (normal) to 27 (very severe).
Measured at Month 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of Life Inventory
Time Frame: Measured at Month 7
The Quality of Life Inventory (QOLI) is a 32-item comprehensive self-report of satisfaction in 16 areas of life, such as love, work, and health. Each area is rated in terms of satisfaction and the relationship of that area to overall quality of life. It yields an overall raw score and satisfaction ratings for the 16 individual areas of life. The QOLI raw score is an average of weighted satisfaction ratings computed only over areas of life judged to be Important or Extremely Important to the respondent. Higher scores indicate higher reported quality of life.
Measured at Month 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center
  • Study Director: Stephen R. Wisniewski, PhD, University of Pittsburgh
  • Study Director: Diane Warden, PhD, MBA, University of Texas Southwestern Medical Center
  • Study Director: Kathy Shores-Wilson, PhD, University of Texas Southwestern Medical Center
  • Study Director: David W. Morris, PhD, University of Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2008

Primary Completion (Actual)

September 1, 2009

Study Completion (Actual)

September 1, 2009

Study Registration Dates

First Submitted

December 26, 2007

First Submitted That Met QC Criteria

December 28, 2007

First Posted (Estimate)

January 11, 2008

Study Record Updates

Last Update Posted (Estimate)

April 23, 2014

Last Update Submitted That Met QC Criteria

April 21, 2014

Last Verified

April 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N01 MH090003-02
  • DSIR AT (NCT00590863)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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