This open-label, parallel-group, randomized clinical trial (n=0; withdrawn) aimed to compare the efficacy, safety, and acceptability of adjunctive intranasal esketamine versus adjunctive aripiprazole in veterans with unipolar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
This is an open-label, parallel-group, randomized clinical trial of up to 6 months treatment of adjunctive intranasal (IN) esketamine (ESK) vs. adjunctive aripiprazole (ARI) in Veterans with unipolar Treatment Resistant Depression (TRD). This study will assess the efficacy, safety, and acceptability of adjunctive IN ESK in comparison to ARI, one of the best studied and most widely used adjunctive therapies for TRD. The primary hypothesis is that participants receiving adjunctive IN ESK will be significantly more likely to achieve remission after six weeks of treatment as compared to those who receive adjunctive ARI. Depressive symptoms will be assessed by central raters (CR), blinded to treatment assignment, using the clinician rated version of the Quick Inventory of Depressive Symptomatology (QIDS-C16), a well-validated tool that is commonly used and is easily translated across other depression inventory scales. The study is powered to detect an absolute difference in remission rates of 10%, or larger, at 6 weeks. Additional outcomes of interest include symptom reduction across 6 months of randomized therapy, side effects and other tolerability indices, attrition rates and measures of quality of life and cost-effectiveness.NCT Number NCT05554627
Sponsors & Collaborators
US Department of Veteran AffairsThe 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.