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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

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Abstract

Background: Following reports of sudden death in patients taking medication to treat attention-deficit hyperactivity disorder (ADHD), this study aimed to identify cases of death in patients prescribed stimulants and atomoxetine and to determine any association between these and sudden death.

Method: The UK General Practice Research Database (GPRD) was used to identify patients aged 2–21 years from 1 January 1993 to 30 June 2006 with a prescription for methylphenidate, dexamfetamine or atomoxetine. Patients were followed from the date of first prescription until whichever came first: date of death, transferred-out date, age >21 years or end of the study period.

Results: From a cohort of 18 637 patient-years, seven patients died. Cause of death was obtained for six of the patients. None were deemed to be cases of sudden death. Compared with a general population rate of sudden death in the literature, the worst-case scenario of one case of sudden death gave an incident rate ratio of 1.63 (95% CI 0.04, 9.71). Although it was not the primary outcome of the study, following reports of suicide in the cohort the standardized mortality ratio (SMR) of suicide was calculated. Due to differences in the definition of suicide used for children and adults, patients were categorized into two age groups: 11–14 years and 15–21 years. The SMR for suicide for patients aged 11–14 years was 161.91 (95% CI 19.61, 584.88). The SMR for suicide for patients aged 15–21 years was 1.84 (95% CI 0.05, 10.25).

Conclusion: This study demonstrated no increase in the risk of sudden death associated with stimulants or atomoxetine. However, an increased risk of suicide was seen. Although we cannot exclude that the medications may contribute to the increased risk of suicide, there are other factors such as depression and antisocial behaviour that frequently co-exist with ADHD, which can also predispose to teenage suicide. Clinicians should identify patients at increased risk of cardiovascular events and identify those patients at increased risk of suicide, particularly males with co-morbid conditions, and monitor them appropriately.

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Acknowledgements

The license for the General Practice Research Database was funded by the European Commission via the Taskforce European Drug Development for the Young (TEDDY) network of Excellence European Commission Framework 6 Programme 2005–2010. ## The School of Pharmacy has received an education grant from Janssen Cilag for professional continued development courses. No specific funding was obtained for the conduct of this study. Ian Wong was funded by a UK Department of Health Public Health Career Scientist Award to investigate the safety of psychotropic drugs in children. ## Eric Taylor and Ian C.K. Wong were members of the NICE guideline committee for the diagnosis and management of ADHD in children, young people and adults. The other authors have no conflicts of interest relevant to the content of this study.

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Authors and Affiliations

  1. Centre for Paediatric Pharmacy Research, The School of Pharmacy, University of London and The Institute of Child Health, University College London, BMA House, Tavistock Square, London, WC1H 9JP, UK

    Suzanne McCarthy &  Ian C. K. Wong

  2. Murdoch Children’s Research Institute & the Royal Children’s Hospital, University of Melbourne, Parkville, Victoria, Australia

    Noel Cranswick

  3. Mental Health and Neuroscience Clinical Trial Unit, Institute of Psychiatry, De Crespigny Park, London, UK

    Laura Potts

  4. Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Denmark Hill, London, UK

    Eric Taylor

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  1. Suzanne McCarthy
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  2. Noel Cranswick
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  3. Laura Potts
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  4. Eric Taylor
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  5. Ian C. K. Wong
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Correspondence to Ian C. K. Wong.

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McCarthy, S., Cranswick, N., Potts, L. et al. Mortality Associated with Attention-Deficit Hyperactivity Disorder (ADHD) Drug Treatment. Drug-Safety 32, 1089–1096 (2009). https://doi.org/10.2165/11317630-000000000-00000

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