Cardiac Safety of Central Nervous System Stimulants in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder

Abstract

OBJECTIVES. Case reports have raised concerns about the risk of cardiac events associated with central nervous system stimulants for the treatment of attention-deficit/hyperactivity disorder. PATIENTS AND METHODS. This was a retrospective cohort study that used 10 years (July 1994 to June 2004) of Florida Medicaid claims data cross-linked to Vital Statistics Death Registry data. The cohort was composed of all youth 3 to 20 years old who were newly diagnosed with attention-deficit/hyperactivity disorder. Each month of follow-up was classified according to stimulant claims (methylphenidate, amphetamines, and pemoline) as current use (active stimulant claim), former use (time after periods of current use), or nonuse (time preceding the first stimulant claim, including follow-up of youth who were never exposed to stimulants). The study's end points were (1) cardiac death, (2) first hospital admission for cardiac causes or (3) first emergency department visit for cardiac causes. Risks were compared with time-dependent Cox regression analysis adjusting for various cardiac risk factors. RESULTS. During 124932 person-years of observation (n = 55383), 73 youth died, 5 because of cardiac causes. No cardiac death occurred during 42612 person-years of stimulant use. Hospital admissions for cardiac cause occurred for 27 children (8 during stimulant use, 11 during 35671 person-years of former use, and 8 during 46649 person-years of nonuse); and 1091 children visited the emergency department for cardiac causes (8.7 per 1000 person-years). Current stimulant use was associated with a 20% increase in the hazard for emergency department visits when compared with nonuse. No increased risk was found for periods of former use when compared with nonuse. CONCLUSIONS. Incidence rates of cardiac events requiring hospitalization were small and similar to national background rates. Stimulants were associated with an increase in cardiac emergency department visits. More evidence is needed that addresses the long-term risk/benefit of the various treatment options and the effect of other cardiac risk factors and comedications.