Long-Term Treatment With Extended-Release Methylphenidate Treatment in Children Aged 4 to <6 Years

J Am Acad Child Adolesc Psychiatry. 2022 Jan;61(1):80-92. doi: 10.1016/j.jaac.2021.03.019. Epub 2021 Apr 20.


Objective: To investigate long-term (12-month) safety and symptom control of extended-release methylphenidate (MPH-MLR) in children aged 4 to <6 years after treatment optimization.

Method: A total of 90 children aged 4 to <6 years with attention-deficit/hyperactivity disorder (ADHD) were enrolled from 2 MPH-MLR studies. Treatment-emergent adverse events (TEAEs) and ADHD symptom control were assessed in the safety population (n = 89) and modeled with mixed model analyses.

Results: Most TEAEs (89.9%) were rated by investigators as of mild or moderate severity. One serious AE was reported (unrelated to study drug). Ten children discontinued because of TEAEs. Two discontinued because of weight loss; no significant increase in the rate of underweight children from baseline to endpoint was observed. Overall, 18% lost weight and 18% reported decreased appetite. Weight and height z scores and obesity rates decreased significantly from baseline to endpoint. Insomnia was reported (9%); none of these children discontinued. Sleep quality did not change significantly. Hypertension was reported (6.7%); none of these children dropped out. Diastolic, but not systolic, blood pressure increased significantly during the follow-up. Control of ADHD symptoms was maintained throughout follow-up.

Conclusion: These data contribute to the understanding of the long-term safety of an extended-release stimulant in children 4 to <6 years of age. The observed risk of a TEAE-related discontinuation was ∼11%. TEAEs were not dose related, and most were of mild to moderate severity. Symptom control was maintained through the year-long study.

Clinical trial registration information: A 12-Month Open Label Safety Study of Aptensio XR® in Children Ages 4-5 Years Diagnosed With ADHD (EF004); https://clinicaltrials.gov; NCT02677519.

Keywords: ADHD; methylphenidate; preschool children; safety.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Central Nervous System Stimulants* / adverse effects
  • Child
  • Child, Preschool
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Methylphenidate* / adverse effects
  • Sleep Quality
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Methylphenidate

Associated data

  • ClinicalTrials.gov/NCT02677519