> 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