Central nervous system stimulants for secondary attention deficit-hyperactivity disorder after paediatric traumatic brain injury: a rationale and protocol for single patient (n-of-1) multiple cross-over trials

BMC Pediatrics

Geoffrey K Mitchell²  Owen Lloyd³  Adrienne Epps⁵  Mary-Clare Waugh⁴  Sue-Ann Carmont²  Philip J Schluter¹  Jane Nikles²  Lynne McKinlay³  Hugh EJ Senior² 

[1] School of Nursing and Midwifery, The University of Queensland, Queensland 4305, Australia;Discipline of General Practice, School of Medicine, The University of Queensland, 11 Salisbury Rd, Ipswich 4305, Australia;Queensland Children’s Medical Research Institute, Level 4, Foundation Building, Royal Children's Hospital, Herston, Queensland 4029, Australia;Rehabilitation Department, The Children's Hospital at Westmead, Cnr Hawkesbury Rd and Hainsworth St, Westmead, Sydney, NSW, 2145, Australia;Rehabilitation Department, Sydney Children's Hospital, High St, Randwick, NSW 2031, Australia

关键词: n-of-1 trial;    Dexamphetamine;    MPH;    Methylphenidate hydrochloride;    Children;    TBI;    Traumatic brain injury;   

Others  :  1144768
DOI  :  10.1186/1471-2431-13-89

 received in 2013-05-22, accepted in 2013-05-22,  发布年份 2013

【 摘 要 】

Background

It is estimated that 22,800 children were living with an Acquired Brain Injury (ABI) (0.6% of children aged under 15 years) in Australia during 2003. Many children after a traumatic brain injury will experience difficulties with attention and concentration; a condition termed secondary Attention Deficit-Hyperactivity Disorder. There is conflicting evidence on whether treatment with stimulant therapy with medications such as methylphenidate or dexamphetamine will improve the attention and behavior of children with this condition.

Methods/Design

Single patient trials (n-of-1s or SPTs) evaluate the effect of titrated doses of psychostimulants methylphenidate or dexamphetamine compared to placebo on attention and behavior, in children with TBI and secondary ADHD. The aggregation of multiple SPTs will produce a population estimate of the benefit. Forty-two children will be registered into the trial through rehabilitation services at three large children’s hospitals in Australia. Patients will complete up to 3 cycles of treatment. Each cycle is 2 weeks long comprising seven days each of treatment and placebo, with the first two days of each cycle considered a washout period and the data not analysed. The order of treatment and placebo is randomly allocated for each cycle. The Conners’ Parent Rating Scales long forms will be employed to measure change in attention-deficit/hyperactivity and related problems of the child, and the primary outcome measure is the Conners’ Global Index Parent Version. Secondary outcomes include the teacher and child (if aged > 12 years) Conners’ Rating Scales, the Behaviour Rating Inventory of Executive Function among other measures. This study will provide high-level evidence using a novel methodological approach to inform clinicians about the most appropriate treatment for individual children. Through aggregation of individual trials, a population estimate of treatment effect will be provided to guide clinical practice in the treatment of children with secondary ADHD after a traumatic brain injury.

Discussion

This study employs an innovative methodological approach on the effectiveness of CNS stimulants for secondary ADHD from a brain injury. The findings will both guide clinicians on treatment recommendations, and inform the concept and acceptance of SPTs in paediatric research.

Trial registration

Australian New Zealand Clinical Trials Registry. ACTRN12609000873224

【 授权许可】

   
2013 Senior et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Australian Bureau of Statistics: Survey of Disability, Ageing and Carers 2003: summary of findings. Canberra: Australian Bureau of Statistics; 2004.
• [2]Australian Institute of Health and Welfare (AIHW): Disability updates: children with disabilities. Bulletin No. 42. AIHW cat. no. AUS 19. Canberra: AIHW; 2006.
• [3]Catroppa C, Anderson VA, Morse SA, Haritou F, Rosenfeld JV: Children's attentional skills 5 years post-TBI. J Pediatr Psychol 2007, 32(3):354-369.
• [4]Yeates KO, Armstrong K, Janusz J, Taylor HG, Wade S, Stancin T, Drotar D: Long-term attention problems in children with traumatic brain injury. J Am Acad Child Adolesc Psychiatry 2005, 44(6):574-584.
• [5]Max JE, Schachar RJ, Levin HS, Ewing-Cobbs L, Chapman SB, Dennis M, Saunders A, Landis J: Predictors of secondary attention-deficit/hyperactivity disorder in children and adolescents 6 to 24 months after traumatic brain injury. J Am Acad Child Adolesc Psychiatry 2005, 44(10):1041-1049.
• [6]Gerring JP, Brady KD, Chen A, Vasa R, Grados M, Bandeen-Roche KJ, Bryan RN, Denckla MB: Premorbid prevalence of ADHD and development of secondary ADHD after closed head injury. J Am Acad Child Adolesc Psychiatry 1998, 37(6):647-654.
• [7]Brown RT, Amler RW, Freeman WS, Perrin JM, Stein MT, Feldman HM, Pierce K, Wolraich ML: American Academy of Pediatrics Committee on Quality I, American Academy of Pediatrics Subcommittee on Attention-Deficit/Hyperactivity D: Treatment of attention-deficit/hyperactivity disorder: overview of the evidence. Pediatrics 2005, 115(6):e749-757.
• [8]Williams SE, Ris MD, Ayyangar R, Schefft BK, Berch D: Recovery in pediatric brain injury: is psychostimulant medication beneficial? J Head Trauma Rehabil 1998, 13(3):73-81.
• [9]Mahalick DM, Carmel PW, Greenberg JP, Molofsky W, Brown JA, Heary RF, Marks D, Zampella E, Hodosh R, von der Schmidt E: 3rd:Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatr Neurosurg 1998, 29(3):121-126.
• [10]Dans AL, Dans LF, Guyatt GH, Richardson S: Users' guides to the medical literature: XIV. How to decide on the applicability of clinical trial results to your patient. Evidence-Based Medicine Working Group. JAMA: the journal of the American Medical Association 1998, 279(7):545-549.
• [11]Gualtieri CT, Evans RW: Stimulant treatment for the neurobehavioural sequelae of traumatic brain injury. Brain injury : [BI] 1988, 2(4):273-290.
• [12]Nikles J, Mitchell GK, Schluter P, Good P, Hardy J, Rowett D, Shelby-James T, Vohra S, Currow D: Aggregating single patient (n-of-1) trials in populations where recruitment and retention was difficult: The case of palliative care. J Clin Epidemiol 2011, 64(5):471-480.
• [13]Schluter PJ, Ware RS: Single patient (n-of-1) trials with binary treatment preference. Stat Med 2005, 24(17):2625-2636.
• [14]Zucker DR, Schmid CH, McIntosh MW, D'Agostino RB, Selker HP, Lau J: Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment. J Clin Epidemiol 1997, 50(4):401-410.
• [15]Conners CK: Conners 3rd Edition Manual. North Tonawanda, NY: Multi-Health Systems; 2008.
• [16]American Psychiatric Association: Diagnostic and statistical manual of mental disorders : DSM-IV, 4th edn. Washington, DC: American Psychiatric Association; 1994.
• [17]Gioia GA, Isquith PK, Guy SC, Kenworthy L: Behavior rating inventory of executive function. Child neuropsychology: a journal on normal and abnormal development in childhood and adolescence 2000, 6(3):235-238.
• [18]Bakker K, Waugh MC, Epps A, Mandalis A, Brookes N, Levick W, Smith RL: Efficacy of stimulant medication in paediatric acquired brain injury. In Motor Accidents Authority NSW: Motor Accidents Authority NSW. Sydney: Motor Accidents Authority; 2008:1-14.
• [19]Lunn DJ, Thomas A, Best N, Spiegelhalter D: WinBUGS - A Bayesian modelling framework: Concepts, structure, and extensibility. Stat Comput 2000, 10(4):325-337.
• [20]Nikles CJ, Mitchell GK, Del Mar CB, Clavarino A, McNairn N: An n-of-1 trial service in clinical practice: testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder. Pediatrics 2006, 117(6):2040-2046.