Double-Blind, Sham-Controlled, Pilot Study of Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder

Abstract

Objective: Trigeminal nerve stimulation (TNS), a minimal-risk noninvasive neuromodulation method, showed potential benefits for attention-deficit/hyperactivity disorder (ADHD) in an unblinded open study. The present blinded sham-controlled trial was conducted to assess the efficacy and safety of TNS for ADHD and potential changes in brain spectral power using resting-state quantitative electroencephalography.

Method: Sixty-two children 8 to 12 years old, with full-scale IQ of at least 85 and Schedule for Affective Disorders and Schizophrenia-diagnosed ADHD, were randomized to 4 weeks of nightly treatment with active or sham TNS, followed by 1 week without intervention. Assessments included weekly clinician-administered ADHD Rating Scales (ADHD-RS) and Clinical Global Impression (CGI) scales and quantitative electroencephalography at baseline and week 4.

Results: ADHD-RS total scores showed significant group-by-time interactions (F1,228 = 8.12, p = .005; week 4 Cohen d = 0.5). CGI-Improvement scores also favored active treatment (χ21,168 = 8.75, p = .003; number needed to treat = 3). Resting-state quantitative electroencephalography showed increased spectral power in the right frontal and frontal midline frequency bands with active TNS. Neither group had clinically meaningful adverse events.

Conclusion: This study demonstrates TNS efficacy for ADHD in a blinded sham-controlled trial, with estimated treatment effect size similar to non-stimulants. TNS is well tolerated and has minimal risk. Additional research should examine treatment response durability and potential impact on brain development with sustained use.

Clinical trial registration information: Trigeminal Nerve Stimulation for ADHD; https://ichgcp.net/clinical-trials-registry/NCT02155608" title="See in ClinicalTrials.gov">NCT02155608.

Keywords: attention-deficit/hyperactivity disorder; clinical trial; neuromodulation; trigeminal nerve stimulation.

Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Attention-Deficit/Hyperactivity Disorder-Rating Scale (ADHD-RS) Total Scores Over Four-Week Blinded Trial: Active vs. Sham Trigeminal Nerve Stimulation

Figure 2.. Treatment Related Change in Electroencephalography (EEG) Spectral Power at F4 Electrode

Note: During eyes-open resting state, active Trigeminal Nerve Stimulation (TNS) treatment was associated with increased broad band spectral power from baseline to Week 4 (orange solid and dashed line, respectively) compared to sham treatment, which showed no change or slight decrease from baseline to week 4 (blue solid and dashed lines, respectively), particularly in the right frontal region (panel A). Amount of change for each treatment group in the active and sham TNS groups (panel B), suggests increased power in the active group and decreased power in the sham group across multiple frequency bands. Depiction of the significant group by time interaction effect for F4 gamma power (panel C), data for other frequency bands and the Fz electrode show similar patterns. Base=baseline, W4=week4 treatment end, a p<0.05, b p<0.01.