Bristol-Myers Stops Sale of Serzone in Europe
January 9, 2003
Bristol-Myers Will Stop Sale Of Antidepressant in Europe
By GARDINER HARRIS
Staff Reporter of THE WALL STREET JOURNAL
Bristol-Myers Squibb Co. said it will stop selling in Europe its
antidepressant drug Dutonin, known as Serzone in the U.S. The drug can cause
rare but sometimes fatal liver failure in some patients.
A company spokesman said sales of the drug are small in Europe. He said the
company will continue to sell Serzone in the U.S., where lawsuits involving
the drug have been piling up. European regulators had become increasingly
concerned in recent months about the drug's potentially severe effects on the
liver.
In June 2001, Bristol-Myers sent letters to doctors in Canada warning of the
drug's sometimes fatal effects on the liver. Six months later, the U.S. Food
and Drug Administration required that a similar letter be sent to U.S.
doctors. A so-called black-box warning also was added to the drug's label,
highlighting dangerous side-effects.
Sales of Serzone totaled $409 million in 2001, but dropped off sharply last
year amid the safety concerns.
U.S. sales of the drug fell 46% in the 12 months ended in November, according
to NDCHealth, a health-care information-services company. In 2002,
Bristol-Myers stopped highlighting Serzone's sales figures in its quarterly earnings reports.
Earlier this week, Bristol-Myers's Dutch subsidiary said it will stop
marketing the drug in the Netherlands in April after the Netherlands Medicine
Assessment Board said it is investigating the drug after receiving 26 reports
of serious liver failure and some deaths related to the drug's use. The drug
also was pulled from the market in Sweden.
Serzone works somewhat differently than the more popular antidepressants such
as Prozac and Zoloft by affecting two neurotransmitters instead of one.
Serzone hasn't been shown to work any better than its more popular brethren
but is thought to slow down the sex drive less than Prozac.
Bristol-Myers shares fell 3.8%, or 95 cents, to $24.15 each in 4 p.m.
composite trading on the New York Stock Exchange.
URL for this article:
http://online.wsj.com/article/0,,SB1042059215784148704,00.html
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Write to Gardiner Harris at
gardiner.harris@wsj.com
Updated January 9, 2003
Bloomberg News reported that the antidepressant, Serzone had been
linked to twenty-six deaths from liver damage. On Jan 8, 2003 European
authorities removed the drug from the European market. On Jan. 9, 2003, the FDA
required a black box warning to be added to the Serzone label but left it on the
American market.
~~~~
Bloomberg News
January 9, 2003, Thursday
BUSINESS/FINANCIAL DESK
COMPANY NEWS; BRISTOL-MYERS TO PULL DRUG IN EUROPE BUT NOT IN U.S.
The Bristol-Myers Squibb Company will pull the antidepressant Dutonin from the
European market after 18 patients who took it died. Twenty-five cases of liver
failure, including the 18 deaths, were linked to the drug worldwide, a
Bristol-Myers spokesman, Bob Laverty, said. European sales make up less than 10
percent of the drug's $409 million in revenue, analysts said. The company will
keep selling the drug in the United States as Serzone. The label carries the
Food and Drug Administration's highest alert, which notes that liver failure has
been reported. Susan Cruzan, an F.D.A. spokeswoman, said, ''The F.D.A. continues
to monitor it and take everything into consideration.'' Bristol-Myers has been
sued by former users of Serzone.
Published New York Times: 01-09-2003, Late Edition- Final,
Section C, Column 1 , Page 3
~~~~~~~~~
Why do FDA officials think Americans deserve less protection from unsafe
drugs than do Europeans?
Drug analysts who have examined the clinical trial data submitted to the FDA
prior to gaining approval, have found that the much-touted antidepressant drugs
known as selective serotonin reuptake inhibitors (SSRI) show little, if any,
greater positive effect on depression than placebo.
[See, for example, JAMA Vol. 287 No. 14,April 10, 2002
http://jama.ama-assn.org/issues/v287n14/rfull/joc11936.html ]
But, unlike placebo, these drugs come with severe adverse reactions, including
dependence and withdrawal symptoms. [See: David Healy, MD, Dependence on
Antidepressants at:
http://www.seroxatusergroup.co.uk/WITHDRAWAL2.pdf]
Serzone failed six out of eight clinical trials during pre-marketing testing.
The “positive” findings of two trials were found to have been manipulated to
exclude unfavorable results from the “findings.”
In 1997 Thomas J. Moore (author of Prescription for Disaster) wrote an
insightful (highly readable) analysis of the FDA Serzone trial data and of the
drug’s approval process. [Thomas J. Moore, “Hard to Swallow” published in The
Washingtonian at:
http://www.washingtonian.com/health/hardtoswallow.html]
Moore noted that "Serzone failed to show a clear benefit in six of the eight
clinical trials. Three more clinical trials were discontinued before results
were available." "Serzone was tested further at a higher dose. One of these
high-dose trials failed by everyone's evaluation, and two more were borderline.
However, two other trials were declared a success."
"If six Serzone trials failed or were inconclusive, what results did the two
claimed successes achieve? In one "successful" trial the placebo patients showed
a dramatic improvement. Their depression scores dropped 17 points in six weeks.
Serzone patients didn't do as well, with average scores improving 14 points.”
Among the adverse effects suffered by patients in clinical trials: confusion,
impaired memory, abnormal dreams, decreased concentration, lack of coordination,
psychomotor retardation, and tremors. Some experienced seizures, episodes of
mania, addiction, and heart problems, and some committed suicide.
FDA data reveal that suicide was disturbingly frequent in clinical trials
testing SSRIs. Moore reported the suicide results for patients given Serzone
compared to Placebo in 6-week trials:
Serzone treated patients: 3,496
Placebo group: 875
Suicides by Serzone patients: 9
Suicides in placebo group: 0
Suicide attempts by Serzone patients: 12
Suicide attempts in placebo group: 1
Attempted suicide rate in patients prescribed Serzone: 1 in 166
Suicide rate in patients taking placebo: 1 in 875
Clearly, the evidence reveals that suicides and suicide attempts occurred among
those taking Serzone, not those given a placebo.
“On this data, a rational patient would choose to take the placebo rather than
the drug.”
But FDA officials and an FDA advisory panel whose members had financial ties to
drug companies ensured that the drug was approved despite the negative findings.
Moore reports how these “experts” diverted the focus from the drug’s poor
showing and high suicide rate for patients taking Serzone. They allowed negative
results to be excluded from consideration, pointing instead to minor details
which they declared “an interesting fact" to justify FDA approval of Serzone.
But, Moore, points out, “excluding results unfavorable to Serzone after the fact
was like conducting a jury trial and, if no guilty verdict resulted, allowing
the prosecution to remove the jurors with doubts. But even when the most
unfavorable results were excluded, Serzone patients' depression scores improved
by 13 points, the placebo patients' by 12."
Moore describes how the statistical analysis was tainted by selective inclusion
exclusion of data. The high drop out rate during trials was not calculated, “it
was permissible to pretend that those who dropped out had continued to the end
of the trial. The final results included all the scores, even for those who had
quit after one week.”
“Suppose, for example, that a Serzone patient had improved dramatically at the
third-week examination but was hospitalized the next week for severe adverse
effects. The three-week score showing a great benefit still would be
included--and there would be no penalty for the participant's not continuing to
the end.”
“This is using statistical adjustments to try to prove an effect that was not
detected by direct scientific observation. What's more, it makes the test an
unrealistic estimate of what will be achieved in actual use. Antidepressants are
prescribed for months and sometimes years."
By disregarding the negative results—-which will have an adverse impact on
millions of future patients--FDA’s advisory panel recommended approval of
Serzone in 1993. The panel was headed by Dr. Carol Tamminga, whose research
ethics were severely criticized in 1998 in (among others) The New York Times and
The Boston Globe:
http://www.ahrp.org/AHRPinNews/NYTimes051998.html
http://www.boston.com/globe/nation/packages/doing_harm/day1.htm
Complete article by Moore at:
http://www.washingtonian.com/health/hardtoswallow.html
For adverse drug reports, see:
http://www.fda.gov/medwatch/SAFETY/2002/safety02.htm#serzon
FDA Patient Information:
http://www.fda.gov/medwatch/SAFETY/2002/serzone_PPI.pdf
Bristol Myers Dear Doctor:
http://www.fda.gov/medwatch/SAFETY/2002/serzone_deardoc.PDF
Complete package insert:
http://www.fda.gov/medwatch/SAFETY/2002/serzone_label.pdf
Last Updated on
04/14/04
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