Liam Davenport

May 29, 2015

GLASGOW, Scotland ― Emotional dysregulation should be considered a core aspect of ADHD because it is commonly seen in patients, including those without comorbidities, and responds to treatment, new research shows.

Presenting data from a study in adult prisoners alongside a review of the literature, Philip Asherson, MD, PhD, professor of molecular psychiatry at King's College London, in the United Kingdom, told delegates attending the 5th World Congress on Attention Deficit Hyperactivity Disorder (ADHD) that although emotional lability is not unique to ADHD, it is a unique source of impairment in these patients.

Consequently, it should always be considered in the diagnosis of patients presenting with chronic emotional or mood instability, said Dr Asherson.

Dr Asherson noted that "traditional" diagnostic criteria for ADHD included emotional lability. However, this domain, which includes mood instability and affective lability, became separated out as clinicians concentrated on hyperactivity, impulsivity, and inattention.

This may not reflect the true picture of ADHD, he continued, because the severity of emotional instability surely contributes to impairments related to home life, occupation, education, criminal activity, driving, and financial outcomes.

To determine whether emotional lability is a "third dimension" of ADHD, however, it would need to be demonstrated that treatment can have an impact on lability, that there are case-control differences in lability, that it demonstrably contributes to impairment, and that it shares genetic factors with the other dimensions.

Better Focus, Improved Mood

In an attempt to answer some of these questions, Dr Asherson launched the CIAO project, which is an open-label study of methylphenidate (multiple brands) in adult offenders with ADHD.

Of 1922 male prisoners aged 18 to 30 years, 19.3% met the DSM-5 criteria for ADHD, and 40% were treated with methylphenidate. For these patients, the dose was up-titrated during a 4-week period and was then maintained at a stable dose for 8 weeks.

During 12 weeks, there were significant improvements on the Inattention/Memory Problems and Hyperactivity/Restlessness subscales of the Conners' Adult ADHD Rating Scales (P < .0001 for both), indicating that treatment was effective.

When the team repeated the assessments using the Emotional Dysregulation Scale of the Wender-Reimherr Interview for Adult ADHD, there were again significant improvements in scores on all domains (P < .0001 for all baseline changes to week 5).

Dr Asherson explained that prisoners were better able to focus and were less restless and that their mood was more stable. This translated into a significant reduction in the total number of critical incidents between baseline and week 12 (P < .001) and a significant increase in the number of positive reports (P < .03).

Further analysis revealed that, even after accounting for changes in inattention and hyperactivity due to treatment, improvements in emotional dysregulation was independently associated with reductions in the number of adjudications against prisoners (P < .0001).

These findings, which were collated in February of this year, have led to the study being refunded and converted to a randomized, controlled trial to examine the effects of methylphenidate on emotional dysregulation.

Confirmatory Findings

Dr Asherson told delegates that his findings reflect those of several previous studies in adults, as well as in children and adolescents. Crucially, there have also been a number of investigations, including twin, genetic, and neurobiological studies, that have demonstrated that emotional lability is a core feature of ADHD.

He nevertheless pointed out that despite the common genetic influences, more work needs to be done to untangle the connection between ADHD and emotional dysregulation, particularly because the latter is not unique to ADHD.

For example, there are two potential models: that the same neural processes lead to both ADHD and emotional dysregulation, which would imply, for example, a role for executive control; and that different neural processes lead to ADHD and emotional symptoms, such as via amygdala dysfunction.

Speaking to Medscape Medical News after the session, Dr Asherson said that, in a way, emotional instability is "particularly poor" at signaling which mental health problem a patient has, but that does not mean it is not an aspect of ADHD.

"Within that context, for people with ADHD who are emotionally unstable, the evidence is that there's a good treatment response of stimulants and atomoxetine [Strattera, Eli Lilly and Company] on those emotional symptoms in people who have ADHD," he added.

"In general, it's not been used as a primary outcome, because everyone is so focused on the core ADHD symptoms, but I think if you set up a study where it was the primary outcome, you'd expect to see very similar results."

Turning to the reasons why emotional instability was dropped from the key domains of ADHD in the first place, Dr Asherson commented: "When the DSM came along, they started to view ADHD as more of a cognitive and educational model, and perhaps this executive function model became more prominent."

"There was a group of people in the states in particular who felt it often reflect other conditions, like bipolar disorder, rather than perhaps a core feature of ADHD, but it seems the tide has very much turned, and so most of the experts in the field have come around to thinking, 'Yeah, actually, it does seem to be part of ADHD,' " he added.

Dr Asherson noted that the DSM-5 says that emotional lability is a core feature of ADHD and that, although it should not be used in the differential diagnosis, it can support the diagnosis.

"But I think, as a clinician, and particularly in adult psychiatry, where people are less familiar with ADHD, if they see mood instability, they'll often be thinking bipolar, depression, or personality disorder, and they forget that ADHD can also cause it," he said.

Need for Biological Markers

The problems with, and new developments in, the diagnosis of ADHD was the theme of the session. Chair Andreas Warnke, MD, PhD, professor emeritus of child and adolescent psychiatry at the University of Würzburg, Germany, explained why this is such an important consideration.

Dr Andreas Warnke

Dr Warnke told Medscape Medical News that information given by patients and parents is the basis of the diagnosis of ADHD.

"The critique on the diagnosis is that's very subjective, it's age dependent, and there are only some of the symptoms, [and] of course, there is a dependence on the task you have to solve," he said, adding: "If you can run all the day, it's not a problem, but if you have to sit still, then it's a problem."

Dr Warnke noted that the result is that there are large discrepancies in the recorded prevalence of ADHD both between and within countries, including the Unite States.

The answer, he said, is that biological markers are needed to help definitively diagnose ADHD: "We need more and more markers that [a patient] really has this diagnosis, because we give medication, and in this case, it's very important that we don't treat the wrong people."

5th World Congress on Attention Deficit Hyperactivity Disorder (ADHD). Abstract PL-1-002. Presented May 29, 2015.


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