Spotlight on Neurostimulation for ADHD

Stimulant and nonstimulant medications have improved symptoms for many individuals with attention-deficit/hyperactivity disorder (ADHD). However, some patients show an inadequate response to these treatment strategies, while others have contraindications or experience prohibitive side effects with the use of such therapies. In recent years, neurostimulation techniques have emerged as a potential nondrug treatment option for pediatric and adult patients with ADHD.¹

“We do not yet have solid evidence that neuromodulation works well for ADHD symptoms, although initial findings look promising,” according to Soonjo Hwang, MD, a child and adolescent psychiatrist and research director in the department of psychiatry at the University of Nebraska Medical Center in Omaha. He points to a 2019 review article that examined 30 studies focused on neurostimulation for ADHD.² “Although some of studies reported improvement of symptoms, most had small sample sizes — less than 30 patients per study — and lacked standardized methods so far,” he said.

Sandra Loo, PhD, professor-in-residence in the division of child psychiatry and director of pediatric neuropsychology training at the David Geffen School of Medicine at the University of California, Los Angeles, agrees that findings on the topic are largely inconclusive to date. She told us, “current research suggests that 2 types of neurostimulation have demonstrated efficacy in reducing ADHD symptoms in people diagnosed with ADHD,” including transcranial direct current stimulation and external trigeminal nerve stimulation.

“Both types of neurostimulation are thought to affect brain functioning in areas that are thought to play a role in ADHD symptomatology, such as the frontal lobes,” she said.  These 2 approaches were the focus of recently published randomized controlled trials (RCTs).

Transcranial Direct Current Stimulation (tDCS)

In a study described in 2022 in JAMA Psychiatry, Leffa et al conducted a randomized, double-blind, parallel, sham-controlled trial to evaluate the safety and efficacy of home-based tDCS treatment (30 minutes per day for 4 weeks) for inattention symptoms in adult patients (mean age, 38.3 years; 47% women) with ADHD.³

Participants were randomly assigned to an active tDCS treatment group or a sham tDCS group. Individuals receiving stimulant drug treatment for ADHD and those with comorbid psychiatric disorders were excluded from the study. The primary outcome was the mean inattention score on the clinician-administered version of the Adult ADHD Self-report Scale version 1.1 (CASRS-I).³

Among the 55 patients who completed the trial, the active treatment group showed a mean inattention score of 18.88 (SD, 5.79) on the CASRS-I after 4 weeks, compared to 23.63 (SD, 3.97) in the sham group. Further analyses revealed a significant treatment by time interaction for CASRS-I (β interaction=-3.18; 95% CI, -4.60 to -1.75; P <.001), indicating symptom reduction in the treatment vs sham group across 3 assessments.³

The treatment group experienced a greater number of mild adverse events such as skin redness and scalp burn.³

The authors concluded that home-based tDCS could ultimately represent a nonpharmacological treatment alternative for individuals with ADHD.³ “However, a similar study in adolescent males with ADHD did not show any effect on ADHD symptoms, so the results are somewhat mixed at this point,” Dr Loo said.⁴

Trigeminal Nerve Stimulation (TNS)

In 2019, a TNS device received approval from the US Food and Drug Administration as a prescription-based treatment of ADHD in children ages 7-12 years.^5,6 In a double-blind, sham-controlled pilot study published in 2019, Loo and colleagues investigated the effects of 4 weeks of nightly treatment with TNS in children ages 8-12 years with ADHD. After undergoing training on the use of the TNS device, parents administered TNS each night as participants slept.⁷

The results demonstrated reductions in both inattentive and hyperactive-impulsive symptoms after TNS, based on scores on clinician-administered ADHD-Rating Scales (ADHD-RS) and Clinical Global Impression (CGI) scales. “Approximately 50% of these children showed significant improvement in ADHD-related impairment with TNS,” Dr Loo stated.⁷

She and her co-authors reported that the medium-sized treatment effect size observed with TNS at 4 weeks was similar to that observed with nonstimulant ADHD medications. They are continuing their investigation of TNS for pediatric ADHD in ongoing trials (NCT05374187).⁸

Dr Loo notes that TNS has not yet been evaluated for ADHD treatment in adolescents or adults.

Clinical Considerations

Dr Hwang says it is difficult to recommend which ADHD patients might be most appropriate for neurostimulation or how to gauge treatment response because “at this point, there is no definitive treatment regimen or well-established treatment modality” for this approach.

Dr Loo explains that “TNS may be desirable for families that do not want to try ADHD medications or for individuals who have adverse side effects to medications,” and adds that many families also prefer the ability to administer the treatment at home.

“Clinicians should seek more information about the benefits and risks of neurostimulation treatments before referring patients for this treatment,” she advised. When TNS is indicated, patients should be referred to clinicians with experience using this approach. “While there are virtually no risks or adverse side effects with TNS treatment, parents tend to have many questions that should be answered knowledgably.”

In a follow-up study of secondary outcomes from their pediatric TNS trial, Loo et al found evidence suggesting that scores on certain subscales of the parent-completed Behavioral Rating Inventory of Executive Function (BRIEF), especially the Working Memory scale, may be modest predictors of TNS response. This finding will be further explored in ongoing studies.⁹

Meanwhile, to monitor treatment response with any approach, she recommends that providers use “weekly clinical interview and behavior ratings to document whether there are improvements in ADHD symptoms and related behaviors with treatment, whether it is medication or nonmedication strategies such as neurostimulation.”

Ongoing Needs

Among remaining gaps in the study of neurostimulation, there is a need for “clinical trials with larger sample sizes, standardized methods and treatment parameters, and objective outcome measures,” Dr Hwang stated. “There is still a long way to go before we can reliably deliver this treatment strategy for patients with ADHD.”

Dr Loo said there is a particular need to explore the effects of neurostimulation in populations and settings that have not previously been tested, such as patients with comorbid psychiatric diagnoses and in combination with pharmacologic ADHD therapies.

Information and education represent other pressing needs in the realm of neurostimulation for this patient population, she added. “Clinicians who work with individuals with ADHD should seek continuing education regarding this new nonmedication treatment for ADHD. This is a rapidly evolving area!”