FDA Panel OKs Newer Antipsychotics for Children
June 12 -- WEDNESDAY, June 10 (HealthDay News) -- A U.S. Food and Drug Administration advisory panel voted overwhelmingly Wednesday that Seroquel and Zyprexa, two powerful antipsychotic drugs, be approved to treat schizophrenia and bipolar disorder in children aged 13 to 17.
The panel also endorsed Geodon, a third antipsychotic in the same class, as safe and effective for the treatment of bipolar mania in children aged 10 to 17.
All three drugs are part of the new-generation "atypical" antipsychotics, currently approved for adult use. The medications have been prescribed "off-label" by many doctors for years to treat schizophrenia and bipolar disorder in children aged 10 to 17, despite possible serious side effects, including diabetes and heart woes.
Seroquel is made by drug maker AstraZeneca. Pharmaceutical giant Lilly makes Zyprexa, and Geodon is made by Pfizer.
There is a pressing need for effective antipsychotics for children, one expert noted.
"Schizophrenia and bipolar disorder are very real illnesses, which collectively affect between 1 percent and 3 percent of all young people," noted Dr. David Fassler, a clinical professor of psychiatry at the University of Vermont College of Medicine, who testified before the panel. "Without treatment, children have problems at school, at home, and with their friends. They're also at increased risk of accidents, hospitalization, and death at an early age from multiple causes, including suicide."
And yet safety concerns plague many of these drugs. In 2004, the FDA ordered AstraZeneca to add a special "black box" warning to Seroquel's packaging, outlining increased risks of hyperglycemia, high blood pressure and diabetes associated with use of the drug. Also, older patients with dementia-related psychosis treated with Seroquel are at an increased risk of death, according to the FDA.
In a unanimous vote in early April, an FDA advisory panel determined that Seroquel should not be approved as first-line therapy for adult depression, because of continued questions about its safety profile -- most notably, a link to higher risk for sudden cardiac death. However, the drug was approved for use in patients for whom other antidepressants didn't work.
The family of atypical antipsychotics has other well-documented potential side effects, including weight gain and high blood sugar, which can increase the risk of diabetes, as well as rapid heartbeat, difficulty sleeping and trouble concentrating.
Ronald T. Brown, dean and professor of public health at Temple University Health Sciences Center, testified before the panel. Speaking to HealthDay before the panel voted, he said there was still too little known about the efficacy and side effects of these medications in children for the FDA to approve their use in kids.
"The problems are what we don't know rather than what we do know," Brown said. "We don't know anything about the long-term effects of these medications; they have only been through a six-week trial."
"I am not convinced about the long-term safety of these drugs," he added.
"Particularly with children, when you don't know, I don't think you should approve it," Brown said. "In this country, we are very overzealous to approve drugs. I think we need to be more conservative, particularly because this is a pediatric population."
Brown believes off-label use may be safe, because it is done for particular patients, with the family's consent. "That's a lot different than saying this drug has been approved for children and adolescents," he said.
Prior studies have also found that these newer drugs are no more effective than older medications. Their main advantage is that they do not cause the tremors and muscle spasms associated with older agents.
Diana Zuckerman, president of the National Research Center for Women & Families, a Washington, D.C.-based advocacy group, believes much more study is needed before good decisions can be made as to the use of these antipsychotics by youngsters.
According to Zuckerman, the small studies that are out there suggest that, while on these drugs, "between 20 to 30 percent of kids were gaining weight, heart rates were increased, many of the kids were so knocked out [sedated] that they could barely function."
Overall, the trials submitted to the FDA panel were small, Zuckerman added, noting there were "usually less than 100 at a specific dosage."
"If you want to prove that the benefits outweigh the risks," she said, "it is necessary to study thousands of kids for at least a year in double-blind studies, preferably longer. These studies don't come close to doing that."
Fassler took a more measured view.
"None of these medications should be used without careful consideration of the risks and benefits," he said. "Children and adolescents taking these medications should be monitored closely for evidence of significant side effects or adverse reactions. Nonetheless, when used appropriately, these medications can be a helpful and effective component of treatment for children and adolescents with schizophrenia or bipolar disorder."
In any case, drugs should never be viewed as the only therapeutic option open to young patients, according to Fassler.
"Medication, including the atypical antipsychotics, can be helpful to control some of the signs and symptoms associated with these disorders, but medication alone is rarely an adequate or sufficient intervention. It should only be used as part of a comprehensive treatment plan, individualized to the needs of the child and family," Fassler said.
Dr. Howard Hutchinson, chief medical officer of AstraZeneca, issued the following statement after the panel's endorsement of Seroquel: "We are pleased that the committee found Seroquel to be effective and acceptably safe for treating adolescents with schizophrenia and children and adolescents with bipolar mania, and we look forward to having further discussions with the FDA regarding the sNDAs [supplemental new drug applications]."
Although the FDA isn't required to follow advisory committee recommendations, it usually does.
More information
For more information on atypical antipsychotics, visit the U.S. Food and Drug Administration .
SOURCES: David Fassler, M.D., clinical professor, psychiatry, University of Vermont College of Medicine, Burlington; Diana Zuckerman, Ph.D.,president, National Research Center for Women & Families, Washington, D.C.; Ronald T. Brown, Ph.D., dean and professor, public health, Temple University Health Sciences Center, Philadelphia; June 10, 2009, statement, U.S. Food and Drug Administration; June 10, 2009, statement, AstraZeneca, Wilmington, Del.