Healthy Skepticism Library item: 10739

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Publication type: report

Klotz SG, Kruszewski SP
Open letter to the FDA re pending approvals for atypical antipsychotic use in adolescents
2007 Jun 11
http://www.bmj.com/cgi/eletters/332/7556/1464

Notes:

Open Letter to the FDA

US Senate Finance Committee
Charles Grassley (R-IA)
Max Baucus (D-MT)

Andrew C. von Eschenbach, M.D.
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Max Baucus, Chairman
Charles Grassley, Ranking Member
United States Senate Committee on Finance
219 Dirksen Senate Office Building
Washington, DC 20510-6200

Dear Commissioner Eschenbach:

As reported in Bloomberg News by Rapaport, Pettypiece and Waters on 24 May 2007, several manufacturers of atypical antipsychotic medications have discussed pending applications/approvals from, and/or plans to submit such ‘new indication’ applications to, the US Food and Drug Administration(FDA). According to the article, the manufacturers would seek to obtain FDA approval for the specific ‘indication’ to use atypical antipsychotics in teenagers. Already approved in the US adult population, marketing for atypical antipsychotic drugs from Eli Lilly (makers of Zyprexa), Janssen, a division of Johnson and Johnson (makers of Risperdal) and Bristol Myers Squibb/Otsuka (makers of Abilify) would be affected.

Dr. R. Findling mentions that these new ‘indications’ would be able to enhance the confidence level of providers and parents when they, respectively, prescribe or permit these potent psychotropic agents to be used in a younger population.

Schizophrenia and Bipolar Disorders are painful mental illnesses, often with varying courses of stability/instability and unpredictable functional disabilities. We agree that all available therapies should be sought to minimize the emotional damages and maximize the return to health for
individuals and their families affected by the symptoms categorized under these diagnoses. However, second-generation atypical antipsychotic medications have not clearly proven to be safer, more efficacious or more effective than older agents. Furthermore, some of the atypicals medications may have risks (significant weight gain, pancreatitis, diabetes, cardiovascular complications, hyperprolactinemia, or infections) that may outweigh their benefits when compared to other first-generation agents. Studies already suggest that younger patients may be more prone to suffer from severe side effects for longer periods of time. We are unaware of any evidence suggesting that an indication will make prescribing habits safer.

We see no compelling reason for the drug manufacturers to seek specific FDA approval of atypical antipsychotics in the teenage population. Our reasons are not complex. They include:

1. All of these drugs are already available in the marketplace.
2. These drugs are already widely prescribed/over-prescribed in the adolescent population.
3. Doctors are already permitted to use these drugs off-label.
4. A patient is not declined care because he or she is under the age indicated by the FDA approved package insert. A doctor may still prescribe the correct medications after discussing the off-label nature, risks and benefits with the family of the minor.
5. There is no safety gain by requesting the FDA to approve this new indication.
6. If the pharmaceutical manufacturers have additional efficacy and safety data about these drugs, the release of that data does not require FDA sanction.
7. By seeking this indication, there is no possible clinical benefit to any individual young person since the drugs are currently and widely prescribed to them.
8. There is no life-saving or novel approach to chemotherapy in seeking this indication.
9. Requesting the abundant time and resources required from the FDA to accept, review and consider this indication is untimely when the FDA is already inundated with requests for reviews of novel or orphan drugs or indications for drugs used in novel ways.
10. There is the very likely possibility that FDA approval of a teenage ‘indication’ will provide a false sense of security and reliability for physicians not sufficiently trained (pediatricians, primary care physicians) to accurately assess, diagnose and treat individuals with these complicated disorders. It would not surprise us that this ‘indication’ approval would function as the means by which aggressive pharmaceutical marketing could easily persuade more practitioners to prescribe more potent medications without the concomitant ability to provide risk-benefit analysis or informed
consent and thereby rapidly and seriously escalate the potential harm that comes from the effects and side-effects of overzealous prescribing.
11. We heartily urge the companies involved in teenage ‘indication’ proposals to release all their data that support and do not support their request. Release of this data depends upon a willingness to be transparent, not any FDA action.
12. Failing to approve this indication or delaying its approval should have no effect on any patent extension requests for these atypical manufacturers since the ability to obtain six-month pediatric extension for patent protection is based upon the agreement to conduct appropriate
pediatric research, not the ability to successfully obtain a ‘new’ indication.

We strongly recommend that the FDA re-consider and delay administrative reviews and approvals for indications that have little merit other than for ostensible marketing purposes. That delay does not compromise patient care. Doctors who assess young patients with diagnostic accuracy and treat them carefully and compassionately will not increase their personal liability if they apply informed consent to use off-label medications correctly. Furthermore, delaying the administrative FDA approval for this ‘new’ indication (but current practice) may prevent the escalation of excessive use of atypical antipsychotic medications whose occasional and predictable serious side-effects can compromise both medical and psychiatric care.

Sincerely,

Steven G Klotz, MD
Stefan P. Kruszewski, M.D.
31 May 2007

…..

Dr. Klotz is an academically trained child, adolescent and adult psychiatrist now in private practice in central Pennsylvania.
Dr. Kruszewski is an adult, geriatric, adolescent and addiction psychiatrist practicing in Harrisburg, Pennsylvania.
Both Drs. Klotz and Kruszewski have previously consulted for and spoken on behalf of multiple pharmaceutical companies.