Comparative Effectiveness Research Trial for Antidepressant Incomplete and Nonresponders With Treatment Resistant Depression (ASCERTAIN-TRD)

Objective: This study compared the effects of augmenting antidepressants with aripiprazole or repetitive transcranial magnetic stimulation (rTMS) versus switching to venlafaxine XR/duloxetine on quality of life (QoL) among patients with treatment resistant depression (TRD). Methods: In a predefined secondary analysis of a multisite, open-label, effectiveness trial, patients with TRD were randomly assigned to aripiprazole augmentation, rTMS augmentation, or switching to venlafaxine XR/duloxetine in a 1:1:1 ratio, and they were treated for 8 weeks. TRD was defined as an inadequate response to 2 or more antidepressant trials of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire. QoL was predefined as a key secondary end point for this study and assessed using the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). A mixed-effects model with repeated measures was applied. This study was conducted from July 13, 2017, to December 22, 2021. Results: Among 258 randomized participants with at least 1 postbaseline Q-LES-Q-SF measurement, augmentation with aripiprazole demonstrated statistically significant superiority over switching on the Q-LES-Q-SF (P=.002), while rTMS did not (P=.326). At end point, changes from baseline in the Q-LES-Q-SF scores were 10.61 (SE=1.0) for aripiprazole augmentation, 11.59 (SE=1.1) for rTMS augmentation, and 8.68 (SE=0.9) for venlafaxine XR/duloxetine switch. Conclusion: Augmentation with aripiprazole, but not rTMS, improved QoL significantly versus venlafaxine XR/duloxetine switch in TRD patients. However, a much smaller than expected sample size for the rTMS group may explain the lack of statistical significance rendering the latter finding of indeterminate nature. Trial Registration: ClinicalTrials.gov identifier: NCT02977299.