- Design
- Single-centre, randomised, double-blind, three-arm trial
- Population
- 123 adults with major depressive disorder or bipolar II depression and at least one antidepressant failure
- Primary outcome
- Percentage reduction in 17-item Hamilton Depression Rating Scale at week 2
- Effect
- Structural-connectivity vs 5-cm: difference 8.79 points (2.19 to 15.40), d 0.70 at week 2; gap gone by week 12
A single-centre, double-blind, three-arm trial randomised 123 adults with major depression or bipolar II depression and at least one failed antidepressant to 20 sessions of intermittent theta-burst stimulation over two weeks, targeted three ways: the standard 5-cm rule, functional-connectivity guidance, or structural-connectivity guidance to the subgenual anterior cingulate.
Structural-connectivity-guided stimulation beat the 5-cm rule on depression-score reduction at week 2 (least-squares mean difference 8.79 percentage points, 95% CI 2.19 to 15.40; Cohen's d 0.70). At week 6 both connectivity-guided arms were ahead of the 5-cm group, with a large effect for the structural approach. By week 12 the differences were no longer significant. There were no seizures or mania.
This supports moving away from scalp-measurement targeting towards individualised, connectivity-based siting — but it is one centre, modest in size, and the between-group gap had closed by three months, so it is a direction to watch rather than a settled change to how transcranial magnetic stimulation is delivered.
- Three-arm trial, 123 randomised (119 analysed), in major or bipolar II depression with prior antidepressant failure.
- Structural-connectivity-guided stimulation beat 5-cm targeting at week 2 (difference 8.79 points, 95% CI 2.19 to 15.40; d 0.70).
- At week 6 both connectivity-guided arms were ahead; by week 12 differences were no longer significant.
- No seizures or mania; adverse events were comparable across arms.
- Connectivity-guided targeting needs neuronavigation and imaging, which limits where it can be offered now.
Why it matters
It challenges the long-standing 5-cm scalp rule for siting stimulation, pointing towards individualised, imaging-based targets.
Don't overread it
This was a single-centre trial and the between-group difference had disappeared by 12 weeks, so it is preliminary.
The statistics, in plain English
A Cohen's d around 0.7 to 1.0 is a moderate-to-large effect; the intervals exclude zero at weeks 2 and 6, but losing significance by week 12 means the early advantage may not persist, and one centre cannot settle that.
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