Strategies for augmentation or switching
Only one-third of the patients with depression achieve remission on the first antidepressant medication. The American Psychiatric Association’s current management guidelines2 for patients who do not respond to the first-choice antidepressant include multiple options. Switching strategies recommended in these guidelines include changing to an antidepressant of the same class, or to one from a different class (eg, from a selective serotonin reuptake inhibitor [SSRI] to a serotonin-norepinephrine reuptake inhibitor, or from an SSRI to a tricyclic antidepressant). Augmentation strategies include augmenting with a non-monoamine oxidase inhibitor antidepressant from a different class, lithium, thyroid hormone, or an atypical antipsychotic.
The VAST-D trial5 evaluated the relative effectiveness and safety of 3 common treatments for treatment-resistant MDD:
- switching to bupropion
- augmenting the current treatment with bupropion
- augmenting the current treatment with the second-generation antipsychotic aripiprazole.
3. Mohamed S, Johnson GR, Chen P, et al. Effect of antidepressant switching vs augmentation on remission among patients with major depressive disorder unresponsive to antidepressant treatment: the VAST-D randomized clinical trial. JAMA. 2017;318(2):132-145.
Study design
- A multi-site, randomized, single-blind, parallel-assignment trial of 1,522 patients at 35 US Veteran Health Administration medical centers with nonpsychotic MDD with a suboptimal response to at least one antidepressant (defined as a score of ≥16 on the Quick Inventory Depressive Symptomatology-Clinician Rated questionnaire [QIDS-C16]).
- Participants were randomly assigned to 1 of 3 groups: switching to bupropion (n = 511), augmenting with bupropion (n = 506), or augmenting with aripiprazole (n = 505).
- The primary outcome was remission (defined as a QIDS-C16 score ≤5 at 2 consecutively scheduled follow-up visits). Secondary outcome was a reduction in QIDS-C16 score by ≥50%, or a Clinical Global Impression (CGI) Improvement scale score of 1 (very much improved) or 2 (much improved).
Outcomes
- The aripiprazole group showed a modest, statistically significant remission rate (28.9%) compared with the bupropion switch group (22.3%), but did not show any statistically significant difference compared with the bupropion augmentation group.
- For the secondary outcome, there was a significantly higher response rate in the aripiprazole group (74.3%) compared with the bupropion switch group (62.4%) and bupropion augmentation group (65.6%). Response measured by the CGI– Improvement scale score also favored the aripiprazole group (79%) compared with the bupropion switch group (70%) and bupropion augmentation group (74%).
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