Comparing Aripiprazole vs rTMS Augmentation vs SNRI Switch in TRD
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📌 Background
Treatment-resistant depression (TRD), defined as failure of ≥2 adequate antidepressant trials, remains a major clinical challenge.
- Beyond symptom reduction, quality of life (QoL) is increasingly recognized as a critical outcome.
- The ASCERTAIN-TRD trial compared augmentation strategies versus switching antidepressants in terms of QoL improvement.
🧪 Study Design
Design: Multisite, open-label, randomized effectiveness trial (2017–2021)
Participants: Adults with TRD (n = 258 with QoL data)
Arms (1:1:1 randomization):
Aripiprazole augmentation
rTMS augmentation
Switch to venlafaxine XR/duloxetine
Primary Outcome: QoL change, measured with Q-LES-Q-SF (Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form)
📊 Key Results:
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Aripiprazole augmentation: Significant QoL improvement vs switch (P = .002)
Mean change: +10.6 points
rTMS augmentation: Numerical benefit but not statistically significant (P = .326)
Mean change: +11.6 points
Small sample size may explain lack of significance
Switching to venlafaxine/duloxetine:
Mean change: +8.7 points
🩺 Clinical Implications
Aripiprazole augmentation clearly improved QoL beyond switching, supporting its use as a preferred TRD strategy when symptom and life-functioning improvements are both treatment goals.
rTMS remains promising, but underpowered data in this trial prevent firm conclusions.
Switching antidepressants alone may not provide the same QoL gains, highlighting the potential benefit of augmentation approaches in TRD.
✅ Clinical Takeaway
For patients with TRD, aripiprazole augmentation improves quality of life more effectively than switching to venlafaxine or duloxetine. While rTMS also showed encouraging results, more robust trials are needed to confirm its role.
This study underscores the importance of targeting functional outcomes, not just symptom reduction, in the management of TRD.
📚 References
- 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. J Clin Psychiatry. 2025 Aug 11;86(3):24m15614. doi: 10.4088/JCP.24m15614. PMID: 40801757. (article)
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