Connectivity-guided theta-burst stimulation beat 5-cm targeting in early weeks

Design

Single-centre, randomised, double-blind, three-arm trial

Population

119 analysed adults with major depression or bipolar II depression and at least one antidepressant failure

Primary outcome

Percentage reduction in 17-item Hamilton Depression Rating Scale score at week 2

Effect

Structural-connectivity-guided versus 5-cm: 8.79 percentage points greater (95% CI 2.19 to 15.40), no significant difference at week 12

In a single-centre, double-blind trial, 123 adults aged 18 to 65 with major depression or bipolar II depression and at least one failed antidepressant were randomised to 20 sessions of intermittent theta-burst stimulation over two weeks. Targets were set by the 5-cm scalp rule, by functional connectivity, or by structural connectivity to the subgenual anterior cingulate.

At week 2 the structural-connectivity group had a Hamilton score reduction 8.79 percentage points greater than the 5-cm group (95% CI 2.19 to 15.40). At week 6 both individualised groups were ahead: 12.87 points for structural (6.21 to 19.54) and 9.41 for functional (2.84 to 15.98). By week 12 the differences were no longer significant. No seizures or mania occurred.

This needs replication in more centres, and the lack of difference at week 12 matters for anyone hoping for durable gains. Robotic neuronavigation and tractography are not available in most services in India.

• Individualised targeting gave faster early improvement than the 5-cm rule.
• Differences were gone by week 12.
• No seizures or manic switches were reported in this trial.
• Requires neuronavigation and imaging, so availability will be limited.
• Treat it as promising preliminary evidence rather than a reason to change local practice.

Why it matters

It tests whether the long-standing scalp rule is leaving benefit on the table for some patients.

Don't overread it

A single-centre trial with 40 per arm and a primary endpoint at two weeks cannot establish a lasting advantage.

The statistics, in plain English

A Cohen's d of 0.70 to 1.03 is a large standardised difference, but with about 40 people per arm the confidence intervals are wide. The loss of difference at week 12 means the faster response did not translate into a lasting gap.

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