A series of n-of-1 trials of stimulants in brain injured children

NeuroRehabilitation. 2017;40(1):11-21. doi: 10.3233/NRE-161386.

Abstract

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.

Keywords: Paediatrics; acquired brain injury; traumatic brain injury.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Attention / drug effects
  • Attention / physiology*
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / etiology
  • Australia
  • Brain / physiopathology
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Child
  • Double-Blind Method
  • Executive Function / drug effects
  • Executive Function / physiology*
  • Female
  • Humans
  • Male
  • Treatment Outcome

Substances

  • Central Nervous System Stimulants