Comorbidity moderates response to methylphenidate in the Preschoolers with Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS).
OBJECTIVE
The aim of this study was to examine whether demographic or pretreatment clinical and social characteristics influenced the response to methylphenidate (MPH) in the Preschoolers with ADHD Treatment Study (PATS).


METHODS
Exploratory moderator analyses were conducted on the efficacy data from the PATS 5-week, double-blind, placebo-controlled six-site titration trial. Children (N = 165, age 3-5.5 years) were randomized to 1 week each of four MPH doses (1.25, 2.5, 5, and 7.5 mg) and placebo administered three times per day (t.i.d.). We assessed the fixed effects on the average slope in the regression outcome on moderators, weight-adjusted dose, and the moderator-by-dose interaction using SAS PROC GENMOD.


RESULTS
A significant interaction effect was found for a number of co-morbid disorders diagnosed in the preschoolers at baseline (p = 0.005). Preschoolers with three or more co-morbid disorders did not respond to MPH (Cohen's d at 7.5 mg dose relative to placebo = -0.37) compared to a significant response in the preschoolers with 0, 1, or 2 co-morbid disorders (Cohen's d = 0.89, 1.00, and 0.56, respectively). Preschoolers with more co-morbidity were found to have more family adversity. No significant interaction effect was found with the other variables.


CONCLUSIONS
In preschoolers with ADHD, the presence of no or one co-morbid disorder (primarily oppositional defiant disorder) predicted a large treatment response at the same level as has been found in school-aged children, and two co-morbid disorders predicted moderate treatment response; whereas the presence of three or more co-morbid disorders predicted no treatment response to MPH.
Ghuman
Jaswinder K
JK
University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USA. jkghuman@email.arizona.edu
Riddle
Mark A
MA
Vitiello
Benedetto
B
Greenhill
Laurence L
LL
Chuang
Shirley Z
SZ
Wigal
Sharon B
SB
Kollins
Scott H
SH
Abikoff
Howard B
HB
McCracken
James T
JT
Kastelic
Elizabeth
E
Scharko
Alexander M
AM
McGough
James J
JJ
Murray
Desiree W
DW
Evans
Lori
L
Swanson
James M
JM
Wigal
Tim
T
Posner
Kelly
K
Cunningham
Charles
C
Davies
Mark
M
Skrobala
Anne M
AM
D000367:Age Factors; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000150:complications / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002653:Child Behavior Disorders / Q000150:complications* / Q000523:psychology; D002675:Child, Preschool; D004311:Double-Blind Method; D004493:Education; D004651:Employment / Q000523:psychology; D005006:Ethnicity; D005190:Family; D005260:Female; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012727:Sex Characteristics; D020954:Single-Parent Family; D012959:Socioeconomic Factors; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate