Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD.
OBJECTIVE
The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD).


METHODS
The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale.


RESULTS
Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001) t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the preschoolers (n=114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD.


CONCLUSIONS
MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication.
Greenhill
Laurence
L
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.. Electronic address: greenhil@childpysch.columbia.edu.
Kollins
Scott
S
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Abikoff
Howard
H
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
McCracken
James
J
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Riddle
Mark
M
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Swanson
James
J
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
McGough
James
J
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Wigal
Sharon
S
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Wigal
Tim
T
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Vitiello
Benedetto
B
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Skrobala
Anne
A
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Posner
Kelly
K
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Ghuman
Jaswinder
J
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Cunningham
Charles
C
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Davies
Mark
M
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Chuang
Shirley
S
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
Cooper
Tom
T
Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD.
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002675:Child, Preschool; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate