Medication augmentation after the failure of SSRIs for depression

N Engl J Med. 2006 Mar 23;354(12):1243-52. doi: 10.1056/NEJMoa052964.

Abstract

Background: Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach.

Methods: We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology--Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more).

Results: The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009).

Conclusions: Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. (ClinicalTrials.gov number, NCT00021528.).

Publication types

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

MeSH terms

  • Adult
  • Bupropion / administration & dosage
  • Bupropion / adverse effects
  • Bupropion / therapeutic use*
  • Buspirone / administration & dosage
  • Buspirone / adverse effects
  • Buspirone / therapeutic use*
  • Citalopram / administration & dosage
  • Citalopram / adverse effects
  • Citalopram / therapeutic use*
  • Delayed-Action Preparations
  • Depressive Disorder, Major / drug therapy*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopamine Uptake Inhibitors / adverse effects
  • Dopamine Uptake Inhibitors / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Logistic Models
  • Male
  • Remission Induction
  • Serotonin Receptor Agonists / adverse effects
  • Serotonin Receptor Agonists / therapeutic use*
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Treatment Failure

Substances

  • Delayed-Action Preparations
  • Dopamine Uptake Inhibitors
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Bupropion
  • Citalopram
  • Buspirone

Associated data

  • ClinicalTrials.gov/NCT00021528