Treatment Resistant Depression: Switch or Augmentation


Q: Which of the following strategy is preferred in patient's who are not responsive to highest therapeutic dose of antidepressants?


The VAST-D Randomized Clinical Trial published in JAMA answered this question. This post will focus on details and findings of this trial.


VAST-D: VA Augmentation and Switching Treatments for Improving Depression Outcomes.



  • Multisite randomized, single-blind, parallel-assignment trial.



  • Suboptimal response to SSRI, SNRI or Mirtazapine.
  • Suboptimal response = QIDS-C16 score of >16 (after 6 weeks of treatment) or >11 (after 8 weeks of treatment) with 3 most recent weeks at stable “optimal” dose.

QIDS-C16 = 16-Item Quick Inventory of Depressive Symptomatology-Clinician Rated.



  • current treatment with bupropion or any antipsychotic.
  • history of bipolar disorder, schizophrenia, schizoaffective disorder, or other psychosis.
  • current dementia
  • eating disorder
  • seizure disorder
  • suicidal ideation requiring inpatient treatment
  • unstable medical condition
  • need of immediate psychiatric hospitalization
  • substance dependence requiring detoxification in the past 30 days
  • pregnant, lactating, or planning to become pregnant
  • unable or unwilling to provide informed consent or declined to participate prior to randomization.


RANDOMIZATION: to one of the three treatment:-

  • SWITCH GROUP: switch to bupropion sustained release.
  • AUGMENT-BUPROPION GROUP: augment current treatment with bupropion sustained release.
  • AUGMENT- ARIPIPRAZOLE GROUP: augment current treatment with aripiprazole. 



  • SWITCH GROUP: dose of bupropion reached max of 200 mg twice daily by 6 weeks and remained at that level through 12 weeks. 
  • AUGMENT-BUPROPION GROUP: also reached max of 200 mg twice daily by 6 weeks.
  • AUGMENT- ARIPIPRAZOLE GROUP: dose of aripiprazole was 5 mg daily from weeks 2 through 10 and reached 10 mg daily at week 12. 



(1) Remission rates at 12 weeks: Higher for Aripiprazole augmentation.

  • Switch group: 22.3% (n = 114)
  • Augment- bupropion group: 26.9% (n = 136)
  • Augment- aripiprazole group: 28.9% (n = 146)


(2) Response rate:Higher for Aripiprazole augmentation.

  • Switch group: 62.4%
  • Augment- bupropion group: 65.6%
  • Augment- aripiprazole group: 74.3%


(3) Side Effect Profile:

(A) Anxiety was more frequent in the bupropion augmentation group.

  • Switch group: 24.3%
  • Augment- bupropion group: 22.5%
  • Augment- aripiprazole group: 16.6%

(B) Adverse effects more frequent in the augment-aripiprazole group included

  • somnolence,
  • akathisia, and
  • weight gain. 



Augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy.



  1. JAMA. 2017 Jul 11;318(2):132-145.

Question by forum member:
I wonder how/if those statistics would differ for people with a comorbid anxiety disorder?

The presence of comorbid anxiety is considered negative prognostic factor in patients with major depression disorder. The following findings in this study will attempt to answer this question:

(a) Anxiety was more frequent in the both bupropion groups:

  • SWITCH GROUP: 24.3% [n = 124]
  • AUGMENT-BUPROPION GROUP: 22.5% [n = 114]

(b) These results were mixed with treatment-emergent anxiety favoring the augment-aripiprazole group and akathisia, somnolence, and weight gain favoring the switch group and the augment-bupropion group.


Based on this above information: Aripiprazole is preferred over bupropion as augmentation agent in patient’s with comorbid anxiety disorder, but be cautious of restlessness side effect from aripiprazole. 


Please do post your questions or comments below. 

Dr. Harvinder Singh, M.D. (Admin)

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