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Dr. Graham Emslie, a professor of psychiatry at the University of
Texas Southwestern Medical Center who was a researcher in four of
GlaxoSmithKline's studies of Paxil, said he suspected that the other
studies went unpublished at least in part because the results were
"Some of these studies were finished a couple of years ago," Dr.
Emslie said. "But negative trials tend not to get published."
Dr. Perera, the GlaxoSmithKline official, said that publishing
studies "takes time." He declined to say if the company would seek
to publish the eight Paxil studies that have not appeared in
According to Dr. Emslie, other companies have withheld negative
studies of S.S.R.I.'s. "I know of at least a half-dozen other
studies of antidepressant treatments in children and adolescents
that have been completed but as yet have not been published," he
said. "More than enough time has passed for these to be published at
least in abstract form." He refused to identify the companies or the
drugs involved because he, like other researchers involved in
similar research, has signed contracts promising secrecy.
With negative results not disclosed, researchers and physicians
often believe that drugs are more effective and safer than they
actually are, according to Dr. Marcia Angell, a former editor of The
New England Journal of Medicine. "It changes the way medicine is
practiced," Dr. Angell said.
Back in 1991, in their presentation to the blue-ribbon committee
reviewing Prozac, Lilly scientists made much of the fact that
studies analyzing Zoloft and Paxil failed to show any link between
those drugs and an increase in suicides.
"There is simply no scientific evidence whatsoever, no
placebo-controlled double-blind study, that has established a
cause-and-effect relationship between antidepressant pharmacotherapy
of any class and suicidal acts or ideation," said Dr. Charles B.
Nemeroff, a professor of psychiatry at Emory University who worked
as a consultant and spoke on behalf of Lilly.
In an interview, Dr. Nemeroff said he believed that his statement
was accurate then and remains so, since he has not seen any
published study to contradict it.
The British and American regulators have reached a different
conclusion. And experts hired by lawyers suing the manufacturers
over claims that the drugs led to suicides question whether the
F.D.A. received a full picture of the available research in
For instance, F.D.A. procedures required Lilly to inform the
agency of any concerns about Prozac raised by other national health
authorities. But court records show that Lilly never told the F.D.A.
or the expert panel that German regulators initially refused to
approve Prozac's sale in 1985 because of concerns over a link with
In their analysis of Lilly's data, the German authorities said
that Prozac seemed to have caused a substantial increase in suicide
among users, according to court records. Ultimately, the Germans
approved Prozac with a warning that physicians should consider using
sedatives for patients at risk of suicide.
No such warning is included in Prozac's label in the United
States, although the risk of suicidal thinking is listed among the
drug's side effects.
Gary Tollefson, a Lilly executive who spoke before the 1991
panel, was asked in a deposition why he did not tell the experts
about the German concerns.
"That was not a question I was asked," he said, according to
court records, "so I did not answer that question."
Documents brought to light in other cases suggest that Lilly
struggled for years to reconcile suicidal events among patients
taking Prozac in its trials. One memo shows that a top Lilly
executive asked the company's own researchers to record suicide
attempts as "overdose" and thoughts of suicide as "depression."
In another memo, a Lilly employee objected to those instructions,
making reference to the German health authority, known by its
initials as the B.G.A. "I do not think I could explain to the
B.G.A., a judge, to a reporter or even to my family why we would do
this especially on the sensitive issue of suicide and suicidal
ideation," he wrote.
In a recent statement, Lilly said: "There is no credible
scientific evidence that establishes a causal connection between
Prozac and violent or suicidal behavior. To the contrary, scientific
evidence shows that Prozac and other antidepressant medications
appear to reduce these behaviors."
Lilly representatives told the 1991 panel that the company had
put together a series of proposed studies to examine the suicide
issue and said one of the studies had already been started.
According to plaintiffs' lawyers, Lilly never completed the study;
Lilly declined to comment.
Were the F.D.A. to reconstitute the 1991 panel, its members would
again be presented with a confusing mix of data on the issue —
despite the passage of 16 years since Prozac's introduction and the
use by tens of millions of people of it and other S.S.R.I.'s.
Under the circumstances, one member of the panel, Dr. Keh-Ming
Lin, a professor of psychiatry at the University of California at
Los Angeles, said the new information unearthed by regulators might
lead him to change his vote absolving S.S.R.I.'s of suicide
"If you have data that's worrisome, you tend to be conservative,"
Dr. Lin said, "even when the question isn't resolved."