ADHD Drugs: Label Cautions, but No Black Box

May 1, 2006

A second opinion on the need for new warnings on attention deficit hyperactivity disorder (ADHD) drugs from the FDA advisory committee contradicts The Pediatric Advisory Committee recommendation.

An FDA advisory committee has given a second--and very different--opinionon the need for new warnings onattention deficit hyperactivity disorder(ADHD) drugs. The Pediatric AdvisoryCommittee recommended that the FDArequire additional label language onthese drugs to warn about potentialcardiovascular risks to children withpreexisting heart problems and the rarerisk of psychotic events. At the sametime, the committee rejected therecommendation, made 1 month previouslyby the FDA's Drug Safety and Risk Management advisory committee,to require a black box warning onADHD drugs concerning cardiovascularrisks.

The Pediatric Advisory Committeelooked at evidence that those drugscaused excessive psychotic and cardiovascularadverse events in children andadolescents. A March 3 memo by 2psychiatric drug reviewers in theagency's Office of Drug Safety statedthat since January 1, 2000, the agencyand drug companies had receivedhundreds of reports of psychosis ormanic behavior, particularly hallucinations,in patients with no known riskfactors who took the usual dose of anADHD medication. Current approvedlabeling for ADHD drugs does notclearly address the risk of drug-inducedpsychosis or symptoms of mania in suchpatients, medical epidemiologist KateGelperin, MD, MPH, and safety evaluatorKate Phelan wrote. “We recommendthat these issues be addressed,” they added.

Any new labeling requirementadvanced by the FDA will take intoaccount the softer recommendation ofthe Pediatric Committee, which wasbased on testimony provided by bothpsychiatrists and pharmaceuticalcompanies.

Darrel A. Regier, MD, MPH,research director for the AmericanPsychiatric Association, emphasizedthe risk of limiting access to these“valid and effective treatments . . . whenthe FDA is asked to use non-researchstandards for warnings.”

McNeil Consumer & SpecialtyPharmaceuticals submitted data onmethylphenidate (Concerta) that showedan estimated rate of sudden cardiacdeath of 0.19 per 100,000 patient-yearsin those using the drug. The rate ofsudden cardiac death in children andyoung adults in the general populationis approximately 1.3 to 8.5 per 100,000persons. Regarding psychiatric events,a postmarketing safety review for methylphenidatefound the rate of suicidalideation to be 0.65 cases per 100,000patient-years. The company stated thateven with a correction for under-reporting,the observed rate of suicidal ideationis lower than the rate of suicidal ideationin the general population.

“We appreciate the careful andinformative dialogue demonstrated bythe committee and agree with thecommittee's suggestion to the FDAthat heightened awareness aroundadverse events is important but thatthe data do not support the need fora black box–type of warning,” saidMatt Cabrey, spokesman for ShirePharmaceuticals.