PFPC Daily - December 30, 2004

Report: Prozac Maker Knew of Problems in 1988

Forbes - Dec. 30, 2004

By Amanda Gardner

THURSDAY, Dec. 30 (HealthDayNews) -- Confidential company documents
obtained by a leading medical journal suggest that drug giant Eli
Lilly & Co. was aware that its antidepressant Prozac was linked to
troubling side effects as far back as 1988, the same year the drug
was introduced to the U.S. market.

The discovery is reported in the Jan. 1 issue of the British Medical
Journal, and adds to the growing body of bad news for pharmaceutical
companies. The papers have been turned over to the U.S. Food and Drug
Administration.

Amid the pile of internal reviews and memos, according to the
journal, is a document dated November 1988 that reports Prozac
(fluoxetine)had caused behavioral problems, including agitation and
panic attacks, in clinical trials.

The issue of disclosure is a loaded one. The FDA announced in October
that antidepressants such as Prozac would now have to carry a "black
box" warning that health-care providers should be on the lookout for,
among other things, increased agitation, panic attacks, and
aggression among users of the drugs.

This latest report also fuels the ongoing debate over which clinical
studies should come to the attention of federal regulators and which
should never the see the light of day.

"The discovery of research, reportedly 'missing' for the past 10
years, that connects Prozac to increased suicidal tendencies and
violence is one more tragic example of a greater problem: Unless we
mandate that all research be disclosed to the FDA during the drug
approval process, regulators have no choice but to make their
decisions based on the best-case scenarios that drug companies report
to them," U.S. Rep. Maurice Hinchey (D-N.Y.), whose office is
reviewing the documents, said in a statement. "These decisions affect
the health and lives of millions of Americans. If Eli Lilly's
research indicated dangerous side effects of their product and they
withheld that information, they knowingly jeopardized the public's
health. Their failure to disclose what they knew may have cost lives."

Morry Smulevitz, manager of global product communications at Eli
Lilly, said he could not comment on the documents because he hasn't
seen them.

"Certainly Lilly is committed to public disclosure of all clinical
trial data so health-care providers and patients can make informed
treatment decisions," he said. "Prozac has been prescribed for over
50 million people worldwide. It is one of the most studied drugs in
the history of medicine, and its safety and efficacy is well-studied
and well-documented and well-established. Beyond that, unfortunately,
it's really difficult without having the ability to review the
supposed missing documents that we're not aware of to know what we're
trying to make comments upon."

Smulevitz said he had requested the documents from Jeanne Lenzer, a
New York-based medical investigative journalist who received them and
then sent them on to the BMJ and the FDA. But, he said, the request
was not met.

Dr. Richard Kapit, the FDA reviewer who originally approved
fluoxetine in 1987, told the BMJ that he had never been given the
Lilly data.

"If we have good evidence that we were misled and that data was
withheld, then I would change my mind [about the safety of
fluoxetine]," he said in a statement. "I do agree now that these
stimulatory side effects, especially in regard to suicidal ideation
and homicidal ideation, are worse than I thought at the time that I
reviewed the drug."

The documents in question reportedly disappeared during a product
liability suit brought in 1994 by families of the victims of Joseph
Wesbecker, who, in 1989, killed eight people and wounded another 12
with an AK-47 before turning the gun on himself at his workplace in
Louisville, Ky. Wesbecker, who had suffered a long history of
depression, had started using fluoxetine just one month before the
shootings.

The relatives' civil suit alleged that the company had known about
possible side effects of the drugs, including a tendency towards
violence.

The jury ruled 9-3 in favor of Lilly, but, in a shocking turnaround,
the company later admitted it had made a secret deal with the
plaintiffs. In 1997, the judge on the case, John Potter, amended the
verdict to "dismissed as settled with prejudice," meaning it could be
reopened. Potter was presiding over another case Thursday, and could
not be reached for comment on the latest developments.

"It's been a big puzzle for many years," Lenzer said. "The documents
went missing during a critical period in the [wrongful death] trial."
Lenzer would not reveal who had sent her the documents.

The internal company document that stood out to Lenzer, she said, was
one that discussed the finding that 38 percent of people have a
stimulation effect, such as panic attacks and agitation, and that 19
percent of those could be attributed to the drug.

According to Lenzer, the document stated "one in five [patients]
could be expected to experience this activation. And, later in the
document, they talk about how to do damage control, how to get the
doctors not to worry about this. Maybe the information actually got
out and got buried. It's like a little flicker of a flame. Obviously
they didn't get this out to a wide circulation. They didn't get it
out to the people who needed to know. They didn't get it to the FDA
safety officer who reviewed it."

Dr. Peter Breggin, the medical expert in the Wesbecker case, has said
the activation effects could be higher than 38 percent.

Lenzer, however, said she is concerned that what she called a pattern
of secrecy among drug companies continues.

She referred to the Treatment for Adolescents with Depression Study
(TADS), the results of which appeared in the Aug. 18 issue of the
Journal of the American Medical Association. Although the findings
were hailed as a victory for antidepressants, Lenzer stated in a
September letter to the BMJ that the research had a flawed
methodology and failed to report certain negative results.

"This is still going on. It's not just 16 years ago. It's going on
today, right now," she said.

An FDA spokeswoman said the agency had no comment at this point.