MDD: Switch vs Augmentation?

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

Switching Antidepressants Versus Adding Augmentation Agent in MDD.

How do you decide?

This question is answered by following two studies:

(1) Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder:

(2) 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.
  2. Can J Psychiatry. 2016 Sep; 61(9): 540–560.



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