European Child & Adolescent Psychiatry

, Volume 27, Issue 3, pp 279–288 | Cite as

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
Original Contribution

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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.


Attention-deficit/hyperactivity disorder Traumatic brain injury Methylphenidate 



Attention-deficit hyperactivity disorder






National Health Insurance


Traumatic brain injury



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.

Author 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.

Compliance with ethical standards


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.

Supplementary material

787_2017_1042_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Yin-To Liao
    • 1
    • 2
  • Yao-Hsu Yang
    • 3
    • 4
    • 5
  • Ting-Yu Kuo
    • 4
  • Hsin-Yi Liang
    • 6
    • 7
  • Kuo-You Huang
    • 8
  • Tsu-Nai Wang
    • 9
  • Yena Lee
    • 10
    • 11
  • Roger S. McIntyre
    • 10
    • 11
    • 12
  • Vincent Chin-Hung Chen
    • 7
    • 13
  1. 1.Department of PsychiatryChung Shan Medical University HospitalTaichungTaiwan
  2. 2.Department of Psychiatry, School of MedicineChung Shan Medical UniversityTaichungTaiwan
  3. 3.Department of Traditional Chinese MedicineChiayi Chang Gung Memorial HospitalChiayiTaiwan
  4. 4.Center of Excellence for Chang Gung Research DatalinkChiayi Chang Gung Memorial HospitalChiayiTaiwan
  5. 5.Institute of Occupational Medicine and Industrial HygieneNational Taiwan University College of Public HealthTaipeiTaiwan
  6. 6.Department of Child PsychiatryLinkou Chang Gung Memorial HospitalTaoyuanTaiwan
  7. 7.School of MedicineChang Gung UniversityTaoyuanTaiwan
  8. 8.Department of Speech, Language Pathology and AudiologyChung Shan Medical UniversityTaichungTaiwan
  9. 9.Department of Public Health, College of Health ScienceKaohsiung Medical UniversityKaohsiungTaiwan
  10. 10.Mood Disorders Psychopharmacology UnitUniversity Health Network, University of TorontoTorontoCanada
  11. 11.Institute of Medical ScienceUniversity of TorontoTorontoCanada
  12. 12.Departments of Psychiatry and PharmacologyUniversity of TorontoTorontoCanada
  13. 13.Department of PsychiatryChiayi Chang Gung Memorial HospitalPuzi CityTaiwan, ROC

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