Tagged: paroxetine

Paroxetine Guinea Pig : The Curious Case Of Italia Sudano…


There was an interesting article, about Paroxetine and older adults, which appeared in the Guardian in 2003.

A woman called Italia Sudano (an Italian born/British resident) was apparently used as a Paroxetine (Paxil/Seroxat) guinea pig, by her GP (doctor) without her consent. Her doctor was (allegedly) paid by GSK too, and this was also all done without Sudano’s knowledge. The doctor in question, Dr Robert Adams, was struck off by the GMC (General Medical Counsel) after he was found guilty, of not just unethically pimping out his patients to GSK, but also for using several other patients as guinea pigs for various other drug companies and drugs too (not to mention making thousands of pounds in the process).

This case, is disturbing, and also remarkable, but what is stranger still is- how we heard nothing more about it, apart from the report in the Guardian at the time.

The reason why I bring this case up is, currently GSK are being sued in a court in the US by Wendy Dolin, for the death of her husband, Stewart Dolin, in a ‘Paxil Induced Suicide‘ case. The Dolin case centers on GSK’s dodgy Paroxetine trials, and in my opinion, Paroxetine should never have been licensed in the first place. GSK admit that Paroxetine is dangerous for under 18’s, however, many of us who have taken the drug, are highly aware that all ages can suffer from Paroxetine’s dangerous side effects. Side effects such as akathisia, de-personalization, volatility, suicidality etc are common among all age groups (GSK just don’t give us the full facts).

It would be interesting to find out- What data did GSK obtain from cases such as Sudano’s? Were the results of these (highly unethical) live human guinea pig trials ever seen by anyone outside of GSK? Will GSK present the findings in court, in cases such as Stewart Dolin’s? Were GSK receving data from any other GP’s in relation to Paroxetine testing on patients (with or without their consent) at the time, before it, or any time since? If so, what exactly was GSK trying to study by gleaning data from the case of a 72 year old Woman put on Paroxetine, without her consent, or knowledge , from her dodgy doctor? Did Italia Sudano take a legal case against her doctor? If so- did GSK provide information as to the significance of their Paroxetine testing on her?

https://www.theguardian.com/politics/2003/feb/09/health.nhs

Patients used as drug ‘guinea pigs’

Firms pay out millions to doctors to test medicines

When Italia Sudano went for a check-up with her GP, Dr Robert Adams, she was in good health. Her husband had died a few months earlier and her blood pressure was a little high.

Yet nothing could have prepared Sudano, 72, for the nightmare that was to follow and the discovery of a trail of greed and fraud that went right to the heart of the medical profession.

She was astonished to discover that her trusted GP had been using her as a guinea pig by giving her tablets which had not been medically approved. Worse still, he was being paid to do so by a pharmaceutical company.

An investigation by The Observer has revealed that many doctors are risking their patients’ health by subjecting them to medical trials without their knowledge.

Over the next few weeks Adams asked Sudano to return for more blood tests. By the end of the second month her arms were black and blue. Her son, Joe, said they looked as though they had been slammed in a door. She said: ‘At one point I asked if he was selling my blood.’

Little did Sudano know how close to the truth her comment was. On her last visit, Adams took a bottle of pills from the top drawer of his desk and suggested Sudano take one a day. While she thought it strange she wasn’t being given a prescription, she trusted her doctor.

But within hours of swallowing the pill, she could hardly walk because she was so dazed. Her face had swollen up badly and she was in considerable pain.

She stopped taking the tablets and complained to Hertfordshire Health Authority. This sparked an investigation that led to one of the largest cases of medical research fraud ever uncovered in Britain.

It emerged that over the previous five years Adams had earned more than £100,000 from drug companies, including the European giants AstraZeneca, GlaxoSmithKline and Bayer. They were all paying him to test their new drugs on his patients. Like Sudano, many of his patients had never given their consent and had no knowledge they were being used as human guinea pigs in a medical trial. Patients with no symptoms were given drugs and others who needed proper medication were given placebos. Adams was receiving almost £1,000 for each patient.

Last month Adams was found guilty by the General Medical Council (GMC) of serious professional misconduct and suspended for 12 months. The GMC’s lawyer described it as ‘assault’ and Sudano is now looking to sue Adams.

GlaxoSmithKline was using Adams to study its anti-depressant Paroxetine, but had to cancel the trial at a cost of hundreds of thousands of pounds.

The drugs industry talks of bad apples and the odd errant doctor milking the system but insists that trials using GPs are essential for medical advances and that payment to doctors for the extra work involved is ethically correct.

But an investigation by The Observer suggests the problem of GPs using patients as guinea pigs without their consent is more widespread. Some 3,000 doctors each year are paid by drug firms to sign up their patients to tests and on average 15 patients are needed for each trial. With doctors picking up £1,000 per patient, drug companies are spending £45m on getting doctors onside. There is no suggestion the companies are implicated in moves to carry out the tests by doctors on patients secretly.

Medical fraud experts estimate that one per cent of all drug trials involve fraud, including failure to get proper consent from patients. This means hundreds of patients a year are being given unapproved and potentially dangerous drugs without their knowledge.

The Observer has discovered that in the last five years the GMC has taken action in a dozen cases involving GPs undertaking fraudulent research. Examples include:

· Dr Vasu Agrawal from Chigwell, Essex, removed samples of womb from menopausal women as part of a trial into a new hormone replacement drug called Divina Nova. Agrawal failed to tell the women they were testing a drug that could have serious side-effects. Agrawal, who forged signatures on consent forms, received almost £6,000 from Orion Pharma International.

· Dr Paul Chima from Edinburgh is estimated to have received more than £200,000 from a range of pharmaceutical companies for testing their new drugs for angina, asthma, high blood pressure and depression. He failed to warn patients of possible side-effects and offered one a £2,000 bribe not to give evidence against him.

· Dr James Boschler from south London was given £22,500 from Bayer and Solvay Healthcare. He claimed to have signed up 36 patients, but 25 of the consent forms were discovered to be forgeries.

The country’s foremost investigator of medical research fraud is Peter Jay, the former Metropolitan Police detective chief inspector who arrested serial killer Dennis Nilsen. Since 1996 Jay has run MedicoLegal Investigations, an independent body, and has taken 12 doctors to the GMC.

Jay is investigating six further cases, including one involving a GP in Manchester. Dr Mark Northfield is alleged not to have obtained consent from patients for entering them into trials to test drugs manufactured by Bayer and Roche to treat high blood pressure and heart problems. Northfield is contesting the allegations before the GMC professional conduct committee.

Jay said: ‘While the industry has become more alert to the problems over the last decade there is still clearly a worrying and persistent problem in research fraud involving doctors. This is not just an issue of patient safety, but a problem that might lead to bad drugs being approved or good drugs failing to be approved.’

The Observer’s revelations of the continuing problem of research fraud have sparked calls for industry guidelines to be toughened up. David Hinchcliffe, the Labour chair of the House of Commons Health Select Committee, described the situation as bordering on ‘scandalous’ and said his committee would look into the issue.

He said: ‘The relationship between the drug firms and the medical profession is one that needs to be thoroughly investigated. It is extremely worrying that patients’ trust is being abused by doctors who are more interested in making money from the pharmaceutical industry.’

Dr Evan Harris, health spokesman for the Liberal Democrats, suggested that doctors involved in trials should be subject to on-the-spot inspections and that a patient’s consent to take part in a drug trial should be given outside the GP’s surgery, for example to a research officer acting for the firm.

Additional research by Charlotte Coulon

antony.barnett@observer.co.uk

GSK’s False Seroxat Suicide Statistics: Was Paroxetine A Misservice To Public Health Or Merely An Error?..


In this video, former GSK executive (and psychiatrist), Jeffrey Dunbar, gives his deposition, in a Paxil (Seroxat) induced suicide trial from 2006.

This is really astounding footage to watch.


Former GlaxoSmithKline executive Dr. Geoffrey Dunbar deposition in Paxil suicide case. In his testimony, Dr. Dunbar says that he helped author the drafts of the Paxil suicide report that the U.S. Food and Drug Administration (FDA) asked for in 1991. The calculations in this report showed and suggested that instead of Paxil increasing the suicide risk by nearly 9 times, the drug decreased suicidal behavior.

He admits in his deposition that his reports include improperly counted suicidal behavior events and that publications in which he participated writing had incorrectly conveyed Paxil reduced suicidal behavior.

This deposition was played for the jury in the trial of Dolin v. Smithkline Beecham Corp. (D/B/A GlaxoSmithKline-GSK). The case stems from the alleged paroxetine-induced death of Stewart Dolin, a partner at the law firm Reed Smith. Paroxetine is the brand name version of this medication is called Paxil which was researched, developed, manufactured and marketed by GlaxoSmithKline (“GSK”).

The lawsuit claims that GSK failed to adequately warn Mr. Dolin’s doctor about Paxil/paroxetine’s association with an increased risk of suicidal behavior in adults of all ages. According to the lawsuit, when Mr. Dolin was prescribed paroxetine in 2010, the drug’s label did not accurately warn physicians of the drug’s association with an increased risk of suicidal behavior in adults, despite GSK’s 2006 analysis showing a statistically significant 6.7 times greater risk in adults of all ages, as well as comparable statistically significant suicidal behavior evidence as far back as 1989 in Paxil’s clinical trials performed for its initial marketing approval.

More people could sign on to ‘Paxil’ drug case: lawyer


http://www.am730.ca/syn/112/280217/more-people-could-sign-onto-paxil-drug-case-lawyer

More people could sign on to ‘Paxil’ drug case: lawyer

More people could sign on to 'Paxil' drug case: lawyer

A Vancouver lawyer involved with the suit against pharmaceutical giant GlaxoSmithKline isn’t ruling out more people signing onto the case.

David Moriarty, from the firm Rosenberg Law, says a proposed settlement of $6.2-million was reached in the class action that already involves around 50 mothers and their children.

Moriarty says this settlement, which has yet to be approved in the B.C. Supreme Court, was filed in 2008.

“It’s 2017, this was an incredibly hard fought battle, numerous trips not just to the Supreme Court, but also the Court of Appeal, and we feel that a settlement is in the best interest of our class members.”

Moriarty says part of the settlement included GlaxoSmithKline not admitting any liability for the number of cardiovascular defects in babies born to mothers who took Paxil during the first three months of pregnancy.

Hello To The World Health Organization (WHO)…


I get views regularly from organizations as diverse as the WHO (World Health Organization) and the MHRA, to the US government and the European Medicines Authority. It’s interesting that the WHO were viewing today, because it was back in 2002, that the WHO reported that Paroxetine (Seroxat/Paxil) topped the list of withdrawal symptoms for SSRI drugs.

http://news.bbc.co.uk/2/hi/health/1382551.stm

 

“Dr Healy told BBC News Online, of the 100m people world-wide who were on Seroxat, one in 1,000 could have a suicidal reaction.”

Withdrawal problems

A World Health Organization report which ranked antidepressants in order of withdrawal problems found Seroxat was the hardest to come off.

 

Ian Hudson of The MHRA (ex-GSK Employee)Bluffs And Blunders His Way Through A Grilling By Andy Vickery At A Paxil Induced Suicide Trial (2000)


I have to say I have been incensed watching a video of Dr Ian Hudson of the MHRA when he was defending (his employer at the time) GSK from allegations that Paxil/Seroxat caused a suicide in the US. Hudson did everything he could to defend Paxil/Seroxat  but in many ways he slipped up. This video was recorded in 2000. At this time I would have been on Seroxat for two years, I had no idea that this trial was even happening, there was no access to the web, or information back then- people like me were left suffering in the dark. Some people didn’t make it through, the side effects were too much, and they killed themselves. Akathsia is one of the most crippling and disturbing side effects of any psychiatric drug. On Seroxat I had weeks, often months of regular bouts of akathisa, I wouldn’t wish it on my worst enemy- it was hell, beyond hell actually, it was utterly devastating. I can understand completely how Akathisia would drive some people to kill themselves, I don’t know how I endured it, maybe my youth had something to do with it- often youth protects us from extreme events because we can endure more- and Seroxat was torture, absolute torture.

At the time that Dr Ian Hudson was defending his employers in a Seroxat suicide trial in the US, and denying that Seroxat was even associated with Akathisia, I was probably  climbing up the walls in my bedroom, rocking like a lunatic, crying and pulling on my scalp, feeling like every atom in my body was on fire, intensely suicidal, feeling like my skin was literally burning and crawling off my bones-  but all the while completely unaware that I was experiencing akathisa from Seroxat.

I didn’t even know what akathsia was.

However, I’m sure that Ian Hudson knew what Akathisa was though..

Ian hudson is now the CEO of the MHRA (the Medicines Regulator in the UK). At the time of his video deposition in this Paxil/Seroxat suicide trial- he was the ‘World-wide safety director’ of GSK (the manufacturer of Seroxat).

Imagine that ‘wordwide safety director’ of one of the most controversial drugs of the past 20 years …

I wonder what Ian Hudson’s view is now of Seroxat?

Does he still think that there is no relationship between Seroxat and Suicide?

Does he still think that there is no evidence of a cause and effect relationship of Akathsia with Seroxat?

If so, then why does GSK warn now of these effects in their PILs?

According to the GSK PIL (screen grab below)- Seroxat can cause Akathsia in around 1 in 1000 people.

Seroxat was prescribed to millions of people since it was first licensed 25 years ago- in 1991. So how many people went on to kill themselves because of Akathsia from Paxil/Seroxat? How many people lost their health? How many people killed themselves in the agonizing withdrawals? Can Hudson give us the new stats on that?

He is, after all, now the chief at the medicines regulator, and although he once defended Seroxat for GSK in court, maybe his new role as a patient protector- as opposed to a drug company lackey- he would be able to re-define his views for us and warn the public about the dangers of Seroxat?

Personally I wouldn’t even trust GSK’s PILs, if they say it’s one in 1000, it’s probably one in 100 or worse… they are proven liars and deceivers, nothing can be trusted from them given their track record. They are totally sociopathic when it comes to harming consumers of their drugs and denying that harm when it is revealed. But even if we take 1 in 1000 as an average estimate, that’s a lot of Akathsia from Seroxat.

But according to Ian- Seroxat doesn’t cause Akathsia, so which is it Ian does Seroxat cause Akathisia or not? The PIL says it does, but you said it didn’t…

Maybe Ian would like to-fulfill his role- and protect others from anymore Seroxat horror?

And maybe Ian would now like to do the right thing and apologize to all the people who killed themselves or felt suicidal, or lost their livelihoods, their relationships, and years of their lives, to Seroxat side effects?…

Or maybe he just doesn’t give a damn…

Either way, the whole thing stinks to high heaven in my opinion..

https://www.medicines.org.uk/emc/PIL.3185.latest.pdf

ian-hudsonseroxat-2

http://www.healyprozac.com/Trials/Tobin/Depositions/hudson-depo.txt

 

   Okay.  Dr. Hudson, does Paxil have an
 
        23  association with akathisia?
 
        24  A.    I've seen some case reports of
 
        25  akathisia.  I'm aware that there have been
 
 
 
                     SPHERION DEPOSITION SERVICES
                            (713) 650-3500

 
                   IAN R. B. HUDSON, M.R.C.P., M.D.
                                                     42
 
         1  some cases of akathisia, so it is something
 
         2  that we have received case reports about.
 
         3  Q.    Do you believe, as Worldwide Safety
 
         4  Director of SmithKline Beecham, that Paxil
 
         5  causes some patients to become akathisic?
 
         6  A.    I've seen no evidence to suggest a cause
 
         7  and affect relationship between Paroxetine and
 
         8  akathisia.  I've seen some case reports, but
 
         9  I've seen nothing that suggests a cause and
 
        10  affect relationship

Dr Ian Hudson (Ex GSK Employee and Current Head Of The MHRA- UK Medicines Regulator) Defends Paxil (Seroxat) In US Court Case… Exclusive- From Bob Fiddaman’s Blog…


 

http://fiddaman.blogspot.ie/2016/09/exclusive-dr-ian-hudson-in-defence-of.html

Monday, September 12, 2016

EXCLUSIVE: Dr Ian Hudson: In Defence of the Suicide Pill

A chance meeting, a discussion, a common interest.

That’s all it needs at times to stumble upon something you’ve been seeking for close to 10 years.

Video depositions have always fascinated me, they are better than the written depositions that we see within court documents. Most notably they show the subject answering questions, they show the subject in a much different light, they show the subject being evasive and choosing not to answer questions that may jeopardise the party he is appearing for. Moreover, they can be seen at later dates, when the subject has moved on to a different company or, in this instance, to head of the British drug regulator, the MHRA.

Ian Hudson is the former World Safety Officer for SmithKline Beecham, today they are more commonly known as GlaxoSmithKline or GSK.

On Friday, December 15, 2000, Ian Hudson, who at the time was still employed by GSK, gave a deposition in relation to a case that was to be tried in Wyoming a year or so after this deposition was taken, the result of which found that Paxil was, in fact, a proximate cause of the deaths in this case.

The case in question was brought against GSK by the relatives of a man, Donald Schell, who killed himself and three others after taking the drug Paxil,

Here is Ian Hudson’s video testimony. It’s a bit scratchy in places and the audio drops but it is the first time this has been seen in public.
.
Ian Hudson is the current Chief Executive of the MHRA, the British drug regulator who regulate the drugs you and I take.

You can draw your own conclusions as to whether or not you think Ian Hudson is forthright with his answers in this deposition.

A transcript of the video deposition can be found here.

Ian Hudson was being asked questions by US attorney, Andy Vickery.

(GSK are currently defending another Paxil related suicide in the US – The Stewart Dolin files can be seen here)


Paroxetine (Paxil/Seroxat) And Cognitive Impairment


http://qz.com/720419/when-meds-didnt-cure-my-depression-i-tried-retraining-my-brain-waves-instead/

“….But my experiences with psychotropic medication have shown similar problems. I started on paroxetine (the Paxil generic) in my 20s. It abruptly stopped working in my 30s—while I was taking it—and I slogged through five other medication trials before I found an effective replacement. Since then, paroxetine has been identified as having anti-cholinergic effects, which can include cognitive impairment and memory loss…”

Glad to see that the side effects of Cognitive Impairment from Paroxetine are beginning to be recognized in some media…

The ‘brain fog’ from Paroxetine never fully goes away..

http://i2.cdn.turner.com/cnn/2016/images/04/18/risacheretal_jamaneurology_final_inpress_041116.pdf

How Many People Have To Die Or Be Damaged For Life Before The Regulators Pull Seroxat (Paxil/Paroxetine) From The Market?


I had Akathisa multiple times on my 3 and a half agonizing years on Seroxat- how many people were driven to suicide or self harm etc from the horror of Seroxat/Paxil induced Akathsia?

In the following document, from 2006 (ten years ago now) Dr Peter Breggin drew attention to GSK’s suppression of the dangerous Akathisia side effect from Paxil:

See here

Ethical Human Psychology and Psychiatry, Volume 8, Number 2, Summer 2006

SPECIAL REPORT PART II

How GlaxoSmithKline Suppressed

Data on Paxil-Induced Akathisia:

Implications for Suicidality and

Peter R. Breggin, MD

This is the second in a series of Special Reports on previously suppressed data con-
cerning the selective serotonin reuptake inhibitor (SSRI) antidepressant Paxil (paroxetine) and its capacity to cause violence and suicide. The data were contained in a report that I wrote as a medical expert for a product liability suit against the manufacturer of Paxil, Lacuzong v. GlaxoSmithKline (GSK).1 After taking Paxil 10 mg for 3 days, Mr. Lacuzong drowned his two children and himself in a bathtub. The case was eventually ‘‘resolved’’ without the details of the settlement being made public.

The drug company denied all allegations.

My product liability report was based on numerous sources, most notably a 3-day trip

to the drug company offices to examine its internal files concerning how Paxil was re-
searched, developed, and marketed. Until these Special Reports, the information in these files had not been made public.

Since the publication of my first special report concerning how the manufacturer of

Paxil hid and manipulated data concerning Paxil-induced suicide (Breggin, 2006), the

FDA and the drug company, GlaxoSmithKline, have issued statements confirming that depressed adults of all ages taking the antidepressant have an increased rate of suicidality compared to depressed adults taking placebo (Kraus, 2006). These adults with major depressive disorder suffered a 6.4 times increase in the rate of suicidal ideation and behavior compared to the controls receiving the sugar pill (0.32% vs. 0.05%).

This meta-analysis of placebo-controlled clinical trials also focused on young adults who were prescribed Paxil for anxiety disorders as well as depression. In this broader diagnostic group, young adults (ages 18–24) who were given Paxil were also at increased risk for suicidality.

Summarizing these data, Paxil increased suicidality in depressed adults of all ages and also in young adults with depression, dysthymia, panic disorder, generalized anxiety disorder, and obsessive compulsive disorder.

The rates of Paxil-induced suicidality will be much higher in actual clinical practice where the drug exposure typically lasts much longer than 4–6 weeks, patient monitoring is much less thorough, multiple drugs often exacerbate adverse drug reactions, and many patients are already suicidal.

2006 Springer Publishing Company 91

92 Special Report Part II

By admitting that Paxil causes suicidality in adults, the FDA and GlaxoSmithKline confirmed observations I have been making in my publications and trial testimony for more than a decade (e.g., Breggin, 1997, 2001; Breggin & Breggin, 1994). The FDA and the drug company released their results within weeks after the publication of my initial special report in EHPP, which showed that the drug company had been suppressing the relevant data for many years (Breggin, 2006).

My first Special Report, ‘‘Court Filing Makes Public My Previously Suppressed Analysis of Paxil’s Effects,’’ described how recent court proceedings made my product liability report available to the public despite previously successful efforts by GSK to suppress it. My initial Special Report provided excerpts from my product liability analysis concerning how the drug company manipulated data concerning Paxil-induced suicidality. For example, GSK’s analysis of suicidality left out two attempted suicides and two completed suicides on Paxil, and exaggerated the number of suicidal acts on placebo. The company also reduced the apparent significance of suicide related events by providing separate analyses of overdose, suicide attempt, and suicidality. It is more useful and meaningful to combine all suicide-related activities into one category, suicidality.

For Special Report Part II, I have excerpted sections from my product liability report concerning how the drug company hid both the rates for Paxil-induced akathisia and the relationship between akathisia and suicidality. Akathisia is a drug-induced inner agitation or dysphoria that causes a person to feel compelled to move about. The painful feelings associated with akathisia have been compared to torture and often make people feel as if they are going ‘‘crazy.’’ People who suffer from akathisia often voice dramatic descriptions such as ‘‘electricity streaming through my veins,’’ ‘‘horrible jagged feelings inside my head’’ or ‘‘something pinching my nerves all over my body.’’ These vivid, desperate descriptions

can be mistaken for delusions or hallucinations (American Psychiatric Association, 1994,

2000; Breggin, 1997).

 

When the FDA initially approved Paxil in December 29, 1992, it had already been reported that SSRI antidepressants tend to induce extremely high rates of akathisia. For example, Lipinski, Mallaya, Zimmerman, and Pope (1992) described five cases and, based on a review of the literature, they estimated that Prozac (fluoxetine) causes akathisia in 9.7%–25% of patients. Since the 1970s, studies of neuroleptic-induced akathisia have demonstrated that akathisia causes severe emotional disturbances, including aggression, suicidality, and a worsening of psychosis (van Putten, 1975; van Putten & Marder, 1987; Breggin, 1983, 1997). In the early 1990s, clinical reports began to link Prozac-induced akathisia to severe, acute, and obsessive suicidality (e.g., Rothschild & Locke, 1991; Teicher, Glod, & Cole, 1990).

In 1994, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM- IV, 1994, pp. 744–746) attempted to sum up the available clinical and research data concerning drug-induced akathisia. It stated, ‘‘Akathisia may be associated with dysphoria, irritability, aggression, or suicide attempts.’’ It also linked akathisia to ‘‘worsening of psychotic symptoms or behavioral dyscontrol.’’ The manual focused on neuroleptic-induced akathisia but made clear that the same problems are associated with SSRI antidepressant- induced akathisia: ‘‘Serotonin specific reuptake inhibitor antidepressant medications may produce akathisia that appears to be identical in phenomenology and treatment response to Neuroleptic-Induced Acute Akathisia.’’2

Because it was already known that SSRI-induced akathisia causes suicidality, violence, and overall mental deterioration, it was beholden on GSK to conduct a careful analysis

Special Report Part II 93 of Paxil-induced akathisia. It was also beholden on the company to look for a link between Paxil-induced akathisia and mental or behavioral abnormalities. Instead, GSK went to extreme lengths to hide the fact that Paxil causes akathisia and that the some Paxil akathisia cases were associated with suicidality.

SSRI antidepressants can cause suicidality and violence through means other than aka- thisia, including drug-induced agitation, depression, and mania. Patients who were previ- ously depressed can be pushed into states of agitated depression or manic-like reactions

(Breggin, 2003). The stimulating effects of SSRIs, from akathisia and agitation to mania, are responsible for causing some of the most severe mental and behavioral aberrations.

Some progress has been made by the Food and Drug Administration (FDA) in warning about the risks associated with SSRI stimulation or activation (reviewed in Breggin, 2005). The agency now requires antidepressant labels to carry several warnings related to over- stimulation and akathisia including the following: Clinical Worsening and Suicide Risk: Patients, their families and caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hy- pomania, mania, and other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. (FDA, 2005a, p. 2)

The FDA also requires antidepressant labels to carry a black box warning about the increased risk of suicidality in children who take these drugs (FDA, 2005a). Although specific warning about the increased risk of suicidality in adults who take these antidepressants is not required, the FDA has issued a Public Health Advisory about the potential danger in adults (FDA, 2005b). The data disclosed in this Special Report should lend scientific weight to the FDA’s concerns and encourage a specific label warning about the increased risk of suicidality in adults taking SSRI antidepressants such as Paxil.

The following excerpts from my product liability report dated July 21, 2001, focus on akathisia. In addition to examining how GSK manipulated or suppressed data concerning akathisia, these findings confirm a link between Paxil-induced akathisia and suicidality. The data also confirm that these severe reactions can occur beginning with the first dose of the drug and that they often occur within the first few days of the initial exposure.

My product liability report can be found in its entirety on my website, www. breggin.com. It covers numerous additional concerns about how GSK researched, developed, and marketed Paxil.

EXCERPTS FROM THE REPORT AND AFFIDAVIT OF PETER R. BREGGIN,

MD, IN THE CASE OF LACUZONG V. GLAXOSMITHKLINE

III. Eliminating Akathisia as Preferred Term and as an Investigator’s Term

(1) Definition of Akathisia. Akathisia is a neurological disorder caused by medica-
tions. Stedman’s Medical Dictionary, 27th edition (2000) defines akathisia as ‘‘A syndrome characterized by an inability to remain in a sitting posture, with motor restlessness and a feeling of muscular quivering.’’ The American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, IV (DSM-IV) (1994; 2000) describes akathisia in the context of neuroleptic drugs, but [as noted in the DSM-IV] the clinical manifestations are

94 Special Report Part II the same when akathisia is induced by SSRI antidepressants. The DSM-IV observes that akathisia includes the following symptoms: [S]ubjective complaints of restlessness and at least one of the following observed move-
ments: fidgety movements or swinging of the legs while seated, rocking from foot to foot or ‘‘walking on the spot’’ while standing, pacing to relieve the restlessness, or an inability to stand still for at least several minutes. (p. 744)

In general, if the subjective experience of agitation, anxiety, irritability or similar feelings are accompanied by voluntary motor movements, such as pacing or foot swinging, the syndrome is identified as akathisia.

(2) Akathisia, Violence, and Suicide. The DSM-IV states without qualification,

‘‘Akathisia may be associated with dysphoria, irritability, aggression, or suicide attempts’’

(p. 745).

There is a considerable body of literature to confirm the association between akathisia and violence and suicide. I have reviewed some of the literature in Breggin and Breggin

(1994) and Breggin (1997) [most recently in Breggin 2003] in regard to psychiatric drugs in general and specifically the SSRIs of which Paxil is a member. Teicher et al. (1993) reviewed SSRI-induced violence and suicide. More recently, Glenmullen (2000) devoted a significant portion of a book to reviewing the literature and discussing SSRI-induced violence and suicide.

(3) The Expurgation of Akathisia. It is extremely important for physicians to know that a drug can cause akathisia. Akathisia, as a term, signals the dangers of emotional anguish and the potential for inducing suicide and violence. It is not only fraudulent but also hazardous to patients to hide that a drug can cause akathisia. It is especially dangerous when the drug is being used to treat depression, because akathisia in depressed patients is especially likely to drive them to suicidal or violent acts.

Akathisia was systematically eliminated by SKB (now GSK) as a preferred term from the U.S. and non-U.S. studies. This meant that symptoms typical of akathisia would not be coded as akathisia, but as something else, such as agitation or central nervous system stimulation. (Preferred terms are the words used to describe specific adverse effects, such as akathisia, agitation, or mania. They are selected from a codebook provided by the FDA. If akathisia is not listed by the company as a preferred term in its plan or protocol for a study, then investigators will code or list akathisia as something else, such as agitation. Almost any term is less threatening than akathisia.)

Remarkably, akathisia does not even appear as an investigator’s term on any U.S. reports that I located. It appears only as an investigator’s term in about one dozen non- U.S. reports, whereas symptoms attributable to akathisia abound in the summaries of the U.S. reports of adverse drug reactions. From this it must be concluded that SKB not only removed akathisia from any lists of preferred terms, it also must have communicated to the principal investigators that the term should not be used in any of the adverse drug reports or clinical summaries. Clearly SKB preferred not to let the FDA or the medical profession know that Paxil causes akathisia. Indeed, they left it out of the section entitled ‘‘Adverse Experiences in Clinical Trials: Worldwide Data’’ (Section V—NDA. PAR Safety Summary 20-Nov- 1989, pp. 83–88; also see Table V.7, p. 114).

Similarly, akathisia was left out of the section entitled ‘‘Adverse Experience which occurred during active treatment—U.S. Phase II & III Studies,’’ ‘‘Nervous System’’ Special Report Part II 95 (Appendix V.8, in NDA 20031-Vol 422 November 1989, pp. 189/190–275/276). There is no listing at all for akathisia but many reports of related restlessness and nervousness. (4) Akathisia Slips Through in Non-U.S. Reports. Nonetheless, some akathisia reports slipped through in non-U.S. reports. In the section entitled ‘‘Adverse Experiences which occurred during active treatment-Non-US Phase II-III Studies,’’ V.1, pp. 129–199, we located 13 explicit reports of akathisia and motor akathisia (a synonym). In addition, there were many descriptions of akathisia listed under other preferred terms.

(5) The FDA Adds Akathisia to the Paxil Label. Eventually the FDA insisted that SKB add akathisia as a postmarketing finding without insisting on causation. The demand came in a letter in September 1993 from the FDA’s Paul Leber to SKB (SB 0000247). Had the FDA been informed during premarketing of the large number of cases of akathisia in association with Paxil, it would have been in a position to more firmly determine causation.

In response, a label version created by SKB and dated 2.05.94 does add akathisia and EPS as postmarketing findings.3 They should have been put in the label as a premarketing finding involving multiple cases (p. 000022). One of the two reports cited by the FDA was received from Ireland. However, the company already had many reports of akathisia in its possession from Europe, but must have failed to inform the FDA.

To repeat, the FDA required a mention of akathisia in the label based on merely two postmarketing reports, although SKB already had about one dozen explicitly identified akathisia reports in its possession from the non-U.S. premarketing studies and, as we shall document, dozens of other akathisia cases coded under different preferred terms, such as agitation and central nervous system stimulation, in the U.S. premarketing studies.

(6) How the FDA Codes Akathisia. The FDA has developed a coding system for adverse reaction terms. The dictionary is entitled ‘‘COSTART: Coding Symbols for The-
saurus of Adverse Reaction Terms.’’ I have the Fifth Edition (1995) in my library, but it has not changed in regard to akathisia. Like any other pharmaceutical company, SKB was supposed to base its collection and analysis of adverse reaction data on the COSTART system. This is discussed, for example, in an SKB Memorandum, ‘‘FDA Conversation

Record’’ (9.5.91), which memorializes a conversation with the FDA’s Thomas Laughren concerning, among other things, the use of COSTART terms (SB 0000158). In fact, the memo comments that Laughren (the ‘‘Division,’’ meaning the FDA’s Division of Neu- ropharmacological Drug Products) would make decisions about what terms to cut from the label.

From the beginning, COSTART has coded akathisia as akathisia. That is, the preferred term for akathisia is akathisia. This was true during the development of the first SSRI, Prozac.

Therefore, SKB deviated from the FDA’s coding system in order to classify cases of akathisia as something else, such as agitation. In reclassifying akathisia, as well as stopping the use of the term in general, SKB made it impossible for the FDA or anyone else to

accurately determine the total number of patients who suffered from akathisia as a result of taking Paxil. This was extremely fraudulent.

(7) Purposefulness of the Fraud Concerning Akathisia. The fraud had to be carried out with full knowledge, because it was well known that the original SSRI, Prozac, caused akathisia. The original Prozac label listed akathisia but estimated its occurrence as ‘‘infre- quent.’’ It quickly became apparent, however, that Prozac-induced akathisia was common 96 Special Report Part II and dangerous. In 1989, Joseph Lipinksi and his colleagues from McLean Hospital and

Harvard Medical School published five cases of Prozac-induced akathisia involving con- siderable emotional disturbance. Based on a literature review, the researchers estimated the rate of Prozac-induced akathisia at between 9.7% and 25%. In June 1990, the Public Citizen Health Research Group (related to Ralph Nader’s organization) in their Health

Letter similarly estimated the rate of Prozac-induced akathisia as 15%–25%. Furthermore, as reports by Teicher et al. (1990) and Rothschild and Locke (1991) illustrate, SSRI- induced akathisia as a potential cause of suicide and violence was a subject of discussion in the literature even before the approval of Paxil.

In the next section, we shall find a direct link between suicide and stimulation, in-
cluding akathisia, in SKB’s own NDA files.4

IV. Reanalysis of Preferred Terms in U.S. Trials

In addition to akathisia, Paxil commonly causes a variety of related symptoms of central nervous system stimulation (CNS), including CNS stimulation itself, anxiety, agitation, nervousness, irritability, and insomnia. These symptoms of stimulation are extremely im- portant because they, too, are associated with suicide and violence (Breggin & Breggin,

1994; Breggin 1997 [and more recently, Breggin 2003]). It is common knowledge in the medical profession that stimulation can induce depressed patients to make acts of suicide.Therefore, it is extremely important for physicians to know that an antidepressant drug causes stimulation, and it is fraudulent and dangerous to hide that information from them.

Unfortunately, SKB not only tried to hide the facts about Paxil-induced stimulation and akathisia, the company made false claims concerning Paxil in this regard. I have already documented that the FDA protested at times against these false claims. As another example, SKB developed a lengthy document entitled ‘‘Paxil (paroxetine hydrochloride):

Hospital Formulary Product Information’’ (SB 0000261, dated December 11, 1992). In it, SKB claimed that Paxil was effective in ‘‘depressed patients with associated symptoms of anxiety’’ (SB 0000271) and that the drug possessed an adverse reaction profile with ‘‘a low incidence of nervousness, agitation, and anxiety.’’ These statements are false. In fact, as the FDA stated (see previous) and as we shall continue to document, Paxil causes nervousness, agitation, irritability, anxiety, and related symptoms of stimulation in a large percentage of depressed patients, often in the first 3 days.

We shall also find that cases of akathisia were hidden in company-defined preferredterms (i.e., terms preferred by the drug company such as agitation, anxiety, stimulation, nervousness, and tremor).

The following is a reanalysis of several categories of CNS-related adverse effects that the company organized according to its selected preferred terms:

(1) Preferred Term Agitation. Agitation had 75 entries (pp. 191–193). A total of

49 of 75 agitation patients were in fact suffering from akathisia. Of these, 47 were described

by the term ‘‘restless’’ and 10 mentioned leg or foot (one case) movement. As the defi nition of akathisia indicated (see previous), these cases are most likely akathisia. Consistent with the Lacuzong case, 21 occurred in the first 1 to 3 days. Another 11 occurred in 4 to 5 days. Again consistent with the Lacuzong case, seven cases developed on low doses of 10 mg.

(2) Preferred Term Anxiety. Of the 86 reports in the category for ‘‘anxiety,’’ 24 were described as ‘‘tense’’ and 1 as ‘‘restlessness.’’ Although it is not as definitive as in the case Special Report Part II 97 of the preferred term ‘‘agitation,’’ many of these cases were probably akathisia. Of great importance, 26 occurred in the first 1 to 3 days. Another 9 occurred in 4 to 5 days; 8 occurred at the 10 mg dose.

(3) Preferred Term Nervousness. Under the category ‘‘nervousness’’ (pp. 235–238), 44 of 91 were probably related to akathisia. They were identified by the following terms: pacing, jumpy, jittery, and fidgety. Jittery was the most common. In all, 23 of 91 reports occurred in the first 1 to 3 days. Another 15 occurred in 4 to 5 days.

(4) Preferred Term Tremor. Under the ‘‘Preferred Term Tremor,’’ there were a very

large number of reports (pp. 268–273) that I have not fully evaluated. Many were related to akathisia.

V. Analysis of Akathisia in the Non-U.S. Phase II and III Clinical Trials

(1) Reports of Akathisia by Investigator Term. Unlike in the United States, a few

cases of akathisia were reported using the investigator’s term akathisia in the non-U.S.

Phase II–III studies (for Aropax, another brand name for paroxetine, November 1989,

Appendix V.1). They were coded under the preferred term CNS stimulation rather than

under akathisia:

Patient # Onset—days

1. 2218 072 (p. 137) NA

2. NA (p. 138) 1

3. 664 015 (pl 138) 1

4. NA (p. 138) 9

5. 664 012 (p. 139) 2

6. NA (p. 139) -6

7. 6 162 005 (p. 139) 4—Suicide attempt

8. NA (p. 139) 5

NA indicates Not Available.

(2) Akathisia Linked to Suicide Attempt. Of the eight patients diagnosed with aka-
thisia, only four were identified by patient number [and therefore could be traced back to their detailed clinical reports]. Of the four identified patients diagnosed with akathisia, one (25%) attempted suicide. Furthermore, the patient attempted suicide on the same day as the akathisia report (see NDA Suicide Report, Appendix 2, page 17).

It is very important to have the company identify the other four patients.

(3) Rapidity of Akathisia Onset. Of special importance to the Lacuzong case, aka-
thisia often begins within the first few days of treatment. Of the four identified patients, one did not have onset data. Of the seven patients with onset data, all were diagnosed in 9 or fewer days of treatment. Six were diagnosed within 1 week of treatment. Three were diagnosed within 1 to 2 days of treatment.

(4) Reports of ‘‘Motor Akathisia’’ by Investigator Term. Motor akathisia is identical to akathisia. The term simply emphasizes the external manifestation of the symptoms.

There were five cases:

Patient # Date of Onset

1. 7119 028 (p. 157) 16

2. 7119 058 (p. 157) 120

98 Special Report Part II

3. 7121 003 (p. 158 21

4. 7124 012 (p. 158) 6—Suicide (completed)

5. 7126 008 (p. 158) 28

(5) Motor-Akathisia Linked to Suicide. Of the five patients diagnosed with ‘‘motor

akathisia,’’ 1 (20%) committed suicide. Thus, of the 13 identified patients diagnosed with ‘‘akathisia’’ or ‘‘motor akathisia,’’ 2 (15%) attempted or completed suicide.

(6) Completed Suicides Linked to CNS Adverse Effects, Including Akathisia. We

have been able to trace five completed suicide cases to their original case summaries. Of the five patients who successfully committed suicide on Paxil, all were diagnosed with

CNS-related AERs (Adverse Event Reports) before suicide. Of those five cases, at least

two presuicide diagnoses (40%), agitation and motor akathisia, were related to stimulation

and/or akathisia. All of them had CNS adverse drug reactions.

The following are the five completed suicide cases followed by the investigator terms

for their adverse drug reactions.

1. 1.13.126 ‘‘severe insomnia’’

2. 2206.005 light-headedness, drowsiness, malaise

3. 2406.149 ‘‘restlessness (agitation)’’

4. 6.47. 003 vertigo

5. 7124–012 motor akathisia. ‘‘mild hyperkinesia’’

VI. Rapid Onset of Adverse Drug Reactions (ADRs) Documented From the

Spontaneous Reporting System

Postmarketing data from the Spontaneous Reporting System dated July 1993 confirms

that severe ADRs can develop in the first day or two of treatment, including reactions

that adversely affect behavior (NDA20031; SB 0000912). Here is a small sample excerpted

or extracted from the Adverse Experience Reports.

Day 1: Afraid, agitated, insomnia, tension. (p. 000152)

Day 1: EPS reaction. (p. 000156)

Day 1: Tremors, restlessness, tearful. (p. 000187)

Day 1 or 2: Disorientation, insomnia. (p. 000081)

Day 1: Severe akathisia. (p. 000340)

Day 1: Extremely restless, felt like screaming, dysphoric. (p. 000543)

Day 1: Hallucinations. (p. 000579)

Day 1: Hallucinations of insects and objects moving, dizzy. (p. 000507)

Day 1: Drugged, out of body, shaky. (p. 000487)

Day 1: Amnesia. (p. 000467)

Day 1: Distressed, hot flashes, sort of breath. (p. 000416)

Day 1: Distressed, hot flashes. (p. 000417)

Day 2: Dystonia. (p. 000138)

Day 2: Hallucination. (p. 000471)

Day 2: Bugs crawling, feeling high. (p. 000472)

Day 2: Drastic blood-sugar drop. (p. 000482)

Day 2: Numbness all over. (p. 000513)

Day 3: Severe muscle spasms. (p. 140)

Special Report Part II 99

Day 3: Dystonia, anxiety. (p. 172)

Day 3: Suicide attempt. (p. 000106)

Day 4: Insomnia, could not walk or talk on 10 mg. (p. 000372)

Day 5: Extreme agitation, jumped out window, disappeared 2 days. (p. 000554)

Day 5: Extremely jittery, very dizzy. (p. 115)

VII. The Role of ‘‘Central Nervous System Stimulation,’’ ‘‘Irritability,’’ and

‘‘Excitement’’ in Suicide and Violence

(1) Stimulation and Irritability in U.S. Trials. ‘‘Irritability’’ is used in psychiatry to

describe the emotional hyper-reactivity of individuals that can lead to inappropriate or

immoderate hostility and violence. It is closely related to excitability. (See, for example,

Stedman’s Medical Dictionary, 2000, or the PDR Medical Dictionary, 1995.)

Irritability is a much stronger term in psychiatry than in common use. In the Diagnostic

and Statistical Manual of Mental Disorders, IV (1994), a diagnosis of Substance-Induced

Mood Disorder can be made on the basis of any of ‘‘irritable mood’’ by itself (p. 374).

Appendix V.8, ‘‘Adverse Experiences Which Occurred During Active Treatment: U.S.

Phase II-III Trials’’ (SB 0000669, p. 198, stamped 199), lists CNS Stimulation as a preferred

term. In the category of CNS Stimulation, investigator terms were usually related to abnormal behavioral reactions, such as ‘‘irritable,’’ ‘‘irritability,’’ and ‘‘increased irritability.’’

There were 19 reports relating to irritability. There were 7 reports related to ‘‘excite-
ment’’ and ‘‘intense rushes of excitement.’’ Other reports were related to feeling ‘‘wired’’ and ‘‘wound up.’’

Of these approximately 41 patients with 50 reports of Central Nervous System stimu-
lation, many occurred early in treatment. Eight occurred within 1 to 2 days of the start

of treatment. Five adverse events occurred at the 10 mg dose, none of which were in the

1- to 2-day period.

(2) Anxiety and Suicide From Non-U.S. Phase II and III Studies. A hand count of ‘‘agitation’’ as the preferred term (NDA 420 November 1989, p. 128 ff) disclosed 43 reports, including one completed suicide (2406 149) on the 32nd day of Paxil ex-
posure. A hand count of ‘‘anxiety’’ as the preferred term disclosed 63 reports, with three attempted suicides on the same day, 3 days after the report and 19 days after the report.

Once again there is evidence that suicide is related to stimulation (akathisia, agitation, anxiety) from Paxil.

NOTES

1. Formerly known as SmithKline Beecham (SKB).

2. Bold in original. All quotes from p. 745. The same points are made in identical language in

the more recent edition (American Psychiatric Association, 2000, p. 801).

3. EPS (extrapyramidal symptoms) include a broad array of drug-induced neurological reactions, including akathisia.

4. The NDA (new drug application) contains all documents pertaining to the drug approval process, including all clinical trial data, evaluations of safety and efficacy, proposed advertising and marketing materials, the proposed label for the drug, and communications with the FDA.

100 Special Report Part II

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edition (DSM-IV). Washington, DC: American Psychiatric Association.

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders, fourth

edition, text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association.

Breggin, P. (1983). Psychiatric drugs: Hazards to the brain. New York: Springer Publishing Company.

Breggin, P. (1997). Brain-disabling treatments in psychiatry: Drugs, electroshock and the FDA. New

York: Springer Publishing Company.

Breggin. (2001). The antidepressant fact book. Cambridge, MA: Perseus Books.

Breggin, P. (2003). Suicidality, violence, and mania caused by selective serotonin reuptake inhib-
itors: A review and analysis. Ethical Human Sciences and Services, 5, 225–246.

Breggin, P. (2005). Recent U.S., Canadian and British regulatory agency actions concerning anti-
depressant-induced harm to self and others: A review and analysis. Ethical Human Psychology

and Psychiatry, 7, 7–22.

Breggin, P. (2006). Court filing makes public my previously suppressed analysis of Paxil’s effects.

Ethical Human Psychology and Psychiatry, 8, 77–84.

Breggin, P., & Breggin, G. (1994). Talking back to Prozac. New York: St. Martin’s Press.

Food and Drug Administration. (2005a, January 26). Suicide labeling for antidepressants. Retrieved

May 25, 2006, from http://www.fda.gov

Food and Drug Administration. (2005b, June 30). FDA Public Health Advisory: Suicidality in adults

being treated with antidepressant medication. Retrieved May 25, 2006, from http://www.fda.org

Glenmullen, J. (2000). Prozac backlash. New York: Simon & Schuster.

Kraus, J. E. (2006, May). Dear healthcare professional: Important prescribing information [for Paxil].

Philadelphia: GlaxoSmithKline. Retrieved from http://www.fda.gov

Lipinksi, J., Jr., Mallaya, G., Zimmerman, P., & Pope, H., Jr. (1989, September). Fluoxetine-induced

akathisia: Clinical and theoretical implications. Journal of Clinical Psychiatry, 50, 339–352.

Rothschild, A., & Locke, C. (1991, December). Reexposure to fluoxetine after serious suicide at-
tempts by three patients: The role of akathisia. Journal of Clinical Psychiatry, 52, 491–493.

Teicher, M., Glod, C., & Cole, J. (1990). Emergence of intense suicidal preoccupation during

fluoxetine treatment. American Journal of Psychiatry, 147, 207–210.

van Putten, T. (1975). The many faces of akathisia. Comprehensive Psychiatry, 16, 43–47.

van Putten, T., & Marder, S. (1987). Behavioral toxicity of antipsychotic drugs. Journal of Clinical

Psychiatry, 48(Suppl.), 13–19.

Paxil/Seroxat/Aropax (Paroxetine) : “Question Of Drug’s Label Goes To Trial…”


http://www.chicagolawbulletin.com/paxil-2-16-16.aspx

Question on drug’s label goes to trial

paxil-2-16-16,ph02

James B. Zagel
Law Bulletin staff writer

A federal judge has again declined to throw out a lawsuit accusing the maker of the anti-depressant Paxil of liability in the suicide of a Chicago lawyer who took a generic version of the drug.

In a written opinion last week, U.S. District Judge James B. Zagel rejected the argument that the negligence claims brought under Illinois law by Stewart Dolin’s wife are pre-empted by federal law.

Wendy Dolin filed the suit in Cook County Circuit Court, and GlaxoSmithKline (GSK) removed it to federal court under diversity jurisdiction.

The suit maintains the labels on Paxil and its generic version are false and misleading because they failed to warn of an increased risk of suicide in adults over the age of 24.

In a motion for summary judgment, GSK argued such a warning is pre-empted by the Federal Food, Drug and Cosmetic Act.

Zagel didn’t see it that way.

A failure-to-warn claim is preempted by federal law, he wrote, citing Wyeth v. Levine, 555 U.S. 555 (2009), only if there is “clear evidence” the U.S. Food and Drug Administration would not have approved the warning the plaintiff alleges is required by state law.

GSK presented no such evidence, Zagel wrote.

In 2007, he wrote, the FDA invited GSK to discuss the option of keeping language on Paxil’s label warning of the possibility of an increased risk of suicide or suicidal thoughts in adults.

GSK didn’t take the FDA up on that invitation, Zagel wrote.

GSK, he wrote, did not ask for a formal meeting with the FDA and did not ask to include additional language on the label concerning Paxil’s possible effect on adults.

Under those circumstances, GSK failed to meet the “demanding burden” of showing it would have been futile to seek permission from the FDA to add an adult suicide warning on Paxil’s label, Zagel held.

Wendy Dolin is represented by attorneys who include R. Brent Wisner of Baum, Hedlund, Aristei & Goldman P.C. in Los Angeles.

The lead attorney for GSK is Alan S. Gilbert of Dentons U.S. LLP.

Neither attorney could be reached for comment.

In 2010, Stewart Dolin killed himself by leaping in front of a Chicago Transit Authority train at the Blue Line station at Washington and Dearborn streets in the Loop.

Dolin, 57, was a partner in Reed, Smith LLP.

He had started taking a generic version of Paxil, the brand-name version of paroxetine hydrochloride, six days before he committed suicide.

In addition to alleging the warning on the paroxentine label was inadequate, Wendy Dolin contends GSK concealed and manipulated data concerning the drug.

GSK wanted to obscure the fact that paroxetine carries a 6.7 times higher risk of suicide in adults who take the drug compared to those who take a placebo, Dolin contends.

In 2014, Zagel dismissed all claims against Mylan Inc., which made the paroxetine taken by Dolin.

But he held GSK must face claims under Illinois law of common-law negligence, negligent misrepresentation and product liability based on a negligence theory.

In the 2014 opinion, Zagel conceded GSK did not manufacture the paroxetine taken by Dolin.

But the federal Hatch-Waxman Act requires that a generic drug’s design and warning label must match those of the name-brand drug, Zagel wrote.

Therefore, he held, the brand-name maker must in some circumstances face claims based on the warnings on the generic version’s label.

In last week’s opinion, Zagel declined to reverse his 2014 ruling.

Noting that GSK and Wendy Dolin plan to call expert witnesses to the stand during the trial, Zagel also declined to hold that the Paxil’s label is adequate as a matter of law.

And Zagel rejected arguments that the doctor who prescribed Paxil for Stewart Dolin knew of the drug’s risk and, therefore, GSK could not be liable in Dolin’s suicide.

The doctor’s testimony suggests he didn’t know of the increased risk of suicide in adults over 24, Zagel wrote, and he relied on the 2010 Paxil label before prescribing the drug.

The suit is to go to trial on Sept. 19.

Zagel issued the opinion Thursday in Wendy B. Dolin v. SmithKline Beecham Corp., No. 12 C 6403.

Seroxat: GSK’s ‘Thalidomide Moment’?….


I have long been calling the Seroxat scandal ‘the mental health thalidomide’… I even sub-headed this blog with ‘Seroxat the mental health thalidomide’, when I set it up 9 years ago…

In the following article, by academic Redmond O’ Hanlon, Redmond discusses the implications of GSK’s notorious Seroxat Study 329..

Redmond calls this ‘Psychiatry’s Thalidomide Moment’

I think it was GSK’s thalidomide moment..

Psychiatry has had its thalidomide moment regularly since its inception..

The scale of harm which psychiatry has caused for over a century now is colossal..

Seroxat caused death and destruction on a much larger scale than Thalidomide, and GSK’s 3 Billion dollar Fine (see whistleblower Greg Thorpe’s complaint to the Dept of Justice here) lists endless pages of harm to consumers from several drugs over decades..

GSK have their thalidomide moment regularly too, at least once a year it seems.. Myodil, Seroxat, Avandia, Pandemrix, Wellbutrin…

..they really do live up to their nick-name of ‘Global Serial Killers’..

 

 


http://www.madinamerica.com/2015/11/study-329-psychiatrys-thalidomide-moment-part-2/

Study 329: Psychiatry’s Thalidomide Moment, Part 2

Nobody has retracted or apologized for a study that was an academic disgrace—but a marketing coup for GSK—which may well have caused untold numbers of deaths, suicide attempts and irreversible anguish to myriad families. Can we stand idly by when we’re told that it “accurately reflects the honestly-held views of the clinical investigator authors who do not agree that the article is false, fraudulent or misleading.”? What is the current market value of the honestly-held views of people who tell lies?

I’d like to reflect on a few major aspects of Study 329 and the recent BMJ restoration study (RS) which raise fundamental ethical issues, and which pose some theoretical problems or raise other important issues which haven’t yet been scrutinized. And, by counterpointing Paxil against Thalidomide, I shall suggest that a seismic cultural shift has made studies like Keller’s almost inevitable.

1. Ethics and Academic Integrity

Study 329 forces us to confront the ethical question once again, before it’s too late, and question the claim that the investigators were chosen only for their expertise, their interest in the subject and their capacity to recruit volunteers.  Might they not have been in the pay of GSK, or have been friends, ex-students or colleagues of people like Biederman, Keller, Krystal or Nemeroff? Or chosen for their commitment to drug solutions, regardless of awkward research findings, in line with the FDA which wrote at the time that there may be negative findings even in trials of drugs they know really work? Even at the initial stages, then, there was plenty of room for manoeuvre, allowing GSK and its (paid?) investigators to take advantage of a fuzzy diagnostic category, to cherry-pick the subjects most likely to produce favourable outcomes and to discount the gravity or relative severity of an adverse event if it suited their purposes.

The sociopathic lack of remorse and moral consciousness shown by GSK, Keller, et al., became most shockingly apparent early on, in GSK’s serial re-writing and occlusion of troubling data — designed to stop negative results leaking out to doctors, the public or their sales staff. In fact, a GSK internal memo showed that the company knew that their studies had failed to demonstrate efficacy since at least 1998; and in 2003 the MHRA revealed that GSK’s own studies showed that the drug actually trebles the risk of suicidal thoughts and behaviour in depressed children. Outside the Holocaust, I’ve never come across a more chilling, amoral or sociopathic memo than the one they sent out to senior management, clarifying their decision “to effectively manage the dissemination of these data in order to minimize any potential negative commercial impact…It would be commercially unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine.”  In the same cynical vein, an email from a PR executive working for GSK said: “Originally we had planned to do extensive media relations surrounding this study until we actually viewed the results. Essentially the study did not really show it was effective in treating adolescent depression, which is not something we want to publicize.”

An important ethical barometer is the prevalence of authors’ conflicts of interest (COIs), though it is really a wider, cultural, problem, for a large majority of medical and science journals in the world have no COI policy. While we weren’t told about the authors’ COIs here, we now know those of Keller, Ryan, and of GSK employee Mc. Cafferty, whose affiliation was hidden. We know, for example, that Shelley Jofre sent emails to Dr. Ryan in 2002 asking questions about the safety of Paxil, whereupon this “independent” researcher forwarded them to GSK, asking for advice on how to respond to her! We know also, thanks to Peter Doshi, the extent to which Karen Wagner was beholden to BP. I have since followed up her case: it beggars belief.  Hunting down the COI hare of the other “authors” could bring to light some very damning evidence indeed.

The prevalence of ghostwriting is another disturbing example of ethical indifference: David Healy, who has monitored this phenomenon rigorously for years, estimates that up to 50% of apparently serious academic psychiatric studies are ghostwritten. Could this be a devious way of getting around the ban on off-label promotion?

The rampant, unethical ubiquity of ghost writing has sullied the reputation of numerous academics and their institutions in the U.S. Hannah Arendt’s reflection is apposite here: “When all are guilty, no one is; confessions of collective guilt are the best possible safeguard against the discovery of culprits, and the very magnitude of the crime the best excuse for doing nothing.” Here, however, we have no confession of collective guilt; not surprising, since guilt implies a minimal moral conscience, which was so rare here and among Chemie-Grünenthal’s (C-G) top brass in the thalidomide tragedy, some of whom had seen active service in the camps, and most of whom had impeccable Nazi credentials. This brings to mind those studies some years ago showing that a large proportion of industry CEOs could be classified as sociopaths: another indicator of a huge cultural shift. Are we now simply facing the inevitable consequences of rampant neo-liberal economics?

We could of course argue that this entire affair could be reduced to just one issue: is there any justification for ghost-written academic studies, especially when they have serious safety implications? If it is deemed to be professionally acceptable, then the “authors” of Study 329 have committed no sin at all: it’s just par for the course. After all, PLoS Medicine, which has been leading the charge against ghostwriting, found that only 13 of the top 50 medical schools in the U.S. have a policy that prohibits it.

At a 2011 U. Toronto conference on ghostwriting, Trudo Lemmens, a law professor, said that biomedical ghostwriting is a public health issue needing serious attention, since erroneous use of pharmaceuticals is a leading cause of hospitalization. Many studies, like Keller’s, contribute to that by hiding adverse events, negative data, and over-emphasizing benefits, so academics fronting such studies are responsible for any ensuing prescriptions and harms. Yet there seems to be no backing in law for those wanting to hold academics legally and professionally accountable: ghostwriting is perfectly legal, widely practiced yet officially considered unethical, so universities are nicely protected when they routinely protect shady researchers, who bring them prestige and large research grants. McGill, though, showed commendable rigour and oversight in the Sherwin/Wyeth case.

Doshi and Healy have no doubt that Study 329 was ghostwritten, but I’m not yet absolutely sure about this, though the circumstantial evidence is overwhelming. Keller’s recent letter defending his study and criticizing the RS does indicate that the “authors” were centrally involved at all stages of the study. Could they be forced to take an oath on this, as was Sally Laden? I’m still very unclear about which authors knew what, if anything: the much- compromised JAMA tried, unsuccessfully, to find this out when first offered the article. Keller’s slippery filmed statements and his facial language made me very suspicious indeed, as he repeatedly dodged interviewers with statements like: “I don’t remember matters like this…I never read such tables.”

However, let’s now suppose it wasn’t ghost written, then Keller has painted himself into an inescapable corner, since the only excuse he could proffer for producing scholarly work that drew conclusions contradicting the raw data was that it was, in fact, ghost written. Either that or they produced scholarship that would not have been accepted from an undergraduate, but was accepted by the editor of a prestigious journal who brushed aside THE JOURNAL’S OWN REVIEWERS’ DEEP RESERVATIONS about the study.  Why?

2. Pseudo-science, Lies, Damn Lies, and Statistics

Another ethical casualty of Study 329 was peer review, a protocol designed to guarantee the integrity, independence and rigour of published scholarship: JAMA followed the protocol strictly, and rejected the study, but JAACAP did not. How did it get away with so few official criticisms or sanctions? The story behind the editor’s ultimate acceptance of it could prove very incriminating, and throw up even more serious questions about academe’s failure to uphold minimal standards by publishing a labyrinth of lies, half-truths and lies by omission. The intellectual dishonesty displayed here by members of a prestigious Ivy League university is a bloody blot on the escutcheon of American academic integrity. Standards like this in very high places should not be tolerated by any academic community worth its salt.

The RS also highlighted an area which is rarely discussed: statistical analysis. We have become hung up on whether the results of a trial had statistical or clinical significance, but this study reminds us of the value of patient narratives, “merely anecdotal” reports and descriptive statistics, as did the thalidomide tragedy. Here, the commitment to descriptive statistics was abandoned, probably because they might have allowed non-specialists to make judgments and informed decisions, whereas more sophisticated techniques offered a smokescreen to hide behind for years, thus allowing billions to accrue. How many of us are sufficiently qualified to evaluate what the statisticians tell us, and how they tell it?  Unsurprisingly, GSK told us that they employed the best ones here: this may well have been the only true statement they uttered. It was in their interest to hire the top people, pay them a fortune and make it clear that, without making fools of themselves professionally, they should choose designs, protocols and methods of analysis likely to give the required positive results.

Jureidini’s team forces us to radically critique another untouchable: RCTs, whose status, integrity and even utility must now be thrown into question. Following Breggin, Cohen, Doshi, Harrow, Healy, Kirsch, Moncrieff, Timimi, Whitaker et al., we RCT sceptics now have much more precise ammunition to fight with. In their wake, can we continue to have faith in any previous RCTs and meta-analyses when so many negative trial results are never published and when fundamentals like blinding and adherence to protocols are so flagrantly flouted? Is this just the tip of a very large, murky and treacherous iceberg? After all, Study 329 was published in a top journal, yet deviated from the original protocols, added several new outcome measures, sometimes after un-blinding, and drew conclusions directly at odds with their own findings. In particular, I am deeply suspicious about its level of sustained adherence to blinding protocols.

Over the years, we have had many scandalous instances of unethical manipulation which allowed BP an easy ride. Keller et al. gave us an egregious example of this when they disbanded reliance on Hamilton, but never registered the change, blithely declaring that since the profession had moved beyond Ham-D between 1993 and 1998, they needed to look at other more appropriate measures! As we say in Dublin: ”Pull the other one, it has bells on it!” I know of no evidence that he was right, and their unseemly scratching around for scales, criteria and about 20 new secondary outcomes that might show Paxil in a more favourable light was sad, desperate, even comical.

In short, we’ve had many reasons to be extremely sceptical of RCTs and critical of the uses to which they have been put: Study 329, for example, was merely a super-lucrative advertisement for a dangerous, addictive drug with doubtful benefits and numerous toxic side-effects. (In 2002 over two million paediatric Paxil prescriptions were written in the USA alone, just in time to beat the patent deadline.) Now whereas the law, the FDA and blind faith in RCTs bought an awful lot of time for GSK to make many billions unimpeded in subsequent years, a modest number of academic articles and individual “anecdotal” reports from doctors between 1958 and 1961 stopped thalidomide in its tracks by 1962. They didn’t hang about too long in those days: one critic was scandalized that C-G knew for six whole weeks of the dangers posed by thalidomide!

The RS, then, may well deal a mortal blow to our naïve faith in academic integrity, our bedazzlement by RCTs, and to our easy acceptance of them as gold-standard benchmarks of truth and rigour. It should, at the very least, put them in their place as one potential, yet fallible, tool in the arsenal of psychiatry, but one that should never be allowed to usurp the centrality of the empathic, dialogic relationship between a singular patient and healer, nor the full story of individual suffering, which is obfuscated by algorithms and statistical averages.

On the other hand, the RS might also, paradoxically, provoke a more positive, nuanced view of RCTs, suggesting that some modicum of scientific respectability could be maintained, but NOT IN THE PRESENT VENAL CULTURE: Jureidini et al. have shown us what they might yield if carried out rigorously by top independent researchers putting in Herculean work for no financial gain: had their study appeared in 2003 many wasted billions and many, many lives might have been saved. But how often are we going to get such a highly qualified, deeply committed, hard-working group together in the present climate, with its routine financial inducements? Should we not, perhaps, use the thalidomide case to reconsider the value of strong, repeated “anecdotal” pointers, thus emphasizing individual stories of psychotropic drug use and the withdrawal therefrom? David Healy, Luke Montagu and James Davies have given us a very strong lead in this domain.

Another problem hovering over, but not addressed, by both studies is that of causality: in psychiatric and neuroscientific discourse there’s a lot of slippery semantic skating going on – “linked to,” “associated with,” ”implicated in,” “correlated with,” and the like, but rarely “caused by.” This is not always helpful, but it does bespeak an understandable and judicious reluctance to assign one cause to any outcome.  The Study 329 authors cleverly exploited this difficulty when they tried to minimize serious adverse effects related to treatment by declaring that “causality cannot be determined conclusively.” A single cause for any illness can rarely be proven conclusively – even in cancer, as a number of commentators have pointed out. Thalidomide, however, does appear to have been the sole cause of all those awful deformities; but even in a case like PKU, which is habitually deemed to have a purely genetic aetiology, the gene will not express itself if rigorous environmental controls are put in place – in this case, diet.

Now while it seems clear that judges, biomedical academics and psychiatrists have grossly underestimated antidepressants’ (ADs) contribution to suicidal behaviour, it is also possible to overstate the case by insisting that a given SSRI caused violent, murderous or suicidal behaviour, thus negating the potential impact of other confounding variables. Yet some, but not many judges, taking the advice of people like Peter Breggin and David Healy, have declared that an AD like Prozac had indeed induced a murder.  But, pace both of these great fighters, I’d suggest that legal sanctions would be far easier to obtain if we focussed not on a conclusive single cause for a violent act, but on the very high risk factors associated with a given SSRI and on the full personal and contextual story.

3. The Matter of Suicide

In the opening of The Myth of Sisyphus, Camus argued that suicide is the only serious philosophical question, but for many, suicidal ideation (SI) is a dangerous by-product of SSRI consumption; a serious adverse effect. And further, SI means different things to different researchers.  For some, it is a particular preoccupation with suicide, ranging from regular random thoughts, to more sustained and frequent thoughts of suicide. For others, however, SI includes suicidal gestures or behaviours such as the planning or rehearsing of the act, incomplete attempts, or more serious attempts designed to fail. Even the MedDRA confuses the issue by coding suicidal ideation OR self-harm OR attempted suicide as suicide events. The RS rightly criticizes Keller for using the term “emotional lability” to fudge the severity and differences in suicidal behaviours, but have they not also engaged in some fudging by lumping suicidal thinking and events under one heading, “suicide-related adverse events”?

There is too much fuzzy thinking here: surely logic and scientific rigour oblige us to clarify our terms and avoid assigning the same weight to SI and clear suicide attempts, since most people who have suicidal ideation do not go on to end their lives, even though it must be considered a (low?) risk factor for suicide? To put this in context, it was estimated that in 2008-9 over 8.3 million adults aged 18+ in the U.S. reported suicidal thoughts in the previous year, but of these, only one adult in 140, 60,000 people, actually took their own lives. SI does not usually mean that someone wants to die, but that s/he does have a desperate need to express her/his hopelessness, impotence, overwhelming pain or collapse of meaning. It may often be a natural strategy employed in a hopeless situation: an imaginative rehearsal or symbolic expression of entrapment in the reptilian freeze response; of the impossibility of fight, flight or social engagement, to put it in terms of Polyvagal Theory.

I’m suggesting, then, that we must beware of falling into the trap of dramatizing or pathologizing something that may be absolutely normal, even healthy, in certain circumstances: for example, if one is homeless, disadvantaged or marginalized, living in unbearable social conditions, or trying to deal with overwhelming loss or failure the lack of SI would surely be a highly dissociative move.

Pain, danger and thoughts of suicide often attend the birth-pangs of any major life transition or change in status, as it did for Tolstoy and J.S. Mill. (See James Davies’ fascinating book, The Importance of Suffering.) Camus’s Meursault normalizes suicide  by reminding us that everyone at some time has wanted to kill the one s/he loves: for adolescents needing to separate and carve out their own identity such thoughts are routine, healthy, and not necessarily caused by SSRIs. And for them SI can be one way of managing the maelstrom of hormonal turmoil, passionate intensity, emotional lability and high-risk behaviour attending the scary transition from childhood to adulthood. It may simply well be a way of saying that s/he sees no meaning in life and cannot go on this way any more, especially at a time of collapse in traditional values.

We need to remember, too, that modern adolescence, bereft of mentors, is a particularly fraught, unstable time, in which risky behaviour is far more common than in childhood or adulthood; one in which accidents are the main cause of death, followed by suicide, regardless of any SSRI consumption. (See Sarah-Jayne Blakemore’s research on risk-taking behaviour in adolescents.) For example, in one recent case it became clear that a vicious racism had fueled multiple murders in a local school. In another, a recent school killer’s notebooks showed that he was in a state of absolute despair because doctors had told him he was condemned to live with “a broken brain” for life.

However, well-documented adolescent suicide attempts do have to be taken very seriously, even though they may well be just last-ditch screams for help or understanding: after all, David Healy and others point out that for every eleven suicide attempts there’s one actual suicide.

I believe, then, that it is important to de-emphasize and downgrade SI since the term is used too loosely and can a have a positive valency. Why not confine the term solely to thoughts, and prioritize clear suicidal behaviours? And, taking into account the wider cultural framework, would it not make more sense for judges and researchers to focus on the individual contexts and narratives subtending acts of serious self-harm, clear suicide attempts and very uncharacteristic acts of violence? Drug are usually part of a much bigger story, which we neglect at our peril.  Why not, then, let the law get on with assessing the strength of the circumstantial evidence and decide whether a given drug is a major contributor to a suicide beyond any reasonable doubt?

4. Neo-liberal Culture

Martin Keller recently made the point that since nobody has been able to pin anything on the authors, there’s obviously nothing to apologize for. The terrible thing is that he’s right: they have merely acted in a way that is condoned by academic journals, the FDA and the universities; sanctioned by the psychiatric establishment and the wider culture which makes it so easy for negative findings to run for cover, since there is no firm regulatory obligation to report all the results from clinical trials. In this case, Brown is in the dock, but numerous U.S. academic establishment have been regularly shamed, even though a few of them, like Harvard, have had the courage and integrity to come clean in similar cases, so why not Brown, whose officials conveniently lost some vital incriminating data? (Precisely the same thing happened with a vital incriminating registered letter at the C-G thalidomide trial.) Harvard did take some nebulous action against Biederman et al., but only when the scale of the deceit had become too blatant to hide. It is quite shameful that most U.S. universities routinely offer no comment when the media or people like Senator Grassley ask the tough questions about questionable research or COIs. Indeed, Grassley has said that they seem incapable of monitoring the COIs of faculty. Like the all-powerful gun lobby that even Obama can do little to tame, Marcia Angell’s 800-lb. gorilla has run amok, and thumbs its nose with impunity at the helpless Sorcerer’s Apprentice. And at all of us who protest so loudly and so often. But is this enough? Do the times not demand more concrete, radical action?

Is Study 329, then, not just one more shocking example of the mercantile values and the druggy doxa that permeate our entire culture? Obama’s choice when appointing the new FDA director is a stark incarnation of just how bad things are. So, before we all get too righteous and complacent we mustn’t forget that JAACAP, GSK, Keller et al. are simply following the ethos of our culture in which ethics and transparency have been all but abandoned, even at the top. Earlier this year, Scott, Rucklidge and Mulder studied the adherence, from 2009-13, by the editors of the five leading psychiatric journals to their own pious protocols of oversight and integrity, concluding that “most trials were either not prospectively registered, changed POMs or the timeframes at some point after registration or changed participant numbers.” When such oversight is so loose at the top, to whom do we turn for safe, rigorous research and unbiased guidelines? Quis custodiet ipsos custodes when they countenance criminal acts?

The Study 329 affair, then, underscores the fact that there is strong, but implicit, cultural permission given to BP and amoral academics for their chicanery since trial periods are so short, and post-marketing surveillance so weak and random. Our modern blind-eye culture has no problem with FDA laxity, blatant academic corruption and an increasingly perfunctory oversight by Congress and the law which permits direct-to-consumer marketing and off-label prescription, which in turn allows BP to profitably dispense with honesty, science or FDA approval.

Counterpointing the thalidomide with the Paxil affair, then, helps us to highlight a monumental shift in culture and values that lies very deep in the neo-liberal psyche, transcending Big Pharma, the universities et al. In the thalidomide case, the culture of the 60s enabled the remarkable integrity, rigour and persistence of the FDA’s Frances Kelsey who seems to have been fully backed by the FDA directorate, though one historian of the FDA wrote that she encountered some opposition there. And where she was supported by the wider culture, which subsequently lavished awards and encomia on her, our culture both encourages and rewards the likes of Keller et al. So in 40 years the 1962 amendment, designed to ensure the efficacy and safety of drugs, was emasculated, abused and disempowered by Big Pharma PR and cynical academics. Had thalidomide arrived in 1994 and been researched by such people, the laxity of the FDA, enabled by an ethics-free drug culture, would likely have ensured its continued presence on the market for years, producing millions of deformed babies facing early death or wrecked lives. Fortunately for mothers and new-borns back then academics had integrity: and the meteoric rise of BP power, allied to the prestige and often spurious truth-value of RCTs, was still some way off. Thus a small number of early academic studies, often in the BMJ, and many “merely anecdotal” reports, succeeded in ousting the drug before it got into its stride.

But, once again, what we’re really talking about here is a seismic cultural shift, over 40 years, which is underwritten by government and the law; one which finds no place for ethics, which favours permissive drug regulation, and a neo-liberal ethos in psychiatric practice, academia and the press.

Redmond O'Hanlon

Redmond O’Hanlon is an academic who has taught university courses in Ireland, the U.S. and Oxford, where he wrote his doctorate. He is at present tidying up the final draft of a book  which attempts to bring some insights from the worlds of psychology, philosophy and the arts into critical psychiatry, with special emphasis on the importance of narrative, and on the dangerous fantasy of psychiatric diagnoses. His particular interests are depression, ADHD, trauma, the so-called personality disorders – and the greatest scam of them all, “schizophrenia.”