title: Safety and tolerability of methylphenidate in preschool children with ADHD.
abstract: 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.
  
  
  METHODS
  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 (chi=5.4, p<.03), trouble sleeping (chi=5.4, p<.03), and weight loss (chi=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.
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Tim
authors.initials: T
authors.lastname: Wigal
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.. Electronic address: larrylgreenhill@cs.com.
authors.forename: Laurence
authors.initials: L
authors.lastname: Greenhill
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Shirley
authors.initials: S
authors.lastname: Chuang
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: James
authors.initials: J
authors.lastname: McGOUGH
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Anne
authors.initials: A
authors.lastname: Skrobala
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: James
authors.initials: J
authors.lastname: Swanson
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Howard
authors.initials: H
authors.lastname: Abikoff
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Scott
authors.initials: S
authors.lastname: Kollins
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: James
authors.initials: J
authors.lastname: McCRACKEN
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Mark
authors.initials: M
authors.lastname: Riddle
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Kelly
authors.initials: K
authors.lastname: Posner
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Jaswinder
authors.initials: J
authors.lastname: Ghuman
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Mark
authors.initials: M
authors.lastname: Davies
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Ben
authors.initials: B
authors.lastname: Thorp
authors.affiliation: Drs. T. Wigal, S. Wigal, Stehli, Thorp, and Swanson are with the University of California, Irvine; Dr. Abikoff is with the New York University Child Study Center, New York; Drs. McCracken and McGough are with the University of California, Los Angeles; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Kollins is with Duke University Medical Center; Durham, NC; Drs. Greenhill, Chuang, and Posner, Ms. Skrobala, and Mr. Davies are with New York State Psychiatric Institute/Columbia University, New York; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD; and Dr. Ghuman is with the University of Arizona, Tucson.
authors.forename: Annamarie
authors.initials: A
authors.lastname: Stehli
mesh_terms: D000855:Anorexia / Q000139:chemically induced; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000627:therapeutic use; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects* / Q000627:therapeutic use; D012893:Sleep Wake Disorders / Q000139:chemically induced
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate