The first-of-a-kind brain-stimulation device approved to treat attention-deficit/hyperactivity disorder (ADHD) in the US has had its efficacy questioned, with scientists believing that its Food and Drug Administration (US) approval was based on too small a study.
Researchers are working hard to find non-invasive, drug-free ways to treat conditions such as ADHD and major depressive disorder (MDD), and there have been a lot of promising studies on experimental therapies. However, these new brain-stimulation devices don't have a lot of data behind them.
This is what scientists at Kings College London, in collaboration with researchers at the University of Southampton, found when reviewing the prescription-only external Trigeminal Nerve Stimulation (TNS) System that was approved in 2019 by the FDA. The maker, Monarch, got federal approval following a trial involving 62 children with ADHD using the device every night for eight hours over a period of one month.
The issue is, the researchers say, is that the study's experimental design was faulty – a control group involved no stimulation, preventing blinding and raising the chances of the placebo effect in those who did use the device.
Now, in a larger, multicenter study featuring 150 children and adolescents with ADHD, aged between eight and 18, the scientists tested the device using a different approach. The kids and teens wore the TNS for nine hours at night for four weeks – which involved connecting battery-powered electrodes to the forehead – except half of the cohort received the Monarch treatment and the remaining participants received just 30 seconds of stimulation every hour at a lower frequency and pulse width. This is thought to be ineffective and therefore met the criteria of experimental control.
"This multicenter trial was designed to address key limitations of the previous pilot study that informed FDA clearance of TNS for ADHD, particularly by using a rigorously controlled sham condition that supported successful blinding across the treatment period," said Dr. Aldo Conti, postdoctoral researcher at King’s College London and first author on the study. "Unlike the earlier study, which was limited to younger children, we also included adolescents, a clinically important group given well-documented challenges with long-term medication adherence. These design choices enabled a more robust and clinically relevant evaluation of TNS.”
What they found was that the device was safe to use but provided no significant relief of symptoms in the group receiving the treatment, compared with the short-stimulation cohort. The symptoms they assessed were broad but typical ADHD ones, including mind-wandering and attention, depression and anxiety, and sleep quality.
The researchers say that the study underlines the importance of robust scientific trials before treatments are approved for public use. Because while the device was deemed safe and was considered by users as fairly easy to use, it may not live up to the promise with which it gained approval.
"Rigorous evidence, such as that generated by this study, is essential for supporting shared decision-making regarding interventions for ADHD," said Professor Samuele Cortese, the study lead for the Southampton site. "It empowers individuals with ADHD and their families to make informed choices about the treatment of ADHD. Clinicians, individuals with ADHD, and their families need to know which treatments work, and which do not based on the best evidence."
Existing evidence has highlighted that stimulating the TNS, thought to activate regions associated with attention like the frontal and thalamic areas via the brainstem, could be an alternative to using stimulants to treat ADHD. However, the research is still in its early stages with wide-ranging results. And eliminating the placebo effect in clinical trials is crucial.
"Our study shows how important it is to design an appropriate placebo condition in clinical trials of brain therapies," said Professor Katya Rubia, Professor of Cognitive Neuroscience at King’s College London. "There is a large placebo effect with high-tech brain therapies, in particular for patients and families that have an expectation that they can adjust brain differences associated with ADHD. It is hence paramount to control for placebo effects in modern brain therapies to avoid false hopes."
The research was published in the journal Nature Medicine.
Source: Kings College London
