Combining Medications to Enhance Depression Outcomes (CO-MED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT00590863
First received: December 26, 2007
Last updated: April 21, 2014
Last verified: April 2009
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: SSRI + placebo
Drug: Escitalopram + Bupropion SR
Drug: Venlafaxine XR + Mirtazapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Combining Medications to Enhance Depression Outcomes

Resource links provided by NLM:


Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:
  • Quick Inventory of Depressive Symptoms [ Time Frame: Measured at Month 7 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Quality of Life Inventory [ Time Frame: Measured at Month 7 ] [ Designated as safety issue: No ]
    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.


Enrollment: 665
Study Start Date: March 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • escitalopram
  • placebo
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590863

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT00590863     History of Changes
Other Study ID Numbers: N01 MH090003-02, DSIR AT
Study First Received: December 26, 2007
Results First Received: November 28, 2012
Last Updated: April 21, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):
depression, medication, antidepressant, chronic, recurrent

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Venlafaxine
Citalopram
Mianserin
Bupropion
Mirtazapine
Dexetimide
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists

ClinicalTrials.gov processed this record on September 30, 2014