The authors of “Sudden Death and Use of Stimulant Medications in Youths”, published online on June 15th by the American Journal of Psychiatry, concluded there may be an association between the use of stimulant medications and sudden death in healthy children. The article by Madelyn Gould, PhD, M.P.H. and coauthors is available online.

CADDRA clinicians have reviewed the study and have concluded that there is insufficient evidence to indicate a need to change practice with respect to medication use for ADHD.

The psycho stimulant drugs included in the study currently carry warnings about possible increased risk of cardiac events or death in children with underlying heart conditions. Despite this newly published report, the medical consensus based on available research is that these medications do not present a risk to young patients with no known heart disease or risk factors for sudden death.

CADDRA does not recommend a change in practice regarding prescribing or risk assessment, which can be done by the prescribing physician. Routine assessment by a cardiologist before beginning ADHD treatment is not considered necessary by our Board.

Study Summary and Findings

The matched, case-control, epidemiological study compared the use of psycho stimulant medications (including amphetamines, dextroamphetamine, methamphetamine and methylphenidate) in 564 healthy children from across the United States who died suddenly to the use of psycho stimulant medications in 564 children who died as passengers in a motor vehicle accident. Use of the medication was determined from parents, medical examiners and toxicology reports.

• Out of 564 health children who died suddenly, ten (1.8%) were reported to be taking a stimulant medication at the time of death.
• Out of 564 healthy children who died in a motor vehicle accident, two (0.4%) were reported to be taking a stimulant medication at the time of death.

Study Limitations

CADDRA has concerns about the methodology used in the study and questions the statistical relevance of the data.

The study was partially funded by the Food and Drug Administration (FDA) but, according to agency experts, its methods - which relied on interviews with parents years after a child's death - may have caused errors. It warns that the low frequency of stimulant use in both groups, as well as possible difference in the type of post-mortem inquiry, could have a profound biasing effect on the result. The agency urges parents to discuss safety concerns with their doctor, but to keep children on the treatments. The FDA is collecting data for a larger, more in-depth study of the drugs' risks.

An accompanying editorial published in the AMJ by Benedetto Vitiello, M.D., and Kenneth Towbin, M.D. noted that while the study underscores the fact that “stimulants are not innocuous and that their therapeutic use requires careful diagnostic assessment, diligent safety screening, and ongoing monitoring … it is equally clear that 1) sudden unexplained death is a rare event, 2) this is only the first such study, 3) it relies on small numbers, and 4) it is not possible to quantify the risk beyond estimating that it is very small”.

Expert Response

The overwhelming consensus of experts in the field both in Canada and the US in response to the new data is that prescribing practice should not be changed for young people with ADHD.

CADDRA endorses the joint position statement currently being produced in response to the new study by the Canadian Pediatric Society, the Canadian Cardiovascular Society and the Canadian Academy of Child and Adolescent Psychiatry: Cardiac risk assessment prior to the use of stimulant medications in children and youth.

As the American Association of Child and Adolescent Psychiatrists points out in a statement for members: “Using the metrics of evidence-based medicine for describing the benefit to risk ratio, it only takes two children to show that stimulants have beneficial effects on the symptoms of ADHD, but it requires treating 250,000 children before one might encounter sudden unexpected death associated with stimulant treatment.”

CADDRA urges its members to continue to adhere to The American Academy of Pediatrics/American Heart Association recommendations from May 2008:

• Continue a careful assessment of all children, including those starting stimulants, using a targeted cardiac history (e.g. patient history of previously detected cardiac disease, palpitations, syncope, or seizures; a family history of sudden death in children or young adults; hypertrophic cardiomyopathy; long QT syndrome) and a physical examination, including a careful cardiac examination. (Evidence Quality: C; Strength: Recommendation).
• Continue currently recommended treatment for ADHD, including stimulant medications, without obtaining routine ECGs or routine subspecialty cardiology evaluations for most children before starting therapy with these medications.
• Support further research on risk factors for sudden cardiac death among all children and adolescents, including those with ADHD treated with stimulant medications. Improved methods to detect children with hidden cardiac disease should be another focus of such research efforts.

Health Canada

To date, Health Canada has not issued any new advisory to physicians on prescribing stimulant medication since the release of the new research data published in the AJP.

CADDRA

CADDRA is a national, Canadian alliance of professionals working in the area of ADHD who are dedicated to world class research, education, training and advocacy. Our board members are leaders in the field and conduct research, treat patients and design practice guidelines for treating ADHD in Canada.

Yours truly,

Dr. Umesh Jain MD PhD MED FRCPC

Chair, Canadian ADHD Resource Alliance (CADDRA)