A new study by researchers in the US suggests there may be a link between the use of stimulant drugs for attention-deficit hyperactivity disorder (ADHD) and sudden cardiac death in healthy children, but the US Food and Drug Administration (FDA), who funded the study with the National Institute of Mental Health, said because of its limitations, parents and carers should not stop giving children such medication on the basis of this study but should discuss any concerns with their prescribing doctor.
The study was the work of lead author Dr Madelyn S Gould of Columbia University, New York, New York, and colleagues, and is published in the 15 June issue of the American Journal of Psychiatry.
In the case-control study, using state-based mortality data from 1985 to 1996, Gould and colleagues compared the use of stimulant drugs in 564 healthy children aged 7 to 19 from across the US who died suddenly and most likely due to sudden cardiac disturbance with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents.
The primary measure of exposure was the presence of stimulant medication as noted in the medical examiner records, toxicology reports and death certificates. The stimulants involved were amphetamine, dextroamphetamine, methamphetamine, and methylphenidate.
The results showed that out of the 564 healthy children who died suddenly, 10 (1.8 per cent) were taking stimulants, specifically methylphenidate (better known in the US under its brand name of Ritalin). This compared with only 2 children (0.4 per cent) in motor vehicle accident comparison group, only one of whom was taking Ritalin (methylphenidate).
Logistical regression, a tool commonly used by epidemiologists, showed a statistically significant link between stimulant use and sudden unexplained death in a primary analysis. This result was supported qualitatively in a further “comprehensive series of sensitivity analyses”, wrote the authors, who concluded that:
“This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents.”
“Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment,” they added.
In a Safety Communication released on 15 June, the FDA said that:
“The FDA can not conclude that the data in the study affect the overall risk-benefit profile of stimulant medications used to treat ADHD in children.”
What they are saying is they are not going to change their advice about the risks versus the benefits of the medication because of the study’s limitations, which they say include:
- The significant time lag between when the deaths occurred and when the data was collected.
- The different circumstances around each death that may have affected how well family members and/or carers may have remembered details of any medication the deceased child had been using.
- Sudden unexplained death in a child would be more likely to initiate a post-mortem inquiry than a death due to blunt force trauma in a motor vehicle accident.
- The low frequency of stimulant medication use by the children in both the study and the control groups.
When scientists highlight a study’s limitations they are in effect saying that another study looking at the same things might reach a different result if it didn’t have those limitations.
With subjects as serious as this, and with parents and carers rightly concerned about what to do about any ADHD medication their children have been prescribed, it is important that research in the service of public health produces results that are robust and reliable, so a small study like this one really needs to be confirmed by more research, preferably with a larger study, especially if there are concerns about its limitations.
In fact, the FDA is already co-sponsoring another larger study that is looking at the link between increased risk of heart attack, stroke and other cardiovascular problems and use of stimulant medication by children, the results of which are expected to come out later this year.
Dr Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research told the press:
“The FDA continues to review drug safety information for stimulant medications used to treat ADHD so that we can give health care professionals and families the most up-to-date drug safety information available.”
The federal agency urged doctors to follow the current prescribing information that accompanies the product label, which recommends that young and adult patients being considered for ADHD treatment:
“Work with their health care professional to develop a treatment plan that includes a careful health history for cardiovascular disease in the child and his or her family.”
Such preparation should include a physical exam that pays particular attention to the cardiovascular system, and should consider screening tests such as electrocardiogram and echocardiogram, depending on the patient’s history and whether it suggests possible risk factors for heart disease.
“Sudden Death and Use of Stimulant Medications in Youths.”
Gould, Madelyn S., Walsh, B. Timothy, Munfakh, Jimmie Lou, Kleinman, Marjorie, Duan, Naihua, Olfson, Mark, Greenhill, Laurence, Cooper, Thomas.
Am J Psychiatry, Published online 15 June 2009.
Additional sources: FDA.
Written by: Catharine Paddock, PhD