A series of n-of-1 trials of stimulants in brain injured children.
BACKGROUND
There is controversy about whether central nervous system stimulant (CNS) medication is an effective method of treating acquired attention deficits in children with acquired brain injury (ABI).


OBJECTIVE
The primary objective was to determine the effectiveness of stimulants on attention, concentration and executive function in children with ABI.


METHODS
Randomised, double-blind, placebo-controlled, multi-centre n-of-1 trials of stimulants assessing effect on attention, concentration and executive function in 53 children and adolescents with ABI who were outpatients of three tertiary hospitals in Australia. Trials consisted of 3 two-week cycles, each cycle consisting of stimulant medication at doses titrated by physician (1 week) and placebo (1 week) in random order. The effect on parent and teacher Conners' 3 and Behaviour Rating Inventory of Executive Function (BRIEF) was analysed using hierarchical Bayesian methods.


RESULTS
Overall, Teacher Conners' Hyperactivity/Impulsivity and Teacher BRIEF Global Executive scales showed important improvement (T-score mean change 2.6; 95% credible interval (CI): 0.4, 4.9; posterior probability of mean change >0 : 0.99; T-score mean change 3.1; 95% CI: -0.1, 6.4; posterior probability of mean change >0 : 0.97). There were no important improvements in parent/guardian-reported primary outcomes. There was heterogeneity in response identified through individual results of the N-of-1 trials.


CONCLUSIONS
N-of-1 trials have a clear role in identifying those children/adolescents with ABI and secondary Attention Deficit Hyperactivity Disorder (ADHD) who have important improvements, or worsening on stimulants. The results can only be generalized to children/adolescents who have an apparent pre-trial clinical effect from stimulants.
The University of Queensland, Brisbane, QLD, Australia.
Jane
J
Nikles
The University of Queensland, Brisbane, QLD, Australia.
Geoffrey
G
Mitchell
Lady Cilento Children's Hospital, Brisbane, QLD, Australia.
Lynne
L
McKinlay
The Children's Hospital at Westmead, NSW, Australia.
Mary-Clare
MC
Waugh
Sydney Children's Hospital, Sydney, NSW, Australia.
Adrienne
A
Epps
The University of Queensland, Brisbane, QLD, Australia.
Sue-Ann
SA
Carmont
The University of Queensland, Brisbane, QLD, Australia.|University of Canterbury, Christchurch, New Zealand.
Philip J
PJ
Schluter
Lady Cilento Children's Hospital, Brisbane, QLD, Australia.
Owen
O
Lloyd
The University of Queensland, Brisbane, QLD, Australia.|Massey University, Auckland, New Zealand.
Hugh
H
Senior
D000293:Adolescent; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000209:etiology; D001315:Australia; D001921:Brain / Q000503:physiopathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants
Paediatrics; acquired brain injury; traumatic brain injury