1: Ned Tijdschr Geneeskd. 2006 Aug 5;150(31):1713-4.  
[ADHD drugs and cardiovascular risk]
[Article in Dutch]
Langendijk PN, Wilde AA.
Academisch Medisch Centrum/Universiteit van Amsterdam, Postbus 22.660, 1100 DD Amsterdam.

Recently, the FDA recommended a black-box warning describing the increased risk of cardiovascular events associated with the use of stimulant drugs (amphetamines; in the Netherlands: dexamphetamine, methylphenidate) in the treatment of attention deficit hyperactivity disorder (ADHD). The recommendation was based largely on the increased use of these drugs in children and adults in the USA, voluntary reporting of adverse events, and the pharmacological analogy with other sympathomimetic amines, such as ephedrine, pseudoephedrine and phenylpropanolamine, for which similarwarnings have been given previously. The Adverse Event Reporting System documented 25 cases of sudden death based on WHO criteria with the use of amphetamines and methylphenidate; most of the cases were children aged less than 18 years. Sudden death in children is most often caused by fatal arrhythmias due to congenital heart diseases, such as long QT syndrome and hypertrophic cardiomyopathy. An increase in heart rate can potentially provoke life-threatening arrhythmias when the QT interval does not compensate for the increase. In adults, increased blood pressure and heart rate are well-documented risk factors for cardiovascular events. The use of methylphenidate is increasing in the Netherlands, indicating that greater caution is warranted when prescribing these drugs.

PMID: 16924941 [PubMed - in process]
 
2: Pediatrics. 2006 Sep;118(3):1215-9.  
 
Stimulants and sudden death: what is a physician to do?

Wilens TE, Prince JB, Spencer TJ, Biederman J.

Clinical Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. twilens@partners.org

OBJECTIVE: Recently, a US Food and Drug Administration advisory committee raised concerns about cardiovascular risks and sudden death in children and adolescents with attention-deficit/hyperactivity disorder who are receiving stimulants. METHODS: We comment on the risk of sudden death in children/adolescents taking stimulants compared with population rates, biological plausibility, and known cardiovascular effects of stimulants to determine specific risk.
RESULTS: There does not seem to be higher risk of sudden death in stimulant-treated individuals compared with the general population. Although there is evidence of biological plausibility, the known effects of the stimulants on cardiovascular electrophysiology and vital signs seem to be benign. CONCLUSIONS: There does not seem to be compelling findings of a medication-specific risk necessitating changes in our stimulant treatment of children and adolescents with attention-deficit/hyperactivity disorder. The use of existing guidelines on the use of stimulants (and psychotropic agents) may identify children, adolescents, and adults who are vulnerable to sudden death.