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Cited by 131Attention Deficit Hyperactivity DisorderVagus Nerve Stimulation ResearchTranscranial Magnetic Stimulation Studies

Double-blind, sham-controlled, pilot study of trigeminal nerve stimulation for attention-deficit/hyperactivity disorder

Open access
McGough, James J., Sturm, Alexandra, Cowen, Jennifer, Tung, Kelly, Salgari, Giulia C., Leuchter, Andrew F., Cook, Ian A., Sugar, Catherine A. +1 more·2019·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2018.11.013PMC PMC6481187
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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 (χ 21,168 = 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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a 4-week double-blind, sham-controlled pilot, nightly trigeminal nerve stimulation (TNS) in 62 children aged 8–12 with ADHD improved clinician-rated ADHD-RS total scores versus sham (group-by-time F = 8.12, df = 1/228, p = .005; week 4 Cohen’s d = .50) and CGI-I (χ² = 8.75, df = 1/168, p = .003; NNT = 3). TNS was well tolerated with no serious adverse events, and qEEG showed increased right frontal and frontal midline spectral power with active treatment.

Key findings

  • ADHD-RS totals showed a significant group-by-time interaction (F = 8.12, df = 1/228, p = .005), with week 4 Cohen’s d = .50. CGI-I also favored active treatment (χ² = 8.75, df = 1/168, p = .003), NNT = 3; raw CGI-I improvement rates for active vs sham were 25% vs 13%, 34% vs 15%, 47% vs 12%, and 52% vs 14% at weeks 1–4.
  • Resting-state qEEG showed increased broadband power with active TNS and decreased power with sham in the right frontal region. Significant group-by-time effects occurred for right frontal F4 delta, theta, beta, and gamma bands and frontal midline Fz gamma, with trend-level effects for Fz delta, theta, and beta. Week 4 changes in F4 theta/beta and Fz gamma 1 correlated with ADHD-RS total and hyperactive/impulsive changes (r’s range −.34 to −.41).
  • After treatment discontinuation, ADHD-RS worsened in both groups from week 4 to week 5: active means 23.39 (SD 7.88) to 25.52 (7.84); sham 27.50 (8.08) to 29.11 (7.79). Time effect was significant (F = 6.23, df = 1/57, p = .02), with a trend for group differences (F = 4.18, df = 1/57, p = .05) but no group-by-time interaction (F = .12, df = 1/57, p = .73); week 5 Cohen’s d = .46.
  • No serious adverse events occurred and no participant withdrew for adverse events. Active TNS was associated with significant increases in weight and pulse versus sham, and side-effect ratings showed notable increases in fatigue, headache, and increased appetite with active TNS, and increased hyperactivity with sham.

Methods

  • Randomized, double-blind, sham-controlled pilot: 62 children aged 8–12 years with KSADS-diagnosed ADHD, full-scale IQ ≥ 85, baseline ADHD-RS ≥ 24, and CGI-S ≥ 4 were randomized 1:1 to active (n = 32) or sham (n = 30) TNS, stratified by low/high parent ARI scores. Treatment was nightly for 4 weeks, followed by 1 blinded week without intervention.
  • Outcomes included weekly clinician-administered ADHD-RS and CGI scales, parent/teacher behavioral ratings, cognitive tests, safety measures, and resting-state qEEG at baseline and week 4. qEEG data for 3 participants were excluded for movement artifact, leaving 56 participants (active n = 30; sham n = 26) for EEG analyses.
  • Analyses used SAS 9.4 general linear mixed models with group, time, and group-by-time predictors, subject-level random intercepts, and a piecewise linear time trend (time2 after week 1); categorical CGI-I was assessed by chi-square. Effect sizes used Cohen’s d and NNT, with uncorrected α = .05.

Limitations

  • The paper states the study assessed only acute 4-week response and does not inform whether additional improvement would accrue with ongoing treatment or whether benefits persist over time; it did not assess TNS as adjunctive therapy; it failed to support open-label executive functioning (BRIEF) and selected sleep (CSHQ) benefits, though mean ratings on those measures were subclinical; pulse increases were statistically significant but not clinically abnormal and may be outlier findings from a small sample; replication in additional patient groups is needed.
  • Evident from the text: this was a small pilot with uncorrected significance for exploratory outcomes, blinding was assessed only by parent questionnaire, qEEG analyses included 56 of 62 randomized participants, and the study does not address potential effects on brain development with sustained use.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jaac.2018.11.013

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 23 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Active TNS compared with sham increased resting-state qEEG spectral power in right frontal and frontal midline frequency bands.

    “Resting-state qEEG showed increased spectral power in right frontal and frontal midline frequency bands with active TNS.”
    • Also stated in: § Efficacy Measures · boosted
      “With resting state qEEG, active TNS demonstrated increased broadband power, whereas sham exhibit decreased power in the right frontal region (Figure 2).”
    • Also stated in: § Efficacy Measures · plain
      “reveal significant group-by-time effects for frequency bands in the right frontal (F4 delta, theta, beta, gamma) and frontal midline (Fz gamma) channels”
    Quote in the paperSubstantial claim
  • Findingown data

    The Inattentive and Hyperactive-Impulsive ADHD-RS subscales showed the same pattern of time, time2, and group-by-time effects as the total score.

    “The same pattern of time, time2, and group-by-time effects was found with both Inattentive and Hyperactive-Impulsive ADHD-RS subscales as with total scores.”
    Quote in the paperNot a substantial claim
  • Findingown data

    At week 5, 13% of active and 7% of sham participants were CGI-I improved relative to baseline (chi-square=0.53, df=1, p=.46).

    “Week 5 CGI-I ratings showed 13% improved in active vs.7% improved in sham groups compared to baseline (X2 = .53, df = 1, p = .46).”
    Quote in the paperNot a substantial claim
  • Findingown data

    C-SSRS responses showed no suicidality.

    “C-SSRS showed no responses suggestive of suicidality.”
    Quote in the paperNot a substantial claim
  • Findingown data

    ADHD-RS total scores worsened in both active and sham groups between weeks 4 and 5 after treatment discontinuation.

    “ADHD-RS totals worsened in both groups between weeks 4 and 5 following treatment discontinuation.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 45
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    Active TNS compared with sham produced greater CGI-I improvement over four weeks (chi-square=8.75, df=1/168, p=.003), with an NNT of 3 at week 4.

    “CGI-Improvement also favored active treatment (Chisq = 8.75, df = 1/168, p = .003); number-needed-to-treat (NNT) = 3.”
    • Also stated in: § Efficacy Measures · plain
      “CGI-I over the 4-week course similarly favored active over sham (X2 = 8.75, df = 1/168, p = .003).”
    • Also stated in: § Efficacy Measures · plain
      “Number-needed-to-treat (NNT) based on CGI-I at week 4 was 3.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither the active nor the sham TNS group experienced clinically meaningful adverse events.

    “Neither group had clinically meaningful adverse events.”
    • Also stated in: § Safety and Tolerability · plain
      “There were no serious adverse events in either group and no participant withdrew for adverse events.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    In children aged 8-12 with ADHD, active TNS compared with sham produced a significant group-by-time interaction on clinician-rated ADHD-RS total scores over four weeks (F=8.12, df=1/228, p=.005), with an estimated week-4 Cohen's d of 0.50.

    “ADHD-RS totals showed significant group-by-time interactions (F = 8.12, df = 1/228, p = .005); week 4 Cohen’s d = .5.”
    • Also stated in: § Efficacy Measures · boosted
      “ADHD-RS totals showed significant group-by-time interaction, demonstrating a differential treatment effect (F = 8.12, df = 1/228, p = .005).”
    • Also stated in: § Efficacy Measures · hedged
      “Estimated Cohen’s d at week 4 was 0.50, suggesting a medium-size treatment effect.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Active TNS compared with sham produced significant increases in weight and pulse over four weeks, with no group differences in height or blood pressure changes.

    “Significant increases in weight and pulse were seen with active TNS compared with sham over four weeks, but there were no group differences in increased height or blood pressure (Table 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    During the discontinuation week, ADHD-RS scores worsened significantly over time (F=6.23, df=1/57, p=.02), with a trend for group differences (F=4.18, df=1/57, p=.05) but no group-by-time interaction (F=0.12, df=1/57, p=.73), indicating similar deterioration rates.

    “Time effect was significant (F = 6.23, df = 1/57, p = .02), with a trend for group differences (F = 4.18, df = 1/57, p = .05), but no significant group-by-time interaction (F = .12, df = 1/57, p = .73), suggesting both groups deteriorated at similar rates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mean ADHD-RS total scores were 23.39 (SD 7.88) for active and 27.50 (SD 8.08) for sham at week 4, and 25.52 (SD 7.84) and 29.11 (SD 7.79) at week 5.

    “Week 4 mean (SD) scores for active vs. sham groups were 23.39 (7.88) and 27.50 (8.08) respectively; with week 5 scores of 25.52 (7.84) and 29.11 (7.79).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    ADHD-RS total scores improved in both groups over the first week, with greater improvement in the active TNS group.

    “The significant main effect of time (F = 39.97, df = 1/228, p < .0001) revealed initial improvement in both groups, greater with active TNS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MASC Child Report, CDRS-R, BRIEF, remaining CSHQ scales, teacher Conners, and ARI scales showed no significant effects.

    “Other behavioral outcomes, including the MASC Child Report, CDRS-R, BRIEF, remaining CSHQ scales, teacher Conners, and ARI scales were not significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    CGI-I improvement rates in the active group increased from 25% at week 1 to 52% at week 4, compared with 13% to 14% in sham, with a non-significant trend for increasing improvement over time (chi-square=5.08, df=3/168, p=.17).

    “Improvement rates for active vs. sham were 25% vs. 13%, 34% vs. 15%, 47% vs. 12%, and 52% vs. 14% based on raw CGI-I at weeks 1, 2, 3, and 4 respectively, with a trend for increasing improvement with active TNS over time (X2 = 5.08, df = 3/168, p = .17).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After week 1, ADHD-RS improvement leveled off equally in both groups, with no group-by-time2 interaction.

    “Time2 also demonstrated a significant effect (F = 28.96, df = 1/228, p < .0001), but no group-by-time2 interaction, indicating an equal leveling-off of improvement following week 1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Significant group-by-time effects on qEEG spectral power were found in right frontal (F4 delta, theta, beta, gamma) and frontal midline (Fz gamma) channels, with trend-level effects in mid-frontal (Fz delta, theta, beta).

    “reveal significant group-by-time effects for frequency bands in the right frontal (F4 delta, theta, beta, gamma) and frontal midline (Fz gamma) channels, with trend level effects for frequency bands in the mid-frontal region (Fz delta, theta, beta).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Left frontal (F3) qEEG effects were generally in the same direction but not significant (all p>0.2).

    “Left frontal region (F3) effects were generally in the same direction but did not reach significance (all p’s > 0.2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The observed pulse increases with active TNS were statistically significant but not clinically abnormal and not associated with clinical symptoms.

    “Pulse increases in this study, while statistically significant, were not within a clinically abnormal range and were not associated with clinical symptoms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There were no serious adverse events in either group and no participant withdrew because of adverse events.

    “There were no serious adverse events in either group and no participant withdrew for adverse events.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Skin discoloration resolved with subsequent sun exposure and time.

    “Skin discoloration resolved with subsequent sun exposure and time.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Active TNS increased broadband resting-state qEEG power in the right frontal region, while sham decreased it.

    “With resting state qEEG, active TNS demonstrated increased broadband power, whereas sham exhibit decreased power in the right frontal region (Figure 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Parent-reported MASC showed trend-level time and group-by-time effects (F=3.58, df=1/53, p=.06; F=2.90, df=1/53, p=.09) with estimated Cohen's d=0.33.

    “The MASC-Parent Report showed trends for time (F = 3.58. df = 1/53, p = .06) and group-by-time (F = 2.90, df 1/53, p = .09) effects, with estimated Cohen’s d =.33.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Skin whitening/discoloration under the patch site occurred in some darker-skinned participants in both active and sham groups and was attributed to patch removal and loss of superficial skin layers.

    “One initially concerning adverse event, skin whitening/discoloration under the patch site in some darker skinned participants, occurred in active and sham groups and was attributed to patch removal and concomitant loss of superficial skin layers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Side Effects Rating Scale responses showed notable increases in fatigue, headache, and increased appetite with active TNS, and increased hyperactivity with sham.

    “Side Effects Rating Scale responses are summarized in Table 3, with notable increases in fatigue, headache, and increased appetite with active TNS, and increased hyperactivity with sham.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Parent-completed Conners ratings showed a similar piecewise linear trajectory over time but no group or group-by-time effects.

    “A similar piecewise linear trajectory, but no group or interactive effects, was seen with the parent-completed Conners.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Correlations between spectral power changes and inattentive symptoms were weaker and none were statistically significant (all p>0.13).

    “Spectral power changes had weaker correlations with inattentive symptoms and none were statistically significant (all p’s > 0.13).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Central and parietal electrodes showed no significant group, time, or group-by-time effects (all p>0.2).

    “No significant group, time, or group-by-time effects were seen in central or parietal electrodes (all p’s > 0.2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Headache and fatigue were associated with active TNS, but no participant discontinued treatment because of side effects.

    “While reports of headache and fatigue were associated with active TNS, no one abandoned treatment due to side effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    CSHQ Bedtime Resistance, Sleep Anxiety, and Total Sleep Problems showed significant time and time2 effects but no group-by-time interactions.

    “The CSHQ revealed significant time and time2 effects, but no group-by-time interactions, for Bedtime Resistance, Sleep Anxiety, and Total Sleep Problems.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    TNS is well tolerated and poses minimal risk in children with ADHD.

    “TNS is well-tolerated and minimal risk.”
    • Also stated in: § DISCUSSION · boosted
      “As with previous reports, results confirm that TNS carries minimal risk and is well tolerated and accepted by ADHD-affected children and their parents.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] McGough, 2015, An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulant in youth with attention-deficit/hyperactivity disorder, Brain Stimul source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Parent Conners ratings showed significant time effects in both groups but no group-by-treatment differences, likely due to placebo response among all raters.

    “In contrast, parent Conners ratings have significant time effects in both groups, but no group-by-treatment differences, likely due to some placebo response among all raters.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    TNS is extremely well tolerated in adults and virtually without adverse events.

    “Finally, TNS is extremely well tolerated in adults and virtually without adverse events, suggesting suitability for pediatric testing.16”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] DeGiorgio, 2011, Trigeminal nerve stimulation: seminal animal and human studies for epilepsy and depression, Neurosurg Clin North Am source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Further improvement over subsequent weeks in the active TNS group suggests emergence of true treatment effects, as shown by clinician-rated ADHD-RS and CGI-I scores.

    “Nonetheless, further improvement over subsequent weeks with active TNS suggests emergence of true treatment effects, demonstrated in both clinician-rated ADHD-RS and CGI-I scores.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The study assessed only acute response over four weeks and does not inform whether additional improvement would accrue with ongoing treatment or whether benefits persist over time.

    “The study assessed acute response to TNS over four weeks. It does not inform on whether additional improvement would accrue with ongoing treatment or whether benefits persist over time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    TNS is known to elicit parasympathetic activity, which is expected to result in pulse decreases or bradycardia.

    “As with the vagus nerve, TNS is known to elicit parasympathetic activity, which is expected to result in pulse decreases or bradycardia.43”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Kumada M, Dampney RA, Reis DJ. The trigeminal depressor response: a novel vasodepressor response originating from the trigeminal system. Brain Res. 177;119:305-326. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prior scalp qEEG studies found increased delta, theta, and beta power at right frontal electrodes during successful stopping in a stop-signal task, suggesting an association between right frontal cortex and inhibitory control.

    “Previous scalp qEEG studies reported increased power in delta, theta, and beta frequency bands at right frontal electrodes with successful stopping within a stop signal task,39, 40 suggesting a significant association between right frontal cortex and inhibitory control.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Huster, 2013, Electroencephalography of response inhibition tasks: functional networks and cognitive contributions, Int J Psychophysiol source

      Not checked in the free run.

    • cites [40] Wagner, 2018, Establishing a right frontal beta signature for stopping active in scalp electroencephalography: implications for testing inhibitory control in other task contexts, J Cognitive Neuroscience source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Active and sham groups did not differ significantly at baseline on age, sex, race/ethnicity, height, weight, vital signs, IQ, ADHD subtype, or baseline behavioral ratings.

    “No significant group differences were found for age, sex, race/ethnicity, height, weight, vital signs, IQ, ADHD subtype, or baseline behavioral ratings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    Dependent variables were normally distributed and sphericity assumptions were not violated.

    “Initial analyses demonstrated that dependent variables were normally distributed and that assumptions of sphericity were not violated.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Participants were randomized 1:1 to active or sham TNS using random block lengths of four and six, stratified by parent ARI score.

    “Randomization was 1:1, using random block lengths of four and six, to active or sham TNS, with equal stratification on low (≤ 6) or high parent ARI scores to assess potential effects on irritability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The trigeminal nerve projects to brainstem regions including the locus coeruleus, reticular activating system, and nucleus tractus solitarius, which are involved in selective attention.

    “Similar to the vagus nerve, the trigeminal conveys sensory inputs from skin, muscles, and skull to extensive connections within the locus coeruleus, reticular activating system, and nucleus tractus solitarius,12 regions involved in selective maintenance of attention.13”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Nolte, 1999

      Not checked in the free run.

    • cites [13] Peterson, 2012, The attention system of the human brain: 20 years after, Annu Rev Neurosci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Blinding integrity was assessed with the Early Impressions Questionnaire completed by parents after the first treatment week.

    “To assess study blinding effectiveness, parents completed an Early Impressions Questionnaire25 after the initial treatment week to quantify expectations of success with their assigned condition.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Devilly, 2000, Psychometric properties of the credibility/expectancy questionnaire, J Beh Ther Exp Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    The trial was double-blind and sham-controlled.

    “The study was a four-week, double-blind, sham-controlled trial, followed by one blinded week without intervention.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In an earlier open-label trial in ADHD-diagnosed youth, TNS was associated with substantial reductions in parent- and clinician-rated ADHD symptoms and improvements in executive functioning and response inhibition.

    “A preliminary open trial in ADHD-diagnosed youth suggested TNS was 1) readily accepted by parents and children; 2) associated with substantial reductions in parent and clinician ADHD symptom ratings and significant improvements on multiple indices of parent-reported executive functioning; and, 3) associated with dramatic improvements in laboratory measures of response inhibition.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] McGough, 2015, An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulant in youth with attention-deficit/hyperactivity disorder, Brain Stimul source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    One sham participant discontinued after week 3, and one participant in each group withdrew between weeks 4 and 5.

    “One participant randomized to sham left the trial after week 3. One additional participant in each group withdrew between weeks 4 and 5.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The estimated week-5 Cohen's d was 0.46, suggesting maintenance of a medium-size treatment effect one week after treatment cessation.

    “Cohen’s d at Week 5 =.46, suggesting maintenance of a medium-size treatment effect one week after treatment cessation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    TNS is efficacious and safe for ADHD treatment, confirming and expanding previous open-label findings.

    “This study demonstrated the efficacy and safety of TNS in ADHD treatment, confirming and expanding previous open-label findings.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] McGough, 2015, An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulant in youth with attention-deficit/hyperactivity disorder, Brain Stimul source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TNS is a non-invasive, minimal-risk neuromodulation method approved in Canada and Europe for treating medication-resistant major depression and epilepsy in adults.

    “Trigeminal nerve stimulation (TNS) is a non-invasive, minimal risk neuromodulation method approved in Canada and Europe for adult treatment of medication-resistant major depression,9, 10 and epilepsy.11”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Schrader, 2011, Trigeminal nerve stimulation in major depressive disorder: first proof of concept in an open pilot trial, Epilepsy Behav source

      Not checked in the free run.

    • cites [10] Cook, 2016, Trigeminal nerve stimulation for comorbid posttraumatic stress disorder and major depressive disorder, Neuromodulation source

      Not checked in the free run.

    • cites [11] Cook, 2015, The potential use of trigeminal nerve stimulation in the treatment of epilepsy, Ther Deliv source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The greatest TNS-related improvement in ADHD-RS scores occurs during the first week, with additional improvement accruing with continued use.

    “ADHD-RS response patterns suggest that the greatest degree of TNS-related improvement occurs during the first week, with additional improvement accruing with ongoing use.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    qEEG data from 3 participants were excluded for excessive movement artifact, leaving 56 participants for EEG analyses.

    “qEEG data for 3 participants were excluded due to excessive movement artifact; leaving a total of 56 participants (active n=30; sham n=26) for EEG analyses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Parents in the study might have been biased toward non-medication approaches, but this view is common among parents seeking ADHD treatment.

    “There might have been some bias toward non-medication approaches to ADHD management by parents of study participants, but this view is common among many parents seeking ADHD treatment for their children.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    The results should be widely generalizable, though replication in additional patient groups would strengthen support for TNS.

    “As such, results from this study should be widely generalizable, but support for TNS would be strengthened if replicated in additional patient groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    TNS is a non-medication, minimal-risk intervention with proven efficacy in reducing ADHD symptoms.

    “TNS is a non-medication minimal risk intervention with proven efficacy in reducing ADHD symptoms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The quality of evidence for TNS exceeds that available for many commercially available complementary interventions.

    “The quality of evidence for TNS exceeds that which is available for many commercially available complementary interventions.”
    Quote in the paperNot a substantial claim
48 of 48

  • The authors state this as an assumption.

    Benefits of vagal nerve stimulation rely in part on the same brain connections as trigeminal nerve stimulation.

    “Assuming that benefits of vagal stimulation rely in part on the same brain connections, it was hypothesized that TNS similarly improve seizures and mood, but without costs and risks associated with surgical device implantation.”

  • The paper relies on this without support.

    This is the first blinded sham-controlled trial of TNS for ADHD or any pediatric condition.

    “This is the first blinded sham-controlled trial of TNS for ADHD or any pediatric condition.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Week 5 effect is below the paper's medium-effect cutoff

    Minor

    The paper defines .5 as the cutoff for a medium Cohen's d, but calls the week 5 value of .46 medium-sized.

1 of 1

Cites

Flagged first, then by citations

1 of the 47 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Weaver, 2012, Transcranial magnetic stimulation (TMS) in the treatment of attention-deficit/hyperactivity disorder, J ECT, 28, 98

Cited by

Sorted by citations

Related

Authors
McGough, J. J., Sturm, A., Cowen, J., Tung, K., Salgari, G. C., Leuchter, A. F., Cook, I. A., Sugar, C. A., & Loo, S. K.
Affiliations
University of California, Los Angeles (US)
Corresponding author
McGough, James J.
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2019-04
Volume
58
Issue
4
Pages
403-411.e3
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2018.11.013
PMC
PMC6481187
OpenAlex
W2914647410
Semantic Scholar
8d6d8f15fe2c3b0e48ab4ffd88fafca077c02746
Cited by
131
References
47
Citations by year
2026: 14 · 2025: 20 · 2024: 21 · 2023: 23 · 2022: 15 · 2021: 18 · 2020: 12 · 2019: 7
FWCI
10.36
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institute of Mental Health (R34MH101282)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
Keywords
trigeminal nerve stimulation, attention deficit hyperactivity disorder, non-invasive neuromodulation, children, quantitative EEG, treatment efficacy, treatment safety
MeSH terms
Attention Deficit Disorder with Hyperactivity, Child, Double-Blind Method, Electric Stimulation Therapy, Female, Humans, Male, Pilot Projects, Psychiatric Status Rating Scales, Trigeminal Nerve, United States, Logistic Models, Treatment Outcome, Executive Function

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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