blems in children? It is a controver- sial topic—and not just among psychia- trists. Cardiologists and pediatricians have done battle over this issue, and their respective medical societies have
opposite recommendations on whether to get EKGs in children before treat- ment. The cardiologists say “yes,” while the pediatricians say, “no, not really necessary.”
In the past, the FDA has looked into this issue and decided not to issue a black box warning, but they recom- mended that manufacturers of stimulant medications add label warnings regard- ing the risk of sudden death in patients with known cardiac abnormalities. Now a new study complicates the debate. Funded by the FDA and the NIMH, epi- demiologists searched state vital statis- tics for all cases of unexplained sudden death in children occurring in the U.S. from 1985-1996. They found a total of 564 cases of sudden death over that period. They then looked at how many of these children had been taking stimu- lants at their time of death. Using a vari- ety of information sources, such as toxi- cology reports and parental reports, they determined that a total of 10 of these children—1.8% of the total—were taking stimulants when they died. In all 10 cases, the identified stimulant was Ritalin (methylphenidate). (They did not limit their analysis to Ritalin—this was simply the most commonly prescribed stimulant during the period they studied.)
he next step of the study was the crucial one, because the 1.8% figure means nothing by itself. It could mean that these 10 children happened to be taking Ritalin when they died, and that the cause of death had nothing at all to do with the medication. In order to shed light on this figure, the researchers found a comparison group of children who had also died suddenly, but for whom the cause of death was known. They chose as their control group 564 matched cases of children who died in motor vehicle accidents. They chose this comparison group because this was a close match for the children who died from unknown reasons. They figured that since both unexplained sudden deaths and deaths from car accidents involved parents or guardians experienc- ing a sudden and traumatic loss of a child, the accuracy of parental recall about whether the children were taking stimulants would be about the same. We’ll come back to this.
The results? Out of 564 children who died of MVA, only two children were identified as having used stimu- lants (0.4%), fewer than the 10 children stimulant-taking children who had died of unknown causes. They concluded that stimulants led to a six- to seven-fold increased risk of sudden death.
Sounds bad. So why did the FDA immediately come out with a statement urging “caution” in interpreting these results, and why did Dr. Robert Temple, the director of medical policy for the FDA's Center for Drug Evaluation and Research, discount the study by saying, "I don't think it makes the case that there is real risk here.”
Various reasons. One is the very small number of events. After all, the researchers were basing their conclu- sions on a total of 12 children who had
ed over an 11 year period in the United States. Many millions of children were prescribed stimulants over that time, so to base conclusions of risk on only 12 cases is a stretch. In addition, Temple and others believe that the prob- lem of recall bias is significant. After all, if your child died suddenly of unex- plained causes, wouldn’t you spend quite a bit of time and energy trying to figure out the cause of death? That might lead you to blame a medication, even if your child was no longer taking it. (Gould MS et al. Am J Psychiatry 2009; online ahead of print).
TCPR’s Take: We agree with the FDA that the small number of events and possible recall bias in this study are seri- ous and limit the confidence we can have in the results. Having said that, we do know that stimulant medications are linked to increased blood pressure and heart rate in children, so it is biologically plausible that such medications could lead to increased risk of sudden death. We recommend asking patients about a history of cardiac problems before start- ing stimulants, and following up with an EKG if indicated. But screening every potential stimulant-taker with an EKG could end up leading to multiple false positive findings, which would in turn lead to unnecessary and expensive cardiac work-ups. While one might argue that even a single prevented death would make mass screening worthwhile, given the methodological problems, these data do not prove that screening would provide any benefit.
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