Level 2: Mid-level evidence
In the past, concern had been raised that stimulants may increase risk for sudden cardiac death in patients with attention-deficit hyperactivity disorder (ADHD) and underlying heart disease. 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 (Am J Psychiatry. 2009 Jun 15 early online). Researchers used mortality data from 1985-1996 to compare 564 cases of sudden death in children aged 7-19 years 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, based on informants, medical examiner records, toxicology findings, or death certificate. Among children excluded from analysis were those considered to be at high risk with stimulant use because of a cardiac condition (e.g., Wolff-Parkinson-White syndrome, prolonged QT syndrome, Marfan syndrome). Stimulant use was found in 1.8% of cases compared with 0.4% of controls (odds ratio for sudden unexplained death 7.4, 95% confidence interval 1.4-74.9). Researchers were unable to determine the rate of untreated ADHD and could not exclude ADHD itself as a risk factor for sudden death.

The research was funded by the FDA and the National Institute of Mental Health, but the FDA is recommending that stimulant medication not be stopped on the basis of this study. The agency cites several methodologic limitations, 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 (FDA News Release. 2009 Jun 15; and FDA MedWatch. 2009 Jun 15).

The American Heart Association 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; 117:2407-2423). The American Academy of Pediatrics does not recommend routine ECG prior to treatment of ADHD in children (grade C recommendation [lacking direct evidence]) (Pediatrics. 2008;122:451-453).