REPORTS LINK PROZAC, SUICIDES

The best-selling antidepressant is said to be responsible for causing
suicidal reactions in a small but significant number of patients.

Just as the 14-year patent on Prozac is about to expire and the drug's
maker, Eli Lilly and Co., is preparing to launch a new version, a body
of evidence has come to light revealing the antidepressant's dark side.

The company's internal documents, some dating to the mid- 1980s, as
well as government applications and patents, indicate that the
pharmaceutical giant has known for years that its best-selling drug
could cause suicidal reactions in a small but significant number of
patients. The reports could become critical as Lilly seeks government
approval for its new Prozac.

Among the findings:

o Internal documents show that in 1990, Lilly scientists were
pressured by corporate executives to alter records on physicians'
experiences with Prozac, changing mentions of suicide attempts to
"overdose" and suicidal thoughts to "depression."

o Three years before Prozac received approval by the Food and Drug
Administration in late 1987, the German BGA, that country's FDA
equivalent had such serious reservations about Prozac's safety that it
refused to approve the antidepressant based on Lilly's studies showing
that previously nonsuicidal patients who took the drug had a five-
fold higher rate of suicides and suicide attempts than those on older
antidepressants, and a three-fold higher rate than those taking placebos.

o Lilly's own figures, in reports made available to the Globe,
indicate that one in 100 previously nonsuicidal patients who took the
drug in early clinical trials developed a severe form of anxiety and
agitation called akathisia, causing them to attempt or commit suicide
during the studies.

o Though Lilly has steadfastly defended the drug's safety and
downplayed studies linking Prozac to suicide, the patent for the new
Prozac, R-fluoxetine, expected to be marketed by Lilly beginning in
2002, notes that the new version will not produce several existing
side effects including "akathisia, suicidal thoughts, and self-
mutilation," which the patent calls "one of its more significant side
effects."

o A researcher at McLean Hospital in Belmont, Mass., who is an
associate professor at Harvard Medical School, Martin Teicher, whose
early 1990s studies linked Prozac to akathisia and suicide, is a
co-inventor of the new Prozac, along with Timothy J. Barberich, chief
executive officer of Sepracor Inc., a Marlborough, Mass., drug
company, and James W. Young.

o A just-published book, "Prozac Backlash" by Cambridge psychiatrist
Joseph Glenmullen, has drawn Lilly's ire for discussing Prozac's link
to suicide, tics, withdrawal symptoms, and other side effects of
Prozac and similar anti-depressants.

Lilly officials continue to defend the drug's effectiveness, saying
its track record is borne out by the fact it is still the most widely
prescribed drug of its kind.

In a written statement Jeff Newton, a Lilly spokesman, said: "There is
no credible evidence that establishes a causal link between Prozac and
violent or suicidal behavior. "There is, to the contrary, scientific
evidence showing that Prozac and medicines like it actually protect
against such behaviors."

Using figures on Prozac both from Lilly and independent research,
however, David Healy, an expert on the brain's serotonin system and
director of the North Wales Department of Psychological Medicine at
the University of Wales, estimated that "probably 50,000 people have
committed suicide on Prozac since its launch, over and above the
number who would have done so if left untreated."

Healy, meanwhile, is conducting a new study that he says is the first
of its kind, giving antidepressants to healthy people to study

Prozac's success is certainly unquestioned. The introduction of the
drug to the U.S. market in the late 1980s changed the way Americans
viewed their most intimate emotions and limitations.

Billed as a wonder drug to combat depression by boosting levels of the
brain chemical serotonin, Prozac and others like it were also said to
remedy a host of human frailties from poor self-esteem and
concentration to fear of rejection.

By the end of last year, more than 35 million people worldwide were
using the drug, which provided Lilly with more than 25 percent of its
$10 billion in 1999 revenue.

Yet the problems with Prozac were known even before it was introduced
to the U.S. market. Figures in a 1984 Lilly document indicated that
akathisia, the severe agitation that can lead to suicide, occurs in at
least 1 percent of patients, a level considered a "frequent" event,
and as such must be disclosed in a company's product literature and
package inserts.

But there is no such disclosure in Prozac's U.S. literature, and it is
not clear whether the FDA panel charged with approving Prozac simply
overlooked or did not have access to certain critical data of Lilly's

As a result, researchers say most U.S. doctors do not know to warn
patients of the potentially dangerous effect which, according to
published literature on the topic, can be alleviated with sedatives or
by going off the drug.

Akathisia is listed in Lilly's U.S. product literature, but as an
infrequent event in Prozac users. No mention is made of its potential
relationship to suicide.

A relationship, however, was found in a Globe search of U.S. patents.
The patent for the new Prozac or R-fluoxetine (U.S. Patent No.
5,708,035), which Lilly will market after the existing patent expires
in 2001, contains a wealth of information about the original Prozac.

According to the patent, the new Prozac will decrease side effects of
the existing Prozac such as headaches, nervousness, anxiety, and
insomnia, as well as "inner restlessness (akathisia), suicidal
thoughts and self-mutilation" - the same effect Lilly has contended
has not occurred in any substantial way in some 200 lawsuits against
it over the past decade. Most of the suits were settled out of court
and the terms kept confidential.