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Dosage of methylphenidate and traumatic brain injury in ADHD: a population-based study in Taiwan

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Abstract

Preventive effect of stimulants on the risk of brain injuries had been reported. The aim of this study is to determine the extent to which methylphenidate (MPH) prescription moderates the risk of traumatic brain injuries (TBI) in individuals with attention-deficit/hyperactivity disorder (ADHD). Individuals with a recent diagnosis of ADHD between January 1997 and December 2013 (n = 163,618) were identified from Taiwan’s National Health Insurance Research Database. A total of 124,438 adolescents and children with ADHD and without prior TBI diagnoses were included and evaluated for subsequent TBI. Methylphenidate prescription duration was subgrouped by the annual average cumulative defined daily dose (DDD): 0, >0 to ≤28, > 28 to ≤84, and >84. We identified 11,463 diagnoses of TBI among 124,438 adolescents and children with ADHD. A Cox regression model was used to investigate whether MPH prescription influenced the risk for TBI after adjusting for sex, age, level of urbanization, seizure, autism and sedative–anxiolytics use. A reduced TBI incidence was observed with MPH prescription DDDs > 84. The protective effect of MPH against TBI persisted after adjusting for confounding factors [hazard ratio (HR) = 0.49; 95% confidence interval (CI): 0.47–0.51]. There was also statistically significant difference in risk for TBI in subjects receiving > 0 to ≤28 or >28 to ≤84 DDDs of MPH treatment (HR = 0.88, 95% CI = 0.83–0.92; HR = 0.76, 95% CI = 0.72–0.80, respectively) when compared with subjects not receiving treatment with MPH. Treatment with MPH for greater than 84 DDDs reduced the risk for TBI among children with ADHD.

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Abbreviations

ADHD:

Attention-deficit hyperactivity disorder

ATX:

Atomoxetine

MPH:

Methylphenidate

NHI:

National Health Insurance

TBI:

Traumatic brain injury

References

  1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942–948

    Article  PubMed  Google Scholar 

  2. Visser SN, Bitsko RH, Danielson ML, Perou R, Blumberg SJ (2010) Increasing prevalence of parent-reported attention-deficit/hyperactivity disorder among children—United States, 2003 and 2007. MMWR Morb Mortal Wkly Rep 59:1439–1443

    Google Scholar 

  3. Barkley RA, Fischer M, Smallish L, Fletcher K (2006) Young adult outcome of hyperactive children: adaptive functioning in major life activities. J Am Acad Child Adolesc Psychiatry 45:192–202

    Article  PubMed  Google Scholar 

  4. Man KK, Chan EW, Coghill D, Douglas I, Ip P, Leung LP, Tsui MS, Wong WH, Wong IC (2015) Methylphenidate and the risk of trauma. Pediatrics 135:40–48

    Article  PubMed  Google Scholar 

  5. Clancy TA, Rucklidge JJ, Owen D (2006) Road-crossing safety in virtual reality: a comparison of adolescents with and without ADHD. J Clin Child Adolesc Psychol 35:203–215

    Article  PubMed  Google Scholar 

  6. Rowe R, Maughan B, Goodman R (2004) Childhood psychiatric disorder and unintentional injury: findings from a national cohort study. J Pediatr Psychol 29:119–130

    Article  PubMed  Google Scholar 

  7. Ertan C, Ozcan OO, Pepele MS (2012) Paediatric trauma patients and attention deficit hyperactivity disorder: correlation and significance. Emerg Med J 29:911–914

    Article  PubMed  Google Scholar 

  8. Barkley RA, Fischer M, Smallish L, Fletcher K (2002) The persistence of attention-deficit/hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder. J Abnorm Psychol 111:279–289

    Article  PubMed  Google Scholar 

  9. Swanson JM (2003) Role of executive function in ADHD. J Clin Psychiatry 64(Suppl 14):35–39

    CAS  PubMed  Google Scholar 

  10. Cairney J (2014) Deficits in attention, motor control, and perception and increased risk of injury in children. Dev Med Child Neurol 56:1040–1041

    Article  PubMed  Google Scholar 

  11. Tai YM, Gau SS, Gau CS (2013) Injury-proneness of youth with attention-deficit hyperactivity disorder: a national clinical data analysis in Taiwan. Res Dev Disabil 34:1100–1108

    Article  PubMed  Google Scholar 

  12. Parslow RC, Morris KP, Tasker RC, Forsyth RJ, Hawley CA, Group UKPTBISS, Paediatric Intensive Care Society Study G (2005) Epidemiology of traumatic brain injury in children receiving intensive care in the UK. Arch Dis Child 90:1182–1187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Centers for Disease C, Prevention (2011) Nonfatal traumatic brain injuries related to sports and recreation activities among persons aged ≤19 years—United States, 2001–2009. MMWR Morb Mortal Wkly Rep 60:1337–1342

    Google Scholar 

  14. Mikolajczyk R, Horn J, Schmedt N, Langner I, Lindemann C, Garbe E (2015) Injury prevention by medication among children with attention-deficit/hyperactivity disorder: a case-only study. JAMA Pediatr 169:391–395

    Article  PubMed  Google Scholar 

  15. Vaughan B, Kratochvil CJ (2012) Pharmacotherapy of pediatric attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 21:941–955

    Article  PubMed  Google Scholar 

  16. Chang Z, Lichtenstein P, D’Onofrio BM, Sjolander A, Larsson H (2014) Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication: a population-based study. JAMA Psychiatry 71:319–325

    Article  PubMed  PubMed Central  Google Scholar 

  17. Raman SR, Marshall SW, Haynes K, Gaynes BN, Naftel AJ, Sturmer T (2013) Stimulant treatment and injury among children with attention deficit hyperactivity disorder: an application of the self-controlled case series study design. Inj Prev 19:164–170

    Article  PubMed  Google Scholar 

  18. Gajria K, Lu M, Sikirica V, Greven P, Zhong Y, Qin P, Xie J (2014) Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder - a systematic literature review. Neuropsychiatr Dis Treat 10:1543–1569

    PubMed  PubMed Central  Google Scholar 

  19. Hong J, Novick D, Treuer T, Montgomery W, Haynes VS, Wu S, Haro JM (2013) Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia. Patient Prefer Adherence 7:987–995

    Article  PubMed  PubMed Central  Google Scholar 

  20. Tsai CJ, Lee CT, Liang SH, Tsai PJ, Chen VC, Gossop M (2015) Risk of ADHD after multiple exposures to general anesthesia: a Nationwide Retrospective Cohort Study. J Atten Disord. doi:10.1177/1087054715587094

    Google Scholar 

  21. Lee MJ, Yang KC, Shyu YC, Yuan SS, Yang CJ, Lee SY, Lee TL, Wang LJ (2016) Attention-deficit hyperactivity disorder, its treatment with medication and the probability of developing a depressive disorder: a Nationwide Population-Based Study in Taiwan. J Affect Disord 189:110–117

    Article  PubMed  Google Scholar 

  22. Lichtenstein P, Halldner L, Zetterqvist J, Sjolander A, Serlachius E, Fazel S, Langstrom N, Larsson H (2012) Medication for attention deficit-hyperactivity disorder and criminality. N Engl J Med 367:2006–2014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chen CY, Yeh HH, Chen KH, Chang IS, Wu EC, Lin KM (2011) Differential effects of predictors on methylphenidate initiation and discontinuation among young people with newly diagnosed attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 21:265–273

    Article  PubMed  Google Scholar 

  24. Fine JPGR (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509

    Article  Google Scholar 

  25. Dalsgaard S, Leckman JF, Mortensen PB, Nielsen HS, Simonsen M (2015) Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study. Lancet Psychiatry 2:702–709

    Article  PubMed  Google Scholar 

  26. Aduen PA, Kofler MJ, Cox DJ, Sarver DE, Lunsford E (2015) Motor vehicle driving in high incidence psychiatric disability: comparison of drivers with ADHD, depression, and no known psychopathology. J Psychiatr Res 64:59–66

    Article  PubMed  Google Scholar 

  27. Winston FK, McDonald CC, McGehee DV (2013) Are we doing enough to prevent the perfect storm?: novice drivers, ADHD, and distracted driving. JAMA Pediatr 167:892–894

    Article  PubMed  Google Scholar 

  28. Clemow DB, Bushe CJ (2015) Atomoxetine in patients with ADHD: A clinical and pharmacological review of the onset, trajectory, duration of response and implications for patients. J Psychopharmacol 29(12):1221–1230

    Article  CAS  PubMed  Google Scholar 

  29. Gazer-Snitovsky M, Brand-Gothelf A, Dubnov-Raz G, Weizman A, Gothelf D (2015) High familial correlation in methylphenidate response and side effect profile. J Atten Disord. doi:10.1177/1087054715580844

    PubMed  Google Scholar 

  30. Fredriksen M, Dahl AA, Martinsen EW, Klungsoyr O, Haavik J, Peleikis DE (2014) Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity. Eur Neuropsychopharmacol 24:1873–1884

    Article  CAS  PubMed  Google Scholar 

  31. Setyawan J, Fridman M, Hodgkins P, Quintero J, Erder MH, Katic BJ, Harpin V (2015) Relationship between symptom impairment and treatment outcome in children and adolescents with attention-deficit/hyperactivity disorder: a physician perspective. Atten Defic Hyperact Disord 7:75–87

    Article  PubMed  Google Scholar 

  32. Schweren LJ, de Zeeuw P, Durston S (2013) MR imaging of the effects of methylphenidate on brain structure and function in attention-deficit/hyperactivity disorder. Eur Neuropsychopharmacol 23:1151–1164

    Article  CAS  PubMed  Google Scholar 

  33. Wiguna T, Guerrero AP, Wibisono S, Sastroasmoro S (2012) Effect of 12-week administration of 20-mg long-acting methylphenidate on Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the prefrontal cortices of school-age children in Indonesia: a study using 1H magnetic resonance spectroscopy (MRS). Clin Neuropharmacol 35:81–85

    Article  CAS  PubMed  Google Scholar 

  34. van der Marel K, Bouet V, Meerhoff GF, Freret T, Boulouard M, Dauphin F, Klomp A, Lucassen PJ, Homberg JR, Dijkhuizen RM, Reneman L (2015) Effects of long-term methylphenidate treatment in adolescent and adult rats on hippocampal shape, functional connectivity and adult neurogenesis. Neuroscience 309:243–258

    Article  PubMed  Google Scholar 

  35. Amiri A, Torabi Parizi G, Kousha M, Saadat F, Modabbernia MJ, Najafi K, Atrkar Roushan Z (2013) Changes in plasma Brain-derived neurotrophic factor (BDNF) levels induced by methylphenidate in children with Attention deficit-hyperactivity disorder (ADHD). Prog Neuropsychopharmacol Biol Psychiatry 47:20–24

    Article  CAS  PubMed  Google Scholar 

  36. Yeoh C, Davies H (1993) Clinical coding: completeness and accuracy when doctors take it on. BMJ 306:972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH (2014) Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol 24:500–507

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lee MJ, Yang KC, Shyu YC, Yuan SS, Yang CJ, Lee SY, Lee TL, Wang LJ (2015) Attention-deficit hyperactivity disorder, its treatment with medication and the probability of developing a depressive disorder: a Nationwide Population-Based Study in Taiwan. J Affect Disord 189:110–117

    Article  PubMed  Google Scholar 

  39. Bali V, Kamble PS, Aparasu RR (2015) Predictors of concomitant use of antipsychotics and stimulants and its impact on stimulant persistence in pediatric attention deficit hyperactivity disorder. J Manag Care Spec Pharm 21:486–498

    Article  PubMed  Google Scholar 

  40. Hsu YC, Chien IC, Tan HK, Lin CH, Cheng SW, Chou YJ, Chou P (2013) Trends, correlates, and disease patterns of antipsychotic use among children and adolescents in Taiwan. Soc Psychiatry Psychiatr Epidemiol 48:1889–1896

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The present study was supported in part by the Ministry of Science and Technology, R.O.C. (MOST 102-2314-B-040-004-MY3) and Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital (CMRPG6E0261). The authors would like to thank the Center of Excellence for Chang Gung Research Datalink (CORPG6D0161) for the comments and assistance in data analysis. This study was supported by a grant from the Chang Gung Memorial Hospital, Chia-yi Branch, and based on the National Health Insurance Research Database provided by the Central Bureau of National Health Insurance, the Department of Health, and managed by the National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes.

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    Authors and Affiliations

    1. Department of Psychiatry, Chung Shan Medical University Hospital, Taichung, Taiwan

      Yin-To Liao

    2. Department of Psychiatry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan

      Yin-To Liao

    3. Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

      Yao-Hsu Yang

    4. Center of Excellence for Chang Gung Research Datalink, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

      Yao-Hsu Yang & Ting-Yu Kuo

    5. Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan

      Yao-Hsu Yang

    6. Department of Child Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

      Hsin-Yi Liang

    7. School of Medicine, Chang Gung University, Taoyuan, Taiwan

      Hsin-Yi Liang & Vincent Chin-Hung Chen

    8. Department of Speech, Language Pathology and Audiology, Chung Shan Medical University, Taichung, Taiwan

      Kuo-You Huang

    9. Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan

      Tsu-Nai Wang

    10. Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Toronto, Canada

      Yena Lee & Roger S. McIntyre

    11. Institute of Medical Science, University of Toronto, Toronto, Canada

      Yena Lee & Roger S. McIntyre

    12. Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Canada

      Roger S. McIntyre

    13. Department of Psychiatry, Chiayi Chang Gung Memorial Hospital, 6-8, West Section, Jiapu Road, Puzi City, 613, Chiayi, Taiwan, ROC

      Vincent Chin-Hung Chen

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    1. Yin-To Liao
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    Contributions

    Dr. Liao and Dr. Chen had the original idea for the study, designed the study, and drafted and revised the manuscript. Dr. Yang, Dr. Kuo, Dr. Huang, and Dr. Wang extracted and analyzed the data from the database. Dr. Liang, Dr. Lee, and Dr. McIntyre provided critical revision of the manuscript. Dr. Chen reviewed the literature, interpreted the analyzed data, drafted and revised the manuscript, and approved the final manuscript as submitted.

    Corresponding author

    Correspondence to Vincent Chin-Hung Chen.

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    Funding

    The present study is supported in part by the Ministry of Science and Technology, R.O.C. (MOST 102-2314-B-040-004-MY3) and the Chang Gung Medical Foundation, Chiayi Chang Gung Memorial Hospital (CMRPG6E0261). All funding sources had no role in the study design, data collection, and analysis.

    Conflict of interest

    Author Vincent Chin-Hung Chen has received speaking honoraria from Pfizer, Eli Lilly, Janssen, Astellas, GlaxoSmithKline ,and AstraZeneca, and has been an investigator in two clinical trials from Eli Lilly and Janssen. All other authors declare that they have no conflicts of interest.

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    Liao, YT., Yang, YH., Kuo, TY. et al. Dosage of methylphenidate and traumatic brain injury in ADHD: a population-based study in Taiwan. Eur Child Adolesc Psychiatry 27, 279–288 (2018). https://doi.org/10.1007/s00787-017-1042-7

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    • DOI: https://doi.org/10.1007/s00787-017-1042-7

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    Article history

    1. Latest

      Dosage of methylphenidate and traumatic brain injury in ADHD: a population-based study in Taiwan
      • Yin-To Liao
      • Yao-Hsu Yang
      • Ting-Yu Kuo
      • Hsin-Yi Liang
      • Kuo-You Huang
      • Tsu-Nai Wang
      • Yena Lee
      • Roger S. McIntyre
      • Vincent Chin-Hung Chen
      Published:
      01 March 2018
      Received:
      27 October 2016
      Accepted:
      23 August 2017

      DOI: https://doi.org/10.1007/s00787-017-1042-7

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