Safety and tolerability of methylphenidate in preschool children with ADHD

Tim Wigal, Laurence Greenhill, Shirley Chuang, James McGough, Benedetto Vitiello, Anne Skrobala, James Swanson, Sharon Wigal, Howard Abikoff, Scott Kollins, James McCracken, Mark Riddle, Kelly Posner, Jaswinder Ghuman, Mark Davies, Ben Thorp, Annamarie Stehli

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD) during 1 year of treatment. METHOD: Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n = 183); a 5-week placebo-controlled, double-blind phase (n = 165); a 5-week double-blind, parallel phase (n = 114); and 10 months of open-label maintenance (n = 140 entered, 95 completed). Mean total daily MPH doses rose from the titration trial best dose, 14.1 (±8.1) mg/day, to 20.5 (±9.7) mg/day mean total daily dose at the end of maintenance. Pulse, blood pressure, and the presence of treatment emergent adverse events (AEs), parent and teacher AE ratings, and vital signs were recorded in each phase. RESULTS: Thirty percent of parents spontaneously reported moderate to severe AEs in all study phases after baseline. These included emotional outbursts, difficulty falling asleep, repetitive behaviors/thoughts, appetite decrease, and irritability. During titration, decreased appetite (χ = 5.4, p < .03), trouble sleeping (χ = 5.4, p < .03), and weight loss (χ = 4.0, p < .05) occurred statistically more often on MPH than on placebo. During maintenance, trouble sleeping and appetite loss persisted and other MPH-related AEs decreased. There were transient, one-time pulse and blood pressure elevations in five children. Twenty-one children (11%) discontinued because of drug-attributed AEs. CONCLUSIONS: Eleven percent of preschoolers discontinued treatment because of intolerable MPH AEs. Of the serious AEs reported, one occurred in baseline, two in lead-in, three in titration, one in parallel, and one in maintenance. Only one was possibly related to MPH. Copyright 2006

Original languageEnglish (US)
Pages (from-to)1294-1303
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number11
StatePublished - Nov 2006


  • Adverse events
  • Attention-deficit/hyperactivity disorder
  • Methylphenidate
  • Preschoolers
  • Safety
  • Tolerability

ASJC Scopus subject areas

  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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