FDA Orders New Guides for ADHD Prescriptions

Medications prescribed to treat attention-deficit/hyperactivity disorder (ADHD) must be accompanied by a patient medication guide, the U.S. Food and Drug Administration (FDA) said last month. The announcement came a year after two advisory committees urged the agency to provide more complete and clear information on the benefits and risks of taking medications most commonly prescribed to treat ADHD (Psychiatric News, April 21, 2006).

There are 14 amphetamine and methylphenidate preparations and one nonstimulant medication, atomoxetine, approved for the treatment of ADHD. Draft medication guides (“med guides”) for each of the medications are now posted on the FDA's Web site (see the link at end of article). They are aimed at prescribers, adult patients, and the parents or caregivers of children taking the medications.

The final med guides should be available in pharmacies within the next three to four months, according to Thomas Laughren, M.D., director of the FDA's Division of Psychiatry Products.

The language in the draft med guides was written by FDA staff. FDA officials have requested that each manufacturer review the drafts, and companies often suggest changes. The final content is negotiated between the FDA and the manufacturers of each medication.

The med guides use lay language to point out two specific areas of concern associated with taking stimulant medications: the potential for an increased risk of serious cardiovascular adverse events, including heart attack, stroke, and sudden death; and the potential for an increased risk of adverse psychiatric events such as the worsening of existing symptoms or the development of treatment-emergent mania, delusions, or hallucinations.

In a box at the beginning of each med guide is the question, “What is the most important information I should know about [medication name]?” For the amphetamines and methylphenidate preparations, the box notes that spontaneous reports have occurred with patients taking stimulant medications, concerning “heart-related problems” and “mental (psychiatric) problems.”

The box goes on to warn that sudden death, heart attacks, strokes, and increases in heart rate and blood pressure have all been reported. Patients and parents are urged to discuss with their doctor any heart problems that they, the child, or their immediate relatives have and are told that their doctor should check for heart problems before starting the medication.

In addition, patients and parents are instructed to call their doctor immediately if “any signs of heart problems such as chest pain, shortness of breath, or fainting” develop while taking the ADHD medication. Similarly, they should be on the lookout for “new or worse behavior and thought problems, new or worse bipolar illness, or new or worse aggressive behavior or hostility.” Parents are specifically told to watch for “new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious), or new manic symptoms” in children and teenagers.

The med guide for atomoxetine carries the same warnings about“ heart-related problems” and “new mental (psychiatric) problems in children and teenagers”; however, these warnings come much later in the med guide. Because atomoxetine is a dual reuptake inhibitor (serotonin/norepinephrine reuptake inhibitor, or SNRI) rather than a stimulant, the most prominent warning, listed at the beginning of the atomoxetine med guide, concerns “suicidal thoughts and actions in children and teenagers.”

The FDa's Laughren told reporters at a press briefing last month that the agency decided to follow the advice of its Drug Safety and Risk Management Advisory Committee and Pediatric Advisory Committee, even though there is no documented direct link between the medications and the spontaneous adverse events of cardiovascular or psychiatric problems.

Laughren noted that the advisory committees reviewed reports of cardiovascular events associated with patients who took ADHD medications. There were 39 deaths and 54 reports of “serious but nonfatal” cardiac events. The information “arose entirely from spontaneous reports [through the agency's MedWatch drug surveillance system].” Many of the cases, he noted, involved young patients with unknown cardiac disease or congenital defects or patients taking multiple medications.

“While the possibility exists,” Laughren said, “that these events are related to the underlying cardiovascular disease and not the drug, [the advisory committees] advised us to go ahead and alert the public to the possibility that the drug might have had a role.”

Evidence of a “causal link” between the ADHD medications and psychiatric adverse events “is stronger than for the cardiovascular events,” said Laughren. He noted that reports of treatment-emergent mania or psychotic symptoms arose not just from MedWatch, but also from a pooled analysis of clinical-trials data.

More information and links to the draft med guides are posted at<www.fda.gov/cder/drug/infopage/ADHD/default.htm>.▪