CNN
Tuesday, January 4, 2005

Documents: Prozac use reports more likely to list suicide


(CNN) -- Internal documents from Eli Lilly and Co. appear to indicate that
the drug maker had data more than 15 years ago showing that adverse-effect
reports for Prozac were far more likely to list suicide attempts and
violence than reports for other antidepressants.

One memo suggests a strategy for talking to doctors about unfavorable
clinical trial data showing an increased risk of nervousness, anxiety,
agitation, insomnia and sedation among patients.

Lilly officials said Tuesday numbers in the documents made public Monday
represented not clinical trials but "adverse effects" reported to the U.S.
Food and Drug Administration. The company acknowledged the documents belong
to Lilly.

The data were reviewed extensively at the time, said Dr. Charles Beasley of
Lilly, but "we did not believe this data, for a number of reasons, were
terribly useful or informative in terms of suggesting anything about a
causal link between the drug and the adverse effects being reported."

The documents were provided to CNN by the office of Rep. Maurice Hinchey,
D-New York, who has called for tightening FDA regulations on drug safety.

"The case demonstrates the need for Congress to mandate the complete
disclosure of all clinical studies for FDA-approved drugs so that patients
and their doctors, not the drug companies, decide whether the benefits of
taking a certain medicine outweigh the risks," he said.

One of the documents cites what a Lilly official told CNN were 14,198
adverse-effect reports in which 3.7 percent were suicide attempts by people
on fluoxetine -- the generic name for Prozac. That rate was far higher than
those cited for any of four other commonly used antidepressants.

The document also states that 2.3 percent of those adverse-effect reports
concerned psychotic Depression while on the drug, more than double the
next-highest rate of patients using any of the other antidepressants. In
addition, the document said that 1.6 percent were reported incidents of
hostility -- more than double the rate reported on any of the other commonly
used antidepressants.

And, the document says, 0.8 percent of adverse-effect reports concerned
patients causing an intentional injury -- eight times the rate associated
with any of the other antidepressants.

Lilly officials said Prozac had only recently been approved in the United
States at the time those data were compiled and as a result the drug was
under close scrutiny by physicians, receiving more adverse effect reports
than the older antidepressants. Such reports would be expected to decrease
the longer any drug remains on the market, Beasley said.

Among the documents is a memo in which the author says the drug may produce
nervousness, anxiety, agitation or insomnia in 19 percent of patients, and
sedation in 13 percent of patients.

Beasley did not dispute the contents and said he likely authored the memo,
titled "Activation and sedation in fluoxetine clinical trials."

The memo said, "Several suggestions may be helpful in presenting this
information to physicians," including emphasizing that more patients on
another class of antidepressants stopped taking their drugs than did those
on Prozac.

The existence of the documents obtained by CNN and other documents was
reported last week by the British Medical Journal. Its editors said the
documents had been reported missing from a 10-year-old murder case, and that
they had sent them to the FDA for review.

The journal said the documents disappeared in 1994, during the case of
Joseph Wesbecker, a printing press operator who had killed eight people at
his Louisville, Kentucky, workplace five years before, while taking
fluoxetine. He then shot and killed himself.

Each of the four pages of the documents obtained by CNN is stamped
"Confidential" and "Fentress," the name of one of Wesbecker's victims.

That stamp, said Lilly spokesman Morry Smulevitz, likely was used because
the documents were provided to plaintiffs' attorneys in the trial. He said
the documents did not disappear, but have always been available.

In a civil suit against Eli Lilly, victims' relatives contended the company
had long known about the side effects of fluoxetine, including its alleged
role in increasing a user's propensity to violence.

Lilly initially won the case, but it was later forced to admit that it had
made a secret settlement with the plaintiffs during the trial, which meant
that the verdict was invalid, the journal said.

The FDA has recently warned that antidepressants can cause side effects such
as agitation, panic attacks, insomnia, and aggressiveness.

In a statement posted on Lilly's Web site, the company said, "To our
knowledge, there has never been any allegation of missing documents from the
Wesbecker trial or any other trial involving Lilly. Further, it has always
been Lilly's objective to publicly disclose data about both the safety and
efficacy of fluoxetine.

"Lilly has made several requests to the BMJ to obtain copies of the supposed
'missing' documents; we still await these documents. We are surprised and
concerned that a leading medical journal would not find it important to
share these documents with us so that we could respond to the public in a
meaningful way."

Based on its history of having provided regulatory authorities with study
results, the statement said, "Lilly believes that there is no new scientific
information to review on this topic."

About 54 million people worldwide have taken Prozac, Smulevitz said.

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