(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.
