Comparative Effectiveness Research Trial for Antidepressant Incomplete and Nonresponders With Treatment Resistant Depression (ASCERTAIN-TRD): Effect of Aripiprazole or Repetitive Transcranial Magnetic Stimulation Augmentation Versus Switching to the Antidepressant Venlafaxine on Quality of Life.

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.