Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features: A CO-MED report

• Published in: Journal of affective disorders 2011-10, Vol.133 (3), p.467-476
• Main Authors: Bobo, William V, Chen, Helen, Trivedi, Madhukar H, Stewart, Jonathan W, Nierenberg, Andrew A, Fava, Maurizio, Kurian, Benji T, Warden, Diane, Morris, David W, Luther, James F, Husain, Mustafa M, Cook, Ian A, Lesser, Ira M, Kornstein, Susan G, Wisniewski, Stephen R, Rush, A. John, Shelton, Richard C
• Format: Article
• Language: English
• Subjects: Adult; Adult and adolescent clinical studies; Affective disorders; Aged; Antidepressant drugs; Antidepressants; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Antidepressive Agents, Second-Generation - therapeutic use; Biological and medical sciences; Bupropion; Bupropion - therapeutic use; citalopram; Citalopram - adverse effects; Citalopram - therapeutic use; Clinical trials; Cyclohexanols - therapeutic use; Data processing; Demography; Depression; Depressive Disorder - chemically induced; Depressive Disorder - diagnosis; Depressive Disorder - drug therapy; Depressive Disorder, Major - chemically induced; Depressive Disorder, Major - diagnosis; Depressive Disorder, Major - drug therapy; Depressive personality disorders; Drug Therapy, Combination; Drugs; Escitalopram; Female; Humans; Major depressive disorder; Male; Medical sciences; Melancholic features; Middle Aged; Mirtazapine; Mood disorders; Neuropharmacology; Outpatients; Pharmacology. Drug treatments; Premature; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Release; Remission; Selective Serotonin Reuptake Inhibitors - adverse effects; Selective Serotonin Reuptake Inhibitors - therapeutic use; Serotonin uptake inhibitors; Single-Blind Method; Treatment Outcome; Venlafaxine; Venlafaxine Hydrochloride
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2011.04.032

Abstract Background The clinical effects of antidepressant combinations vs. monotherapy as initial treatment for major depression with melancholic features (MDD-MF) are unknown. Methods Outpatients with chronic or recurrent major depression (MDD) were randomized to initial treatment with escitalopram + placebo (the MONO condition), bupropion-sustained release + escitalopram, or venlafaxine-extended release + mirtazapine (the COMB conditions) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial. Secondary data analyses were conducted to compare demographic and clinical characteristics, and contrast clinical responses according to drug treatment, in patients with MDD-MF (n = 124) and non-melancholic MDD (n = 481). Results While numerically lower, remission rates in MDD-MF did not differ significantly from those with non-melancholic MDD either at 12 (33.1% vs. 41.0%, aOR 1.16, p = 0.58) or 28 (39.5% vs. 46.8%, aOR = 1.02, p = 0.93) weeks of treatment. Remission rates did not differ significantly between combination and monotherapy groups in either MDD-MF or non-melancholic MDD patients at either time point. Similar conclusions were reached for response rates, premature study discontinuation, and self-rated depression symptom severity. Limitations This is a secondary analysis of data from the CO-MED trial, which was not designed to address differential treatment response in melancholic and non-melancholic MDD. Conclusions We found no evidence of differential remission or response rates to antidepressant combination or monotherapy between melancholic/non-melancholic MDD patients, or according to antidepressant treatment group, after 12 and 28 weeks. Melancholic features may not be a valid predictor of more favorable response to antidepressant combination therapy as initial treatment.