Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
665 participants
INTERVENTIONAL
2008-03-31
2009-09-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Are Two Antidepressants a Good Initial Treatment for Depression?
NCT00296712
Does Dual Therapy Hasten Antidepressant Response?
NCT00519428
Hippocampal Volume in Young Patients With Major Depression Before and After Combined Antidepressive Therapy
NCT00150839
An Investigation of the Antidepressant Efficacy of the 5-HT2A Antagonist, M100907, in Combination With Citalopram in Treatment Resistant Depression
NCT00070694
Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure
NCT05603104
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
SSRI + placebo
Participants will take escitalopram plus placebo.
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
Participants will take escitalopram + bupropion-SR.
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 + mirtazapine.
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Mental Health (NIMH)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Madhukar H. Trivedi, MD
Role: PRINCIPAL_INVESTIGATOR
University of Texas Southwestern Medical Center
Stephen R. Wisniewski, PhD
Role: STUDY_DIRECTOR
University of Pittsburgh
Diane Warden, PhD, MBA
Role: STUDY_DIRECTOR
University of Texas Southwestern Medical Center
Kathy Shores-Wilson, PhD
Role: STUDY_DIRECTOR
University of Texas Southwestern Medical Center
David W. Morris, PhD
Role: STUDY_DIRECTOR
University of Texas Southwestern Medical Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Tuscalossa VA Mental Health Clinic
Tuscaloosa, Alabama, United States
Harbor UCLA Family Health Care Center
Harbor City, California, United States
UCLA Internal Medicine Clinic
Los Angeles, California, United States
Veterans Affairs Medical Center/FIRM Primary Care Clinic
San Diego, California, United States
Northwestern Psychiatric Outpatient Treatment Care Center
Chicago, Illinois, United States
Clinical Research Institute
Wichita, Kansas, United States
MGH/Northshore Medical Center (Salem Psychiatric Facility)
Salem, Massachusetts, United States
General Psychiatric Ambulatory Clinic
Ann Arbor, Michigan, United States
Irving Goldman Primary Care at North Shore Hospital
New York, New York, United States
UNC Chapel Hill Adult Diagnostic & Treatment Clinic
Chapel Hill, North Carolina, United States
Laureate Psychiatric Clinic and Hospital
Tulsa, Oklahoma, United States
Bellefield Clinic of WPIC
Pittsburgh, Pennsylvania, United States
Vine Hill Community Clinic
Nashville, Tennessee, United States
UT Southwestern Family Medicine Clinic
Dallas, Texas, United States
VCU Outpatient Psychiatry Clinic
Richmond, Virginia, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
DSIR AT
Identifier Type: REGISTRY
Identifier Source: secondary_id
N01 MH090003-02
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.