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

William V. Bobo, Helen Chen, Madhukar H. Trivedi, Jonathan W. Stewart, Andrew A. Nierenberg, Maurizio Fava, Benji T. Kurian, Diane Warden, David W. Morris, James F. Luther, Mustafa M. Husain, Ian A. Cook, Ira M. Lesser, Susan G. Kornstein, Stephen R. Wisniewski, A. John Rush, Richard C. Shelton

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalJournal of Affective Disorders
Volume133
Issue number3
DOIs
StatePublished - Oct 2011

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Citalopram
Major Depressive Disorder
Serotonin Uptake Inhibitors
Antidepressive Agents
Depression
Drug Therapy
Therapeutics
Bupropion
Outpatients
Placebos
Demography

Keywords

  • Bupropion
  • Escitalopram
  • Major depressive disorder
  • Melancholic features
  • Mirtazapine
  • Venlafaxine

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

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

In: Journal of Affective Disorders, Vol. 133, No. 3, 10.2011, p. 467-476.

Research output: Contribution to journalArticle

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. / Randomized comparison of selective serotonin reuptake inhibitor (escitalopram) monotherapy and antidepressant combination pharmacotherapy for major depressive disorder with melancholic features : A CO-MED report. In: Journal of Affective Disorders. 2011 ; Vol. 133, No. 3. pp. 467-476.
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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.",
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AU - Chen, Helen

AU - Trivedi, Madhukar H.

AU - Stewart, Jonathan W.

AU - Nierenberg, Andrew A.

AU - Fava, Maurizio

AU - Kurian, Benji T.

AU - Warden, Diane

AU - Morris, David W.

AU - Luther, James F.

AU - Husain, Mustafa M.

AU - Cook, Ian A.

AU - Lesser, Ira M.

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N2 - 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.

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