Combining Medications to Enhance Depression Outcomes

NCT00590863 | Completed Phase 4 Results DMC

• 3 other identifiers: N01 MH090003-02DSIR ATN01MH090003
• Study Type: interventional
• Target: 665
• Locations: 1 country
• Sites: 15

Brief 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.

Conditions

Major Depressive Disorder

Keywords

depression, medication, antidepressant, chronic, recurrent

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Quality of Life Inventory

  Measured at Month 7

Study Arms (3)

SSRI + placebo

ACTIVE COMPARATOR

Participants will take escitalopram plus placebo.

Drug: SSRI + placebo

Escitalopram + Bupropion SR

ACTIVE COMPARATOR

Participants will take escitalopram + bupropion-SR.

Drug: Escitalopram + Bupropion SR

Venlafaxine XR + Mirtazapine

ACTIVE COMPARATOR

Participants will take venlafaxine-XR + mirtazapine.

Drug: Venlafaxine XR + Mirtazapine

Interventions

SSRI + placebo DRUG

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.

Also known as: escitalopram, placebo

SSRI + placebo

Escitalopram + Bupropion SR DRUG

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.

Also known as: escitalopram, bupropion-SR

Escitalopram + Bupropion SR

Venlafaxine XR + Mirtazapine DRUG

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.

Also known as: venlafaxine-XR, mirtazapine

Venlafaxine XR + Mirtazapine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (15)

Tuscalossa VA Mental Health Clinic

Tuscaloosa, Alabama, 35404, United States

Location

Harbor UCLA Family Health Care Center

Harbor City, California, 90710, United States

Location

UCLA Internal Medicine Clinic

Los Angeles, California, 90024, United States

Location

Veterans Affairs Medical Center/FIRM Primary Care Clinic

San Diego, California, 92161, United States

Location

Northwestern Psychiatric Outpatient Treatment Care Center

Chicago, Illinois, 60611, United States

Location

Clinical Research Institute

Wichita, Kansas, 67214, United States

Location

MGH/Northshore Medical Center (Salem Psychiatric Facility)

Salem, Massachusetts, 01970, United States

Location

General Psychiatric Ambulatory Clinic

Ann Arbor, Michigan, 48105, United States

Location

Irving Goldman Primary Care at North Shore Hospital

New York, New York, 11040, United States

Location

UNC Chapel Hill Adult Diagnostic & Treatment Clinic

Chapel Hill, North Carolina, 27599-7160, United States

Location

Laureate Psychiatric Clinic and Hospital

Tulsa, Oklahoma, 74135, United States

Location

Bellefield Clinic of WPIC

Pittsburgh, Pennsylvania, 15213, United States

Location

Vine Hill Community Clinic

Nashville, Tennessee, 37212, United States

Location

UT Southwestern Family Medicine Clinic

Dallas, Texas, 75390, United States

Location

VCU Outpatient Psychiatry Clinic

Richmond, Virginia, 23298, United States

Location

Related Publications (20)

• 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 outcomes of a single-blind randomized study. Am J Psychiatry. 2011 Jul;168(7):689-701. doi: 10.1176/appi.ajp.2011.10111645. Epub 2011 May 2.

  PMID: 21536692 RESULT

• Olgiati P, Serretti A. Antidepressant emergent mood switch in major depressive disorder: onset, clinical correlates and impact on suicidality. Int Clin Psychopharmacol. 2023 Sep 1;38(5):342-351. doi: 10.1097/YIC.0000000000000479. Epub 2023 Jun 9.

  PMID: 37351585 DERIVED

• Olgiati P, Fanelli G, Serretti A. Clinical correlates and prognostic implications of severe suicidal ideation in major depressive disorder. Int Clin Psychopharmacol. 2023 Jul 1;38(4):201-208. doi: 10.1097/YIC.0000000000000461. Epub 2023 Feb 27.

  PMID: 36853754 DERIVED

• Olgiati P, Fanelli G, Atti AR, De Ronchi D, Serretti A. Clinical correlates and prognostic impact of binge-eating symptoms in major depressive disorder. Int Clin Psychopharmacol. 2022 Nov 1;37(6):247-254. doi: 10.1097/YIC.0000000000000422. Epub 2022 Jul 12.

  PMID: 35815954 DERIVED

• Olgiati P, Serretti A. Persistence of suicidal ideation within acute phase treatment of major depressive disorder: analysis of clinical predictors. Int Clin Psychopharmacol. 2022 Sep 1;37(5):193-200. doi: 10.1097/YIC.0000000000000416. Epub 2022 Jul 7.

  PMID: 35695646 DERIVED

• Olgiati P, Fanelli G, Serretti A. Obsessive-compulsive symptoms in major depressive disorder correlate with clinical severity and mixed features. Int Clin Psychopharmacol. 2022 Jul 1;37(4):166-172. doi: 10.1097/YIC.0000000000000396. Epub 2022 Feb 21.

  PMID: 35191860 DERIVED

• Olgiati P, Serretti A. Post-traumatic stress disorder and childhood emotional abuse are markers of subthreshold bipolarity and worse treatment outcome in major depressive disorder. Int Clin Psychopharmacol. 2022 Jan 1;37(1):1-8. doi: 10.1097/YIC.0000000000000380.

  PMID: 34686642 DERIVED

• Medeiros GC, Prueitt WL, Minhajuddin A, Patel SS, Czysz AH, Furman JL, Mason BL, Rush AJ, Jha MK, Trivedi MH. Childhood maltreatment and impact on clinical features of major depression in adults. Psychiatry Res. 2020 Nov;293:113412. doi: 10.1016/j.psychres.2020.113412. Epub 2020 Aug 18.

  PMID: 32950785 DERIVED

• Jha MK, Minhajuddin A, South C, Rush AJ, Trivedi MH. Irritability and Its Clinical Utility in Major Depressive Disorder: Prediction of Individual-Level Acute-Phase Outcomes Using Early Changes in Irritability and Depression Severity. Am J Psychiatry. 2019 May 1;176(5):358-366. doi: 10.1176/appi.ajp.2018.18030355. Epub 2019 Mar 29.

  PMID: 30922100 DERIVED

• Sies A, Demyttenaere K, Van Mechelen I. Studying treatment-effect heterogeneity in precision medicine through induced subgroups. J Biopharm Stat. 2019;29(3):491-507. doi: 10.1080/10543406.2019.1579220. Epub 2019 Feb 22.

  PMID: 30794033 DERIVED

• De La Garza N, Rush AJ, Killian MO, Grannemann BD, Carmody TJ, Trivedi MH. The Concise Health Risk Tracking Self-Report (CHRT-SR) assessment of suicidality in depressed outpatients: A psychometric evaluation. Depress Anxiety. 2019 Apr;36(4):313-320. doi: 10.1002/da.22855. Epub 2018 Oct 29.

  PMID: 30370613 DERIVED

• Gadad BS, Jha MK, Grannemann BD, Mayes TL, Trivedi MH. Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial. J Psychiatr Res. 2017 Nov;94:1-6. doi: 10.1016/j.jpsychires.2017.05.012. Epub 2017 May 26.

  PMID: 28628884 DERIVED

• Jha MK, Minhajuddin A, Gadad BS, Greer T, Grannemann B, Soyombo A, Mayes TL, Rush AJ, Trivedi MH. Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. Psychoneuroendocrinology. 2017 Apr;78:105-113. doi: 10.1016/j.psyneuen.2017.01.023. Epub 2017 Jan 24.

  PMID: 28187400 DERIVED

• Chekroud AM, Zotti RJ, Shehzad Z, Gueorguieva R, Johnson MK, Trivedi MH, Cannon TD, Krystal JH, Corlett PR. Cross-trial prediction of treatment outcome in depression: a machine learning approach. Lancet Psychiatry. 2016 Mar;3(3):243-50. doi: 10.1016/S2215-0366(15)00471-X. Epub 2016 Jan 21.

  PMID: 26803397 DERIVED

• Warden D, Trivedi MH, Carmody T, Toups M, Zisook S, Lesser I, Myers A, Kurian KR, Morris D, Rush AJ. Adherence to antidepressant combinations and monotherapy for major depressive disorder: a CO-MED report of measurement-based care. J Psychiatr Pract. 2014 Mar;20(2):118-32. doi: 10.1097/01.pra.0000445246.46424.fe.

  PMID: 24638046 DERIVED

• Toups MS, Myers AK, Wisniewski SR, Kurian B, Morris DW, Rush AJ, Fava M, Trivedi MH. Relationship between obesity and depression: characteristics and treatment outcomes with antidepressant medication. Psychosom Med. 2013 Nov-Dec;75(9):863-72. doi: 10.1097/PSY.0000000000000000. Epub 2013 Oct 25.

  PMID: 24163386 DERIVED

• Sung SC, Haley CL, Wisniewski SR, Fava M, Nierenberg AA, Warden D, Morris DW, Kurian BT, Trivedi MH, Rush AJ; CO-MED Study Team. The impact of chronic depression on acute and long-term outcomes in a randomized trial comparing selective serotonin reuptake inhibitor monotherapy versus each of 2 different antidepressant medication combinations. J Clin Psychiatry. 2012 Jul;73(7):967-76. doi: 10.4088/JCP.11m07043. Epub 2012 May 29.

  PMID: 22687487 DERIVED

• Morris DW, Budhwar N, Husain M, Wisniewski SR, Kurian BT, Luther JF, Kerber K, Rush AJ, Trivedi MH. Depression treatment in patients with general medical conditions: results from the CO-MED trial. Ann Fam Med. 2012 Jan-Feb;10(1):23-33. doi: 10.1370/afm.1316.

  PMID: 22230827 DERIVED

• Chan HN, Rush AJ, Nierenberg AA, Trivedi M, Wisniewski SR, Balasubramani GK, Friedman ES, Gaynes BN, Davis L, Morris D, Fava M. Correlates and outcomes of depressed out-patients with greater and fewer anxious symptoms: a CO-MED report. Int J Neuropsychopharmacol. 2012 Nov;15(10):1387-99. doi: 10.1017/S1461145711001660. Epub 2011 Dec 1.

  PMID: 22129562 DERIVED

• Zisook S, Lesser IM, Lebowitz B, Rush AJ, Kallenberg G, Wisniewski SR, Nierenberg AA, Fava M, Luther JF, Morris DW, Trivedi MH. Effect of antidepressant medication treatment on suicidal ideation and behavior in a randomized trial: an exploratory report from the Combining Medications to Enhance Depression Outcomes Study. J Clin Psychiatry. 2011 Oct;72(10):1322-32. doi: 10.4088/JCP.10m06724.

  PMID: 22075098 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Bronchiolitis Obliterans Syndrome; Recurrence

Interventions

Selective Serotonin Reuptake Inhibitors; Escitalopram; Mirtazapine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Detailed results avaiable. A. J. Rush et al. Combining Medications to Enhance Depression Outcomes (CO-MED): Acute and long-term outcomes: a single-blind randomized study. American Journal of Psychiatry, 2011; 168:689-701.

Results Point of Contact

• Title: Madhukar H. Trivedi, M.D.
• Organization: Univeristy of Texas Southwestern Medical Center, Dallas

Madhukar.Trivedi@UTSouthwestern.edu

214-648-0188

Study Officials

• Madhukar H. Trivedi, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 11, 2008
• Study Start: March 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: April 23, 2014
• Results First Posted: April 23, 2014

Record last verified: 2009-04

Locations

US (15)