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Updated: Apr 18, 2026
Conventional Repetitive Transcranial Magnetic Stimulation for Depression: A Step-by-Step Protocol
Published on: November 21, 2025
Effect of a 10-day trigeminal nerve stimulation (TNS) protocol for treating major depressive disorder: a phase II,
Pedro Shiozawa1, Mailu Enokibara da Silva1, Geraldo Teles Machado Netto1
1Clinical Neuromodulation Laboratory, Santa Casa de São Paulo School of Medicine, Brazil.
Background:
Considering both the burden determined by major depressive disorder (MDD) itself and the high refractoriness and recurrence index, alternative strategies, such as trigeminal nerve stimulation (TNS), are the cutting edge instruments to optimize clinical response and to avoid treatment discontinuation and relapse of symptoms. Trigeminal nerve stimulation is an incipient simple, low-cost interventional strategy based on the application of an electric current over a branch of the trigeminal nerve with further propagation of the stimuli towards brain areas related to mood symptoms.
Method:
The study was a phase II, randomized, sham-controlled trial with 40 patients with MDD. Patients with moderate or severe depressive symptoms as assessed by adequate clinical scales underwent a 10-day intervention protocol. Regarding main clinical outcome, analysis of variance (ANOVA) was performed to evaluate mean change scores in depressive symptoms as assessed by the HDRS-17 between baseline (t1), after intervention protocol (t2), and during one-month follow-up (t3).
Results:
There was a significant interaction between the mean percentage changes in depressive symptoms according to the HDRS in the two groups across the three assessments (F=6.38, df=2, p=0.0033). Post hoc analyses (Bonferroni method) demonstrated a statistically significant difference between depressive symptoms at baseline and t1 (p=0.01) and between depressive symptoms at baseline and t2 (p=0.009). No severe adverse effects were reported.
Discussion:
Our results in the present controlled trial highlight the possibility of more practical treatment protocols for clinical research, which are similar to those for different neuromodulation strategies such as transcranial direct current stimulation (tDCS). The in-office administration of TNS in our protocol is similar to the schedule for repetitive transcranial magnetic stimulation (rTMS), though over fewer treatment sessions.
Conclusion:
Further controlled studies will contribute to the establishment of the clinical relevance of this new treatment strategy for MDD.
