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.
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.
Authors: Timothy E Wilens; Paul G Hammerness; Joseph Biederman; Anne Kwon; Thomas J Spencer; Sarah Clark; Megan Scott; Amy Podolski; Jeffrey W Ditterline; Matthew C Morris; Hadley Moore Journal: J Clin Psychiatry Date: 2005-02 Impact factor: 4.384
Authors: Paula Louise Thompson; Ruth E Gilbert; Paul F Long; Sonia Saxena; Mike Sharland; Ian Chi Kei Wong Journal: Pediatrics Date: 2009-02 Impact factor: 7.124
Authors: Victoria L Vetter; Josephine Elia; Christopher Erickson; Stuart Berger; Nathan Blum; Karen Uzark; Catherine L Webb Journal: Circulation Date: 2008-04-21 Impact factor: 29.690
Authors: Laurel A Habel; William O Cooper; Colin M Sox; K Arnold Chan; Bruce H Fireman; Patrick G Arbogast; T Craig Cheetham; Virginia P Quinn; Sascha Dublin; Denise M Boudreau; Susan E Andrade; Pamala A Pawloski; Marsha A Raebel; David H Smith; Ninah Achacoso; Connie Uratsu; Alan S Go; Steve Sidney; Mai N Nguyen-Huynh; Wayne A Ray; Joe V Selby Journal: JAMA Date: 2011-12-12 Impact factor: 56.272
Authors: Ruth Ackers; Frank M C Besag; Elaine Hughes; Waney Squier; Macey L Murray; Ian C K Wong Journal: Drug Saf Date: 2011-05-01 Impact factor: 5.606
Authors: Mark Wolraich; Lawrence Brown; Ronald T Brown; George DuPaul; Marian Earls; Heidi M Feldman; Theodore G Ganiats; Beth Kaplanek; Bruce Meyer; James Perrin; Karen Pierce; Michael Reiff; Martin T Stein; Susanna Visser Journal: Pediatrics Date: 2011-10-16 Impact factor: 7.124
Authors: Esther W Chan; Kirin Q L Liu; Celine S L Chui; Chor-Wing Sing; Lisa Y L Wong; Ian C K Wong Journal: Br J Clin Pharmacol Date: 2015-06-01 Impact factor: 4.335
Authors: Stephan Linden; Regina Bussing; Paul Kubilis; Tobias Gerhard; Richard Segal; Jonathan J Shuster; Almut G Winterstein Journal: Pediatrics Date: 2016-05 Impact factor: 7.124
Authors: Mark Olfson; Cecilia Huang; Tobias Gerhard; Almut G Winterstein; Stephen Crystal; Paul D Allison; Steven C Marcus Journal: J Am Acad Child Adolesc Psychiatry Date: 2011-12-20 Impact factor: 8.829
Authors: Hedi Schelleman; Warren B Bilker; Brian L Strom; Stephen E Kimmel; Craig Newcomb; James P Guevara; Gregory W Daniel; Mark J Cziraky; Sean Hennessy Journal: Pediatrics Date: 2011-05-16 Impact factor: 7.124