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.
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.


METHODS
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).


CONCLUSIONS
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.
McCarthy
Suzanne
S
Centre for Paediatric Pharmacy Research, The School of Pharmacy, University of London and The Institute of Child Health, University College London, London, UK.
Cranswick
Noel
N
Potts
Laura
L
Taylor
Eric
E
Wong
Ian C K
IC
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000401:mortality*; D002423:Cause of Death; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016208:Databases, Factual; D003645:Death, Sudden / Q000209:etiology*; D003913:Dextroamphetamine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use; D011437:Propylamines / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D012307:Risk Factors; D013405:Suicide / Q000706:statistics & numerical data; D006113:United Kingdom; D055815:Young Adult
D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D003913:Dextroamphetamine