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

James J McGough; Alexandra Sturm; Jennifer Cowen; Kelly Tung; Giulia C Salgari; Andrew F Leuchter; Ian A Cook; Catherine A Sugar; Sandra K Loo

doi:10.1016/j.jaac.2018.11.013

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

J Am Acad Child Adolesc Psychiatry. 2019 Apr;58(4):403-411.e3. doi: 10.1016/j.jaac.2018.11.013. Epub 2019 Jan 28.

Authors

James J McGough¹, Alexandra Sturm², Jennifer Cowen², Kelly Tung², Giulia C Salgari², Andrew F Leuchter², Ian A Cook³, Catherine A Sugar⁴, Sandra K Loo²

Affiliations

¹ Semel Institute for Neuroscience and Human Behavior and the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), Los Angeles, CA. Electronic address: jmcgough@mednet.ucla.edu.
² Semel Institute for Neuroscience and Human Behavior and the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), Los Angeles, CA.
³ David Geffen School of Medicine at UCLA, the Henry Samueli School of Engineering and Applied Science at UCLA, and NeuroSigma, Inc., Los Angeles, CA.
⁴ David Geffen School of Medicine and the Fielding School of Public Health at UCLA, Los Angeles, CA.

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 (F_1,228 = 8.12, p = .005; week 4 Cohen d = 0.5). CGI-Improvement scores also favored active treatment (χ²_1,168 = 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; http://clinicaltrials.gov/; NCT02155608.

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

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural

MeSH terms

Attention Deficit Disorder with Hyperactivity / therapy*
Child
Double-Blind Method
Electric Stimulation Therapy / methods*
Executive Function
Female
Humans
Logistic Models
Male
Pilot Projects
Psychiatric Status Rating Scales
Treatment Outcome
Trigeminal Nerve / physiology*
United States

Associated data

ClinicalTrials.gov/NCT02155608

Grants and funding

R34 MH101282/MH/NIMH NIH HHS/United States