rTMS versus medication changes in late-life resistant depression

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 at 10 weeks

Effect

MADRS lower with rTMS by 4.16 points vs aripiprazole (95% CI 2.32 to 6.00), 6.08 vs bupropion augmentation, 6.36 vs switch to bupropion

Researchers pooled individual data from two trials in adults aged 60 or older with treatment-resistant depression: 758 people in all. One trial gave bilateral rTMS once daily for four to six weeks. The other compared aripiprazole augmentation, bupropion augmentation and a switch to bupropion. Propensity weighting and restriction were used to make the groups comparable.

At 10 weeks, rTMS was associated with MADRS scores about 4 points lower than aripiprazole augmentation and about 6 points lower than either bupropion strategy. Odds of response were roughly four times higher with rTMS, though with wide confidence intervals. Headache was more common with rTMS.

Older adults with resistant depression often accumulate drugs, interactions and falls risk. A non-drug option that performs at least as well would change the order of treatments. But this was not a head-to-head trial: participants in the two trials were recruited differently, and weighting cannot remove every difference.

Where rTMS is available, it is reasonable to offer it earlier in the sequence for older adults rather than after several failed drug steps. Access in India is largely limited to larger centres and private practice.

• Consider offering rTMS before a second or third medication change in over-60s with resistant depression
• Weigh falls, interactions and side effects of aripiprazole or bupropion in older patients
• Warn patients that headache is common during rTMS courses
• The MADRS gain over aripiprazole was about 4 points, a clinically meaningful difference
• Guidelines have not changed; rTMS remains one option among several

Why it matters

It challenges the habit of exhausting drug strategies before considering neuromodulation in older adults.

Don't overread it

The two arms came from separate trials, so this is an adjusted observational comparison, not a head-to-head result.

The statistics, in plain English

The MADRS differences have confidence intervals well clear of zero. The response odds ratios are around 4 but their intervals run from about 1.1 to 14 or more, so the true size of the response benefit is uncertain. Because the arms came from different trials, the result is an adjusted comparison, not a randomised one.

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