Randomized controlled double-blind trial of optimal dose methylphenidate in children and adolescents with severe attention deficit hyperactivity disorder and intellectual disability.

Abstract

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.

METHOD:

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.

TRIAL REGISTRATION:

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.

• Authors: Emily Simonoff, Eric Taylor, Gillian Baird, Sarah Bernard, Oliver Chadwick, Holan Liang, Susannah Whitwell, Kirsten Riemer, Kishan Sharma, Santvana Pandey Sharma, Nicky Wood, Joanna Kelly, Ania Golaszewski, Juliet Kennedy, Lydia Rodney, Nicole West, Rebecca Walwyn, Fatima Jichi
• Journal: Journal of child psychology and psychiatry, and allied disciplines (J Child Psychol Psychiatry) Vol. 54 Issue 5 Pg. 527-35 (May 2013) ISSN: 1469-7610 [Electronic] England
• PMID: 22676856 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

Chemical References

• Central Nervous System Stimulants
• Methylphenidate

Topics

• Adolescent
• Attention Deficit Disorder with Hyperactivity (diagnosis, drug therapy, epidemiology, psychology)
• Central Nervous System Stimulants (administration & dosage, adverse effects)
• Child
• Comorbidity
• Dose-Response Relationship, Drug
• Double-Blind Method
• England
• Female
• Humans
• Intellectual Disability (diagnosis, drug therapy, epidemiology, psychology)
• Male
• Methylphenidate (administration & dosage, adverse effects)
• Personality Assessment