CDC Downplays Birth Defects of SSRIs
Wednesday, 25 July 2007, 12:24 pm
Column: Evelyn Pringle CDC Downplays Birth Defects of SSRIs to Boost
Sales
by Evelyn Pringle
On July 27, 2007 the Bush's Big Pharma friendly
CDC issued a press release clearly aimed at increasing the
sale of SSRIs to pregnant women. "Use of certain
antidepressants, selective serotonin-reuptake inhibitors
most commonly known as SSRIs, during pregnancy does not
significantly increase the risk for most birth defects," the
CDC wrote.
The press release cited a new CDC study
released in the New England Journal of Medicine and further
stated, "a second study on SSRI and birth defects, also
published in the June 28 issue of NEJM, did not find such an
association with birth defects overall, but did find
significant associations between specific SSRIs and several
birth defects."
Since the CDC put out the press release,
hundreds of headlines have flooded the internet citing the
new studies as proof that there is a low risk of birth
defects with SSRI use during pregnancy, and the results of
the studies have been reported as breaking health care news
by every major media outlet in the US.
The pharmaceutical
industry as a whole has spent a fortune buying influence in
the media since 1997, when the government lifted
restrictions on direct-to-consumer advertising.
In an
article titled, Physicians and Bribery, published by News
Target on July 7, 2005, Dani Veracty says the real story
about prescription drugs is not being told because the drug
makers are controlling the budgets of the major media
companies by pumping hundreds of millions of dollars into
TV, magazine, newspaper and online advertising.
"Because
of this," he states, "the media companies out there don't
want to say anything bad about these prescription drugs."
In the July-August Columbia Journalism Review,
contributing editor Judy Lieberman, reported that at the end
of 2004, drug-company ad revenue for Time Magazine totaled
$67 million; for Newsweek $43 million; and for The New York
Times took in $13 million.
By 2004, she reported,
advertising revenues for the five networks including CNN and
Fox news was $1.5 billion.
The drugs in the NEJM studies
included Prozac by Eli Lilly, Zoloft from Pfizer; Paxil by
GlaxoSmithKline, Celexa and Lexapro from Forest Labs; Luvox
by Solvay, Effexor by Wyeth, and generic SSRI makers include
Barr Pharmaceuticals, Ranbaxy Labs and Genpharm.
Prior to
the arrival SSRIs on the market, depression was estimated to
affect only 100 people per million and patients with
depression sought help from a medical professional trained
in psychiatry and the treatment of disorder.
However, the
rate of depression is now estimated to be in the range of
50,000 to 100,000 cases per million, or between a 500 to
1,000-fold increase, according to Jane Currie in the
Marketization of Depression, in the May 2005 journal Women
and Health Protection.
In April 2004, the CDC reported
that antidepressants topped the list of drugs prescribed to
women at visits to doctor's offices and outpatient
departments, followed by estrogens and progestins,
antiarthritics, and medicines for acid/peptic disorders, in
the Journal of Women's Health.
By 2005, the CDC recently
reported, antidepressants were the most prescribed drugs in
the US during visits to doctors and hospitals and were
prescribed far more often than even medications used to
treat high blood pressure, cholesterol, diabetes, and
headaches.
Yet, a recent analysis of studies on the
efficacy of 12 second-generation antidepressants including
SSRIs and serotonin and norepinephrine reuptake inhibitors
(SNRIs), released on January 25, 2007, by the Agency for
Healthcare Research and Quality's (AHRQ), a division of the
US Department of Health and Human Services, offers little
support for the wide-spread use of these medications.
The
AHRQ reviewed efficacy in treating major depressive
disorder, dysthymia and subsyndromal depression (including
minor depression), and also evaluated comparative efficacy
for maintaining remission and for treating accompanying
symptoms such as anxiety or insomnia or neurovegetative
symptoms.
The review included 187 studies deemed to be of
good or fair quality, including 89 head-to-head randomized
controlled trials, 57 placebo-controlled randomized studies,
with 126 of the studies sponsored by drug companies and 17
funded by government agencies or independent sources, and
analyzed the effectiveness of Cymbalta, Wellbutrin, Effexor,
Celexa, Lexapro, Prozac, Luvox, Remeron, Serzone, Paxil,
Zoloft, and Desyrel, many of which are now also sold in
generic form.
Overall the analysis found that in
controlled studies, during 6 to 12 weeks of treatment, well
over a third of the patients, or 38%, saw no improvement in
their condition and 54% had only partial improvement and did
not achieve remission.
In light of this clear lack of
efficacy, it should be noted that as early as August 2004,
the FDA label for SSRIs warned that “anxiety, agitation,
panic attacks, insomnia, irritability, hostility,
aggressiveness, impulsivity, akathisia (psychomotor
restlessness), hypomania, and mania have been reported in
adult and pediatric patients being treated with
antidepressants for major depressive disorder as well as for
other indications, both psychiatric and nonpsychiatric”
According to one of the world's leading experts on
SSRIs, Dr Peter Breggin, author of The Antidepressant Fact
Book, “few physicians realize that meta-analyses have
shown that antidepressants work no better than placebo at
lifting depression.”
So in the case of pregnant women
he says, “The risk/benefit ration weighs a placebo effect
against increased parental suicide and violence, and babies
with congenital defects, babies undergoing withdrawal
reactions, and babies whose brains have been forever changed
by being soaked in SSRIs during their development.”
Dr
Breggin also notes that the NEMJ researchers failed to
consider the serious withdrawal reaction in newborns and the
potentially disastrous consequences of SSRI use by pregnant
women. "Withdrawal reactions confirm that the brain of the
fetus has been bathed in SSRIs and that it has suffered
significant functional changes," he warns.
"It should be
no surprise that it is not good to bath the growing brain in
toxic drugs like SSRIs," he says, "because serotonin is
intimately involved in the development of the brain in utero
and SSRIs inhibit normal brain cell development."
Experts
say, SSRI use creates an unnecessary risk for fetus. Dr
David Healy, another leading authority on SSRIs, and the
author of "The Creation of Psychopharmacology," and "The
Antidepressant Era," says, "the overwhelming majority of
women who are prescribed SSRIs are at little or no risk for
suicide or other adverse outcomes from their nervous state."
He points out that every pregnant woman may have symptoms
of depression such as anxiety, disturbed sleep, fatigue, or
a loss of interest in sex. "But having depressive symptoms
and being depressed are two different things," he states.
Dr Healy also notes the lack of efficacy shown with
SSRIs, and says the risks of the neonatal withdrawal
syndrome and serious birth defects to the infant far
outweigh any benefits of their use by expectant mothers.
Houston Attorney, Robert S Kwok is outraged by the new
campaign to promote the use of SSRI with pregnant women.
“It's ludicrous to think a woman is at greater risk of
depression during her pregnancy and should take
antidepressants despite the proven risk to her developing
fetus," he states, "yet physician "opinion leaders" with
industry ties are actively trying to convince doctors and
patients of just that.”
Mr Kwok represents the family
of Gavin Shore, a baby born with a severe cardiac defect
known as Shone's Anomaly (Related) after his mother was
prescribed the SSRI Celexa during pregnancy and says Gavin's
mother was not warned that taking an SSRI could double the
risk of her baby being born with a severe heart defect.
Although some of the reports citing the NEMJ studies in
media mentioned that Glaxo money was involved in funding the
CDC study, most neglected to mention the financial
contributions of the other drug companies for the study, or
the steady stream of drug money that flows to the medical
facilities and researchers involved in the studies.
When
combined, the named universities, hospitals and researchers
involved have received money from Lilly, Pfizer, Wyeth,
Glaxo, Aventis, Sanofi Pasteur, and the 3 companies that
make generic versions of SSRIs.
The CDC study lists
Harvard Medical School and Massachusetts General Hospital as
participating and the Harvard Medical School receives nearly
25% of its funding from non-government sources, including
nearly $3.5 million from Aventis Pharmaceuticals, $2.5
million from Bristol-Myers Squibb, and $2.1 million from
Merck, according to an April 12, 2006 report in The Phoenix.
In addition, The Phoenix noted, SEC filings showed
Harvard stock holdings of $16 million with Merck, $8 million
of Bristol Myers Squibb, $34 million of Johnson & Johnson,
and $33 million of Pfizer.
In one NEJM study, Dr Jan
Friedman reported receiving honoraria for consulting from I3
Research, which is actually a huge conglomerate of
"research" firms with names that begin with i3. The April
12, 2006 Phoenix reported that a firm called i3 Innovus,
which co-authored 16 medical-journal articles in 2005,
“provides integrated scientific strategies and solutions
throughout the pharmaceutical product lifecycle.”
The
Phoenix also noted that this i3 firm had a Boston office for
its vice-president of US operations, Milton Weinstein, who
also happened to be a professor at Harvard Medical School
and Harvard School of Public Health.
The same group of
industry backed research institutions credited in the NEJM
CDC study, began the disinformation campaign to boost the
sale of SSRIs to pregnant women more than a year ago when
"experts" at Harvard and Mass General published a study to
intentionally dilute the finding of a mounting number of
studies that found serious birth defects to be associated
with the use of the drugs by pregnant women.
In response
to a study in the February 2006, New England Journal of
Medicine that showed infants exposed to SSRIs in the womb
were 6 times more likely to be born with the
life-threatening lung disorder, persistent pulmonary
hypertension, a study appeared in the Journal of the
American Medical Association the same month warning that
stopping SSRIs could greatly increase the risk of pregnant
women relapsing into depression.
On February 1, 2006, the
Associated Press described the methods used by the
Massachusetts gang when conducting the JAMA study and said
researchers "followed 201 pregnant women with histories of
major depression who were taking drugs such as Prozac,
Zoloft, Effexor and Paxil."
"Because of ethical
concerns," the article said, "the researchers did not
randomly assign the women to either stop or continue
medication."
Instead, the AP reported, the women decided
what to do and then the "researchers watched what happened."
But the actual report on the study shows that of the 201
participants, 13 miscarried, 5 terminated their pregnancy,
12 were lost to follow-up prior to the end of pregnancy, and
8 chose to withdraw from the study.
So when reporting on
the few pregnant women that remained, the study said mothers
were 5 times more likely to suffer a relapse than those who
continued taking the drugs.
However, a highly relevant
finding rarely mentioned, in what turned out to be this wee
little study, is that 26% of the women who remained on the
drugs became depressed anyways.
The study authors noted
that of the 82 women who continued antidepressant treatment
throughout pregnancy, 21 or 26% relapsed. But there were
only 65 women in the group that discontinued the drugs, so
the results logically showed a higher rate of relapse when
45 became depressed.
Moreover, nearly 2 years before the
study was published in JAMA, on January 13, 2004, the lead
author, Dr Lee Cohen was quoted in the New York Times as
saying about 75 to 80% of pregnant women who go off
antidepressants will relapse during the pregnancy.
Six
months after JAMA ran the study, the July 11, 2006 Wall
Street Journal explained why the 13 "experts" might
encourage pregnant women to keep taking SSRIs, in stating
the lead author, Dr Cohen, who was a Harvard Medical School
professor and director of the research program at
Massachusetts General, was a longtime consultant to the 3
antidepressant makers, a paid speaker for 7, and his
research work was funded by 4 drug companies.
In fact,
the Journal reported, “the study and resulting television
and newspaper reports of the research failed to note that
most of the 13 authors are paid as consultants or lecturers
by the makers of antidepressants," and "the authors failed
to disclose more than 60 different financial relationships
with drug companies."
And just like clock-work, the
Cohen's study was widely cited in other journals promoting
the sale of SSRIs to pregnant women. "In summary, it seems
clear that the risks of not receiving adequate
antidepressant treatment thus far outweigh the risks of
adverse events, not only in infants but in mothers as well,"
wrote Dr Pierre Blier of the University of Ottawa in
editorial in the Journal of Psychiatry and Neuroscience,
2006;31(4):226-8.
"The population," he warned, "should
therefore learn to fear the illness more than the
antidepressant."
But as it turns out, Dr Blier
conflicting interests included among others, being a
consultant with Lilly, Forest Labs, Janssen, Wyeth and
Sanofi-Aventis, and a contract employee with Forest Labs. He
was also in the speaker's bureau for Lilly, Forest Labs, and
Wyeth, and received grant funding from Lilly, Forest Labs
and Wyeth.
The JAMA study, along with a brief note from
Dr Cohen himself, was also featured in the Spring 2006 issue
of Massachusetts General Hospital's Center for Women's
Health Newsletter, in a publication that downplayed the risk
of just about all the birth defects discovered in recent
years including heart birth defects and the infant
withdrawal syndrome.
Since 1990, JAMA has required
authors of studies to list all financial interests and has
published the disclosures. In an online editorial in July
2006, JAMA editor, Dr Catherine DeAngelis announced her
intention to enforce the policy in part by publicizing any
author's failure to follow the rules and specifically noted
that 3 consecutive nondisclosures involved authors from
Harvard Medical School and included Dr Cohen's study.
On
July 11, 2006, citing material promoting the events, the
Wall Street Journal reported that the Massachusetts General
psychiatry academy planned to conduct Continuing Medical
Education seminars in a dozen cities across the US, with Dr
Cohen overseeing a segment on the treatment of pregnant
women with psychiatric disorders.
One of the funding
sources for the seminars was revealed less than a year later
on May 1, 2007, when the Journal reported the major
recipients of the $11.8 million that Eli Lilly gave out
during the first three months of 2007, and said the largest
single grant "was $825,000 to Massachusetts General
Hospital's psychiatry department for a year-long educational
program with more than 150,000 registrants."
It should be
noted that Lilly introduced the first SSRI, Prozac, in the
late 1980s and its current best-selling antidepressant
Cymbalta earned the company $1.3 billion in 2006.
The
financial ties between the researchers and SSRI makers was
brought to the attention of the JAMA editor by Dr Adam Urato
and a letter from Dr Urato was also published in JAMA,
stating that being the study dealt in part with the question
of stopping antidepressants during pregnancy, the readers
should be aware of the potential for pro-drug bias.
However, all that being said, the Cohen study is still
being cited to promote the use of SSRIs with pregnant women,
and as recently as April 26, 2007, in a paper by Dr Claudio
Soares, director of Women's Health Concerns Clinic, McMaster
University, Ontario in Journal Watch Women's Health, a
publication put out by the NEJM.
"Results of a recent
prospective study of pregnant women," he wrote, "who were
taking antidepressants at or near the time of conception
demonstrated that women who opted to discontinue treatment
during pregnancy were five times more likely to relapse than
were those who stayed on treatment."
"Despite the
cautionary remarks commonly made by most regulatory agencies
and medical societies about the use of psychotropic
medications during pregnancy," Dr Soares states,
"considerable data supporting the efficacy and reproductive
safety of antidepressants have accrued."
"Conversely," he
warns, "evidence suggests that untreated depression has
negative consequences for both mother and child."
"In
summary," Dr Soares states, "clinicians should bear in mind
the mounting evidence about the adverse effects of
uncontrolled depression during pregnancy."
But here too,
Dr Urato, wrote a response to this obvious sales pitch
objecting to the total lack of citations to studies that
support the assertion that the risks of birth defects
associated with SSRI are rare and that the benefits of SSRIs
use to avoid relapse into depression outweigh the risks.
But most concerning, Dr Urato wrote, "is the complete
lack of financial disclosure information to go along with
the article."
"As I was reading this piece," he wrote, "I
kept thinking to myself "'Boy, this sounds like it was
written by someone working for the antidepressant makers.'"
And sure enough, Dr Urato found that Dr Soares is on the
Speaker's Bureau for Forest Labs, Wyeth, Glaxo, and Pfizer
and has received honoraria as a research consultant for
Sepracor, Glaxo, Wyeth, and Neurocrine.
Mr Kwok is also
highly critical of the increasingly common practice of using
"opinion leaders" like Dr Soares to sell SSRIs to pregnant
women, but states, “there will come a time when the drug
manufacturers will have to face the music on SSRIs causing
PPHN, and that time is coming soon."
He says his firm has
an abundance of new cases that prove it's no coincidence
that pregnant mothers on SSRIs have an increased likelihood
of giving birth to babies with PPHN in families where there
is no history of respiratory illness.
“Just
yesterday,” Mr Kwok states, “I spoke to a mother who
birthed a baby with a serious breathing disorder that
requires regular use of a nebulizer, a device used to
administer medication via liquid mist to the airways,
commonly used in treating asthma (Related) and other respiratory diseases (Related) ."
"This young
mother is now at risk of losing her job," Mr Kwok reports,
"since her infant requires full time care."
He says
doctors should be instructed to screen patients who are
pregnant or planning to become pregnant and inform them of
the risks of SSRIs to a developing fetus. "At least educate
this “class” of women," he says, "so they may make
informed personal decisions."
"Sure, the loss of this
“class” may cost the drug manufacturers some profit," he
notes, "but it's the right thing to do and it will save many
families a lifetime of torture caring for a sick child like
we see over and over again.”
The need to recapture
pregnant women as customers is crucial for some SSRI makers.
For instance, Forest Labs reported that Lexapro and Celexa
accounted for 68% of the firm's total sales for the year
ending March 31, 2006, in its Annual Report filed with the
SEC.
Back in May 2005, researchers from the University
of Pittsburgh estimated that in any given year at least
80,000 pregnant women in US are prescribed SSRIs, in JAMA.
Families seeking legal advice for infants born with heart
or lung birth defects to mothers who were prescribed Celexa
during pregnancy may contact Robert Kwok at Robert Kwok &
Associates, LLP at (888)466-5965; http://www.kwoklaw.com/about.php (Related) ]
*************
(This article is written as part of a series
on Celexa related litigation and is sponsored by Robert Kwok
& Associates, LLP)
(Evelyn Pringle is a regular columnist
for OpEd News and an investigative journalist focused on
exposing corruption in government and corporate America) evelyn-pringle@sbcglobal.net (Related)