I am pleased to have the opportunity to testify as president of the National Research Center for Women & Families. Our nonprofit research and education center does not accept contributions from companies that make medical products that we evaluate, or competing companies, and so I have no conflicts of interest.

Our Center is dedicated to improving the health and safety of adults and children, and we do that by scrutinizing medical and scientific research to determine what is known and not known about specific treatments and prevention strategies, and to compare their safety and effectiveness.

In addition, I am a fellow at the University of Pennsylvania Center for Bioethics, and a board member for two nonprofit organizations that work to improve resources for the FDA: the Alliance for a Stronger FDA, and the Reagan Udall Foundation.

My doctorate is in clinical psychology and my post-doctoral training is in epidemiology and public health, and I have clinical and research experience with patients with depression, anxiety, and schizophrenia.

I was trained in epidemiology at Yale Medical School; I have worked on federal health policy issues in Congress, the White House, the Institute of Medicine, and for nonprofit organizations for 25 years; and I have reviewed FDA safety issues for almost 20 years.

The key questions of the day are:
Are the benefits of Seroquel likely to outweigh the risks for depressed patients or patients with generalized anxiety?

The benefits are statistically significant in most, but not all the studies provided to the FDA. But, let’s be clear here: the patients on placebo are improving greatly in these studies – almost as much as those taking Seroquel. Most of the improvement for patients is apparently due to the placebo effect. The drug itself adds little benefit. The difference between depression scores for patients taking Seroquel are just slightly better than the scores for the patients taking placebo. These differences are sometimes statistically significant, but they are not especially meaningful.

What about the adverse reactions? Again, the placebo patients report quite a few minor adverse reactions, as do the Seroquel and active controls. However, the Seroquel patients are significantly more likely to drop out of the study because of adverse reactions than the placebo patients.

How serious are these adverse reactions? These studies are not designed to tell us the answer to that question, because these are short-term studies. Patients who take drugs for depression don’t usually stop after 6 weeks or 8 weeks. Many will take drugs for many months or many years. As the FDA reviewers pointed out, there is very clear evidence that Seroquel causes weight gain, and less conclusive evidence that it increases the risk of diabetes and tardive dyskinesia. In his presentation today, Dr. Wayne Ray of Vanderbilt University School of Medicine indicated that sudden cardiac death is associated with atypical anti-psychotics such as Seroquel.

We all know how serious diabetes is. It is absolutely not acceptable to approve Seroquel for depression or anxiety if it increases the risk of diabetes more than other drugs approved for depression or anxiety. Of course, the risk of sudden cardiac death, even if a rare adverse reaction, would also make the expanded use of Seroquel unacceptable.

I have experience seeing patients with tardive dyskinesia, from when I worked in a psychiatric hospital. The uncontrolled movements, including grimacing, tongue protrusion, and lip smacking are very obvious, very embarrassing to the patient, and are virtually impossible to ignore. There is a lack of effective treatments and stopping the drug after the problems have started usually doesn’t work. The nonprofit organization that educates people about movement disorders such as tardive dyskinesia is clear about the importance of avoiding drugs that can cause this disorder; they say: “every effort should be made to limit the use of these drugs to those patients for whom no other treatment options are available.”

Drugs that can cause tardive dyskinesia should therefore never be given to anyone with depression or anxiety unless every other, safer drug has already been tried and failed. You all know that even if a label warns to try other medications first, that is not how new anti-depressants are prescribed.

AstraZeneca should not even want to sell Seroquel for these purposes unless the company can conclusively prove that the drug does not increase the risk of diabetes or tardive dyskinesia or sudden cardiac death, but unfortunately they have chosen a different path. For that reason, it is your job to keep Seroquel off the market for this expanded use unless the company can eventually, conclusively prove that it does not increase the risk of diabetes or tardive dyskinesia or sudden cardiac death. That is the ethical thing to do, and it is also consistent with FDA’s mandate to ensure that products are safe and effective before they are approved. It is not enough to say that we don’t know for sure how much of a risk Seroquel poses. We need to know conclusively that the drug is safe for long-term use.