Mortality Associated with Attention-Deficit Hyperactivity Disorder (ADHD) Drug Treatment
- First Online:
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.
- 1.American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
- 2.NICE. Attention deficit hyperactivity disorder: diagnosis and management of ADHD in children, young people and adults CG72. London: National Institute for Health and Clinical Excellence, 2008Google Scholar
- 4.Atomoxetine SPC. Summary of product characteristics. Strattera® Eli Lilly and Company Limited. Electronic medicines compendium [online]. Available from URL: http://emc.medicines.org.uk [Accessed 2007 Jul 27]
- 5.Wilens TE, Biederman J, Lerner M, and the Concerta® Study Group. Effects of once-daily osmotic-release methylphenidate on blood pressure and heart rate in children with attention-deficit/hyperactivity disorder: results from a one-year follow-up study. J Clin Psychopharmacol 2004; 24: 36–41PubMedCrossRefGoogle Scholar
- 13.Food and Drug Administration, Center for Drug Evaluation and Research. Review of AERS data for marketed safety experience during stimulant therapy: death, sudden death, cardiovascular SAEs (including stroke) [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4202B1_05_FDA-Tab05.pdf [Accessed 2006 Oct 3]
- 14.Food and Drug Administration news. FDA directs ADHD drug manufacturers to notify patients about cardiovascular adverse events and psychiatric adverse events [online]. Available from URL: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01568.html [Accessed 2007 May 5]
- 15.Food and Drug Administration news: ADRQ and FDA to collaborate in largest study ever of possible heart risks with ADHD medications [online]. Available from URL: http://www.fda.gov/bbs/topics/NEWS/2007/NEW01700.html [Accessed 2007 Nov 6]
- 25.Wong ICK, Ackers R, Besag F, et al. Mortality following antiepileptic drug use in paediatrics (MAP). MHRA commissioned Pharmacoepidemiology Research final report. London: Medicines and Healthcare product Regulatory Agency, 2009Google Scholar
- 28.Breslow NE, Day NE. Statistical methods in cancer research. Vol. II: the design and analysis of cohort studies. Lyon: International Agency for Research on Cancer, 1987Google Scholar
- 30.Medicines and Healthcare products Regulatory Agency. Yellow Card System. Drug analysis prints [online]. Available from URL: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&nodeId=742 [Accessed 2007 Sep 6]
- 31.Vetter V, Elia J, Erickson C, et al. Cardiovascular monitoring of children and adolescents with heart disease receiving medications for attention deficit/hyperactivity disorder: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young Congenital Cardiac Defects Committee and the Council on Cardiovascular Nursing. Circulation 2008; 117: 2407–23PubMedCrossRefGoogle Scholar