rTMS may boost sertraline response in adolescent depression, but evidence remains uncertain

A review of 24 Chinese trials found better short-term outcomes when repetitive transcranial magnetic stimulation was added to sertraline, but inconsistent methods and low-certainty evidence temper the findings.

A large meta-analysis in Frontiers in Psychiatry suggests that adding repetitive transcranial magnetic stimulation to sertraline may improve short-term outcomes for adolescents with depression, although the authors caution that the evidence is uneven and the benefits may be overstated. The review pooled 24 randomised controlled trials involving 2,155 patients, all of them conducted in China and published in Chinese, and found better symptom reduction and higher response rates with the combined approach than with sertraline alone.

The analysis reported sizeable improvements on two standard depression scales. On the 17-item Hamilton Depression Rating Scale, the pooled effect favoured the combined treatment, while the 24-item version showed an even larger average benefit. Across 20 studies, the chance of clinical response was also higher when rTMS was added to sertraline. The authors said the pattern was consistent, but they also noted marked between-study differences, including variation in stimulation settings, treatment length and reporting quality.

One of the more notable findings was a possible cognitive benefit. In three trials that assessed the Montreal Cognitive Assessment, adolescents receiving the combined treatment scored better than those taking sertraline alone. Even so, the review team stressed that this result rests on a small evidence base and should be treated cautiously. The safety signal was more reassuring: adverse events were slightly more common with the combination, but they were generally mild and temporary, most often scalp discomfort or headache, with no severe complications reported.

The authors argue that standardising rTMS protocols will be essential before the approach can be recommended with confidence. They found that much of the heterogeneity came from outlier studies using unusually long courses or atypical stimulation frequencies. When those were removed in sensitivity testing, the antidepressant effect remained, but it was smaller. The certainty of evidence ranged from very low to moderate under GRADE, with the weakest confidence attached to the symptom score results and the cognitive finding limited by only three studies. The review registered in advance and followed PRISMA methods, but the authors say future multinational, sham-controlled trials are needed to determine whether the combination should have a wider role in adolescent depression care.