Symptom improvement was observed in the majority of preschool-age children with attention-deficit/hyperactivity disorder (ADHD) treated with α2-adrenergic agonists or stimulants, according to the findings of a retrospective review recently published in JAMA.

Management of ADHD in preschool-age children typically begins with behavioral therapy; however, when this is insufficient, the American Academy of Pediatrics guidelines recommend methylphenidate as an initial treatment. It has been reported that despite a lack of evidence for use in this patient population, treatment with α2-adrenergic agonists has become increasingly common in preschool-age children.

This retrospective electronic health record review aimed to evaluate the frequency of reported ADHD symptom improvement and adverse effects associated with these medication classes when used as initial therapy in preschool-age children.

The study authors accessed the health records of children treated at 7 outpatient developmental-behavioral pediatric practices in the Developmental Behavioral Pediatrics Research Network in the US. Records of children younger than 72 months who initiated treatment between January 1, 2013, and July 1, 2017, were included in the analysis. The main outcomes of the study were reported improvement in symptoms of ADHD as well as adverse effects.

The electronic health records of 497 children were accessed and analyzed during the study (median age at medication initiation, 62 months; 82% male); 175 children (35%) received α2-adrenergic agonists as initial AHDH therapy for a median length of use of 136 days, while 322 children (65%) received stimulants for a median length of use of 133 days.

“Improvement was reported in 66% (95% CI, 57.5%-73.9%) of children who initiated α2-adrenergic agonists and 78% (95% CI, 72.4%-83.4%) of children who initiated stimulants,” the study authors reported.

The only adverse event more commonly reported among those receiving α2-adrenergic agonists compared with stimulants was daytime sleepiness (38% vs 3%). Moodiness/irritability (50% vs 29%), appetite suppression (38% vs 7%), and difficulty sleeping (21% vs 11%) were more common among stimulant-treated patients vs those who received α2-adrenergic agonists.  

“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,” said Tanya E. Froehlich, MD, MS, Division of Developmental and Behavioral Pediatrics, Cincinnati Children’s Hospital, in an accompanying editorial. Randomized controlled trials are recommended to further compare the efficacy of α2-adrenergic agonists and stimulants.


  1. Harstad E, Shults J, Barbaresi W, et al. α2-adrenergic agonists or stimulants for preschool-age children with attention-deficit/hyperactivity disorder. JAMA. [published online May 4, 2021.] JAMA. doi: 10.1001/jama.2021.6118
  2. Froehlich TE. Comparison of medication treatments for preschool children with ADHD: A first step toward addressing a critical gap. JAMA. [published online May 4, 2021.] JAMA. doi: 10.1001/jama.2021.5603