Combination antidepressant therapy for major depressive disorder: speed and probability of remission

J Psychiatr Res. 2014 May;52:7-14. doi: 10.1016/j.jpsychires.2013.12.001. Epub 2013 Dec 17.


Introduction: Only about a third of patients with an episode of major depressive disorder remit with a given treatment and few remissions occur within the first weeks of treatment. This study tested whether combining escitalopram and bupropion as initial treatment would result in quicker remission and a higher remission rate than monotherapy with either drug.

Method: Two hundred forty-five outpatients aged 18-65 having non-psychotic, non-bipolar major depression were randomly assigned to double-blind treatment with bupropion or escitalopram or the combination dosed to a maximum of bupropion 450 mg/d and/or escitalopram 40 mg/d for 12 weeks. A Montgomery-Asberg Depression Rating Scale score of 22 was required for randomization, while a Hamilton Rating Scale for Depression score ≤ 7 defined remission. We hypothesized that bupropion plus escitalopram would outperform both monotherapies in both earlier onset of remission and higher rate of remission.

Results: Primary analyses did not demonstrate that dual therapy outperformed both monotherapies in either timing of remission or remission rate. All three treatments were well tolerated.

Discussion: These results do not support initial use of bupropion plus escitalopram to speed or enhance antidepressant response.

Clinical trials registration: NCT00519428.

Keywords: Bupropion; Combination treatment; Escitalopram; Major depression; Remission.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Antidepressive Agents / adverse effects*
  • Bupropion / adverse effects*
  • Canada
  • Citalopram / adverse effects*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / epidemiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Recurrence
  • Treatment Outcome
  • United States
  • Young Adult


  • Antidepressive Agents
  • Bupropion
  • Citalopram

Associated data