Late Breaking News From APSARD 2024 Conference

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CONFERENCE REPORTER

Last week, the American Professional Society for ADHD and Related Disorder’s 2024 conference brought together the nation’s top researchers, educators, and clinicians in conjunction with key governmental stakeholders, including the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). Colleagues from around the world joined the US faction at the Orlando event, including the presidents of the Australian ADHD Association, the World Federation for ADHD, and the International Association for Child and Adolescent Psychiatry, resulting in a truly landmark and global event for the field of ADHD and the lives of those for whom we care.

Thursday’s session began with a standing room only event: “ADHD 201,” a 5-session exploration presented by APSARD Executive Committee members. This was a 5-hour primer “beyond the basics” needed for top tier clinical care of individuals with ADHD.

The first session, presented by Greg Mattingly, MD, was a deep dive into the complex world of ADHD and comorbid conditions. The polygenetic overlapping risk of ADHD with conditions such as disordered eating, impulsive frustration, insomnia, mood disorders, and anxiety were of no surprise to any practicing clinician but bolstered their understanding of the genetic crosstalk between these conditions. The fact that ADHD is associated with accelerated aging of our very DNA, as measured by Grim Age, and the neural impact of untreated ADHD with damages to neural connectivity were then explored, identifying the damage of neural resilience with subsequent increased risk of decompensating into secondary comorbid conditions.

From a diagnostic perspective, the overlapping symptoms of cognitive difficulties, emotional difficulties, and sleep related problems were highlighted, underscoring the need to complete a holistic diagnostic assessment which carefully screens for ADHD amongst other comorbid conditions. A quote from this session included “Do not make the rookie mistake and just treat the chief complaint.” For instance, a mood disorders expert might assume that a patient presenting with emotional frustration and poor memory has a mood disorder, yet an anxiety specialist would interpret the same patient presenting as stressed and overwhelmed to be primarily affected by an anxiety disorder. Geriatricians would diagnose symptoms of anxiety and forgetfulness in a senior as mild cognitive impairment.

The final portion of this session dove into the science regarding the importance of holistic individualized treatment for individuals with a variety of conditions including autism spectrum, depression, bipolar disorder, anxiety disorders, substance use disorders, and suicidal behavior.

The session concluded with a study from the late Joseph Biederman, MD, which looked at the number needed to treat to prevent a secondary negative health outcome in individuals with ADHD.¹ This study found that for every 3 to 5 individuals who received holistic ADHD care, we prevented 1 from developing a secondary depression, repeating a grade in school, developing a complex anxiety disorder, or decompensating into a bipolar episode. For every 8 to 10 individuals receiving ADHD treatment, we prevented 1 from developing nicotine use disorder or a substance related disorder.

In the second session of ADHD 201, David Goodman, MD, LFAPA, explored the impact of ADHD in special populations. This session did a deep dive into the impact of hormones on ADHD symptom expression. The impact of estrogen fluctuations and subsequent changes in dopamine receptor binding was highlighted by looking at times of risk and symptom exacerbation throughout the lifespan. Several studies were referenced that have shown a genetic overlap between ADHD symptoms and severity of premenstrual exacerbations.^2,3 In addition, other studies by our colleagues in the Netherlands and here in the United States have shown that women have worsening cognition during the week preceding ovulation. Of note was a study from the Netherlands which found that 30% to 50% increases in stimulant dose during the week preceding ovulation improved both cognitive issues and issues with emotional frustration.³

Another important deep dive in Dr Goodman’s presentation was the impact of ADHD and aging. ADHD symptoms were shown to worsen during the postmenopausal period. In addition, a recent study by colleagues in Israel was highlighted, which found that ADHD was an independent risk factor that more than doubled the risk of developing various types of dementia.⁴ Reassuringly from this study, the use of psychostimulant medication was not found to exacerbate the risk of dementia and, if anything, was shown to be slightly protective.

The third session by Margaret Sibley, PhD, explored the world of psychosocial treatments and the importance of motivational engagement for individuals with ADHD. She stressed the importance of ongoing psychosocial interventions targeted to specific functional challenges within the lives of a patient with ADHD. She also stressed the importance of sharing with them instead of just speaking to them, understanding their motivators for seeking change, and acknowledging the small steps forward instead of focusing on areas of difficulty or impairment. The importance of meeting our patients where they are instead of where we or they think they should be was discussed, in the context of various examples: a child and family, an adolescent with increasing challenges but perhaps different priorities, or an adult who may be overwhelmed with the many functional responsibilities that can be impacted by ADHD.

A favorite tool to promote discussion and break down barriers is a sheet which includes a variety of circles for what motivates an individual to seek change with ADHD: is it having more friends, making better grades, getting a car, having a romantic relationship, holding a job, being more creative, being funnier, or feeling better about myself. This tool can be utilized by an adolescent seeking treatment to look at their primary motivators as compared with their parents’ agenda and then used to begin a dialogue of therapeutic misalignments as a way to promote collaborative engagement.

The fourth session by APSARD president, Ann Childress, MD, explored the role of various stimulant preparations. This session explored the differences between methylphenidates that block the reuptake of dopamine and norepinephrine versus amphetamines which both block the reuptake and directly increase the release of dopamine and norepinephrine into the synapse. Data from within the United States show that most children are started on a methylphenidate preparation but that by adolescence and adulthood 80% of patients will be receiving an amphetamine preparation. Factors associated with this transition from methylphenidate to amphetamine may include increased cognitive load associated with adolescence and adulthood, breakthrough symptoms at the beginning or end of the day, and or being on an inadequate dose of methylphenidate or a methylphenidate preparation with inadequate duration.

Dr Childress then explored the more than 30+ stimulant preparations available within the market and how to utilize each of these with regard to their unique delivery system, onset of action, offset of action, and duration. The role of single isomer d-methylphenidate and d-amphetamine versus preparations which include combinations of D and R isomers was explored along with the role of pro drug formulations. There was then a discussion of the newer stimulant treatments, including a transdermal amphetamine patch that allows for both flexibility and control of ADHD symptoms, a new pro drug methylphenidate preparation which combines 30% short acting D methylphenidate with 70% pro drug methylphenidate, and our first-ever evening dosed stimulant which enables medication upon awakening with duration into the early evening hours.

The final session of ADHD 201, presented by Jeff Newcorn, MD, explored the role of nonstimulant medications. With 4 nonstimulant medications approved for ADHD treatment, clinicians now have multiple nonstimulant options that can be used either alone or in combination with a stimulant medication. Extended-release clonidine and guanfacine are both approved for child and adolescent ADHD treatment in the United States. In addition, extended release guanfacine has a specific FDA indication for use in combination with a stimulant for residual or breakthrough symptoms, or as a way to minimize the dose of a stimulant. While off label, many clinicians have found small doses of short acting clonidine to be beneficial in the evening for sleep induction.

Both atomoxetine and viloxazine ER have been approved for children and adults with ADHD. Dr Newcorn reviewed data from a study that found a somewhat bifurcated response to atomoxetine.⁵ For approximately 50% of patients, atomoxetine had only a minimal to mild improvement in symptoms. However, for the other 50%, atomoxetine had significant improvement in ADHD symptoms, similar to what might be seen with stimulant treatment. The take home comment was “atomoxetine seems to be really good for those whom it's good for.” More recent data with the approval of viloxazine ER for both children and adults with ADHD was then explored. Viloxazine data demonstrated a faster onset with significant improvement occurring within the first week for children and within 2 weeks for adolescents and adults. A recent study found that viloxazine could be safely added to stimulant partial responders with significant improvement in ADHD symptomatology beyond what was seen with a stimulant alone.⁶ A similar study which looked at 50 children, adolescents, and adults whose ADHD had only been partially responsive to a stimulant preparation, were then consecutively tried on atomoxetine for 4 weeks and then viloxazine for 4 weeks.⁷ Viloxazine was found to have significantly faster onset during the initial 2 weeks and had significantly higher overall patient satisfaction than atomoxetine. An important take home from this study was that 75% of patients were able to either reduce the dose or discontinue the need for stimulants after they have been adequately treated with a nonstimulant medication.

Please join later this week for a deep dive into Day 2 from the APSARD 2024 conference, exploring the world of ADHD in women, the impact of cannabis on ADHD, the emerging world of digital therapeutics and guidance from the FDA and CDC regarding stimulant prescribing and the stimulant crisis in America.

Dr Mattingly is associate clinical professor at Washington University; president of the Midwest Research Group; and president of the American Professional Society for ADHD and Related Disorders.

References

1. Biederman J, DiSalvo M, Fried R, et al. Quantifying the protective effects of stimulants on functional outcomes in attention-deficit/hyperactivity disorder: a focus on number needed to treat statistic and sex effects. J Adolesc Health. 2019;65(6):784-789.

2. Jaholkowski P, Shadrin AA, Jangmo A, et al. Associations between symptoms of premenstrual disorders and polygenic liability for major psychiatric disorders. JAMA Psychiatry. 2023;80(7):738-742.

3. de Jong M, Wynchank DSMR, van Andel E, et al. Female-specific pharmacotherapy in ADHD: premenstrual adjustment of psychostimulant dosage. Front Psychiatry. 2023:14:1306194.

4. Levine SZ, Rotstein A, Kodesh A, et al. Adult attention-deficit/hyperactivity disorder and the risk of dementia. JAMA Netw Open. 2023;6(10):e2338088.

5. Newcorn JH, Sutton VK, Weiss MD, Sumner CR. Clinical responses to atomoxetine in attention-deficit/hyperactivity disorder: the Integrated Data Exploratory Analysis (IDEA) study. J Am Acad Child Adolesc Psychiatry. 2009;48(5):511-518.

6. Childress A, et al. Viloxazine ER added to psychostimulant therapy in children with ADHD. Poster presented at Psych Congress, September 6-10, 2023.

7. Price MZ, Price RL. Extended-release viloxazine compared with atomoxetine for attention deficit hyperactivity disorder. CNS Drugs. 2023;37(7):655-660.