Sex differences in the response of children with ADHD to once-daily formulations of methylphenidate.
OBJECTIVE
Studies of sex differences in methylphenidate response by children with attention-deficit/hyperactivity disorder have lacked methodological rigor and statistical power. This paper reports an examination of sex differences based on further analysis of data from a comparison of two once-daily methylphenidate formulations (the COMACS study), which addresses these shortcomings.


METHODS
Children (184: 48 females; mean [SD] age, 9.58 [1.83] years) entered a double-blind, crossover trial of Concerta, MetadateCD/Equasym XL, or placebo. Attention-deficit/hyperactivity disorder symptoms were recorded at seven time points across the school day on the seventh day of treatment, using a laboratory classroom setting.


RESULTS
More females had comorbid anxiety disorder. Males and females did not differ with regard to other characteristics. Observed sex differences in pharmacodynamic symptom profiles persisted after controlling for placebo and time 0 hours attention-deficit/hyperactivity disorder scores and the presence of an anxiety disorder. Females had a statistically superior response at 1.5 hours post-dosing and an inferior response at the 12-hour time point relative to their male counterparts, no matter which methylphenidate formulation was being assessed.


CONCLUSIONS
Dose titration of once-daily formulations of methylphenidate should ideally be based on systematic evidence of response at different periods across the day. The responses of female patients may require additional assessments later in the day to determine the optimal dose.
Sonuga-Barke
Edmund J S
EJS
Dr. Sonuga-Barke is with the Developmental Brain-Behaviour Unit, University of Southampton, Southampton, UK; Mr. Coghill is with the Department of Psychiatry, The University of Dundee, Dundee, UK; Dr. Markowitz is with the Departments of Pharmaceutical Sciences and Psychiatry and Behavioral Medicine, Medical University of South Carolina, Charleston; Dr. Swanson is with the Child Development Center (UCI-CDC), University of California at Irvine; Dr. Vandenberghe is with UCB Pharma, Brussels, Belgium; and Mr. Hatch is with Simon Hatch Consulting Inc., Pittsford, NY. Electronic address: ejb3@soton.ac.uk.
Coghill
David
D
Dr. Sonuga-Barke is with the Developmental Brain-Behaviour Unit, University of Southampton, Southampton, UK; Mr. Coghill is with the Department of Psychiatry, The University of Dundee, Dundee, UK; Dr. Markowitz is with the Departments of Pharmaceutical Sciences and Psychiatry and Behavioral Medicine, Medical University of South Carolina, Charleston; Dr. Swanson is with the Child Development Center (UCI-CDC), University of California at Irvine; Dr. Vandenberghe is with UCB Pharma, Brussels, Belgium; and Mr. Hatch is with Simon Hatch Consulting Inc., Pittsford, NY.
Markowitz
John S
JS
Dr. Sonuga-Barke is with the Developmental Brain-Behaviour Unit, University of Southampton, Southampton, UK; Mr. Coghill is with the Department of Psychiatry, The University of Dundee, Dundee, UK; Dr. Markowitz is with the Departments of Pharmaceutical Sciences and Psychiatry and Behavioral Medicine, Medical University of South Carolina, Charleston; Dr. Swanson is with the Child Development Center (UCI-CDC), University of California at Irvine; Dr. Vandenberghe is with UCB Pharma, Brussels, Belgium; and Mr. Hatch is with Simon Hatch Consulting Inc., Pittsford, NY.
Swanson
James M
JM
Dr. Sonuga-Barke is with the Developmental Brain-Behaviour Unit, University of Southampton, Southampton, UK; Mr. Coghill is with the Department of Psychiatry, The University of Dundee, Dundee, UK; Dr. Markowitz is with the Departments of Pharmaceutical Sciences and Psychiatry and Behavioral Medicine, Medical University of South Carolina, Charleston; Dr. Swanson is with the Child Development Center (UCI-CDC), University of California at Irvine; Dr. Vandenberghe is with UCB Pharma, Brussels, Belgium; and Mr. Hatch is with Simon Hatch Consulting Inc., Pittsford, NY.
Vandenberghe
Mieke
M
Dr. Sonuga-Barke is with the Developmental Brain-Behaviour Unit, University of Southampton, Southampton, UK; Mr. Coghill is with the Department of Psychiatry, The University of Dundee, Dundee, UK; Dr. Markowitz is with the Departments of Pharmaceutical Sciences and Psychiatry and Behavioral Medicine, Medical University of South Carolina, Charleston; Dr. Swanson is with the Child Development Center (UCI-CDC), University of California at Irvine; Dr. Vandenberghe is with UCB Pharma, Brussels, Belgium; and Mr. Hatch is with Simon Hatch Consulting Inc., Pittsford, NY.
Hatch
Simon J
SJ
Dr. Sonuga-Barke is with the Developmental Brain-Behaviour Unit, University of Southampton, Southampton, UK; Mr. Coghill is with the Department of Psychiatry, The University of Dundee, Dundee, UK; Dr. Markowitz is with the Departments of Pharmaceutical Sciences and Psychiatry and Behavioral Medicine, Medical University of South Carolina, Charleston; Dr. Swanson is with the Child Development Center (UCI-CDC), University of California at Irvine; Dr. Vandenberghe is with UCB Pharma, Brussels, Belgium; and Mr. Hatch is with Simon Hatch Consulting Inc., Pittsford, NY.
D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology*; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage* / Q000494:pharmacology*; D012737:Sex Factors
D000697:Central Nervous System Stimulants; D008774:Methylphenidate