Psychological Medicine

Original Articles

Does early-onset chronic or recurrent major depression impact outcomes with antidepressant medications? A CO-MED Trial Report

S. C. Sunga1 c1, S. R. Wisniewskia2, G. K. Balasubramania2, S. Zisooka3, B. Kuriana4, D. Wardena4, M. H. Trivedia4 and A. J. Rusha1 for the CO-MED Study Team


a1 Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, Singapore

a2 Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

a3 Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

a4 Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA

Background Prior studies have suggested that major depressive disorder (MDD) with pre-adult onset represents a distinct subtype with greater symptom severity and higher rates of suicidal ideation. Whether these patients have poorer response to various types of antidepressant treatment than those with adult-onset MDD is unclear.

Method A total of 665 psychiatric and primary care out-patients (aged 18–75 years) with non-psychotic chronic or recurrent MDD participated in a single-blind, randomized trial that compared the efficacy of escitalopram plus placebo, bupropion sustained-release plus escitalopram, or venlafaxine extended-release plus mirtazapine. We compared participants who self-reported MDD onset (before age 18) to those with a later onset (adult onset) with respect to baseline characteristics and treatment/outcome variables at 12 and 28 weeks.

Results Early-onset chronic/recurrent MDD was associated with a distinct set of sociodemographic (female, younger age) and clinical correlates (longer duration of illness, greater number of prior episodes, greater likelihood of atypical features, higher rates of suicidality and psychiatric co-morbidity, fewer medical problems, poorer quality of life, greater history of child abuse/neglect). However, results from unadjusted and adjusted analyses showed no significant differences in response, remission, tolerability of medications, quality of life, or retention at 12 or 28 weeks.

Conclusions Although early-onset chronic/recurrent MDD is associated with a more severe clinical picture, it does not seem to be useful for predicting differential treatment response to antidepressant medication. Clinicians should remain alert to an increased risk of suicidality in this population.

(Received February 02 2012)

(Revised July 04 2012)

(Accepted July 09 2012)

(Online publication December 11 2012)

Key words

  • Age-of-onset;
  • chronic;
  • depression;
  • early-onset;
  • recurrent


c1 Address for correspondence: S. C. Sung, Ph.D., Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857. (Email:


  Members of the CO-MED Study Team are given in the Appendix.