Psychiatry
Major Depressive Disorder
The VAST-D Study: Augmentation Versus Switching Treatments for Optimizing Treatment of Depression
Overview
Clinical Study Title:
Optimizing Treatment of Depression: The VAST-D Study
Clinical Study Abstract:
The VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study included 1522 veteran outpatients at 35 participating Veterans Affairs (VA) facilities. Participants were randomized to 1 of 3 commonly used next-step approaches for patients with major depressive disorder (MDD). These were veterans whose outcomes had been suboptimal after at least 1 well-delivered trial with their clinician’s choice of antidepressant monotherapy (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs], or mirtazapine). At randomization, these veterans (mean age 54.4; range 21-85 years) were moderately to severely depressed, with about one-third reporting recent suicidal ideation. Most participants had at least some college education (72%). Twenty-six percent of participants reported being employed either full- or part-time; 45% reported being unemployed, on disability, or receiving social assistance. Most participants had recurrent MDD (63%) with a mean number of just over 9 lifetime episodes and an average of 2.4 antidepressant treatment trials documented. General medical and psychiatric comorbidities were highly prevalent, particularly posttraumatic stress disorder (PTSD). A total of 47% met criteria for PTSD per international neuropsychiatric interview evaluation (MINI). Participants were impaired in multiple domains of their lives and had negative self-worth.
Reference:
Thase ME, Rao S, Chen P, et al. Optimizing treatment of depression: the VAST-D study. Presented at the 2017 APA Annual Meeting, May 20-24, 2017, San Diego, CA
Expert Commentary
Michael E. Thase, MD
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Adding Aripiprazole Was Significantly More Effective Than Switching Antidepressants to Bupropion
As shown in the table below, the 3 treatment arms of the study comprised 2 different augmentation strategies and 1 switching strategy.
Findings indicated that adjunctive aripiprazole therapy was significantly more effective than switching antidepressants to bupropion. Adjunctive bupropion was also significantly more effective than switching therapies on some analyses. Adjunctive aripiprazole was nominally superior to adjunctive bupropion on the key outcome measures, but these differences generally were not statistically significant. Weight gain was significantly greater in the adjunctive aripiprazole group.
These results provide further evidence for the utility of adjunctive aripiprazole therapy for patients with difficult-to-treat depression. To some extent, the findings of the adjunctive bupropion vs switch to bupropion comparison parallel those of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study arm. The continuation phase of this study permitted a careful assessment of the longer term tolerability of these strategies, which documented that the effectiveness of adjunctive aripiprazole is associated with a significant risk of weight gain and associated other metabolic side effects. This, of course, is an issue with all of the second-generation antipsychotics (SGAs) that have been approved for adjunctive therapy of difficult-to treat-depressions. As a result, the potential benefits of this strategy must be balanced against these risks. I think that adjunctive SGA therapy is the strategy of choice when there’s urgency, such as when the patient’s suffering and disability warrant the cost and complexity of that medication. But otherwise, I think the relative safety of combining bupropion and either an SSRI or SNRI may be a better choice as the first step past monotherapy. It really does remain to be seen if a treatment sequence that emphasizes adjunctive SGAs offers a convincing advantage in terms of speed of recovery compared to a treatment sequence that emphasizes switching and other adjunctive strategies.
References
Mohamed S, Johnson GR, Vertrees JE, et al. The VA augmentation and switching treatments for improving depression outcomes (VAST-D) study: rationale and design considerations. Psychiatry Res. 2015;229(3):760-770.
Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28-40.
Zisook S, Tal I, Weingart K, et al. Characteristics of U.S. Veteran patients with major depressive disorder who require “next-step” treatments: a VAST-D report. J Affect Disord. 2016;206:232-240.
