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Combining Medications to Enhance Depression Outcomes

Information source: National Institute of Mental Health (NIMH)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Major Depressive Disorder

Intervention: SSRI + placebo (Drug); Escitalopram + Bupropion SR (Drug); Venlafaxine XR + Mirtazapine (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: National Institute of Mental Health (NIMH)

Official(s) and/or principal investigator(s):
Madhukar H. Trivedi, MD, Principal Investigator, Affiliation: University of Texas Southwestern Medical Center
Stephen R. Wisniewski, PhD, Study Director, Affiliation: University of Pittsburgh
Diane Warden, PhD, MBA, Study Director, Affiliation: University of Texas Southwestern Medical Center
Kathy Shores-Wilson, PhD, Study Director, Affiliation: University of Texas Southwestern Medical Center
David W. Morris, PhD, Study Director, Affiliation: University of Texas Southwestern Medical Center


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.

Clinical Details

Official title: Combining Medications to Enhance Depression Outcomes

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Primary outcome: Quick Inventory of Depressive Symptoms

Secondary outcome: Quality of Life Inventory

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.


Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.


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


- 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

Locations and Contacts

Tuscalossa VA Mental Health Clinic, Tuscaloosa, Alabama 35404, United States

Harbor UCLA Family Health Care Center, Harbor City, California 90710, United States

UCLA Internal Medicine Clinic, Los Angeles, California 90024, United States

Veterans Affairs Medical Center/FIRM Primary Care Clinic, San Diego, California 92161, United States

Northwestern Psychiatric Outpatient Treatment Care Center, Chicago, Illinois 60611, United States

Clinical Research Institute, Wichita, Kansas 67214, United States

MGH/Northshore Medical Center (Salem Psychiatric Facility), Salem, Massachusetts 01970, United States

General Psychiatric Ambulatory Clinic, Ann Arbor, Michigan 48105, United States

Irving Goldman Primary Care at North Shore Hospital, New York, New York 11040, United States

UNC Chapel Hill Adult Diagnostic & Treatment Clinic, Chapel Hill, North Carolina 27599-7160, United States

Laureate Psychiatric Clinic and Hospital, Tulsa, Oklahoma 74135, United States

Bellefield Clinic of WPIC, Pittsburgh, Pennsylvania 15213, United States

Vine Hill Community Clinic, Nashville, Tennessee 37212, United States

UT Southwestern Family Medicine Clinic, Dallas, Texas 75390, United States

VCU Outpatient Psychiatry Clinic, Richmond, Virginia 23298, United States

Additional Information

Starting date: March 2008
Last updated: April 21, 2014

Page last updated: August 23, 2015

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