The FDA approval of Seroquel and Zyprexa for America's Children

TO APPROVE THE NEUROLEPTICS 

ZYPREXA AND GEODON 
HERE IS HOW THE FDA ADVISORY COMMITTEE VOTED: 

FDA Psychopharmacologic Drugs Advisory Committee Hearings

June 9 – 10, 2009

Prepared by S. Fleisher

On June 9 - 10, the FDA Psychopharmacologic Drugs Advisory Committee reviewed the requests from three pharmaceutical companies for medication approval for the treatment of schizophrenia and/or acute mania bipolar in pediatric populations. 

AstraZeneca Pharmaceuticals, LP, requested Seroquel (quetiapine fumarate) be granted FDA indication approval for the treatment of schizophrenia in adolescents ages 13 – 17 and acute treatment of bipolar mania in children and adolescents ages 10-17. 

Pfizer, Inc. requested Geodon (ziprasidone hydrochloride) be granted FDA indication approval for the acute treatment of bipolar mania in children and adolescents ages 10 – 17 years. 

Eli Lilly and Company requested Zyprexa (olanzapine) be granted FDA indication approval for the treatment of schizophrenia in adolescents ages 13 – 17 years of age and acute treatment of bipolar mania in adolescents ages 13 – 17.

On Wednesday, June 10, the Committee members reconvened. The morning began with a presentation by Kenneth Towbin, M.D., AACAP member and Chief, Clinical Child and Adolescent Psychiatry Mood and Anxiety Disorder Program of the NIMH. Dr. Towbin provided the Committee with an overview of the controversial diagnosis of bipolar disorder and the varying characterization of symptoms used to diagnose the disorder. Dr. Towbin stressed the fact that bipolar disorder is real and can be diagnosed in the pediatric population. He also indicated bipolar disorder is very rare in children and adolescents and that more children and adolescents suffer from severe mood dysregulation. The Committee thanked Dr. Towbin for his presentation and assistance in helping them understand the pediatric bipolar disorder diagnosis controversy. The Committee then continued their discussions and questioning of the data presented on Tuesday.

After thorough discussion, the Committee held the following votes. The Committee found that Seroquel had been shown to be effective (17 – Yes, 1-No) and acceptably safe (16 – Yes, 2 – Abstain) for the treatment of schizophrenia; and they found that Seroquel had been shown to be effective (17 – Yes, 1 – Abstain) and acceptably safe (13 – Yes, 5 – Abstain) for the acute treatment of bipolar mania. The Committee was concerned about the metabolic and cardiac side effects of this medication, specifically the increased weight gain, heart rate and blood pressure. The Committee additionally recommended labeling clarifications regarding the use of this medication only for the narrowly defined mania aspects of bipolar disorder and clear indication that this medication not be used for severe mood dysregulation such as chronic irritability, oppositional defiance and hyperactivity. (emphasis mine)

The Committee found that Geodon had been shown to be effective (12 – Yes, 4 – Abstain, 2 – No) for the acute treatment of bipolar mania but no conclusion was delivered regarding the safety of this medication (9 – Abstain, 8 – Yes, 1 – No). The Committee members that abstained were concerned about the lack of long-term data, high QTc prolongation intervals, higher rate of side effects in children ages 10 – 14, and unusual number of trial subjects that were lost in the follow-up phase. 

The Committee found that Zyprexa had been shown to be effective (11 – Yes, 5 – No, 2 – Abstain) and acceptably safe (10 – Yes, 4 – No, 4 – Abstain) for the treatment of schizophrenia; and they found that Zyprexa had been shown to be effective (17 – Yes, 1 –  Abstain) and acceptably safe (11 – Yes, 4 – No, 3 Abstain) for the acute treatment of bipolar mania. The Committee recommended the approval as a second line treatment and recommended labeling clarifications regarding the use of this medication for the narrowly defined mania aspects of bipolar disorder and clear indication that this medication not be used for severe mood dysregulation. The Committee was concerned about the high level of metabolic and cardiac side effects of this medication, specifically the increased weight gain. (emphasis mine)

AACAP members serving on the Committee included Rochelle Caplan, M.D., Semel Institute for Neuroscience and Human Behavior, UCLA; Masha Rappley, M.D., Michigan State University; Kenneth Towbin, M.D., National Institute of Mental Health; and Benedetto Vitiello, M.D., National Institute of Mental Health.

To view copies of the data and presentations provided during the hearing, please visit the FDA website. (the FDA website no longer has any of this information posted.)

The testimony that is referred to above:

***FINAL***

June 9, 2009

Psychopharmacologic Drugs Advisory Committee Meeting

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

Good afternoon, my name is Larry Greenhill, M.D., and I am President-elect of the American Academy of Child and Adolescent Psychiatry. Over the past 24 months, I have received research support or have worked on a consultant basis with Otsuka, Johnson & Johnson, Forest, Pfizer, and NIMH. I have both practiced child psychiatry, been federally supported to study long-term adverse events associated with psychotropic medication use, and been a member of AACAP for 30 years. AACAP is a professional medical association of 8,000 child and adolescent psychiatrists established in 1953. 

AACAP is the leading national medical association dedicated to treating and improving the quality of life for the estimated 7 - 12 million American youth under 18 years of age who are affected by emotional, behavioral, developmental and mental disorders. Bipolar and Schizophrenia are severe psychiatric illnesses which first appear in childhood and adolescence. No one treatment option works for all children and adolescents with these disorders so we support a wide array of treatment options being available.

Although a few clinical trials have suggested that these antipsychotic medications can be effective in pediatric populations, the lack of systematically collected safety data when youth are exposed for long periods of time, that may affect development strongly, indicates that large scale Phase IV studies need to be carried out. 

We ask the FDA Advisory Committee to carefully consider whether the number and scope of the clinical trials as well as the duration of the safety trials to date involving children and adolescents justifies the labeling changes being requested today. While these medications may be helpful and even life saving for some children and adolescents suffering with these disorders, there are significant metabolic and cardiac adverse events associated with their use. We advise the FDA not to approve the request for indications in these medications unless they are also requiring that children treated be entered into a registry. These registries can take advantage of large group-practice HMO settings where electronic health records and pharmacological prescription data can be aggregated and compared. The resulting systematically collected information on the risks and benefits of these medications as well as specific methods for effective monitoring of their associated side effects must be made available to the public before direct-to-consumer marketing should be permitted to occur.  (emphasis mine) 

We thank the FDA for the opportunity for the American Academy of Child and Adolescent Psychiatry to provide this testimony. 

via National Injury Board News article FDA Considers Psychiatric Drugs For Kids June 2009

on the AACAP website

source of medical monkeys