Combining Medications to Enhance Depression Outcomes

Major Depressive Disorder Clinical Trial

— CO-MED  

Official title:

Combining Medications to Enhance Depression Outcomes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00590863
• Other study ID #: N01 MH090003-02
• Secondary ID: DSIR AT
• Status: Completed
• Phase: Phase 4
• First received: December 26, 2007
• Last updated: April 21, 2014
• Start date: March 2008
• Est. completion date: September 2009

Study information

• Verified date: April 2009
• Source: National Institute of Mental Health (NIMH)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 665
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	General Psychiatric Ambulatory Clinic	Ann Arbor	Michigan
United States	UNC Chapel Hill Adult Diagnostic & Treatment Clinic	Chapel Hill	North Carolina
United States	Northwestern Psychiatric Outpatient Treatment Care Center	Chicago	Illinois
United States	UT Southwestern Family Medicine Clinic	Dallas	Texas
United States	Harbor UCLA Family Health Care Center	Harbor City	California
United States	UCLA Internal Medicine Clinic	Los Angeles	California
United States	Vine Hill Community Clinic	Nashville	Tennessee
United States	Irving Goldman Primary Care at North Shore Hospital	New York	New York
United States	Bellefield Clinic of WPIC	Pittsburgh	Pennsylvania
United States	VCU Outpatient Psychiatry Clinic	Richmond	Virginia
United States	MGH/Northshore Medical Center (Salem Psychiatric Facility)	Salem	Massachusetts
United States	Veterans Affairs Medical Center/FIRM Primary Care Clinic	San Diego	California
United States	Laureate Psychiatric Clinic and Hospital	Tulsa	Oklahoma
United States	Tuscalossa VA Mental Health Clinic	Tuscaloosa	Alabama
United States	Clinical Research Institute	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT, Warden D, Morris DW, Luther JF, Husain MM, Cook IA, Shelton RC, Lesser IM, Kornstein SG, Wisniewski SR. Combining medications to enhance depression outcomes (CO-MED): acute and long-term o — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quick Inventory of Depressive Symptoms	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	No
Secondary	Quality of Life Inventory	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	No