King's College London

To test whether a home-based medical device called Trigeminal Nerve Stimulation (TNS) could be used as a treatment to reduce the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) in children and adolescents when used at home for 4 weeks during the night compared to a placebo (sham or fake) stimulation.

Also, to test longer-term effects on symptoms after 6 m, effects on other clinical features like depression and anxiety, on cognitive performance, on physiological measures (like arousal and heart rate) and to test the effect on the brain.

Background

ADHD affects ~7% of children and many continue to have ADHD as adults. The most common symptoms are hyperactivity/impulsiveness and/or inattention. Stimulant medication is the most effective treatment but does not cure it. There are many side effects with medication, and it cannot be taken with some other health conditions. About half of adolescents with ADHD stop taking medication. Furthermore, there is no evidence that medications work longer-term and they could potentially pose a substance abuse risk. Many children and parents therefore prefer non-drug treatments which have less side effects.

Treatments like neurofeedback, diet, cognitive training, and exercise, however, have minimal or no effects. Brain stimulation could be an effective new treatment for ADHD. Many brain stimulations are done at a clinic, but a home-based treatment is cheaper and can reach a wider group of children with ADHD that cannot attend clinic regularly.

The TNS device stimulates a nerve called the trigeminal nerve. A patch is placed on the child’s forehead which connects to the battery-operated device via two cables. The device is using during the night. This device is the first device based non-medication treatment that has been cleared for ADHD. This is because a small pilot study in the USA found that it was safe and effective in reducing symptoms of ADHD in children aged 8-12 years old, who had never used medication. Based on this study, the device had clearance by US Food and Drug Administration (FDA) in 2019. This means that it can be prescribed as a treatment for ADHD in the USA. However, this study was very small, and we wanted to test whether this device works on a larger group of children and adolescents with ADHD.

To test the TNS in a larger sample of 150 children and adolescents with ADHD aged between 8 and 18 years old. Some were on stable ADHD medication; others had tried and stopped ADHD medication and others had never tried any form of medication. Recruitment took place across the wider areas around London and Southampton. The children and adolescents with ADHD were randomised “like flipping a coin” to either receive the real (TNS) treatment or the placebo “sham or fake” treatment. Children, parents and researchers did not know which treatment each child received.

The treatment was used for four weeks during the night for about 8-9 hrs. The real TNS provided stimulation for 30s on and 30s off continuously throughout the night (4 hours of stimulation in total). The sham TNS provided 30s stimulation and was then switched off each hour throughout the night at a lower frequency. The nightly setting was set each night by either the parent or child. The child was told to set the device so that he/she would feel it but it should not be painful.

We tested whether TNS:

• improved ADHD symptoms (main outcome)
• improved anxiety, depression, mind wandering and sleep
• improved an objective measure of hyperactivity using a fitbit kind of device
• was safe
• improved cognitive performance in a range of tests where children with ADHD usually underperform, such as measures of attention and self-control
• increased bodily measures like arousal and heart rate
• increased brain activation (optional MRI scans)
• worked over a prolonged time, 6 months after treatment

Both the children and adolescents and their parents were asked to fill in lots of questionnaires about the children's ADHD behaviour, sleep, depression, anxiety, and mind-wandering. Participants also performed computer tests and for some tests an eye tracker was used to measure arousal. At the research centre, the children and adolescents wore a “fitbit” like device to measure their movements.

The families were seen in-person on four separate occasions at the research centre. Some assessments were also done online.

Participants were recruited from CAMHS and private clinics, national and local parent support groups, NHS Consent for Contact (C4C), GPs, schools and social media.

The recruitment took place from September 2022 to November 2024.

Eligibility criteria

Children and adolescents aged 8 to 18 years old with an ADHD diagnosis (either a clinical diagnosis or a research diagnosis based on clinical questionnaires filled in by parents and children conducted by the research team), severe ADHD symptoms, no intellectual disability, no other major mental health conditions apart from conduct disorder and oppositional defiance disorder, mild anxiety or depression, not taking Atomoxetine or Guanfacine, no alcohol or substance abuse, no neurological abnormalities, dermatitis, not currently having any other non-medication treatments, and no TNS contraindications.

If participants were using stimulant medication, they needed to either stop taking it for a week before the trial and during the 4 weeks of treatment or be on a stable dose and take the medication every day.

Patient and Public Involvement (PPI)

Advice was sought during the grant application stage from parent ADHD Support groups and Young Person’s Mental Health Advisory Group (YPMHAG). The study has been modified based on patient comments on the study design and they have therefore co-designed the study.

A dedicated PPI group was created at the start of the project who advised and guided us throughout the trial. The PPI group has also helped with reviewing documents and ways of disseminating the results.

A total of 150 children and adolescents with ADHD took part in the study and half (75) received the real treatment and the other half (75) the sham treatment. A total of 145 participants remained in the study until the end. Nine participants stopped using the treatment, but some still participated in all assessments at 4 weeks.

Most participants did the treatment over the 4 weeks. The sham (placebo) treatment worked very well, and the children and their parents could not guess which treatment they had received. This is very important as it excludes a placebo effect which might have happened in the USA study were the fake stimulation group got no stimulation from the device at all.

The symptoms of ADHD were measured in a questionnaire called ADHD-RS and there was no difference between the real and the sham group after 4 weeks of treatment. Both groups improved after starting the treatment.

In addition, no differences between the real and sham groups were found relating to anxiety, depression and sleep. This means that the device did not reduce levels of anxiety or depression or improve sleep. There was potentially a very small benefit in mind wandering in the real compared to the sham TNS group after 4 weeks. However, there were concerns that the younger participants did not fully understand the measure and the findings were not significant in the older adolescents who understood the measure.

There were no serious adverse events, and most of the adverse events were minor. Only a few were moderate such as having the flu, food poisoning, ear or chest infection and they did not differ between the real or sham treatment groups. The majority of the side effects related to the device were minor and included mild headaches and sleep problems. In conclusion the device is very safe and has only very minor side effects that go away quickly.

The study also measured cognitive abilities during computer games. These games looked at attention, impulse control and staying focused. No improvement was detected in those who had used the real device compared to those that used the sham device.

There was also no effect on the objective bodily measures. There was no difference between the real and the sham group on the effects on objective hyperactivity or heart rate which were measured by a “fitbit” like device. The eye tracker looking at the pupil diameter for signs of increase in arousal in the participants found no difference between the two groups.

There was also no effect of the real compared to the fake treatment on any of these measures at a 6-month follow-up assessment either.

Additional analysis looking at: only children up to age 12, looking only at non-medicated children or only testing in girls or in boys found no differences.

In summary, while TNS is a very safe and tolerable treatment, the device has no benefit to children and adolescents with ADHD.

Discussion

We think that the reason why we found no effect, while the previous smaller study in the USA found an improvement in ADHD symptoms, is because in the USA study the participants who got the sham treatment, got no stimulation at all and might have noticed that. Therefore, the real treatment group might have had a placebo effect that was not controlled for. This means that in the pilot study participant may have known after a while whether they had been given the sham device. The sham device in this study gave a very low stimulation for 30 seconds every hour. The blinding “masking” was good in this study since participants, and their parents could not guess whether they got the real device or the sham device. In this study therefore there was no placebo effect.

The study shows that it is very important to control for the placebo effect in treatment studies. Also, we know that the placebo effect is larger in studies that use technology that modifies the brain as people think this must work.

Limitations

The response rates from teachers were very low and because of that we could not look at ADHD symptoms in school settings.

Sleep diaries were used to see how many hours a night the device was used. This is a subjective measure, and we can’t be sure how accurate it is. Unfortunately, we could not use an objective measure to actually test how many hours the device was being used.

Conclusion

So, what does this mean for families in the UK or clinicians who are looking for effective ADHD treatments?

First, our findings suggest that TNS should not be used as a treatment for ADHD. Despite being safe, a treatment that does not work offers no real benefit and risks diverting time, money and attention away from interventions that do help.

Second, clinicians and services should be cautious about offering or recommending new technologies without strong independent evidence. Regulatory clearance does not always mean a treatment is effective, it can simply mean it is safe enough to be marketed.

Finally, this study reinforces the importance of continuing to invest in high-quality research. Families deserve treatments that are not just appealing in theory but proven to work in practice.

ADHD is a serious and lifelong condition for many. As diagnoses continue to rise, so too does the responsibility to ensure that care is guided by robust evidence -not hype, hope or premature conclusions.

However, it is a very important finding since our larger study contradicts the findings of improvement in ADHD symptoms in the US pilot study based on which TNS is approved by the FDA. Our findings suggest that this treatment is not worth doing and this knowledge saves the NHS and the parents of children and adolescents with ADHD money and hopes by not investing in purchasing this treatment which does not work. Our findings therefore will have a large impact on the field of TNS research in ADHD as they will influence clinical guidelines such as NICE guidelines.

It is important in research to test whether treatments are effective and finding that a treatment is not working for ADHD is very important for the field.

Our study has therefore been published in a very important and widely read medical journal with one of the highest impacts in the world, called Nature Medicine.

We will keep testing alternative, hopefully better working non-medication treatment options for ADHD.