TMS lowered depression more than switching or augmenting antidepressants in older adults with treatment-resistant depression
STUDY: Adler E et al, American Journal of Psychiatry 2026
STUDY TYPE: Pooled individual participant data from different randomized controlled trials
FUNDING: Canadian Institutes of Health Research, Patient-Centered Outcomes Research Institute, National Institute of Mental Health
Background
In two pivotal trials from 2024, TMS outperformed antidepressant augmentation and switching in treatment resistant depression. This study compares these strategies in late-life depression, pooling data from different randomized trials.
The Study
- 758 adults 60 and older with treatment-resistant depression, pooled from two randomized trials.
- One gave daily TMS for 4 to 6 weeks; the other randomized patients to aripiprazole augmentation, bupropion augmentation, or a switch to bupropion.
- Propensity score weighting balanced the samples; the primary outcome was the depression scale (MADRS) at week 10.
Results
At week 10,rTMS produced lower depression scores than aripiprazole augmentation (4.2 points lower), bupropion augmentation (6.1 points lower), and switching to bupropion (6.4 points lower).
Response (at least 50% improvement) was 4 to 5 times more likely with TMS. Remission favored TMS too, though not significantly. TMS’s advantage over aripiprazole only appeared by week 10, not week 4.
Side Effects
Headache was 9-27 times more common with TMS. Nausea, dizziness, fatigue, and falls didn’t differ between groups.
Limitations
This compared two separate trials rather than randomizing patients head-to-head, so some confounding may remain despite adjustment. Anxiety severity, a known predictor of rTMS response, wasn’t measured in the trials.
Practice Implications
- This adds to the evidence favoring TMS over pharmacologic augmentation
- There’s another reason to favor TMS in late-life depression. It has evidence in vascular depression, which affects over half in this age group.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
