Bilateral theta-burst stimulation in late-life depression: no benefit at 6 weeks, a modest one at 12

Design

Triple-blind, sham-controlled randomised trial

Population

108 adults aged 60 or over with moderate to severe major depression, not on antidepressants

Primary outcome

Change in HAM-D score at week 6

Effect

Week 6: -1.65 (95% CI -3.38 to 0.08); week 12: -1.89 (-3.75 to -0.03); response 52% vs 33%

This triple-blind, sham-controlled trial enrolled 108 people aged 60 or over (mean 67 years) with moderate to severe major depression who were not taking antidepressants. They received 20 daily sessions of bilateral theta-burst stimulation (intermittent on the left dorsolateral prefrontal cortex, continuous on the right), plus extra sessions at weeks 6, 8 and 12.

The primary comparison at week 6 was not significant: the HAM-D reduction differed by -1.65 points (95% CI -3.38 to 0.08). At week 12 the difference was -1.89 (95% CI -3.75 to -0.03), with response in 52% of the active group and 33% of the sham group.

The interval at week 12 only just excludes zero, and the gap is small. The trial supports theta-burst stimulation as an option to discuss where drug treatment is unsuitable or has failed, not as an early-response treatment. Because participants were off antidepressants, it also says little about add-on use.

• Set expectations: improvement over sham was not seen at 6 weeks, so do not judge a course on early response alone.
• Consider theta-burst stimulation for older adults who have not responded to, or cannot tolerate, antidepressants.
• Screen for contraindications before referral, including implanted metal and seizure history.
• Record a baseline rating scale so the 12-week change can be judged.
• Remember the 20-weekday schedule; access and travel are a practical barrier in India.

Why it matters

It suggests stimulation may work more slowly in older adults than clinicians expect, and that stopping at 6 weeks could miss the effect.

Don't overread it

A single trial with a borderline 12-week result does not establish that theta-burst stimulation is effective in late-life depression.

The statistics, in plain English

A confidence interval that just excludes zero (-3.75 to -0.03) means the result is barely distinguishable from chance and the true benefit could be tiny. A 2-point HAM-D difference is small against the scale's range. The week 6 interval crossed zero, so that comparison was not statistically significant.

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