Résumé de l'article ci-dessous, paru dans le Boston Globe http://www.boston.com/freearchives/search.cgi?DBLIST=bg00&DOCNUM=23935&TERMV=10821:11:
(nécessite l'inscription comme client aux archives gratuites du journal, si bien que j'ai laissé
l'article anglais ci-dessous, pour les lecteurs désirant d'autres détails).
Titre: Prozac, Nouvelles directions
Le prozac, qui existe depuis 1988, et fait 2,5 milliards de dollars de CA, a été accusé d'avoir
des effets secondaires plus ou moins marqués. Entre autres, le Dr psychiatre et professeur assistant d'Harvard
Martin H. Teicher a fait paraître en 1990, avec deux autres médecins, une étude de 4 pages
indiquant que quelques 3,5 % des patients traîtés au Prozac souffriraient d'une tendance suicidaire
accrue ou renouvelée.
Mais les scientologues laissent entendre que 100 % des consommateurs de Prozac courent ce risque, dans leur guerre
contre les drogues psychiatriques et la psychiatrie.
La scientologie a donc sauté sur l'occasion de cet article de Teicher, et attaqué bille en tête,
puis fini par obtenir une enquète de la FDA américiane, laquelle a finalement conclu à l'absence
Toutefois, un petit industriel d'une "start-up" chimique a contacté Teicher, pour lui demander
d'étudier un produit en quelque sorte "dérivé" du Prozac - en fait, découvrir
lequel des aspects isomères du Prozac (Fluoxetine) n'aurait pas d'inconvénients aussi importants,
suivant en cela les découvertes de Pasteur.
Ce produit a fini par être mis au point et breveté par Teicher, Timothy J. Barberich, PDG de Sepracor
et son associé James V. Young, et finalement vendu à Eli Lilly soi-même, Eli Lilly admettant
"en quelque sorte" par cet achat, que le Prozac pouvait avoir les inconvénients qu'on lui reproche
parfois, sans qu'aucune étude complète n'ait été réellement effectuée,
si bien que quelques clients ont lancé un procès contre Eli Lilly, qui n'a jamais admis que le Prozac
ait ou pourrait avoir ces effets secondaires.
On peut gager que la sceintologie va continuer son combat anti-psychiatrique et anti-prozac: elle est du genre
pit-bull, et agit aussi stupidement.
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PROZAC: NEW DIRECTIONS
SCIENCE , MONEY DRIVE A MAKEOVER
Author: By Mitchell Zuckoff, Globe Staff Date: 06/11/2000 Page: A1 Section: National/Foreign
This is a story about a drug that changed the world, the bravery of rats, the evolution of a psychiatrist, the
Jekyll and Hyde nature of man-made chemicals, the Church of Scientology, and the impulses that lead some people
It is also about money. Lots of money.
The drug is Prozac, and its resume is lore: Introduced by Eli Lilly and Co. in 1988 as the first notable new antidepressant
in two decades, it lifted the spirits of millions and became shorthand for the search for answers in convenient
Yet its triumphs have been clouded by persistent accusations, denied by Lilly, that a small but significant percentage
of Prozac users suffer a side effect that runs counter to the drug's intent: intense agitation that in rare cases
explodes into violence, suicide or both.
Now, as the familiar green-and-white pill approaches the humbling status of a generic drug in 2004, along comes
a new drug derived from Prozac - ostensibly without the dangerous side effects - that is designed to take Prozac's
place in the medicine cabinet and on Lilly's billion-dollar balance sheet.
And along with that new drug comes a most unexpected helpmate for Lilly, a Harvard psychiatrist named Martin H.
Teicher, who in the space of a decade has taken an extraordinary journey.
From Prozac's most prominent critic - author of the first scientific paper to wave the red flag of suicide and
violence - Teicher is now enjoying what he calls his "wonderfully ironic" role as co-inventor of the
Prozac replacement drug.
With a high-flying Massachusetts drug firm acting as middleman, Teicher stands to grow rich from Lilly, despite
its continued rejection of his conclusions about suicide. If the new Prozac clears ongoing trials and proves even
moderately successful compared to its predecessor, Teicher could supplement his associate professor's salary by
more than $5 million a year.
At the same time, Teicher's decade-old observations about Prozac's dangers have resurfaced in a very awkward way
for Lilly. The drug patent obtained by Teicher and his co-inventors says the new Prozac is free from the suicide
side effect, and last week that claim became the basis for a federal fraud lawsuit against Lilly. The lawsuit essentially
accuses Lilly of denying any Prozac-suicide link on the one hand, yet buying an exclusive license for a patent
that says otherwise.
For perspective, imagine if car safety crusader Ralph Nader identified a major safety flaw in, say, the braking
system used in all cars. The automakers deny the flaw exists. Nader then invents a device that fixes the flaw and
offers it to the automakers. Despite denying the problem, they pay him millions for it.
Now substitute Teicher and Lilly in those roles, and that's what makes this a uniquely American tale about the
pursuit of knowledge, the pursuit of profits, and the arranged marriages that sometimes bring them together.
Inside the psychiatrist's den
Teicher's office at the Harvard-affiliated McLean Hospital in Belmont has all the trappings of a psychiatrist's
den. There is the leather couch, the bursting bookcase, and the wall of diplomas - Ph.D. from Johns Hopkins in
1977, M.D. four years later from Yale. A clock chimes to mark the passing hours.
There are personal touches, too: a jar on a shelf jokingly labeled "Ashes of former students"; and a
quote on the wall from Voltaire, "No problem can withstand the assault of sustained thinking." A plaque
commemorating one of Teicher's two Prozac-related patents hangs over his desk. There are two paintings, one of
a sad clown and the other of a frightened child. They were painted by the psychiatrist's mother.
Teicher, 49, is a suit-and-tie native of New York's endless suburb, Long Island. Divorced, he lives in Waltham;
after their divorce, his ex-wife took a job as a cancer researcher for none other than Lilly, which Teicher calls
"an odd happenstance of coincidence."
He does not seek publicity; would-be interviewers have to run a gantlet of McLean public relations officials. Once
he agrees to talk, however, Teicher is gracious, if seemingly detached from the subject that could make him rich
and, in certain circles, famous.
"This is just one small part of what I do, a minor offshoot," Teicher said quietly, preferring to talk
about his recent work on attention deficit and hyperactivity disorders.
In fact, a McLean-supplied biographical sketch that lists 58 of his publications between 1976 and 2000 does not
include the scientific paper that set him on the Prozac path, and for which he is arguably most widely known: "Emergence
of Intense Suicidal Preoccupation During Fluoxetine (Prozac) Treatment."
Its absence notwithstanding, there is no denying the paper's impact.
Just four pages long, it was written by Teicher, a nurse named Carol Glod (who has since earned a doctorate), and
fellow Harvard psychiatrist Jonathan O. Cole. It was published in February 1990 in the prestigious American Journal
In the dry language of academia, the paper describes six depressed patients, ages 19 to 62, five of whom had considered
killing themselves in the past but none of whom had recent suicidal thoughts.
The authors detail how all six became powerfully suicidal - stricken by a "state more intense, obsessive,
and violent than anything they previously had experienced" - within weeks of beginning Prozac treatment, and
remained so for anywhere from three days to three months after discontinuing the drug. One put a loaded gun to
her head, and another had to be restrained to prevent self-mutilation. None committed suicide.
With the imprimatur of Harvard psychiatry, the paper was received by many as proof of the anecdotal and media reports
that flourished in the years after Prozac's introduction.
Among the most dramatic was the story of Joseph Wesbecker, a deeply disturbed Kentucky printing press operator
who in 1989 walked into his workplace and killed eight people, and then himself. Wesbecker had begun taking Prozac
weeks earlier, and its effects had alarmed his psychiatrist, who unsuccessfully urged Wesbecker to discontinue
the drug just days before the carnage.
Prozac doubters seized on Teicher's paper to press the federal Food and Drug Administration to ban, or at least
investigate, Prozac and similar antidepressants.
That is where the Church of Scientology fits in. The most ardent Prozac critics were members of a group affiliated
with Scientology, which was founded by science-fiction writer L. Ron Hubbard, in part based on his hatred of psychiatry.
The group trumpeted Teicher's paper and blanketed the media with claims that Prozac was a "killer drug."
In one press release the group stated that "the numbers of persons who have been driven or are being driven
suicidal or homicidal by Prozac is astronomical." It was one of many subtle and not-so-subtle distortions
of Teicher's paper.
Teicher and his co-authors had written that the dangerous side effect was observed in 3.5 percent of all their
patients, and the Scientologists extrapolated that figure to the entire population of Prozac users. It was a leap
Teicher says had no basis in science and left him deeply frustrated.
Teicher says his contact with the Scientologists was limited to one phone call in which he complained they were
distorting his data. Yet, he suffered "guilt by association," despite the fact that he always believed
Prozac was a valuable addition to the psychiatrist's toolbox, "a breakthrough" drug that simply needed
to be monitored closely for troubling side effects.
But, for the most part, all anyone heard was that Teicher had linked Prozac to suicide, and the Scientologists
were citing him as their most potent ally.
The psychiatric community circled the wagons to oppose the Scientologists' attacks on Prozac and the entire profession,
sweeping up Teicher in what he called a "strange, surreal" process. Lilly fought back as well, offering
studies and scientists to refute Teicher's work and sending out press releases of their own to counter the criticism.
A climax of sorts was reached in 1991, when the FDA dismissed any link between suicide and Prozac or similar antidepressants.
A nine-member panel of experts voted unanimously that there was "no credible evidence" of any association,
and split 6-3 against requiring a stronger warning label.
In the aftermath, critics disparaged the panel - "a kangaroo court" in the words of one lawyer who has
pending lawsuits against Lilly - as riven by conflicts of interest and armed with flawed data from the company's
clinical studies. Lilly also came under fire.
"Lilly's efforts to discredit clinicians, scientists and journalists trying to foster greater discussions,
research and awareness of this side effect is one of the most disgraceful chapters in American corporate history,"
said Harvard psychiatrist Joseph Glenmullen, author of the new book "Prozac Backlash," which focuses
in part on suicidality.
Still, the FDA's finding has been the cornerstone of Lilly's defense of Prozac in public and the courts.
Lilly officials declined several requests for interviews, but in a written statement the company restated the 1991
FDA decision: "There is no scientific evidence that establishes a link between Prozac and violent or suicidal
Today, Teicher looks back on the early 1990s with what seems like preternatural equanimity: "It was a good
life lesson. I basically did fine."
Asked to define the lesson, he said: "What I learned from all this is I cared much less what people thought.
. . . There are always going to be colleagues who disagree with me about this. A definitive study hasn't been done.
Maybe 20 years from now there will be a clear answer, but maybe not."
Partners looking for `cure'
What his critics did not know was that Teicher, since early 1992, had been working on what might be called a "cure"
for the problems he saw in Prozac.
By all accounts, that turn of events began one morning when a bear of a man named Timothy J. Barberich was reading
The Wall Street Journal. He came across a story about the Prozac controversy that mentioned Teicher's work.
Barberich was not just any reader, though. He had parlayed his undergraduate chemistry degree into founder, chairman
and chief executive of an upstart drug company called Sepracor Inc., located in Marlborough, a half-hour west of
Barberich and one of his top scientists, James W. Young, decided to call Teicher to talk about a chemical process
Sepracor had developed to reformulate existing drugs by removing unwanted side effects. By the early 1990s, the
company had targeted 40 or so already-approved drugs - including Prozac - that it hoped to improve, patent, and
then market on its own or in partnership with the old drugs' owner.
Teicher, as it turns out, had been studying the science of that process in his laboratory, feeding different chemical
substances to rats and sending them into a maze. In early 1992, Teicher and Sepracor struck a deal under which
the company would fund about $150,000 of research in his lab.
To understand what happened next requires a painless chemistry lesson, first taught in the 1800s by Louis Pasteur.
Pasteur discovered that most man-made chemical compounds - prescription drugs, for instance - exist at a microscopic
level as twins, called isomers. Although the twins are chemically identical, each one is the mirror image of the
In some drugs, only one of the twins provides the benefits, fitting into chemical receptors in the body to flip
switches on or off to fight illness. The other twin does not fit the same receptors, so it is free to wander through
the body. Sometimes it goes looking for trouble. That is, causing side effects.
The most dramatic example was the 1960s drug thalidomide, one of whose twins was the good Dr. Jekyll, effectively
decreasing morning sickness in pregnant women. The other was the evil Mr. Hyde, a chemical monster that caused
horrible birth defects.
Until the last 20 years or so, it was difficult to separate the twins - and sometimes, both twins have problems
of their own - so government regulators allowed drugmakers to sell medicines with both, as long as the side effects
were not terrible.
That was Lilly's argument for Prozac, which allows brain cells to bathe more freely in a chemical called serotonin,
which affects mood and emotion. To this day, despite millions of prescriptions, scientists are not certain precisely
how Prozac works, but it is generally believed that the added serotonin in a brain on Prozac lessens depression.
Lilly acknowledges that the current formula also causes side effects including non-life-threatening ailments such
as headaches, anxiety, tremors, and sexual dysfunction. But not suicidal tendencies.
Teicher and Sepracor set out to find a way to keep the good parts of Prozac, or improve it, while eliminating the
bad. Within six months of starting his work, Teicher and Sepracor officials say, he recognized which of the Prozac
twins was the one most worth keeping.
Teicher noticed that when he gave his rats the part of Prozac that would be considered the "good" twin
- known chemically as R(-)fluoxetine - the rodents bravely explored the more dangerous, exposed parts of the maze,
spending less time anxiously scurrying to the enclosed, protected areas.
It took a lot more work, lots more rats, and five more years to get a patent, during which both Teicher and Sepracor
experienced bumps in the road. Teicher weathered an embarrassing state medical board investigation into allegations,
eventually dismissed, of sexual misconduct with a patient. Sepracor, meanwhile, was frustrating stockholders with
Eventually, though, Teicher and the two Sepracor officials, Barberich and Young, succeeded in patenting their discovery,
receiving one in 1997 and the second in 1998.
The patents tout their drug's effectiveness as an antidepressant and appetite suppressant, an anxiety reliever,
and a potential treatment for migraine headaches, chronic pain, and obsessive-compulsive disorders. Its residual
effects leave the body sooner than the existing Prozac, the patent says, allowing doctors to try other drugs more
quickly if it proves ineffective.
Lilly has no problem with any of that. But then comes the patent language that has caused the current uproar: "The
adverse affects (sic) which are decreased by administering the [new version of Prozac] include but are not limited
to headaches, nervousness, anxiety, insomnia, inner restlessness (akathisia), suicidal thoughts and self-mutilation."
And so, with one swing of a patent examiner's approval stamp, Lilly's decade-long denials about suicidality ran
headlong into the claims of a promising new drug that Lilly was eager to buy.
Difficulty protecting Lilly
Teicher refers questions about the patent to Sepracor, and Barberich finds himself in the awkward position of defending
the new Prozac without offending his powerful partner, Lilly.
First Barberich downplayed the issue: "I don't want to get my patent disallowed, but it's not as if you have
any evidence for what you're claiming in the broadest sense. . . . There's no court of truth that these patents
go through. I believe that they, Lilly, are correct."
Then, he hedged: "Marty Teicher may be right, Eli Lilly may be right, and the FDA may be right, and we still
wouldn't have any idea whether [the new drug] eliminates a problem that we're not sure exists."
Though Lilly officials would not discuss the patent, their statement sought to put distance between Lilly and the
damaging patent language: "Lilly had no input nor provided content for the patent application. Not all the
`side effects' listed in the patent are scientifically demonstrated facts. . . . Teicher's article was a series
of anecdotal reports, and his suggestions of a `possibility' of a causal relationship have been refuted by multiple
. . . studies that have demonstrated no increased risk of suicide associated with Prozac use."
Barberich also said Lilly had no role in the patent. He said the Indianapolis-based drugmaker opened talks with
Sepracor only after the patent was certain to be approved.
He also said there were no discussions with Lilly about the suicide issue when Lilly purchased exclusive rights
to the patent in late 1998. The deal gives Sepracor $20 million up front - due to be paid by the end of this month
- plus another $70 million if the drug gets FDA approval, as anticipated within the next two years.
If that approval comes, the real money for Sepracor, Teicher, and McLean Hospital could start rolling in as early
as 2002. "It's likely it's going to be a big drug. It's just a question of how big," Barberich said.
Under the terms of the deal with Lilly, Sepracor gets about 10 percent of sales. McLean gets 10 percent of that,
of which the hospital gets half, Teicher personally gets one-quarter and his laboratory gets one-quarter.
Prozac revenues for Lilly were $2.6 billion last year. If the new Prozac becomes a $2 billion-a-year drug, Sepracor
would get $200 million a year, of which McLean gets $10 million, and Teicher and his lab each would receive $5
Back in his office, Teicher acknowledged that he finds himself thinking about the money sometimes. He said a need
for money prompted him to stop seeing patients two years ago, so he could focus on "entrepreneurial"
activities to fund his son's college education.
He also thinks about the potential conflict involved in prescribing and lecturing about a drug in which he has
a big financial stake, but he expects to handle that by simply disclosing his interest.
Teicher said he spends almost no time thinking about a patent on his wall that says he was right all along, and
even less time thinking about vindication.
"I'm not sure vindication will ever come," he said. "I'm not sure I need it or want it."
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