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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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