The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: Rationale and design considerations

Psychiatry Res. 2015 Oct 30;229(3):760-70. doi: 10.1016/j.psychres.2015.08.005. Epub 2015 Aug 6.


Because two-thirds of patients with Major Depressive Disorder do not achieve remission with their first antidepressant, we designed a trial of three "next-step" strategies: switching to another antidepressant (bupropion-SR) or augmenting the current antidepressant with either another antidepressant (bupropion-SR) or with an atypical antipsychotic (aripiprazole). The study will compare 12-week remission rates and, among those who have at least a partial response, relapse rates for up to 6 months of additional treatment. We review seven key efficacy/effectiveness design decisions in this mixed "efficacy-effectiveness" trial.

Keywords: Antidepressants; Antipsychotics; Major depression; Methodology; Study design; Treatment resistance.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antidepressive Agents / administration & dosage*
  • Antipsychotic Agents / administration & dosage*
  • Aripiprazole / administration & dosage
  • Bupropion / administration & dosage
  • Depressive Disorder, Major / drug therapy*
  • Drug Administration Schedule
  • Drug Substitution*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Remission Induction / methods*
  • Research Design*
  • Time Factors


  • Antidepressive Agents
  • Antipsychotic Agents
  • Bupropion
  • Aripiprazole