Of Paxil Suicides Leads
By Evelyn Pringle
16 February, 2007
January 29, 2007, BBC-One broadcasted, “Secrets of the Drug Trials,”
a Panorama program based on an investigation by reporter, Shelley Jofre,
which revealed how GlaxoSmithKline misled doctors into prescribing Paxil
off-label to children, even after its own clinical trials found that
kids could become suicidal when taking the drug.
The program was one in a
series involving the relatively new class of antidepressants known as
the selective serotonin reuptake inhibitors (SSRIs), which have only
been sold in the US for about 20 years.
Paxil is marketed under the
name Seroxat in the UK. It has never been approved for use with children
for any indication in either the US or the UK.
The first program, "Secrets
of Seroxat," was aired in October 2002, and the feedback that followed
was unprecedented, with 67,000 people contacting a BBC helpline and
1,500 people emailing Panorama with stories similar to those revealed
in the broadcast. The second, "Emails from the Edge," was
aired in April 2003, in large part due to the viewer's response from
the first program.
Many of the documents in
the latest program were obtained in a consumer fraud class action lawsuit
filed in the US by the Baum Hedlund law firm alleging that the UK based
GlaxoSmithKline suppressed information about Paxil's failed efficacy
and increased risk of suicidality in children. The case is filed on
the behalf of the general public defined as:
All persons or entities who
purchased and/or paid for paroxetine under the trade name Paxil, Paxil
CR and/or Paxil Oral Suspension in the states of California, Florida,
Massachusetts, Nevada, New Jersey, Pennsylvania, Texas, and Washington
for consumption by a minor.
Baum Hedlund, a US law firm
handling antidepressant cases for more than 15 years, has reviewed thousands
of documents and taken numerous depositions of Glaxo employees and medical
professionals known as academic thought leaders, hired to promote Paxil
over the years.
As usual, in lawsuits against
drug companies, virtually every document produced in the litigation
was stamped "confidential" by Glaxo and sealed under a court
order. However, through a series of legal challenges, Baum Hedlund was
able to get some of the documents released in part, by getting Glaxo
to admit that many did not contain trade secrets and therefore should
not have been sealed to begin with.
Baum Hedlund partner, and
lead attorney on the case, Karen Barth-Menzies, appeared in “Secrets
of the Drug Trials,” and provided many of the documents referred
to by Ms Jofre in the program.
Paxil was hailed as a wonder
drug in the 1990's, sold as an alternative to Prozac for treating depression
in adults. But Glaxo was not satisfied with the profits from treating
adults and wanted to gain a stronghold on the lucrative pediatric market.
According to Ms Menzies,
under FDA rules at the time, if the company conducted tests on Paxil
with children, Glaxo could get a 6-month extension on its patent, which
meant enormous profits. To that end, hundreds of children were recruited
from around the world for several pediatric studies with the largest
conducted in the US, known as Study 329.
During the program, Ms Jofre
interviewed Stephanie Gatchell who described how she had taken her daughter,
Sharise, to a doctor because Sharise had not started her periods yet
and was worried, at which time she was prescribed Paxil.
Although Paxil was also only
approved for adults in Britain, the same as in the US, doctors are allowed
to prescribe a drug off-label for an unapproved use if they believe
it will help a patient. According to Panorama, at the time that Sharise
was prescribed Paxil, around 7,000 children a year were on the drug
Shortly after Sharise began taking Paxil, her mother noticed a dramatic
change. "She became more confident," Stephanie said, "but
with it came aggression and worse."
One day she noticed cut marks
on Sharise's arm and realized that she was self-harming, "something
she'd never ever done before," her mother said.
Stephanie convinced Sharise
to stop taking Paxil but unbeknownst to her parents, she began taking
the drug again without telling them. Not knowing she was on Paxil, her
parents went away for a weekend and when they returned home, they found
Sharise hanging from a loft with a suicide note laying next to a packet
According to Panorama, by
the time of Sharise’s death, Glaxo had already tested Paxil on
children six years earlier and the results showed that Paxil worked
no better than a placebo, and in one study, 7 of the 93 children who
took Paxil had to be taken to hospital and some kids in the study had
self-harmed like Sharise.
Ms Menzies says, in her opinion,
this should have been the time when Glaxo started warning doctors to
stop prescribing Paxil to children, because it appears that the company
knew then from more than one study, that it was ineffective and unsafe.
To verify this claim, during
the program, Ms Jofre read from a non-confidential email dated October
14, 1998, written by the Paxil product director in the UK which stated:
"The results of the studies were disappointing. The possibility
of obtaining a safety statement from this data was considered but rejected."
In other words, Ms Jofre
notes, Glaxo knew it could not get a license to treat children in the
UK. She read another comment in the email that said: "The best
which could have been achieved was a statement that although safety
data was reassuring, efficacy had not been demonstrated."
"Consultation of the
marketing teams confirmed that this would be unacceptable commercially,"
the email noted.
Back in October, 1998, another
document labeled, “SB Confidential - For Internal Use Only,”
clearly shows that Glaxo had decided not to try to get Paxil approved
for children because studies found the drug ineffective and states:
“Data from these 2 studies are insufficiently robust to support
a label change and will therefore not be submitted to the regulatory
authorities.” It further states:
Based on the current data
from Studies 377 and 329, and following consultation with SB country
regulatory and marketing groups, no regulatory submissions will be made
to obtain either efficacy or safety statements relating to adolescent
depression at this time.
The document also explains
the rationale for not attempting to obtain a safety statement on Paxil
at that time as follows:
i) regulatory agencies would
not approve a statement indicating that there are no safety issues in
adolescents, as this could be seen as promoting off-label use
ii) it would be commercially
unacceptable to include a statement that efficacy had not been demonstrated,
as this would undermine the profile of paroxetine.
Although Study 329 was completed
in 1998, it was first submitted for publication in mid-1999. It was
a major step in the marketing plan to get the study published in a reputable
medical journal because doctors look to journals for advice they can
trust. "The first journal GSK tried rejected the article,"
Panorama reports, "so they tried another."
Because publishing the study
in full would have resulted in a negative impact on Paxil profits, Glaxo
decided to find other ways to market Paxil to kids. "Exit the doctors,"
Ms Jofre says, "enter the spin doctors" to help promote Paxil
as safe and effective for teenagers.
"The inconvenient facts,"
she explained, "would be buried and the marketing people would
spread the good news to doctors around the world."
According to Ms Menzies,
Glaxo found ways "to blow up out of proportion the supposed benefits
in Study 329 and downplayed the negative findings."
She explains that by using
opinion leaders in the field, academics who everybody looks up to, doctors
would be far more influenced to prescribe Paxil than they would be if
approached by Glaxo salespersons.
At the time, the name of
Dr Martin Keller, a professor of psychiatry at a prominent university
in the US was apparently worth a lot to drug makers and specifically
Glaxo. In a single year, Panorama reports, Dr Keller earned a half a
million dollars from drug companies, including Glaxo.
Study 329 was finally published
in the July 2001, Journal of the American Academy of Child and Adolescent
Psychiatry, with Dr Keller’s name as the lead author, but his
actual input was seriously questioned by Panorama. In one memo presented
in the broadcast, Dr Keller thanked a ghost writer from a PR firm hired
by Glaxo for preparing the manuscript stating: "You did a superb
job with this. Thank you very much. It is excellent. Enclosed are some
rather minor changes from me..."
Ms Jofre also read a letter
from the ghost writer to Dr Keller, which informed him that all of the
necessary materials were enclosed to enable Dr Keller to send the study
to a journal for publication. The packet even included a cover letter
to submit to the journal with instructions to Dr Keller stating: "please
re-type on your letterhead. Revise if you wish."
Ms Jofre also demonstrated
that it was clear that the PR woman was making crucial decisions about
how to present the data from the study, by quoting one Glaxo executive
as saying in a company document: "She's going too far in burying
"It seems incongruous
that we state it as safe yet report so many serious adverse events,"
another internal Glaxo email dated July 19, 1999 states.
According to Panorama, there
were actually 11 side-effects identified in the study including aggression,
self-harm, and suicidal thoughts, but yet the final ghost written article
read: "Of the 11 patients only headache (one patient) was considered
to be related to the treatment," and concludes that Seroxat is
"generally well tolerated and effective."
During the program, Ms Menzies
told the audience: "They didn't tell the regulators or the physicians
or parents about these risks or the lack of efficacy, instead they went
out and promoted this specific study as remarkably effective and safe
"This was a drug that
doctors were told could help prevent suicide," Ms Jofre pointed
out, "when in reality it was actually making some children suicidal,
a triumph of marketing over science."
Since Study 329, (Keller
et al 2001), was published, it has drawn criticism from medical professionals
around the world. One letter to the Editor by Professors, Dr Jon Jureidini
and Dr Anne Tonkin, from Adelaide, Australia, stated: “We believe
that the Keller et al. study shows evidence of distorted and unbalanced
reporting that seems to have evaded the scrutiny of your editorial process.”
“Given that the research
was paid for by Glaxo-Smith-Klein,” it reads, “it is tempting
to explain the mode of reporting as an attempt to show the drug in the
most favorable light.”
“Given the frequency
with which it is cited in other scientific papers, at conferences and
educational functions, and in advertising,” the letter notes,
“this article may have contributed to the increased prescribing
of SSRI medication to children and adolescents.”
“We believe it is a
matter of importance to public health,” the letter concludes,
“that you acknowledge the failings of this article, so that its
findings can be more realistically appraised in decision-making about
the use of SSRIs in children.”
Another highly critical editorial
was published on June 12, 2004, in The Lancet, which stated in part
that Glaxo “appears to be floundering in the semantic depths.
While it has been earnestly parsing the meaning of ‘suicidal thinking
and acts’ and ‘publicly,’ it appears to have forgotten
what lies behind those words-people.”
To further ensure its ability
to control negative information, Glaxo made investigators sign agreements
not to disclose the study results without the company’s OK. “Those
researchers, including myself, who did see results of negative paroxetine
industry trials were prohibited by nondisclosure contracts from discussing
them,” says Dr Jane Garland, Clinical Professor of Psychiatry,
at the University of British Columbia, “Facing the evidence: antidepressant
in children and adolescents,” in the February 17, 2004, Canadian
Medical Association Journal. In the adolescent paroxetine trials she
10.5% of patients discontinued
paroxetine because of “serious” psychiatric adverse effects,
of which the most common was euphemistically described as “emotional
lability,” further defined as “suicidal ideation/gestures;
conduct problems or hostility, e.g., aggressiveness….
Dr Garland states, “led 7.5% of the outpatient participants prescribed
paroxetine who initially were only mildly depressed to be admitted to
hospital, while none of the placebo group required hospital admission.”
“The authors dismissed
this result,” she says, “by stating that these psychiatric
adverse effects were not attributed to the medication — despite
the fact that numerous reports of agitation and suicidal behaviour in
young people treated with SSRIs have accumulated since the 1990s.”
During the Panorama program,
Ms Jofre interviewed SSRI expert, Professor Dr David Healy, of the North
Wales Department of Psychological Medicine at the University of Wales,
an academic who has long challenged SSRI makers. Dr. Healy is concerned
that doctors were deceived into prescribing Paxil to children.
"We were all hoodwinked,
misled, duped," he stated in the interview.
"If you'd heard the
experts talk," Dr Healy said, "they all say the drug was extremely
safe and very effective."
"They produce these
clinical trials," he noted, "which appear to be evidence and
they aren't, they're adverts."
In five studies, 329, 377,
701, 329-extension and 716, Glaxo coded suicidal thinking and acts,
under “emotional lability.” In a recent paper titled, "Manufacturing
Consensus," in Culture, Medicine and Psychiatry (2006), Dr Healy
describes how regulators came to recognize the significance of the term
“emotional lability,” stating:
As a result of a GlaxoSmithKline
application to the regulators for a license for Paxil to treat childhood
nervous disorders, the raw data from clinical trials were lodged with
a number of national regulators.
Within a fortnight of seeing
the raw data in response to queries as to the events behind the term
emotional lability, in May 2003 the regulators in the United Kingdom
issued a warning against the use of Paxil (Seroxat) for minors.
"A few weeks later,”
Dr Healy reports, “GlaxoSmithKline wrote to all doctors noting
that Paxil use was linked to suicidality and that withdrawal from Paxil
was also linked to
an apparent doubling of the rate of suicidality."
In the Panorama program,
Ms Jofre points out that Sharise Gatchell's doctor, "like thousands
of others, prescribed Seroxat in good faith."
Stephanie discussed how she
and Sharise watched the April 28, 2003, Panorama program together and
how she had told her daughter, aren't "we lucky that you're off
it," not realizing that Sharise was taking Paxil secretly.
Less than a month later,
public health officials in the UK warned that Paxil should not be prescribed
to anyone under 18, after reviewing the secret clinical trials that
Glaxo finally turned over 2 years after the last study was completed.
The warning came 2 weeks
too late for Sharise.
According to Ms Jofre, Glaxo
refused to be interviewed for the program but issued a written statement
saying the company rejects any suggestion that it improperly withheld
trial data and that Paxil was never approved for children under 18.
Its statement seems to place
the blame for off-label prescribing squarely on the doctors. "Any
decision to prescribe a medicine outside its authorised indications,
in the EU or the US," Glaxo wrote, "is made by a doctor on
the basis of his/her clinical judgement and the interests of their patient."
However, this comment infers
ignorance on Glaxo's part of the fact that Paxil was being prescribed
off-label to children in massive numbers. In the US, the company knows
exactly when Paxil is prescribed and by which doctor, because Glaxo
pays a small fortune to purchase the detailed prescribing records for
every physician in the US for use by sales representatives in targeting
One former sales representative
recently said that she could see whether a perk such as a lunch she
purchased for a doctor one week increased the sale of the drug that
she was promoting simply by checking the prescribing records the next
The statement submitted to
Panorama by Glaxo also states:
In the case of study 329
although a numerical difference in adverse events was observed by the
company and the study's investigators, for patients taking Seroxat compared
to placebo, these findings were not, by themselves, considered clinically
meaningful due to the limited number of patients involved and the fact
that suicidal thinking and behaviour is a recognised symptom of the
Critical experts say it is
amazing to hear an SSRI maker still trying to blame suicidal thinking
or behavior on the "recognised symptoms of the underlying disease,"
when it has long been stressed that if that were the case, the kids
on a placebo would become suicidal instead of those on the medication.
According to Ms Jofre, this
Paxil scandal shows how tightly the drug companies control medical research
and Dr Healy agrees. "We're in a situation now," he says,
"where people who are ill generally have been deeply betrayed by
the whole process, deeply betrayed by the pharmaceutical companies and
by all the experts that have been willing to actually lend their names
to the process."
These so-called opinion leaders
are basically unregulated loose canons. According to Dr Healy, "the
role of a drug regulator is to regulate any claims a manufacturer might
make as regards a new product in its advertising or detailing to doctors."
But they have no control
over what academics say in lectures, medical journals or elsewhere and
“no control over what assessments these academics might make in
their roles as experts called on to contribute to an expert consensus
on new versus older drugs," he says.
The European Medicines Agency
(EMEA) alerted the FDA to the suicide risk in mid-2003. Glaxo did not.
According to an internal June 2, 2003, FDA email provided to this author
by Baum Hedlund, written by Dr Russell Katz to Dr Andrew Mosholder,
the FDA had just learned about the increased suicide rate hidden under
the term emotional lability and realized that Glaxo had pulled a fast
one. Dr Katz stated in the email:
We have recently become aware
of a presumed association between Paxil and suicidality in pediatric
patients. We received a call from the EMEA a little over a week ago.
A Dr. Raines told us that the company (GSK) had submitted data that
demonstrated that use of Paxil in kids was associated with increased
suicidality compared to placebo, and that the company proposed labeling
I believe she also said that
it was in the news, and it was a big issue. Tom and I told her that
the company had not informed us of any of this, and we agreed to look
“It turns out that
the sponsor was in the process of submitting to us a partial response
to a question we asked in the Approval letter for the pediatric use
(you, you may recall, were the reviewer). Specifically, we had asked
them to further elaborate the events subsumed under the preferred term
‘Emotional Lability’. Mr Katz further stated:
We received this partial
response, and almost all of these events related to suicidality. The
bottom line is that when data from the controlled trials in depression,
OCD, and Social Anxiety are pooled, for “possible suicide related”
events occurring during treatment or within 4 days after discontinuation,
the rate is 0.14/patient-year on drug, and 0.05/patient-year on placebo,
“We have some problems
with the methodology they used to capture cases,” he said, “but
this is the major finding, and it has us worried.”
“The sponsor has not
proposed labeling changes,” Dr Katz noted, “and makes a
feeble attempt to dismiss the finding.”
“We want to move quickly
to evaluate this signal,” he told Dr Mosholder.
“We are planning to
look at the NDAs for other SSRIs,” he wrote, “to see whether
or not similar events are being hidden by various inappropriate coding
maneuvers, but we’d also like to compare the drugs in other meaningful
ways if we can.”
“We also want to call
the sponsor very soon,” he noted, “and ask some questions
about their methodology.”
“Given your history,
with this application and this general issue," Dr Katz told Dr
Mosholder, "we think you would be the right person to help us think
about the best way to approach the data in the other NDAs (and their
sponsors), as well as to provide ideas for further sources of potentially
relevant data and possible approaches to better evaluate this signal
study (e.g., insurance claims databases, etc.).”
“Also, we’d like
you to be in on the phone call, if possible,” he said.
In responding to the email,
Dr Mosholder told Dr Katz: “As I recall, a number of the other
SSRI pediatric supplements showed signals for behavioral adverse events.
But these were mainly events such as agitation and hypomania, not self-injury
(unless, as you suggest, they were similarly obscured by inappropriate
A February 4, 2004, email
from another highly paid Glaxo academic, Dr Neal Ryan, to fellow Study
329 authors, Dr Karen Wagner and Dr Keller, illustrates their alarm
over the FDA’s order for drug companies to reevalute all SSRI
studies. The email states:
FDA made each company go
line by line through absolutely all documentation of all kids in all
their studies. This is where 4 more subjects in our joint study fell
out, unfortunately all the Paxil group. Don’t know severity or
more information about this yet.
In a curious Glaxo email
titled, “Study 329 Update,” to Dr Ryan, Dr Wagner and Dr
Keller, the investigators who supposedly reviewed the data and authored
the report, a GSK employee wrote:
We want to update you, as
investigators on Study 329, about additional potential pediatric suicidality
cases that were recently discovered. In a manual review of all SAE narratives
and “trauma” cases, 10 additional events potentially suggestive
of intentional self injury, suicidal ideation, or suicide attempt were
identified. Four of the 10 events occurred in study 329, all in the
paroxetine group. Consequently, this could potentially change the number
of paroxetine suicide-related adverse events for that study from 6 to
the email states, “included among those undergoing blinded review
by Dr. Wagner, Dr. Ryan, and Dr. Apter for the pediatric suicidality
This message apparently caused
Dr Ryan to panic because he was being contacted by reporters. In an
email response he stated:
With your email yesterday
(appended below) about 4 additional “events” in Study 329
on the Paxil arm, those of us involved in writing the recent letter
to the reporter asking about details of our article need very very quickly
to get absolutely as much information as you have and understand what
part of this we need to pass on to her. Otherwise we are in the challenging
position of sending her a good-faith effort at directly answering her
questions that we find very shortly thereafter is no longer the most
complete information available to us and which therefore might appear
“Can we get a much
fuller explanation in email?” Dr Ryan asks. “Should we quickly
set up a conference phone call?”
After viewing the Panorama
program, Dr Fiona Godlee, Editor of the British Medical Journal, wrote
an article stating: "Panorama's account of GlaxoSmithKline's successful
attempts to market Seroxat for use in children, despite the fact that
its own published trial found evidence of serious adverse effects and
failed to show benefit, is fascinating but depressingly familiar."
"What is even more depressing,"
she notes, "is that such behaviour is still so widely tolerated
"What is clearly wrong,"
Dr Godlee writes, "is writers, academics, or clinicians concealing
under their coat tails an army of company spin doctors intent on distorting
the scientific record."
As for what can be done to
change what she refers to as "the blind-eye culture of medicine,"
Dr Godlee states: "In the interests of patients and professional
integrity I suggest intolerance and exposure."
"And if journals discover
authors who are guests on their own papers," she says, "they
should report them to their institution, admonish them in the journal
and probably retract the paper."
"Reputations for sale
are reputations at risk," Dr Godlee concludes.
"We need to make that
risk so high it's not worth taking," she states.
In the US, families bereaved
due to Paxil suicides have joined together in lawsuits against Glaxo.
During the BBC program, Ms Menzies described the tragic case of an 11year-old
boy who was prescribed Paxil off-label and hung himself in a closet
with the leash of his new puppy.
Stephanie Gatchell and her
husband have moved away from the home that holds the pain of their daughter's
suicide to try to begin a new life in Ireland, but say they cannot forgive
Glaxo for hiding the truth about Paxil. "They just kept on denying
and denying and denying," Stephanie said.
She notes that a program
like Panorama virtually had to force Glaxo to admit the truth and says,
"were they ever going to come out with the truth on their own?
I don't think so."
"The decision makers
in that company," Stephanie states, "should be brought to
justice. They have a lot to explain."
Link to watch BBC’s
Panorama “Secrets of the Drug Trials”: http://news.bbc.co.uk/2/hi/programmes/panorama/6291773.stm
For more information about
the Baum Hedlund Law Firm call: (800) 827-0087; http://www.baumhedlundlaw.com/
By Evelyn Pringle
No Glaxo confidential documents
are cited or referred to in this article.
(Written as part of the Paxil
Litigation Monthly Round-Up, Sponsored by Baum, Hedlund Aristei, Goldman
& Menzies’ Pharmaceutical Antidepressant Litigation Department)
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