EEG-Based Biomarker May Improve ADHD Diagnosis

Liam Davenport

March 16, 2015

Adding an electroencephalography (EEG)-based biomarker to standard clinician judgement may improve the accuracy of the diagnosis of attention-deficit/hyperactivity disorder (ADHD) and reduce the likelihood of overdiagnosis, new research suggests.

The Neuropsychiatric EEG-Based Assessment Aid (NEBA) System uses electroencephalography to measure beta and theta waves. Previous studies have shown that the theta/beta ratio is increased in children and adolescents with ADHD.

The research was by led NEBA Health, the company behind the system. It showed that adding the EEG test to standard clinical assessment raised the accuracy of ADHD diagnosis to that of a multidisciplinary team (MDT) and reduced the proportion of overdiagnoses by more than a third.

"Our multidisciplinary results showed ADHD may be overdiagnosed in the clinic as much as one third of the time," Steven Snyder, PhD, head of research at NEBA Health, said in a release. "And NEBA separately identified most of those cases."

"Integrating the NEBA biomarker with a clinician's regular evaluation can bring the diagnosis more in line with that of a multidisciplinary team."

The article was published online March 5 in Brain and Behavior.

Added Value

In both the DSM-IV and the DSM-5, ADHD is characterized by developmentally inappropriate attentional and behavioral symptoms, as set out in a series of criteria.

Criterion E requires that the symptoms are not better explained by another disorder in which the symptoms are present, which can complicate ADHD evaluation and necessitate a comprehensive evaluation.

To aid in the differentiation of ADHD and non-ADHD cases and lessen criterion E uncertainty, Dr Snyder and colleagues integrated the EEG biomarker with a clinician's regular evaluation.

In a 13-site prospective clinical cohort study, the team obtained comprehensive clinical evaluation data on 275 children and adolescents presenting with attentional and behavioral concerns.

At each site, a qualified clinician performed a differential diagnosis. EEG data were collected at a different site. The reference standard was assessment by an MDT, consisting of a psychiatrist, a psychologist, and a neurodevelopmental pediatrician.

In all, 209 children were deemed to have met the criteria for ADHD by the individual clinician. However, the MDT judged that 93 children were less likely to have met criterion E, suggesting a potential overdiagnosis of 34%.

Of those 93 children, 85 (91%) were also identified on EEG as being less likely to meet criterion E, because they had a lower beta/theta ratio.

Furthermore, integrating clinician judgement with EEG measurement in the 36 cases identified by the clinician as being uncertain led to agreement with the judgement of the MDT in 97% of children.

The team also found that integrating EEG measurement with clinician judgement improved the accuracy of the clinician's ADHD evaluation, increasing it from 61% to 88% in patients with a relatively lower theta/beta ratio.

ADHD Diagnosis Challenging

Speaking to Medscape Medical News, Dr Snyder discussed the findings alongside Howard Merry, president/sales leader of NEBA Health.

Dr Synder explained that the utility of the test is in helping to identify children who are more likely to have symptoms due to conditions other than ADHD.

"We point out, 'Okay, this child is more likely to have another condition. Here are the other conditions we saw in a study and the probability they might be present with this outcome,' " he said. " 'Now, using your clinical judgement, please consider these other conditions before you proceed.' "

Asked whether he was surprised at the level of misdiagnosis that the study results suggested, Dr Snyder replied: "I was actually a little nervous by it because I knew that it was such a strong result that some people would have a strong reaction to it, and it might overshadow the goal of the study, which was just to show that we added some value."

However, noting that the study was triple-blinded, he said: "Once the study was initiated, I was blinded of the run of the study until independent parties had compiled the database.... It was tightly controlled, blinded, with regulatory standard–type bias controls, and so the evidence is what it is."

Dr Snyder said that the findings "imply that it is a challenge to determine criterion E in many cases and that a rigorous-type evaluation differential diagnosis may be necessary for some of those cases."

Although the NEBA test is designed to point out cases that need further evaluation, Dr Snyder conceded: "It's not always feasible by cost or time to apply a rigorous evaluation for all patients."

"That's the case at least in the US, where, for instance, pediatricians perform a lot of the evaluations, and they're limited in the time that they have available for each patient."

FDA Clearance: What It Means

Commenting on the findings for Medscape Medical News, Stephen V. Faraone, PhD, from the State University of New York Upstate Medical University, in Syracuse, who was not involved in the research, said that although the study was "very well designed" and that the results were reliable, it is "worth considering what they mean."

"They chose a very interesting paradigm for evaluating the utility of their biomarker, and it's important that readers understand what they are doing here.

"They are not saying that they have a method that can diagnose ADHD. What they are saying is that when you have a situation where ADHD is suspected but there's a potential that there may be a wrong diagnosis because there are some other conditions that could cloud the diagnosis, then their method can be useful for that purpose."

One area of concern that Dr Faraone had about the study was in the interpretation of criterion E. He said that the EEG-based test was good at differentiating between ADHD and other conditions, but one of the issues in psychiatry is that ADHD frequently co-occurs with aggression.

"So it doesn't mean that these children don't have a treatable ADHD condition, it just means that their ADHD is complicated with aggression," he explained.

Consequently, it could be that in some of the cases in which clinicians diagnosed ADHD but the gold standard deemed that ADHD was not present, ADHD was, in fact, the secondary diagnosis and, therefore, treatable.

The other "big picture" aspect of the study that Dr Faraone highlighted was that of the test receiving FDA clearance.

"I think it's great to see that there are well-defined studies that are trying to get FDA clearance for the use of their methods by doctors and psychologists and mental health workers," he said.

However, he added: "The people who are reading about this have to understand that FDA clearance doesn't mean that it's an FDA stamp saying that this is something they have to use and it is the best method to use. It's a more broad clearance that people are saying it's not harmful, it's got some utility in the population."

Underdiagnosis Also a Problem

Finally, Dr Faraone discussed the issue of misdiagnosis in ADHD. He said that although misdiagnosis is very important, the question remains: "How big is the problem?"

He believes that the problem of overdiagnosis has been exaggerated in the media and that the issue of underdiagnosis is just as important and, potentially, just as prevalent.

"It's really interesting that the people who tend to talk about overdiagnosis never talk about underdiagnosis. They don't talk about the risks and benefits that doctors are weighing when they are making a diagnosis," said Dr Faraone.

"For example, we know from a lot of studies that...most people are untreated for many years, which is actually underdiagnosis."

"That kind of underdiagnosis is rarely talked about in the media, yet the implications are dramatic for kids in terms of health ― the way they function in school, how they develop peer relationships, their risk of substance abuse, and so forth," he added.

In contrast, overdiagnosis receives more attention because "it's all tied into concerns about overtreatment with medication and, again, exaggeration about the potential adverse effects of medications."

"When overdiagnosis occurs, in many cases it occurs in the sense of a doctor doing what's best practice, doing the best they can, given the ambiguous nature of the clinical presentation."

Dr Faraone noted that if ADHD medication does not work in ambiguous cases, it can simply be stopped.

"The overdiagnosis issue is not discussed in any nuanced way in terms of a lot of media reports, unfortunately."

"I really wish people would talk about the balance between the pros and cons...and what the risk and benefits are. It would really help parents a lot, because the parents get scared, and they don't take the kids for treatment, which is a shame."

The study was supported by a federal grant from the Therapeutic Discovery Project and by NEBA Health. Dr Snyder reports that he is employed by, owns stock shares with, and is board member at NEBA Health. The financial relationships of the other authors are listed in the original article. Dr Faraone reports no relevant financial relationships.

Brain Behav. Published online March 5, 2015. Full text

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