Clinical and cognitive effects of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders: a systematic review and meta-analysis.

This pre-registered (CRD42022322038) systematic review and meta-analysis investigated clinical and cognitive outcomes of external trigeminal nerve stimulation (eTNS) in neurological and psychiatric disorders. PubMed, OVID, Web of Science, Chinese National Knowledge Infrastructure, Wanfang, and VIP database for Chinese technical periodicals were searched (until 16/03/2022) to identify trials investigating cognitive and clinical outcomes of eTNS in neurological or psychiatric disorders. The Cochrane Risk of Bias 2.0 tool assessed randomized controlled trials (RCTs), while the Risk of Bias of Non-Randomized Studies (ROBINS-I) assessed single-arm trials. Fifty-five peer-reviewed articles based on 48 (27 RCTs; 21 single-arm) trials were included, of which 12 trials were meta-analyzed (N participants = 1048; of which ~3% ADHD, ~3% Epilepsy, ~94% Migraine; age range: 10-49 years). The meta-analyses showed that migraine pain intensity (K trials = 4, N = 485; SMD = 1.03, 95% CI[0.84-1.23]) and quality of life (K = 2, N = 304; SMD = 1.88, 95% CI[1.22-2.53]) significantly improved with eTNS combined with anti-migraine medication. Dimensional measures of depression improved with eTNS across 3 different disorders (K = 3, N = 111; SMD = 0.45, 95% CI[0.01-0.88]). eTNS was well-tolerated, with a good adverse event profile across disorders. eTNS is potentially clinically relevant in other disorders, but well-blinded, adequately powered RCTs must replicate findings and support optimal dosage guidance.