Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability.
BACKGROUND
Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks.


METHODS
One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat.


BACKGROUND
ISRCTN 68384912.


RESULTS
Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure.


CONCLUSIONS
Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group.
Department of Child and Adolescent Psychiatry, King's College London, Institute of Psychiatry, London, UK. emily.simonoff@kcl.ac.uk
Emily
E
Simonoff
Eric
E
Taylor
Gillian
G
Baird
Sarah
S
Bernard
Oliver
O
Chadwick
Holan
H
Liang
Susannah
S
Whitwell
Kirsten
K
Riemer
Kishan
K
Sharma
Santvana Pandey
SP
Sharma
Nicky
N
Wood
Joanna
J
Kelly
Ania
A
Golaszewski
Juliet
J
Kennedy
Lydia
L
Rodney
Nicole
N
West
Rebecca
R
Walwyn
Fatima
F
Jichi
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004739:England; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000009:adverse effects; D010552:Personality Assessment
D000697:Central Nervous System Stimulants; D008774:Methylphenidate