CHICAGO ― Trigeminal nerve stimulation (TNS) is safe and effective in alleviating symptoms of attention-deficit/hyperactivity disorder (ADHD) in children, a new study suggests.
In the blinded, sham-controlled trial, which was funded by the National Institutes of Health, use of TNS resulted in an estimated treatment effect comparable to that of nonstimulant medications. The investigators note that additional research is necessary to determine the durability of treatment response, as well as the potential impact of sustained TNS on brain development.
“As far as I know, this is the first sham-controlled study of neuromodulation in youth, and the first study that showed positive results from a minimal-risk neuromodulation technique,” said James J. McGough, MD, of the Ronald Reagan UCLA Medical Center in Los Angeles, California.
“Patients’ ADHD symptoms improved to about the same degree that we see with nonstimulant medications, and those improvements actually correlated with positive changes in spectral power as well,” he added.
The findings were presented here at the American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting.
“Robust and Wonderful Finding”
TNS is a noninvasive neuromodulation technique that poses minimal risk to patients. Although the technology has not been subject to much research in children with ADHD, a previous unblinded, open study showed its potential benefit in this population.
TNS may prove to be a welcome addition to current treatment options in childhood ADHD, McGough noted.
“Our current approach to ADHD predominantly relies on medication. Acutely, we do pretty well. But medications also have their problems, such as side effects,” he said.
“More importantly, no parent wants to hear that they have to give their child a pill every day. This has really led to an ongoing interest in developing nonmedication, low-risk therapies to treat the disorder,” he added.
To gain more insight into the potential efficacy of TNS in this population, the investigators enrolled 62 children aged 8 to 12 years with ADHD into the study. ADHD was diagnosed on the basis of results of the Kiddie Schedule for Affective Disorders and Schizophrenia interview. All the participants had full-scale IQ scores of 85. They were randomly assigned to receive 4 weeks of nightly treatment with either active or sham TNS, after which 1 week passed without intervention.
The children underwent weekly assessments with the clinician-administered ADHD Rating Scale (ADHD-RS) and the Clinical Global Impression (CGI) scale. Resting-state quantitative electroencephalography was performed at baseline and at week 4.
The results were promising. Investigators found that ADHD-RS total scores indicated significant group-by-time interactions at week 4 (F = 8.12; df = 1/228; P = .005).
“Interestingly, we saw a parallel decline in symptoms in both the sham and active groups in the first week. But after that, there was a separation of symptoms: while the sham group flattened out, the active group actually continued improvement over the course of the 4 weeks,” said McGough.
He noted that at the end of the fourth week, the Cohen’s effect size value was 0.5, which is about the same effect that is seen with nonstimulant medications in ADHD.
In the fifth week of the study ― after treatment had been stopped ― there was a parallel deterioration of symptoms in both groups. Nevertheless, the Cohen’s effect size at week 5 remained approximately 0.5.
“This suggests that even a week after cessation of therapy, there is still a positive effect on ADHD in the TNS group,” McGough said.
The investigators also found that improvement in CGI favored the active-treatment group (X2 = 8.75; df = 1/168; P = .003). The number needed to treat was three.
“We saw a stable placebo response in the sham group but increasing responses over time in the active group, suggesting that with ongoing stimulation there may be an increase of effect,” he said.
Similarly, resting-state quantitative electroencephalography demonstrated increased spectral power in the right frontal and frontal midline frequency bands with active TNS.
“I think this suggests that what we’re measuring here isn’t simply a subjective placebo effect. We’re actually showing with a biological test that there were differences between the two groups,” McGough said.
No meaningful adverse events occurred in either group.
A First Step
“These researchers took on the disorder that child psychiatrists feel most comfortable diagnosing and treating, yet silently admit that they really don’t know how to diagnose and treat it,” said Jim Hudziak, MD, of the University of Vermont in Burlington. “But because it’s our hallmark disorder, we need to continue to develop our expertise in this area.
“And that’s just what Dr McGough and his colleagues have done. They continue to build on this vision quest to figure out how we can help the children who suffer with this most common condition,” he added.
McGough noted that this study is only a first step in a lengthy research chain.
“Certainly this work should be replicated in larger samples and at multiple sites,” he concluded. “And very importantly, we need to have a better understanding of who is going to respond to this and what the long-term effects might be,” he said.
J Am Acad Child Adolesc Psychiatry. 2019;58:S125. Abstract
American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting: Abstract 1.2, presented October 17, 2019.