Treatment with α2-adrenergic agonists improved attention-deficit/hyperactivity disorder (ADHD) in the majority of preschool-aged children treated in developmental-behavioral pediatric practices. These agents have very different adverse effect profiles compared with stimulants, and more randomized clinical trials to assess their efficacy are needed, according to results from a recent study published in JAMA.
“Given the increasing use of α2-adrenergic agonists for preschool-age children with ADHD, paucity of data on efficacy or adverse effects of α2-adrenergic agonists, and recommendations for use of methylphenidate when medication is chosen, this retrospective medical records study of α2-adrenergic agonists and stimulants for the treatment of preschool ADHD was conducted to determine reported improvement in ADHD symptoms associated with α2-adrenergic agonist and stimulant medication for initial ADHD medication treatment in preschool-age children and evaluate the frequency of reported adverse effects of α2-adrenergic agonists and stimulants,” explained researchers led by Elizabeth Harstad, MD, MPH, of Boston Children’s Hospital.
For this retrospective review, Harstad and colleagues gathered data from 497 preschool-age children with ADHD who were being treated with α2-adrenergic agonists or stimulants. Median age of ADHD treatment initiation in these children was 62 months, and 82% were boys, 65% were White, and 62% received behavioral therapy before medication initiation. In all, 35% of these children were initially treated with α2-adrenergic agonists, including guanfacine and clonidine preparations, and 65% were prescribed stimulants, including methylphenidate-based and amphetamine-based preparations.
Of the 59 development-behavioral pediatricians of these children, 4 prescribed only α2-adrenergic agonists, 15 prescribed only stimulants, and 40 prescribed both.
Treatment that was “associated with improvement” was reported in 66% of children treated with α2-adrenergic agonists (95% CI: 57.5%-73.9%) compared with 78% of children treated with stimulants (95% CI: 72.4%-83.4%). Children treated with α2-adrenergic agonists were less likely to be rated as “very much improved” compared with those receiving stimulants (25% vs 38%, respectively; difference: 13% [95% CI: 1.4%-24.9%]).
The most common adverse effects in children treated with α2-adrenergic agonists were daytime sleepiness and increased moodiness, and in stimulants, increased moodiness/irritability, and appetite suppression. Daytime sleepiness was the only adverse effect reported more often in children treated with α2-adrenergic agonists compared with stimulants (38% versus 3%, respectively). But several adverse events were more common in those treated with stimulants, including moodiness/irritability (50% versus 29%, respectively), appetite suppression (38% versus 7%), and difficulty sleeping (21% versus 11%), increased stomachaches (13% versus 5%), and increased skin picking/repetitive behaviors (11% versus 5%).
Researchers also found an association between younger age and initiation of treatment with α2-adrenergic agonists compared with stimulants (age at initiation of treatment x medication class interaction P=0.006). Younger children were not more likely to have clinical improvement with α2-adrenergic agonists compared with stimulants, but those younger than 4-years-old who were prescribed these agents were more likely to continue treatment longer than children treated with stimulants. Further, treatment duration with stimulants was longer in children aged 5-less than treated with a stimulant compared with an α2-adrenergic agonist.
This is the first study to compare improvements in symptoms of ADHD and adverse effects in children initially treated with a2-adrenergic agonists and stimulant agents in preschool children, noted Tanya E. Froehlich, MD, MS, of the Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, in an accompanying editorial.
“[T]he report by Harstad et al represents an important contribution. This study is the first step toward filling the void in the evidence base regarding comparative effectiveness of medication treatment for preschool-age children with ADHD. To build on the findings from the study by Harstad et al, randomized clinical trials using standardized measures of efficacy and adverse effects at baseline and during treatment are needed among preschool-aged children to investigate effects of α2-adrenergic agonists as well as α2-adrenergic agonist/methylphenidate comparative effectiveness,” she wrote.
“Although much still needs to be learned regarding comparative effectiveness of medication treatment for preschool ADHD, the study by Harstad et al provides the foundation for future study and its limitations provide a roadmap for next steps,” concluded Froelich.
Study limitations include its retrospective nature, nonstandardized data input, confounding factors that may have influenced clinician choices of ADHD medications, possible overestimation of benefits due to evaluation of ADHD symptoms and adverse events during treatment episodes, lack of randomization to treatment, and inclusion of children treated in developmental-behavioral pediatric practices rather than in primary care practices.
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Most preschool-age children with ADHD treated in developmental-behavioral pediatric practices improved after treatment initiation with both α2-adrenergic agonists or stimulants.
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α2-adrenergic agonists offer similar improvements in children with ADHD as stimulants, but have a significantly different side effect profile.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
DBPNet is supported by cooperative agreement UA3MC20218 from the Maternal and Child Health Bureau, Health Resources and Services Administration, US Department of Health and Human Services.
Harstad reported receiving compensation for serving as a medical reviewer for Understood.org, a website for parents of children with learning and attention issues, and grant funding from the Palmer Family Fund for Autism Research to conduct research related to autism spectrum disorder at Boston Children’s Hospital.
Groelich reported no conflicts of interest.
Cat ID: 136
Topic ID: 85,136,730,136,192,53,925
