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Memos Display Drug Firms' Optimism
Officials Were Confident FDA Would Back Them On Suicide, Violence Issues Involving Paxil, Prozac

September 21, 2003
By JACK DOLAN And DAVE ALTIMARI, Courant Staff Writers

When federal regulators recently warned that the antidepressant Paxil may increase the risk of suicide in children, they stunned the medical community and left thousands of parents wondering whether their children had been exposed to an unsafe drug.

The U.S. Food and Drug Administration's decision also brought legitimacy to the courtroom arguments of some patients and their families, who have said for a decade that Paxil, and other antidepressants such as Prozac, can lead to unexplained violent behavior, including suicide.

Those court filings, some of which have been sealed through the efforts of pharmaceutical industry lawyers, contain internal memos that reveal manufacturers were sure they had the support of FDA scientists investigating the drugs' safety in the early 1990s - long before all the studies on suicide and violence were complete.

While those early studies on Paxil and Prozac did not provide the FDA with reason to stop the approval process, the memos offer a rare glimpse into the discussions between federal regulators and the companies whose drugs they were charged with investigating.

In October 1990, for instance, Thomas Donnelly, an executive from Paxil's maker, SmithKline Beecham, circulated a memo recounting a telephone conversation with the FDA official performing the government's study of the drug's safety. That official, Dr. Martin Brecher, asked Donnelly to produce data on a potential link between Paxil and suicidal thoughts or actions among patients.

Donnelly wrote in the memo to his fellow SmithKline executives that Brecher and the FDA did not "see it as a real issue" and instead considered the concerns a "public relations problem" for the antidepressant drug makers. The memo was written before the data had been reviewed.

Brecher has said since that he did, indeed, view the concerns about suicide as a "real issue" and doesn't think the Donnelly memo fairly characterized the conversation.

"I'm not saying it's untrue. I just don't - it seems to me to be a stronger statement of what I recall thinking at the time," Brecher said in a recent deposition.

Donnelly could not be reached for comment.

A few months earlier, the name of Brecher's boss, Paul Leber, showed up in a similar string of memos at Eli Lilly, the makers of Prozac.

In July 1990, a Lilly executive circulated an internal memo describing Leber as the company's "defender" at the FDA, who had helped the company deflect similar concerns about a link between Prozac and suicide. Leber, then chief of the FDA's psychiatric drug division, is quoted dismissing press coverage of suicide concerns as "trivial" - but at the same time asking Lilly to study the issue because "it will not go away."

The Lilly memo also urges that evidence showing no link between suicide and Prozac be rushed to Leber because higher-ranking FDA officials were considering forcing the company to mention the suicide concern on the drug's label.

In another internal company memo, Lilly executive Leigh Thompson warned that a certain FDA fax number might no longer be safe for sending reports to Leber after it was discovered that other FDA officials also had access to the machine.

Thompson also mentioned a concern about Leber's computer being compromised and strongly recommended that Lilly rent space in a building next to Leber's Washington office so secure communication could be ensured.

Both Prozac and Paxil weathered the early 1990s uproar about a possible link to suicide, which was fueled in large part by patients and their relatives who were deeply mistrustful of psychiatric drugs. Prozac was particularly unpopular among followers of the Church of Scientology.

It was not until this year that data from unpublished clinical trials on children by Paxil's maker, now called GlaxoSmithKline, convinced British and American regulators that there was a scientific basis for the concern about suicide in teens.

"It's a huge breakthrough," said Jessica R. Dart, an attorney with a Los Angeles firm that has represented dozens of patients against Paxil's British maker, GlaxoSmithKline UK. "It almost didn't feel real. They have been denying this for years and years."

Those studies were submitted as part of an FDA initiative to review the effects on teens of all drugs such as Paxil and Prozac, known as selective serotonin re-uptake inhibitors, or SSRIs.

No similar problem was noted with Prozac, which has since been approved for use in children, FDA spokesman Brad Stone said.

Critics charge that pro-industry attitudes among regulators prevented a more thorough examination in the early 1990s.

Months after the Donnelly memo was written, Brecher filed a key safety report with the FDA that concluded there was no link between Paxil and an increased risk of suicide. In October 1992, a panel of doctors convened by the FDA voted unanimously to approve Paxil after a presentation of Brecher's findings and a similar presentation by a doctor employed by Glaxo.

Brecher wasn't around to make the presentation personally. Shortly after submitting his report, he quit his government job and went to work for a European drug company, advising it on how to get its products approved in the United States.

"Brecher was in a hurry to get the report done before he left the FDA, and he didn't look at things as closely as he should have," said Dr. David Healy, a British psychiatrist and well-known SSRI critic. Healy has served as an expert witness in several U.S. court cases against the drugs' manufacturers.

"That's nonsense," Brecher said in a recent interview. "I wasn't rushed. And the review was finished before I even interviewed for the other job."

Brecher said he can't recall the specifics of his conversation with Donnelly, but he dismissed any interpretation of the memo that suggests too much camaraderie between the regulators and the pharmaceutical industry.

"There certainly was a public relations aspect to it. That's a given," Brecher said of the atmosphere surrounding SSRI approval in the early 1990s.

Brecher said he did not believe that there was any scientific evidence of a link to suicide in the clinical trials being done on adults at the time.

In 2001, the Donnelly/Brecher memo became evidence in a Wyoming case in which Glaxo was ordered to pay $6.4 million to the surviving family members of a man who shot and killed his wife, his daughter, his granddaughter and himself after beginning treatment with Paxil.

Last March, Brecher sat through a seven-hour deposition in a separate case filed in California involving patients who claim they became addicted to Paxil. Of all the topics covered, Brecher's discussion of the Donnelly memo is the only section of the transcript Glaxo lawyers insisted be kept confidential.

Glaxo's attorneys supplied The Courant with a copy of the deleted part of the deposition when questioned about why they fought to keep the memo secret. In it, Brecher testifies that in his conversation with Donnelly he might have been referring to concerns over a possible link between anti-depressants and violence, not suicide, as the issue the FDA did not take seriously.

He said he couldn't be sure, because his memory of the conversation was hazy.

Like Brecher, Leber has left the FDA. He now owns a private consulting firm that helps pharmaceutical companies get their drugs approved. Reached by telephone recently, he refused to discuss his work with the FDA.

None of the recent unpublished Glaxo studies linked a suicide to Paxil, according to Andrew Bayman, an Atlanta lawyer hired by Glaxo to defend it against lawsuits.

The nine studies were conducted between late 1998 and fall 2002, said Glaxo spokeswoman Mary Ann Rhyne. The studies looked at more than 1,000 patients under the age of 18. In total, they showed that 3.4 percent of children who were taking Paxil, or recently stopped, had attempted suicide or thought more about it. That compared with 1.2 percent of the children taking a placebo, Rhyne said.

All the data used in the early 1990s to assess the drug's safety looked at adults, Bayman said, explaining why the teen issue might have passed unnoticed.

Paxil became the drug of choice for treating depression in teens because many of its side effects are relatively mild compared with those of other medications, said Dr. Patricia Leebens, director of psychiatry for the Connecticut Department of Children and Families. Common side effects are nausea, dizziness and abnormal vision.

The DCF recently became the first public child-protection agency in the country to stop giving Paxil to children after the FDA's recommendation.

"This is not a decision that was made lightly. There are many members of the committee who have had cases where Paxil had done wonders for a patient," Leebens said.

The DCF also took the anti-depressant Effexor off its list of approved drugs after the drug's maker, New Jersey-based Wyeth Pharmaceuticals, sent a letter to doctors warning about a similar link to suicidal thinking among teens.

Leebens would not say how many of the nearly 8,000 children in DCF care were on Paxil, Effexor or other anti-depressants.

A spokesperson for Lilly said Prozac went through rigorous trials when it was approved for adults in the late 1980s, and again more recently when it was approved to treat obsessive-compulsive disorder and depression, specifically in children. Prozac is the only SSRI approved by the FDA for treating children, Lilly spokesperson Jennifer Yoder said.

The now-retired Lilly executive, Leigh Thompson, acknowledged calling Leber the company's "defender," particularly against attacks by the Church of Scientology, which was lobbying to get Prozac off the market.

Thompson said he talked with Leber as often as three times a week during the controversy and always ordered his scientists to produce whatever studies the FDA wanted.

"Paul Leber was our defender against all of the attacks in the media," he said. "The Scientologists were really after us, and the simplest thing for [the FDA] to do would have been to pull it off the market - and they didn't."

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