- Design
- Observational analysis of individual participant data from two randomised trials, propensity weighted
- Population
- 758 adults aged 60 or over with treatment-resistant depression
- Primary outcome
- MADRS score 10 weeks after starting treatment
- Effect
- rTMS vs aripiprazole augmentation −4.16 points (95% CI 2.32–6.00); vs bupropion switch −6.36 (4.55–8.17)
Researchers pooled individual data from 758 adults aged 60 or over with treatment-resistant depression from two randomised trials: one of once-daily bilateral rTMS for 4–6 weeks, the other comparing aripiprazole augmentation, bupropion augmentation and a switch to bupropion. They used restriction, propensity weighting and regression to make the groups comparable.
At 10 weeks, rTMS was associated with MADRS scores 4.2 points lower than aripiprazole augmentation (95% CI 2.3–6.0), 6.1 lower than bupropion augmentation and 6.4 lower than switching. Odds of response were about four times higher, though with wide intervals (for aripiprazole, OR 3.83, 1.08–13.56). Headache was more common with rTMS.
This is not a head-to-head trial; the arms were recruited separately and patients who enrol in an rTMS trial may differ in ways weighting cannot remove. Still, the size and consistency of the difference is hard to ignore in a group where adding drugs brings falls, sedation and interactions.
Where rTMS is available, it is reasonable to raise it for older patients as soon as treatment resistance is established, rather than only after several augmentation attempts. Guidelines have not yet changed on the strength of this analysis.
- Consider discussing rTMS earlier for adults over 60 after failed antidepressant trials.
- Weigh the falls, sedation and interaction risks of augmentation in older patients.
- Warn patients that headache is the main side effect of rTMS.
- Check local access and cost; daily sessions for 4–6 weeks are a real burden for older adults.
Why it matters
It challenges the habit of reserving rTMS until several medication strategies have failed.
Don't overread it
The groups came from two different trials, so this cannot prove rTMS is superior.
The statistics, in plain English
A 4–6 point MADRS difference is clinically meaningful. The response odds ratios are large but their intervals run from about 1 to 14 or 20, so the true size is very uncertain. Propensity weighting balances measured differences only.
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