FDA Expert Panel Approves Use of Atypical Antipsychotic Drugs in Kids
June 11, 2009 — The US Food and Drug Administration's (FDA's) Psychopharmacologic Drugs Advisory Committee has voted to approve the use of 3 atypical antipsychotic drugs — quetiapine (Seroquel, AstraZeneca Pharmaceuticals, LP), ziprasidone (Geodon, Pfizer, Inc), and olanzapine (Zyprexa, Eli Lilly and Company) — for the treatment of schizophrenia and bipolar mania in children and adolescents, despite a lack of long-term safety data.
Quetiapine and olanzapine were proposed for both schizophrenia and bipolar mania, while the application for ziprasidone was limited to bipolar mania. The claims for the schizophrenia applications were focused on the age range of 13 to 17 years, whereas the claims for bipolar mania for quetiapine and ziprasidone were focused on the age range of 10 to 17 years, and those for olanzapine were focused on the age range of 13 to 17 years.
The 3 drugs are already approved for schizophrenia and bipolar mania in adults and are currently being used off-label by clinicians treating pediatric patients. If approved by the FDA for these indications, they will join the 2 antipsychotic drugs currently approved for treatment of schizophrenia and bipolar disorder in children — risperidone and aripiprazole.
Call for Continuous Monitoring
Although the committee endorsed the sponsors' claims that the drugs were "effective" and "acceptably safe," it advised the FDA to consider setting up registries or other means of monitoring the long-term sequelae of their use in a younger and more vulnerable cohort of patients.
The drugs are known to have significant risks and adverse reactions, including somnolence; weight gain; increases in blood lipids, triglycerides, and glucose; hyperprolactinemia; acute extrapyramidal symptoms; and tardive dyskinesia.
"These risks are a particular concern in pediatric patients primarily because these are lifelong disorders and these children would face many decades of taking these drugs," said Thomas Laughren, MD, director of the Division of Psychiatry Products at the FDA. "There is also a concern about using them in this population because children are growing and developing and viewed as being particularly vulnerable to the effects of these drugs, so for that reason we have to be very mindful of the risks of these drugs."
Many members of the FDA expert panel voiced concerns about the lack of safety data, particularly in the younger 10- to 14-year-old age group of children and called for continued follow-up in this population.
Kenneth Towbin, MD, chief of the Clinical Child and Adolescent Psychiatry Mood and Anxiety Disorders Program at the National Institute of Mental Health, Bethesda, Maryland, said he was concerned about the downward translation of these drugs into younger and younger age groups.
"I'm afraid that by our taking the step to approve these drugs now for adolescents and children that soon we'll be seeing 4-, 5-, and 6-year-olds being treated with these agents."
He suggested to the FDA that they emphasize the lack of evidence to support efficacy in young children. "There is a slippery slope, because we've said that if you can demonstrate a certain trend in adults and then in adolescents, then it's applicable to the 10- to 14-year-olds. So now is it applicable to the 6- to 10-year-olds, and is it applicable to the 2- to 6-year-old? I am worried about where this is going, and I would like language in the labeling to address this."
Another concern was the difficulty in making an accurate and reliable diagnosis of bipolar disorder in children and adolescents. "There are different points of view about making that diagnosis, which could have an impact on the field once these drugs are approved," said Wayne K. Goodman, MD, from the Division of Adult Translational Research and Treatment Development at the National Institute of Mental Health, and acting chair of the committee. "There is the potential that the treatment could expand beyond the [Diagnostic and Statistical Manual of Mental Disorders, 4th edition] criteria."
Critical Need For More Treatment Options
Despite their concerns, the committee was in agreement that schizophrenia and bipolar mania disorder are serious illnesses and that more options to treat these conditions are needed.
"Schizophrenia and bipolar mania disorder put children at increased risk for suicide and accidental death. For many, the seriousness of the illness outweighs any risks these drugs have," said Margy Lawrence, of Potomac, Maryland, a patient representative on the advisory panel. "The symptoms of these illnesses are very severe. The drugs do have side effects, but patients would much rather have weight gain and elevated lipids so that their brain could function normally."
In a statement released just before the FDA hearing, a group of mental health and suicide prevention advocates, including the American Academy of Child and Adolescent Psychiatry and the Child and Adolescent Bipolar Foundation, urged the FDA to carefully consider the importance of viable treatment options for bipolar disorder and schizophrenia in pediatric and adolescent populations, emphasizing that access to safe and effective treatments is crucial for this very serious illness.
"Other treatments for grave childhood illnesses such as cancer can cause hair loss, nausea, compromised immune systems and even death. However, few people question the necessity of these aggressive forms of treatment. Like cancer, aggressive treatment may be needed for some patients with bipolar disorder and schizophrenia, diseases with a higher risk of death than some forms of cancer," they wrote.