For Immediate Release

DODD AND COLLEAGUES QUESTION FDA ABOUT CHILDREN'S ANTIDEPRESSANTS

March 1, 2004

Washington, D.C. - Senator Dodd, along with nine Senate Democratic colleagues, sent a letter today to Food and Drug Administration Commissioner Mark McClellan expressing their concerns about the effectiveness of antidepressants on children. There are mixed messages in the medical community as to the appropriate use of selective serotonin reuptake inhibitors (SSRIs) in pediatric populations, including possible links to youth suicide. Only one SSRI is approved by the FDA to treat children suffering from depression.

The Senators have requested that the FDA provide the answers to a number of questions regarding the status of pediatric studies and pediatric labeling of SSRIs, to help ensure the safety of America’s youth. The letter states, “Families and physicians must have all the necessary information to do what is best for children suffering from depression.”

The Senators have also requested that the FDA consider requiring drug manufacturers to conduct any additional pediatric studies necessary to ensure there is clarity when it comes to prescribing antidepressants to children. Tomorrow Senator Dodd will act as an honorary Co-Chair at a hearing held by the Senate Committee on Health, Education, Labor, and Pensions sub committee on Substance Abuse and Mental Health Services to discuss youth suicide prevention strategies.

March 1, 2004

Mark McClellan
Commissioner of Food and Drugs
Food and Drug Administration
5600 Fisher Lane
Rockville, MD 20857

Dear Commissioner McClellan:

We are writing to express our concern about the more than one million American children and adolescents who are prescribed antidepressants. As you are well aware, recent reports suggest a possible link between selective serotonin reuptake inhibitors (SSRIs) and increased risk of suicide. At the same time, many in the medical community argue that SSRIs are a criticalcomponent of care for depressed children. For the health and well-being of our children, it is imperative that this issue be resolved as soon as possible. Therefore, we ask that the FDA provide answers to several questions regarding pediatric labeling of SSRIs. We also ask that you consider taking several steps to ensure that children afflicted with depression are receiving appropriate care, including, where appropriate, invoking the authority granted by Congress last year allowing the FDA to require pediatric studies.

Families and physicians must have all the necessary information to do what is best for children suffering from depression. Last October, the FDA issued a public health advisory warning physicians to use caution when prescribing SSRIs to children. Earlier this month the FDA convened an advisory committee on this important issue. And we understand that the agency is working with researchers at Columbia University to review the results of 20 clinical trials covering approximately 4,000 children. We commend the FDA for all of these actions.

However, several questions remain regarding the extent to which SSRIs have been studied in children. It is our understanding that the FDA issued written requests for pediatric studies to seven manufacturers of SSRIs. Only one of those drugs is currently labeled for use in children with depression. Given that discrepancy, we request that you report back to us with answers to the following questions:

• What is the status of written requests issued to manufacturers of SSRIs?

• What specific studies were requested? Were manufacturers specifically asked to study the drugs for the purpose of treating depression in children?

• Have manufacturers complied with the written requests?

• If so, why have pediatric studies not resulted in changes to the drug labels?

To the extent that manufacturers have not complied with written requests, or requested studies have not addressed the question of a possible link between SSRIs and increased suicide, we strongly believe that you should consider invoking the authority recently granted to the FDA by Congress to require drug manufacturers to submit additional pediatric studies. The Pediatric Research Equity Act (PREA), which was signed into law in December of last year, allows the FDA to seek additional studies for drugs that have already been approved under section 505 if "the drug or biological product is used for a substantial number of pediatric patients for the labeled indications" and "the absence of adequate labeling could pose significant risks to pediatric patients" (section 505B(b) of the Federal Food, Drug, and Cosmetic Act).

As authors and supporters of this legislation, we believe that SSRIs easily meet the criteria established by PREA. With over one million children being prescribed antidepressants every year, there is no question that this issue affects a "substantial number of pediatric patients." In addition, we can imagine few risks more "significant" than suicide. Because most of these drugs have not been approved for use in children, there are no labeling guidelines for doctors to

follow when prescribing them. Without adequate scientific information regarding the effects of these drugs on children, doctors may unknowingly be harming the patients they are trying to treat. Therefore, we request that you report back to us regarding your intentions to invoke the authority granted by PREA, as well as your reasons for not doing so in cases where you decide that it is inappropriate.
Finally, we ask that FDA take the following additional steps to protect the safety of our children:

• Heed the advice of the advisory committee and strengthen the Public Health Advisory that FDA issued to health care providers on October 27, 2003;

• Continue to work with manufacturers of SSRIs to obtain data from any unpublished and ongoing clinical trials that might prove useful in determining the effect of these drugs on children, including vigorous enforcement of existing obligations to report adverse events;

• As appropriate, disseminate information regarding the effect of SSRIs on children, including the findings from the review of clinical trials, any additional data obtained from drug manufacturers, and the results of clinical trials conducted in accordance with Section 505B(b) of the Federal Food Drug and Cosmetic Act.

It is imperative that the questions surrounding SSRIs be answered as quickly as possible. If these drugs do indeed increase suicidal ideation, physicians and the public must be made aware of this risk as soon as possible. It is equally important to discover the truth in the case that SSRIs do not pose a threat to children's well-being, so that doctors can continue to prescribe these life-saving medicines without fear. In the current environment of uncertainty, there is a legitimate concern that children who now benefit, or who may benefit, from SSRIs will be inappropriately denied access to these drugs.

Thank you for considering our request. We look forward to your response. If you have any questions, please do not hesitate to contact Ben Berwick of Senator Dodd's staff at (202) 224-2823.

Sincerely,

Christopher J. Dodd
United States Senator

Edward M. Kennedy
United States Senator

Hillary Rodham Clinton
United States Senator

Patty Murray
United States Senator

Tom Harkin
United States Senator

Jeff Bingaman
United States Senator

John Edwards
United States Senator

Jon Corzine
United States Senator

Tim Johnson
United States Senator

Barbara Mikulski
United States Senator

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