Combining Medications to Enhance Depression Outcomes - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00590863

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: One of the following: bupropion, escitalopram, mirtazapine, or venlafaxine Drug: Two of the following: bupropion, escitalopram, mirtazapine or venlafaxine	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Active Control, Parallel Assignment, Efficacy Study
Official Title:	Combining Medications to Enhance Depression Outcomes

Resource links provided by NLM:

MedlinePlus related topics: Antidepressants Depression

Drug Information available for: Benzetimide Dexetimide Bupropion hydrochloride Bupropion Citalopram hydrobromide Citalopram Mirtazapine Venlafaxine Venlafaxine hydrochloride Escitalopram Escitalopram oxalate

U.S. FDA Resources

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

Primary Outcome Measures:

Remission rates in patients with chronic and/or recurrent major depression. [ Time Frame: Measured at Month 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Anxiety, social functioning, quality of life, cognitive and physical well being, treatment emergent psychiatric symptoms, and side-effect burden [ Time Frame: Measured at Month 7 ] [ Designated as safety issue: No ]

Enrollment:	665
Study Start Date:	March 2008
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Participants will take one antidepressant medication plus placebo.	Drug: One of the following: bupropion, escitalopram, mirtazapine, or venlafaxine In addition to receiving daily, oral antidepressant medication, participants will also receive daily, oral placebo for up to 28 weeks.
B: Experimental Participants will take a combination of two antidepressant medications.	Drug: Two of the following: bupropion, escitalopram, mirtazapine or venlafaxine Participants will receive daily, oral antidepressant medication combination for up to 28 weeks.

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

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

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

More Information

No publications provided

Responsible Party:	University of Texas Southwestern Medical Center ( Madhukar H. Trivedi, MD )
Study ID Numbers:	N01 MH090003-02, DSIR AT
Study First Received:	December 26, 2007
Last Updated:	April 8, 2009
ClinicalTrials.gov Identifier:	NCT00590863 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

depression, medication, antidepressant, chronic, recurrent

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Parasympatholytics
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Cholinergic Antagonists
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Psychotropic Drugs
Antiparkinson Agents
Depressive Disorder, Major
Mirtazapine
Cholinergic Agents
Mental Disorders

Therapeutic Uses
Venlafaxine
Antidepressive Agents, Second-Generation
Dexetimide
Antidepressive Agents
Depression
Histamine Agents
Adrenergic alpha-Antagonists
Depressive Disorder
Serotonin Uptake Inhibitors
Citalopram
Pharmacologic Actions
Antidepressive Agents, Tricyclic
Behavioral Symptoms
Muscarinic Antagonists

ClinicalTrials.gov processed this record on November 05, 2009