A2As or stimulants: which is better for treatment of ADHD in young children?

Abstract

The use of α2-adrenergic agonists (A2As), like guanfacine and clonidine, in preschool-aged children with ADHD has been on the rise, even though little data support safety and effectiveness for these medications in this patient population. A May 2021 study conducted by Harstad and colleagues and published in JAMA compared the use of A2As with stimulants in childhood ADHD. Similar to other studies, the research team found that both A2As and stimulants were associated with improvement in ADHD symptoms for most children between approximately 4 and 6 years in whom they were initiated, with clinical improvement in 66% and 78% of young children, respectively. The study highlights the potential role that A2As could play in treating young children with ADHD, said Elizabeth Harstad, MD, MPH, a physician at Boston Children's Hospital and an assistant professor of pediatrics at Harvard Medical School. According to the American Academy of Pediatrics (AAP) and the Society for Developmental and Behavioral Pediatrics (SDBP), firstline therapy for ADHD is behavioral intervention, followed by stimulant treatment with methylphenidate (Ritalin) at the lowest effective dose if behavioral interventions are not sufficient. In general, AAP recommends behavioral therapy first then medication treatment, if necessary. Amphetamine salts (Adderall) are FDA-approved for children as young as 3 years because they were grandfathered in, not because there is stronger evidence for their use compared with methylphenidate, said Michael Ellis, DO, a child and adolescent psychologist and clinical associate professor at Mercer College of Medicine in Georgia. He said methylphenidate has more efficacy and safety data to promote its use, even though it is approved for individuals 6 years and older. “In general, I find less irritability with methylphenidate and prefer the use of that medication first, especially for those with ADHD and autism spectrum disorder,” Ellis said. The NIH's Preschool ADHD Treatment study, a randomized, placebo-controlled study, found that children between the ages of 3 and 5.5 years who were treated with methylphenidate had a significant reduction in ADHD symptoms, but often experienced adverse effects like irritability and depressive symptoms, like crying and sadness. The retrospective, medical records study in JAMA examined 497 preschool-age children younger than 6 years with ADHD. They came from seven academic developmental behavioral pediatric programs located in diverse geographical locations across the United States. “We found that developmental behavioral pediatricians use A2As when initiating medication treatment and use stimulant medication about two-thirds of the time,” said Harstad. “Children who were younger, or had a coexisting autism or sleep disorder, were more likely to be initiated on A2As.” Since stimulants are associated with more adverse effects than A2As—like moodiness/irritability (50% vs. 29%, respectively), appetite suppression (38% vs. 7%, respectively), and sleep difficulties (21% vs. 11%, respectively)—some providers prefer to prescribe A2As for their patients. “But these are not as effective for focus [compared with stimulants], and there can be a good deal of somnolence or hypotension,” said Ellis. Daytime sleepiness was the only adverse effect that was more common when young children with ADHD took A2As versus stimulants (38% vs. 3%, respectively), according to the study. A limitation of the study is its retrospective nature, which resulted in the collection of non-randomized and non-controlled data regarding the level of improvement over time, severity of baseline ADHD symptoms, and severity of adverse effects, said Harstad. “Medication may have been influenced by confounding factors [such as coexisting conditions]. Therefore, it is clinically imperative to conduct a prospective clinical study to assess effectiveness,” said Harstad. Preschool-aged children are being diagnosed with ADHD at higher rates than ever before. According to a 2018 article published in the Journal of Clinical Child & Adolescent Psychology, preschool ADHD rates have risen from 1.0% in 2007 to 2.4% in 2016. Since delay in early detection can lead to expulsion from preschool, future underachievement in school, and undue family stress, it is important for parents to have their child evaluated early on. “Preschoolers especially with severe ADHD likely need treatment right away,” said Ellis. While there are benefits and risks to treatments with both A2As and stimulants, options should be assessed with a patient-centered approach to optimize individual needs. Future randomized, controlled studies are also needed to assess efficacy and safety with both medication classes to determine more conclusive results.