VA Aripiprazole vs Esketamine for Treatment Resistant Depression (VAST-D II)

This open-label, parallel-group, randomized clinical trial (n=0; withdrawn) aimed to compare the efficacy, safety, and acceptability of adjunctive intranasal esketamine versus adjunctive aripiprazole in veterans with unipolar treatment-resistant depression over 6 months of treatment.

The study aims to recruit participants from approximately 25 VA medical centres. Participants will be randomised 1:1 to receive either adjunctive aripiprazole (n=470) or adjunctive intranasal esketamine (n=470). The primary outcome is remission at 6 weeks, defined as a QIDS-C16 score ≤5 assessed by remote raters blinded to treatment assignment. Key secondary outcomes include reduction in depressive symptoms from baseline to 6 months. Exploratory outcomes include comparisons of symptom improvement, remission and relapse rates, PTSD symptoms, suicidality, quality of life, and cost-benefit analyses.

The study will provide important data on the effectiveness, safety and acceptability of intranasal esketamine compared to aripiprazole, one of the most widely used adjunctive therapies for treatment-resistant depression, in the veteran population. It will help determine if the potential benefits of esketamine are substantial enough to offset side effects, costs, and patient burden associated with its use.

Trial Details



Trial Number

Sponsors & Collaborators

US Department of Veteran Affairs
The US Department of Veteran Affairs is playing an important role in the psychedelic renaissance by exploring and monitoring advancements in psychedelic therapies and the viability of these therapies for veterans with PTSD.

Data attribution

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