While the researchers said the study raises questions about long-term use of such medicines, a spokeswoman for the company that makes Prozac, one of the drugs studied, said people would have to swallow hundreds of pills to reach the kinds of doses given to rats in the experiment.

      In the research, investigators from Philadelphia's Jefferson Medical College over four days fed rats toxic amounts -- up to 100 times the normal dose -- of the depression-fighting drugs Prozac and Zoloft, or the obesity treatments Meridia and Redux.

      Three of the drugs -- Prozac, Zoloft and Meridia -- are on the market. Redux was removed from the market in 1997.

      At the highest doses, nerve endings suddenly swelled and started to curl, said lead author Madhu Kalia, a Jefferson professor of biochemistry, molecular pharmacology, anesthesiology and neurosurgery. Similar abnormalities were seen in studies with the street drug Ecstasy, which has been shown to destroy brain cells.

      The study is published in the March 6 issue of the journal Brain Research. Laura Miller, a spokeswoman for Indianapolis-based Eli Lilly & Co., makers of Prozac, said the doses given to the rats were too high to be meaningful. Miller said it would be like a person taking 300 capsules a day of Prozac. "That's an extraordinary high dosage," she said.

      Prozac has been on market about 12 years. Miller said no similar effects were seen in research leading up to the drug's approval.

      The drugs belong to a class of medications called selective serotonin reuptake inhibitors and they are designed to boost levels of the mood lifting chemical serotonin.

      Kalia said it is unknown whether therapeutic doses of the drugs over the long-term can produce the same effects and what impact these shape changes have on behavior. She plans other studies to answer these questions.

      Kalia said that even though the drugs have been rigorously tested, doctors should still be cautious about their use. The changes in the rat brains were subtle and similar effects would be difficult to pin down in humans.

      "You can't assume it won't have an effect on the structure of the brain," she said.

(c) 2000 UPI All rights reserved. Copyright 2000 by United Press International.

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