CNS Drugs

, Volume 31, Issue 12, pp 1043–1055 | Cite as

Effectiveness of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Physical Injuries: A Systematic Review and Meta-Analysis of Observational Studies

  • Kenneth K. C. Man
  • Patrick Ip
  • Esther W. Chan
  • Siew-ling Law
  • Miriam T. Y. Leung
  • Evelyn X. Y. Ma
  • Wan-ting Quek
  • Ian C. K. Wong
Systematic Review



Patients with attention-deficit/hyperactivity disorder (ADHD) are more prone to physical injuries, including motor vehicle accidents, fractures and brain injuries. Several observational studies have been published investigating the association between the use of pharmacological treatment for ADHD and the incidence of physical injuries among patients with ADHD; however, the findings are not concordant.


This study is a systematic review and meta-analysis of the existing literature and estimates the overall association between the use of ADHD medications and physical injury. Injury is defined as medically attended physical injuries in the form of hospitalisations, emergency department visits or general practitioners visits.


The PubMed, EMBASE, PsycINFO, CINAHL and Cochrane Review databases were searched for relevant studies published up to May 2017 relating to ADHD medication and risk of injuries. Observational studies with any study design, all age groups (children and adults) and all ADHD medications (stimulant and non-stimulants) were included. Studies relevant to the association between ADHD medication exposure and risk of injuries in ADHD patients were extracted and compiled for meta-analysis. Both within-individual and between-individual analyses were conducted.


Overall, 2001 citations were identified and 10 observational studies were included. Three self-controlled case series and two self-controlled cohorts were eligible for meta-analysis of within-individual studies. Five cohort studies were included in the meta-analysis of between-individual studies. The adjusted rate ratio of the within-individual methods was 0.76 (95% confidence interval [CI] 0.61–0.93) and 0.88 (95% CI 0.85–0.92) for between-individual studies.


The findings of this meta-analysis support a reduced risk of injuries among ADHD patients who were treated with ADHD medications.


Compliance with Ethical Standards


This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors

Conflict of interest

Dr. Ip reports grants from the Research Grants Council (RGC, Hong Kong) and the Health and Medical Research Fund (Food and Health Bureau, Hong Kong). Prof. Wong reports grants from The Research Grants Council (RGC, Hong Kong), Innovative Medicines Initiative (IMI), Shire, Janssen-Cilag, Eli-Lily, Pfizer, and European Union FP7 programme, outside the submitted work. Prof. Wong was a member of the National Institute for Health and Clinical Excellence (NICE) ADHD Guideline Group and the British Association for Psychopharmacology ADHD guideline group, and acted as an advisor to Shire. Mr Man, Dr Chan, Miss Law, Miss Leung, Miss Ma and Miss Quek report no competing interests. No other relationships or activities have been declared that could appear to have influenced the submitted work.


  1. 1.
    National Institute for Health and Clinical Excellence. Attention deficit hyperactivity disorder – diagnosis and management of ADHD in children, young people and adults. NICE Clinical Guideline 72 2008 [cited 4/26/2012].
  2. 2.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.CrossRefGoogle Scholar
  3. 3.
    Ertan C, Ozcan OO, Pepele MS. Paediatric trauma patients and attention deficit hyperactivity disorder: correlation and significance. Emerg Med J. 2012;29(11):911–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Mikolajczyk R, et al. Injury prevention by medication among children with attention-deficit/hyperactivity disorder: a case-only study. JAMA Pediatrics. 2015;169(4):391–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Raman SR, et al. Stimulant treatment and injury among children with attention deficit hyperactivity disorder: an application of the self-controlled case series study design. Injury Prev. 2013;19(3):164–70.CrossRefGoogle Scholar
  6. 6.
    Man KKC, et al. Methylphenidate and the risk of trauma. Pediatrics. 2015;135(1):40–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Kay GG, Michaels MA, Pakull B. Simulated driving changes in young adults with ADHD receiving mixed amphetamine salts extended release and atomoxetine. J Attent Disord. 2009;12(4):316–29.CrossRefGoogle Scholar
  8. 8.
    Esposito DB, et al. Stimulant treatment and risk of traffic accidents requiring acute care in adults with attention deficit hyperactivity disorder. Pharmacoepidemiol Drug Saf. 2015;24:355.Google Scholar
  9. 9.
    Marcus SC, et al. Injury among stimulant-treated youth with ADHD. J Atten Disord. 2008;12(1):64–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. 2011 [4 Aug 2014].
  11. 11.
    Wells G, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Resource document. Ottawa: Ottawa Hospital Research Institute; 2000.Google Scholar
  12. 12.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMedGoogle Scholar
  13. 13.
    van den Ban E, et al. Association between ADHD drug use and injuries among children and adolescents. Eur Child Adolesc Psychiatry. 2014;23(2):95–102.CrossRefPubMedGoogle Scholar
  14. 14.
    Chang Z, et al. Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication a population-based study. JAMA Psychiatry. 2014;71(3):319–25.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chen VCH, et al. The association between methylphenidate treatment and the risk for fracture among young ADHD patients: a nationwide population-based study in Taiwan. PLoS One. 2017;12(3):e0173762.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chien WC, et al. The risk of injury in adults with attention-deficit hyperactivity disorder: a nationwide, matched-cohort, population-based study in Taiwan. Res Dev Disabil. 2017;65:57–73.CrossRefPubMedGoogle Scholar
  17. 17.
    Dalsgaard S, et al. Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: a prospective cohort study. Lancet Psychiatry. 2015;2(8):702–9.CrossRefPubMedGoogle Scholar
  18. 18.
    Merrill RM, et al. Attention deficit hyperactivity disorder and increased risk of injury. Adv Med Sci. 2009;54(1):20–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Chang Z, et al. Association between medication use for attention-deficit/hyperactivity disorder and risk of motor vehicle crashes. JAMA Psychiatry. 2017;74(6):597–603.CrossRefPubMedGoogle Scholar
  20. 20.
    Lao KSJ, et al. Medication safety research by observational study design. Int J Clin Pharm. 2016;38(3):676–84.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Man KKC, et al. Association of risk of suicide attempts with methylphenidate treatment. JAMA Psychiatry. 2017;74(10):1048–55.CrossRefPubMedGoogle Scholar
  22. 22.
    Man KK, et al. Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Transl Psychiatry. 2016;6(11):e956.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    McCarthy S, et al. Mortality associated with attention-deficit hyperactivity disorder (ADHD) drug treatment: a retrospective cohort study of children, adolescents and young adults using the general practice research database. Drug Saf. 2009;32(11):1089–96.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Kenneth K. C. Man
    • 1
    • 2
    • 3
    • 4
    • 5
  • Patrick Ip
    • 5
  • Esther W. Chan
    • 1
  • Siew-ling Law
    • 3
  • Miriam T. Y. Leung
    • 1
  • Evelyn X. Y. Ma
    • 3
  • Wan-ting Quek
    • 3
  • Ian C. K. Wong
    • 1
    • 3
    • 5
  1. 1.Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina
  2. 2.Department of Social Work and Social Administration, Faculty of Social ScienceThe University of Hong KongHong KongChina
  3. 3.Research Department of Practice and PolicyUCL School of PharmacyLondonUK
  4. 4.Department of Medical InformaticsErasmus University Medical CenterRotterdamThe Netherlands
  5. 5.Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina

Personalised recommendations