A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder.
OBJECTIVE
OROS methylphenidate HCL (MPH) is a recently developed long-acting stimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). This study was conducted to examine dosage effects on ADHD symptoms and stimulant side effects and to explore potential moderating effects of ADHD subtype.


METHODS
Children with ADHD combined type (ADHD-CT) or predominantly inattentive type (ADHD-PI; n = 47), ages 5 to 16 years, underwent a placebo-controlled, crossover trial using forced titration with weekly switches at 3 dosage levels. Parent and teacher ratings of ADHD symptoms were used to evaluate efficacy. In addition, vital signs and standardized measures of stimulant side effects were obtained weekly.


RESULTS
Parent ratings were more sensitive to treatment effects than teacher ratings. ADHD symptoms and Clinical Global Impressions Severity Index ratings at each dose condition differed significantly from placebo and baseline ratings, which did not differ from one another. For those with ADHD-CT, there was a clear linear dose-response relationship, with clinically significant reductions in ADHD Rating Scale-IV scores occurring in two thirds to three fourths of the subjects during either 36- or 54-mg dose conditions. Children with ADHD-PI, conversely, were more likely to respond optimally to lower doses and derived less benefit from higher doses, with 60% displaying significant improvement on the ADHD Rating Scale-IV at 36 mg or lower. Mild stimulant side effects were reported during placebo and at all dosage levels. With the exception of insomnia and decreased appetite, which were more common at higher doses, parent report of side effects was not related to dose. In addition, younger and smaller children were more likely to display sleep difficulties and decreased appetite at the higher dose levels Although pulse rate increased slightly with increasing dose, there were no dose effects on blood pressure.


CONCLUSIONS
In children with ADHD-CT, the most common subtype of ADHD, increasing doses of stimulant medication were associated with increased improvement of inattention and hyperactivity symptoms. In children with ADHD-PI, symptom improvement occurred at lower doses and less benefit was derived from higher doses. In both ADHD subtypes, higher doses were associated with parent ratings of increased insomnia and decreased appetite.
Department of Psychiatry, University of Chicago, Chicago, Illinois 60637, USA. mstein@yoda.bsd.uchicago.edu
Mark A
MA
Stein
Christopher S
CS
Sarampote
Irwin D
ID
Waldman
Adelaide S
AS
Robb
Charles
C
Conlon
Phillip L
PL
Pearl
David O
DO
Black
Karen E
KE
Seymour
Jeffrey H
JH
Newcorn
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D001068:Feeding and Eating Disorders / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010290:Parents / Q000523:psychology; D010349:Patient Compliance; D012720:Severity of Illness Index; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D013663:Teaching; D020323:Tics / Q000139:chemically induced
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate