TBS for Late-Life Depression: Effective, But Patience Required
STUDY: Valiengo LCL et al, Am J Psychiatry 2026; doi:10.1176/appi.ajp.20250537
STUDY TYPE: Randomized sham controlled trial
EVIDENCE GRADE: High 9/10
Background
Treating depression in older adults is difficult — antidepressants work slowly, carry more side effects, and often fail. In contrast, older age predicts a better response to transcranial magnetic stimulation (TMS), a magnetic therapy that activates neurons so that they form stronger connections (neuroplasticity). Theta-burst stimulation (TBS) is a newer version of TMS that delivers the magnetic pulses over a briefer period, so that the therapy takes a few minutes a day instead of 20-40 minutes a day. When delivered daily, TBS is generally as effective as TMS.
The Trial
This triple-blind, sham-controlled randomized trial enrolled 108 patients aged 60 and older (mean age 67) with moderate-to-severe major depression. All were antidepressant-free at enrollment. Active treatment was bilateral TBS over the right dorsolateral prefrontal cortex (DLPFC) followed by intermittent TBS over the left DLPFC, 1,800 pulses per side — delivered daily for 20 sessions over four weeks, plus three booster sessions at weeks 6, 8, and 12. They used Magpro X100 by MagVenture for TBS. The primary outcome was HAM-D change at week 6.
The study missed its primary endpoint: the week-6 HAM-D difference between active and sham just failed to reach significance (Cohen’s d effect size = −0.36, p = 0.059). By week 12, however, active TBS pulled ahead — 52% response vs. 33% in sham, with a small but statistically significant HAM-D advantage. Remission rates at week 12 were 33% vs. 20%, a difference that didn’t reach significance. Adverse events were comparable between groups, with no serious safety signals and no treatment-emergent mania.
The sham (or placebo) in this trial was a fake TBS machine, and the blind was intact. Patients were not able to guess which version they got.
One notable finding: younger age within the sample (still 60+) predicted better response to active TBS, a contrast with previous work on TMS in this population.
The MagVenture TBS device used in the study
Practice Implications
- Consider TMS and TBS for late life depression, and they may need a longer (12 week) course
- Though not tested in this study, TMS is effective for vascular depression, where small vessel injuries in the brain build up to cause depression. Vascular depression rises after age 50, and by age 70, 75% of depressions have a vascular origin. Antidepressants are 30-40% less effective in vascular cases.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
Share Your Input in Comments
- Are you seeing older adults respond to TMS or TBS?
- What obstacles get in the way of using these treatments?
