# External trigeminal nerve stimulation for neuropsychiatric disorders: mechanisms, efficacy, and future directions

## TL;DR

External trigeminal nerve stimulation (eTNS) is a noninvasive treatment that shows promise for various neuropsychiatric disorders, though more research is needed to standardize its use.

## Contribution

This paper provides a narrative review of eTNS mechanisms and clinical applications, highlighting the need for standardized protocols and future research directions.

## Key findings

- eTNS shows clinically meaningful benefits for ADHD and migraine.
- Promising adjunctive efficacy is observed in epilepsy and potential for depression and anxiety.
- Standardized clinical protocols and larger trials are needed for broader application.

## Abstract

External trigeminal nerve stimulation (eTNS) is an emerging noninvasive neuromodulation technique that modulates brain network activity implicated in multiple neuropsychiatric disorders through the application of low-intensity electrical currents to the frontal branches of the trigeminal nerve. Based on a search of major biomedical databases, we narratively synthesize clinical and mechanistic studies of eTNS across neurological and psychiatric indications. Current clinical and neurophysiological studies suggest clinically meaningful benefits of eTNS in attention-deficit/hyperactivity disorder (ADHD) and migraine, show promising adjunctive efficacy in epilepsy, and may offer emerging therapeutic potential for conditions such as depression, anxiety, and disorders of consciousness. Although eTNS generally demonstrates a favorable safety profile, existing studies are constrained by small sample sizes, short follow-up periods, and considerable heterogeneity in stimulation parameters, and standardized clinical protocols are still lacking. Future research should prioritize multicenter randomized controlled trials, parameter optimization, and biomarker-guided personalized modulation. By integrating neurophysiological, neuroimaging, and behavioral metrics, such efforts may advance eTNS toward a precisely controlled, closed-loop neuromodulation system. This narrative review provides a concept-driven synthesis of the anatomical foundations, putative mechanisms, and clinical evidence for eTNS and outlines key directions for standardization and translational research, thereby providing a reference framework for the clinical implementation of eTNS in neuropsychiatric disorders.