Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study

Irene M Loe; Nathan J Blum; Justine Shults; William Barbaresi; Ami Bax; Jaclyn Cacia; Alexis Deavenport-Saman; Sandra Friedman; Angela LaRosa; Shruti Mittal; Douglas Vanderbilt; Elizabeth Harstad

doi:10.1016/j.jpeds.2023.01.004

Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study

J Pediatr. 2023 Jun:257:113325. doi: 10.1016/j.jpeds.2023.01.004. Epub 2023 Jan 14.

Authors

Affiliations

¹ Department of Pediatrics, Stanford University, Stanford, CA. Electronic address: iloe@stanford.edu.
² Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA.
³ Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA.
⁴ Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
⁵ Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA.
⁶ Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA; Division of General Pediatrics, Children's Hospital Los Angeles, Los Angeles, CA.
⁷ Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
⁸ Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
⁹ Department of Pediatrics, Atrium Health, Concord, NC.

PMID: 36649794
DOI: 10.1016/j.jpeds.2023.01.004

Abstract

Objectives: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs.

Study design: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019.

Results: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep.

Conclusions: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.

Keywords: adverse events; early childhood; medication; nonstimulant; psychopharmacology; side effects.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adrenergic Agonists / therapeutic use
Attention Deficit Disorder with Hyperactivity* / drug therapy
Central Nervous System Stimulants* / adverse effects
Child
Child, Preschool
Drug-Related Side Effects and Adverse Reactions*
Humans
Pediatrics*
Prospective Studies
Retrospective Studies

Substances

Central Nervous System Stimulants
Adrenergic Agonists