TCPR: Using stimulants as a treatment for attention deficit hyperactivity disorder (ADHD) has been a common practice for a long time. I think a good place to begin, Dr. Vitiello, is to talk about the potential safety issues associated with stimulants: namely cardiac risks and drug diversion and abuse.

Dr. Vitiello: Sure. Let’s start with the cardiac risks. Stimulant medications—amphetamines and methylphenidate—are known to increase blood pressure and heart rate. In 2005, the FDA and the maker of Adderall (Shire) did a review of a number of databases for safety issues related to stimulant use in children. Around the same time, MedWatch also looked into it.

TCPR: And what did they find out?

Dr. Vitiello: There were a number of cases of children in the MedWatch database who had died suddenly while on stimulant med- ications, either amphetamines or methylphenidate. Some of these were dramatic, such as children taking Adderall in the morning, then going to school and doing physical exercise like running, and then collapsing and dying.

TCPR: So what did they conclude from this data review?

Dr. Vitiello: The bottom line was that one could not draw any causal inference from this data because there was no non-medica- tion control and, because of the way MedWatch collects data (physicians call in cases of unusual side effects at their own discre- tion), the database was incomplete. So the tentative conclusion was that the rate of sudden cardiac death when taking stimulants was not greater than what one could expect in this population without medication.

TCPR: However, didn’t the FDA advisory committee vote to take some action on this data?

Dr. Vitiello: Yes. The advisory committee observed in these cases that, when they did autopsies on the children who had died, many of them had some anatomical abnormalities of their hearts, like valvular heart disease or hypertrophy, even though these problems were unknown to the prescribers. So one conclusion was that these drugs may increase the risk of sudden death if there is an anatomic abnormality in the heart. Therefore, the FDA issued warnings that these drugs should not be used or should be used with great care in children with known cardiovascular abnormalities. In addition, it was recommended that before prescribing them, a doctor should do a physical examination and collect a family history to see if there was a first-degree relative who had died suddenly or had a history of cardiovascular conditions.

TCPR: What about other recommendations? Doesn’t the American Heart Association suggest more intense screening?

Dr. Vitiello: The AHA has recommended a systematic screening that includes an electrocardiogram (EKG) of all children for whom stimulants are considered. Neither the American Academy of Child Psychiatry nor the American Academy of Pediatrics has endorsed this recommendation. They believe that the physical and the history are sufficient and an EKG is only needed if there are positive findings in the family or personal history and/or at the physical examination.

TCPR: So for practicing psychiatrists, does that mean that we should call up the pediatrician and ask if the child has any cardiac problems, or should we just start examining all the kids who come into our office?

Dr. Vitiello: Either way. It depends on whether you feel comfortable doing physical examinations, listening to the heart and col- lecting a family history. One has to keep in mind anyway that the majority of stimulants are prescribed by pediatricians in the United States. So psychiatrists prescribe some amount, but not the bulk of them.

TCPR: So assuming we choose to do it, what should we be looking for in the history and physical exam?

Dr. Vitiello: We are listening for rhythm abnormalities. Heart murmurs are fairly common in pediatrics and most of them are benign, but some of them may suggest that there is a valve problem. The history should include asking whether a child (or an adult) has ever had any cardiovascular event such as dizziness, fainting, palpitations, tachycardia or if a first-degree relative like a sibling died suddenly or suffers from any cardiovascular problems.

TCPR: Recently there was a study in The American Journal of Psychiatry about sudden death in children taking stimu- lants (Gould MS et al., Am J Psychiatry 2009;166:992-1001). Can you comment on this?

Dr. Vitiello: That was the first controlled study that linked the use of stimulants—in this case methylphenidate—with sudden death in individuals without obvious cardiovascular abnormalities. They found that the use of stimulants was greater in the group of chil- dren with unexplained sudden deaths than in a control group of children who died suddenly of known causes. However, this study has been criticized because of the potential for recall bias and because of the small number of deaths (a total of only 12 cases over 10 years in the U.S.). [For more information, see "Study Links Ritalin to Sudden Death in Children; FDA Disagrees,"The Carlat Psychiatry Report July/August 2009, p.9].