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Title: Medical Experts Dispute Findings in NEJM Study
URL: http://www.pslgroup.com/dg/CCEE.htm
Doctor's Guide
October 2, 1996


INDIANAPOLIS, Oct. 2, 1996 -- Independent mental health experts question the validity of a study in the October 3 issue of the New England Journal of Medicine that examines the safety of the antidepressant Prozac(R) (fluoxetine hydrochloride) in pregnant women.

The preponderance of data from all other independent published studies that examined the use of Prozac during pregnancy contradict the NEJM conclusions that Prozac can cause minor malformations or premature births.

Medical experts familiar with the study urge women who require antidepressants to consult their physicians before making a decision on their medication.

Mental health experts say women, physicians and advocacy groups should weigh the results from all previous and upcoming studies -- plus an accompanying editorial in the NEJM -- before embracing the findings in the recent study, authored by Christina D. Chambers and four colleagues, including lead investigator Kenneth Lyons Jones, M.D.

"The study is inconsistent with the preponderance of data that has supported the safety of Prozac use during pregnancy consistent with product labeling," said Dr. Lee Cohen, M.D., a psychiatrist at Massachusetts General Hospital in Boston. "The main finding of the study, which supports no higher risk of major birth defects in women who use Prozac during pregnancy compared with those who do not, is reassuring. It is unfortunate that the secondary findings of higher rates of neonatal complications and minor malformations are so limited by the methodological problems outlined in the accompanying editorial by the prominent teratologist in this area.

"Prozac remains unrivaled based on the abundance of data regarding its use in both women who are planning to conceive or who are pregnant," Dr. Cohen said.

The editorial, authored by Dr. Elisabeth Robert, a well-known French teratologist, attacked the NEJM study.

"In contrast to these results, five cohort studies, which included approximately 450 pregnancies and which focused on the relation between fluoxetine and developmental effects, suggested that children exposed in utero, whether early or late in gestation, do not have an increased risk of birth defects, poor perinatal condition or neurodevelopmental delay.

"In sum," Dr. Robert wrote, "it seems unjustified to use these new results as a reason to withhold fluoxetine from women who require an antidepressant drug during pregnancy."

The study, like all previous examinations, found no relationship between Prozac and major malformations in newborns.

Dr. Gideon Koren, director of the Motherisk Program at the Hospital for Sick Children in Toronto, authored a study earlier this year in Teratology that said, "It appears that, when used clinically in recommended doses, in humans, fluoxetine has not been shown to produce an increase in the frequency of morphological abnormalities or effects on neurobehavior."

Dr. Koren also said that, "In Toronto's Motherisk Program, we counsel scores of women every month on the use of Prozac in pregnancy. Our published research points out that Prozac does not cause malformations nor adversely affects normal IQ, language and psychological development."

Chambers, in the publication, acknowledges that the nonrandomized study included participants with various confounding factors. Among the factors acknowledged in NEJM as study limitations were other medications, tobacco and alcohol usage and age of participants and improper comparison groups.

"When it comes to the use of antidepressants during pregnancy, more information exists regarding Prozac than about any other antidepressant, including drugs in the older classes of antidepressants," said David Goldstein, M.D., a researcher at Eli Lilly and Company and author of a previous study on the subject. "These types of examinations are expected because Prozac is the leader among all antidepressants. However, like any drug, Prozac should be used during pregnancy only if clearly needed -- a decision that can only be made by a woman and her physician."

Lilly is a global research-based pharmaceutical corporation headquartered in Indianapolis, Ind., dedicated to creating superior health care solutions -- combining pharmaceutical innovation, existing pharmaceutical technology, disease prevention and management and information technologies -- in order to provide customers worldwide with optimal clinical and economic outcomes.

Complete prescribing information for Prozac (fluoxetine hydrochloride) is available upon request from Eli Lilly and Company.

Medical Experts _______________

Lee Cohen, M.D.
(617) 724-0816 or 8020
Massachusetts General Hospital
Boston, Mass.

Lewis B. Holmes, M.D.
(617) 726-1742
Massachusetts General Hospital
Boston, Mass.

Gideon Koren, M.D.
(416) 813-5778 or 5781
Motherisk Program
Hospital for Sick Children
Toronto, Ontario

Vivien Burt, M.D., Ph.D
(310) 206-5135
UCLA-Neuropsychiatric Institute and Hospital
Los Angeles, CA

Anne Pastuszak, Ph.D.
(416) 813-7881 (phone)
Motherisk Program
(416) 442-9548 (pager)
Hospital for Sick Children
Toronto, Ontario

Zachary Stowe, M.D.
(404) 727-3692
Emory University
Assistant Professor of Psychiatry and Behavior Sciences
Atlanta, Ga.

Kim Yonkers, M.D.
(214) 648-4283
University of Texas
Department of Psychiatry

Freda Lewis-Hall, M.D.
(317) 277-6738
Director,
Lilly Center for Women's Health
Eli Lilly and Company
Indianapolis, Ind.

David Goldstein, M.D.
(317) 276-7047
Clinical Research Physician
Eli Lilly and Company
Indianapolis, Ind.

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