Diet-Drug Research Suggests
A Need for Human Studies
By LAURA JOHANNES
Staff Reporter of THE WALL STREET JOURNAL
A report in Wednesday's Journal of the American Medical Association
concludes that doses of popular diet drugs believed to cause brain damage
in animals are roughly equivalent to those taken by humans.
Drug companies that sell the diet drugs, Redux and Pondimin, have
claimed that doses that appeared to harm laboratory animals would be
gigantic in human terms.
The researchers cautioned that their conclusions, drawn from an analysis
of 71 studies on rats, baboons and monkeys, don't necessarily mean the
drugs also cause brain damage in humans. But they said their findings
provide compelling evidence that human studies are needed.
American Home Products Corp., the Madison, N.J., company that
markets Redux and Pondimin, has agreed to conduct a two-year study on
potential effects of Redux on the brain. But it and Interneuron
Pharmaceuticals Corp., the Lexington, Mass., company that holds the
patent rights to Redux, immediately disputed JAMA's conclusions.
American Home said the brain concentrations of the diet drugs in the test
animals were 10 times that found in humans taking approved doses.
But researcher Una McCann, a psychiatrist at the National Institutes of
Mental Health and the lead author on the paper, said those measures of
brain concentration aren't very accurate. Her analysis converted doses into
human terms using a method called scaling, which takes into account the
weight of the animal and its surface area. She concluded that relatively
small amounts of the drugs "amputate the neurons" that store the
neurotransmitter serotonin.
The Serotonin Connection
Serotonin plays an important role in mood, sleep, regulation of anxiety and
thought processes. In the 16 months Redux has been on the market, the
Food and Drug Administration has received several complaints of
depression, anxiety and sleep disorders from users of Redux -- but there's
no proof that the drug caused those problems.
The diet drugs studied, classified as fenfluramines, stimulate the release of
serotonin into brain synapses, or the spaces between nerves, and make
dieters feel full. The illicit drug Ecstasy, popular in the 1980s, is
chemically similar to the diet drugs and creates "almost identical" neuron
damage in animals, said Dr. McCann. The same effects haven't been seen
for Prozac and other antidepressants, which also affect serotonin but work
by a slightly different mechanism, added Dr. McCann.
The FDA approved Redux in April 1996, despite concerns raised by Dr.
McCann and her husband, Johns Hopkins School of Medicine researcher
George Ricaurte, as well as other scientists. But the agency did require a
postmarketing study. American Home announced last week that the agency
had approved the design of a study that will look for psychological
changes in people taking Redux, Prozac and a placebo.
'Seeing Little Green Men'
Dr. Ricaurte contends that such a study may not uncover brain damage that
could be much subtler. Nonsense, says Interneuron's founder, Richard
Wurtman, the Massachusetts Institute of Technology researcher who
discovered the efficacy of the chemical now called Redux in weight loss.
"My response to George is, 'You're seeing little green men,' " said Dr.
Wurtman.
He disputes Dr. McCann's contention that Redux resembles Ecstasy, and
argues that the benefits of the diet drug in preventing obesity-related
disease beat out the risks. "There are large numbers of people whose lives
could be saved by this drug," he said, "but they are being scared off by
reports of these side effects that don't exist."
James O'Callaghan, head of the molecular-neurotoxicology laboratory at
the Centers for Disease Control and Prevention in Atlanta, agrees. He gave
mice four giant doses of Redux in a single day, then looked for a protein
generally made by the brain when it is damaged by, say, a bullet. Redux,
he concluded, "did not cause brain damage."
It did cause the serotonin levels in the rodents to drop dramatically for
three weeks after the drug was stopped, for reasons that aren't completely
understood. "Is that something you want to have happening? No," said
Dr. O'Callaghan. "But it's a high-dose effect in rodents. We don't know if
it happened in humans.'' |
