A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder.
OBJECTIVE
To compare the efficacy, safety, and tolerability of once-daily administration of modified-release methylphenidate (MPH MR) with placebo in children with attention-deficit/hyperactivity disorder (ADHD).


METHODS
The study was a 3-week, double-blind, 32-site, randomized clinical trial comparing MPH MR with placebo. Children were 6 to 16 years of age, had a diagnosis of ADHD, and had not failed a previous trial of stimulant treatment for ADHD. After a 1-week, single-blind, placebo-washout period, participants received a once-daily dose of MPH MR or placebo, which was started with 1 capsule (20 mg) and individually titrated up to a maximum of 3 capsules (60 mg). The primary outcome measure was specified as a reduction in ADHD symptom severity from the teacher version of the 10-item Conners' Global Index. Investigators, teachers, and parents evaluated safety.


RESULTS
The study randomized 321 children: 158 to MPH MR and 163 to placebo. Children in the MPH MR group were started on a dose of 20 mg/d and reached a mean dose of 40.7 mg/d (1.28 mg/kg/d) at endpoint. Compared with placebo, MPH MR significantly reduced ADHD symptoms ratings on the teacher version of the 10-item Conners' Global Index, on the parent version of the Conners' Global Index, on the parent assessment of global efficacy, and on investigator assessment of global improvement. The most common adverse events in the MPH MR group were headache, anorexia, abdominal pain, and insomnia. Only anorexia occurred at a rate that was significantly greater than placebo.


CONCLUSIONS
MPH MR administered once daily in the morning is effective and safe in controlling ADHD symptoms throughout the school day.
Greenhill
Laurence L
LL
New York State Psychiatric Institute, New York, New York 10032, USA. larrylgreenhill@cs.com
Findling
Robert L
RL
Swanson
James M
JM
D000293:Adolescent; D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D003692:Delayed-Action Preparations; D008774:Methylphenidate