Effect of concurrent substance use disorder on the effectiveness of single and combination antidepressant medications for the treatment of major depression: An exploratory analysis of a single-blind randomized trial

Lori L. Davis, Patricia Pilkinton, Stephen R. Wisniewski, Madhukar H. Trivedi, Bradley N. Gaynes, Robert H. Howland, Sidney Zisook, G. K. Balasubramani, Maurizio Fava, A. John Rush

Research output: Contribution to journalArticle

9 Scopus citations


Background: The co-occurrence of substance use disorder (SUD) and major depressive disorder (MDD) is common and is often thought to impair response to antidepressant therapy. These patients are often excluded from clinical trials, resulting in a significant knowledge gap regarding optimal pharmacotherapy for the treatment of MDD with concurrent SUD. Methods: In the Combining Medications to Enhance Depression Outcomes study, 665 adult outpatients with chronic and/or recurrent MDD were prospectively treated with either escitalopram monotherapy (escitalopram and placebo) or an antidepressant combination (venalfaxine-XR and mirtazapine or escitalopram and bupropion-SR). Participants with MDD and concurrent SUD (13.1%) were compared to those without SUD (86.9%) on sociodemographic and clinical characteristics at baseline and treatment response at 12- and 28-week endpoints. Results: The participants with MDD and SUD were more likely to be male and have current suicidal thoughts/plans, and had a greater lifetime severity and number of suicide attempts, and a higher number of concurrent Axis I disorders, particularly concurrent anxiety disorders. There were no significant differences between the MDD with or without SUD groups in terms of dose, time in treatment, response or remission at week 12 and 28. Furthermore, no significant differences in response or remission rates were noted between groups on the basis of the presence or absence of SUD and treatment assignment. Conclusions: Although significantbaseline sociodemographic and clinical differences exist, patients with MDD and concurrent SUD are as likely to respond and remit to a single or combination antidepressant treatment as those presenting without SUD.

Original languageEnglish (US)
Pages (from-to)111-122
Number of pages12
JournalDepression and Anxiety
Issue number2
StatePublished - Feb 2012



  • Combination antidepressants
  • Dual diagnosis
  • Major depressive disorder
  • Substance use disorder
  • Treatment outcome

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

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