- Design
- Triple-blind, sham-controlled randomised trial
- Population
- 108 adults aged 60 or over with moderate to severe MDD, not on antidepressants
- Primary outcome
- Change in HAM-D score at week 6
- Effect
- Week 6 difference −1.65 (95% CI −3.38 to 0.08); week 12 −1.89 (−3.75 to −0.03), response 52% vs 33%
A triple-blind, sham-controlled trial, published in March 2026, randomised 108 adults aged 60 or over (mean age 67) with moderate to severe major depression who were not taking antidepressants. Active treatment was bilateral theta-burst stimulation — intermittent over the left dorsolateral prefrontal cortex and continuous over the right — given in 20 weekday sessions with boosters at weeks 6, 8 and 12.
The primary endpoint at week 6 was missed: the difference in Hamilton depression score was −1.65 (95% CI −3.38 to 0.08). By week 12 active stimulation was ahead, with a difference of −1.89 (−3.75 to −0.03) and response in 52% against 33% with sham.
Older adults are often the patients who tolerate antidepressants least well, and theta-burst sessions take minutes rather than the 40 minutes of standard rTMS. These results suggest it is a reasonable option, but the benefit emerged later than the protocol expected and the week-12 result is secondary.
In practice: where theta-burst stimulation is available, it is worth discussing with older adults who cannot take or do not want antidepressants, with expectations set for a response over about three months rather than six weeks.
- Consider theta-burst stimulation for older adults with moderate to severe depression who cannot tolerate antidepressants.
- Tell patients that improvement may take up to 12 weeks, and plan booster sessions rather than stopping at six weeks.
- Response was 52% with active stimulation against 33% with sham at 12 weeks in this trial.
- Screen for neurological contraindications, such as seizure history or implanted devices, before referral.
- The trial excluded people on antidepressants, so results may not apply to augmentation.
Why it matters
Judging neuromodulation at six weeks may write off a treatment that is still working in older brains.
Don't overread it
The primary endpoint at week 6 was not met; the week-12 benefit is a secondary result.
The statistics, in plain English
At week 6 the confidence interval just crossed zero, so the trial could not exclude no effect. At week 12 it just stayed below zero, a borderline but positive result. A response gap of 19 percentage points means roughly one extra responder for every five people treated.
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