In the past, concern had been raised that the use of stimulants in patients with attention-deficit hyperactivity disorder (ADHD) and underlying heart disease may increase risk for sudden cardiac death.  A newly published study has reported an association between stimulant use and risk of sudden death in children and adolescents without known cardiac risk factors.  Based on mortality data from 1985-1996, 564 cases of sudden death were compared with 564 matched controls who died as passengers in motor vehicle accidents.  Stimulant use was defined as the use of amphetamine, dextroamphetamine, methamphetamine, methylphenidate or their derivatives immediately prior to death, as noted by informants, medical examiner records, toxicology findings or death certificate.  Among children excluded from analysis were those with cardiac conditions at high risk with stimulant use (such as Wolff-Parkinson-White syndrome, prolonged QT syndrome, Marfan syndrome).  Stimulant use was found in 1.8% of cases compared to 0.4% of controls (odds ratio for sudden unexplained death 7.4, 95% CI 1.4-74.9) (level 2 [mid-level] evidence).  Study researchers were unable to determine the rate of untreated ADHD and could not exclude ADHD itself as the risk factor for sudden death (Am J Psychiatry 2009 Sep;166(9):992 PDF).

The research was funded by the US Food and Drug Administration (FDA) and US National Institute of Mental Health (NIMH), but the FDA is recommending that stimulant medication not be stopped on the basis of these data, citing a number of methodologic limitations in the study, including the low frequency of stimulant use in both groups, the time lag between the deaths and collection of the data, and the possibility of biased recall about medication use at the time of death due to the varying circumstances (FDA News Release 2009 Jun 15, FDA MedWatch 2009 Jun 15).  

The American Heart Association (AHA) has recommended a history and physical exam to detect underlying heart disease and suggested a screening ECG at the discretion of the physician before starting stimulant medications in children (grade C recommendation [lacking direct evidence]) (Circulation 2008 May 6;117(18):2407 PDF).  The American Academy of Pediatrics (AAP) does not recommend routine ECG prior to treatment of ADHD in children (grade C recommendation [lacking direct evidence]) (Pediatrics 2008 Aug;122(2):451).