Category: paroxetine

Just Another Paroxetine (Paxil/Seroxat) Death…


http://www.times-series.co.uk/news/14821695.Prescription_drug_s_side_effects_contributed_to_woman_s_sudden_death/

Prescription drug’s side effects contributed to woman’s sudden death

The Old Court House, Hatfield

The Old Court House, Hatfield

1 day ago / Matthew Lennon

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A woman left weakened by alcohol addiction and painkiller overuse died as a result of the side effect of an anti-depressant, an inquest heard.

Ann Marie Walsh, 46, was found in her Allum Lane home, in Borehamwood, by police on December 16 last year.

Concerns had been raised by her brother after he had been unable to contact her for a couple of days, and found that his key would not work in her front door.

After climbing a ladder and looking in through the first floor window, he saw a shape on the floor of the hallway.

He alerted police, and when officers broke in they found Ms Walsh showing no signs of life. She was confirmed dead at the scene.

An inquest at the Old Court House in Hatfield on Monday heard that having battled depression and anxiety for a number of years, Ms Walsh developed alcohol dependency as a result of work-related stress.

The inquest also heard she had a history of overuse of co-codamol and paracetamol.

She attended meetings at Spectrum Hertfordshire – a drug and alcohol recovery service – and was admitted to Watford General Hospital following an overdose of co-codamol in May 2015.

Two bags of anti-depressant drugs were found by a chair in her living room by police, however a post mortem found no traces of anti-depressants in her blood, according to Dr Mohamid.

It was concluded that, in the time before her death, Ms Walsh was taking the drugs purely for medicinal reasons.

Dr Mohamid told the inquest he believed Ms Walsh collapsed after experiencing a “sudden cardiac death”.

One of the anti-depressants she had been prescribed was Paroxetine, a known side effect of which is cardiac arrhythmia, more commonly known as an irregular heartbeat.

Deputy coroner Graham Danbury concluded that Ms Walsh died “as a result of a known side effect of a prescribed drug, contributed to by her impaired physical condition”.

Inside the 11.9 Million Dollar Seroxat/Paxil Induced Suicide Case..


$11.9 Million Paxil Suicide Verdict: The Inside Story

No one expected a very large award, let alone $11.9 million, in this suicide malpractice case involving the antidepressant Paxil (paroxetine). The jury verdict on September 15, 2016 was gratifying and encouraging (Family of Pennsylvania jail suicide victim awarded $11.9M$11.8M Federal Medical Malpractice Verdict For Prison Inmate’s Suicide). It demonstrates that the judicial system and the public are becoming increasingly aware of the hazards of psychiatric drugs, including their capacity to make people behave in ways that are harmful to themselves and others, and contrary to their past behavior and character.

Great success seemed unlikely in this case. To begin with, suicide malpractice suits are very difficult to win. Juries understandably want to hold people responsible for their behavior when they kill themselves. I was going to testify that a single dose of Prozac 30 mg was the main cause of his suicide, a conclusion that other experts would vigorously challenge.

In addition, the case was in an area of the country where juries are conservative about giving monetary awards to plaintiffs. It was in the U.S. District Court for middle Pennsylvania in the city of Scranton.

Juries also tend to look askance at claims made on behalf of people in jail.  Mr. Mumun  Barbaros, the deceased victim, was in his fourth day of incarceration, awaiting release on bail. The judge did not allow the jury to know the nature of his alleged crime or the charges against him, and I was not permitted to comment on them. If allowed, I would have testified that Paxil-induced disinhibition drove him to vandalize the property of a man in a competing business.

Some people are also less sympathetic to naturalized citizens with strong ties to their countries of origin. Mr. Barbaros was a Bulgarian who became a citizen, but his wife and children spent only part of the year with him and he sent back large amounts of his earnings from his tavern to his extended family back home.

Finally, the case had scientific complexities that the jury had to understand.

The defendants were the independent healthcare provider to the jail, PrimeCare, and several of its personnel or contractors assigned to the jail. Mr. Barbaros had been taking Paxil for anxiety for many years, along with the sedating antidepressant trazodone to help him sleep.

At the time of his arrest, Mr. Barbaros reported that he needed his medication.  Due to a series of errors upon the part of the healthcare personnel, his request for medication went unfilled for four days.  By the second and third day, Mr. Barbaros develop headaches and hypertension, and his chronic stomach problem worsened, but no one attributed these symptoms to withdrawal. However, his intake evaluation and contacts with healthcare providers documented an absence of suicidal thoughts and revealed no great distress.

When the staff finally confirmed Mr. Barbaros’ medications, a licensed practical nurse (LPN) from the jail phoned the psychiatrist on call and asked him to prescribe the Paxil 30 mg and trazodone 100 mg. The LPN did not offer the doctor any information about Mr. Barbaros, such as his age, the reason he was taking the medications, how long he had been taking them, and how long he had been without them in jail. The psychiatrist, in turn, did not ask the nurse any questions, but simply authorized the drugs.

I testified that the psychiatrist’s actions were worse than practicing medicine negligently—he was not practicing medicine at all. He was more like a vending machine. I further testified that this was callous disregard, especially since he admitted to knowing that the drug had dangers associated with it, including suicide, and yet asked no information about the patient, did not come in to see him, and ordered no special supervision.

Following his first morning dose of the Paxil, Mr. Barbaros was seen for a routine evaluation by a staff psychologist in the mid-afternoon. At this point, Mr. Barbaros was drastically changed. He was no longer a man who conversed easily and showed no signs of significant stress, anxiety or depression. According to the psychologist’s deposition, Mr. Barbaros now looked extremely anxious and like a “cornered rat,” spoke very little, made poor eye contact, and looked hunched over and withdrawn. In the psychologist’s scantily written report, his only diagnosis was “rule out depression,” an entirely new diagnosis for Mr. Barbaros.

I attributed these drastic changes in Mr. Barbaros’ condition to the impact of the large dose of Paxil. The psychologist had not checked to see what medications Mr. Barbaros was taking. He did not check the medical record and therefore did not know that his current severely anxious and withdrawn state was entirely new for him during his incarceration.  He did not ask his patient if he was suicidal.

In my direct examination, I testified that restarting the patient on his regular dose of Paxil 30 mg, despite a hiatus of at least four days without the medication, was a direct cause of the suicide later on the same day. Restarting him on Paxil 30 mg, when most of the drug was out of his system, caused akathisia (agitation with hyperactivity) and suicide. I also found that the doctor and the psychologist were negligent in several other ways, including their failure to evaluate the patient and to order careful monitoring.

I further explained that Paxil (paroxetine) is a selective serotonin reuptake inhibitor (SSRI) antidepressant. All antidepressants can cause suicidal and homicidal behavior, especially those like the SSRIs that routinely cause stimulation or activation, including akathisia, agitation, insomnia, disinhibition, emotional lability, hypomania and mania, and a general worsening of the patient’s condition. Of all the antidepressants, Paxil was the only one to show a statistically significant association with suicide in depressed adults in the short and deeply flawed clinical trials used for FDA approval of the drug.

To back me up, I brought a number of documents, including a 2006 letter from the manufacturer to all healthcare providers admitting to the association between Paxil and suicide in depressed adult patients, and further warning that this risk might apply to patients with other diagnoses. I also brought a copy of the 2006 Full Prescribing Information for Paxil that carried the same warning about suicide in adults, before the drug company got the FDA to delete it in later editions. I had written about the subject of medication-induced suicide in my book, Medication Madness: The Role of Psychiatric Drugs in Cases of Violence, Suicide and Crime.

One of the more dramatic moments in my testimony came on the first series of questions during cross-examination. When I began reviewing the case, I was asked to focus on Mr. Barbaros’ medical record going back approximately six years to the time when his primary care doctor had started him on Paxil 10 mg, apparently without difficulty, and then raised it gradually to 20 mg and then 30 mg. To be thorough, I examined all the remaining extensive medical records and came upon something remarkable buried within them that had previously escaped attention.

The day after his first dose of Paxil 10 mg, Mr. Barbaros became so anxious that he thought he was having a heart attack and sought immediate help at a local medical clinic separate from his primary care physician who prescribed the Paxil. That clinic referred him to a cardiologist on an emergency basis who evaluated him and found no physical disorder. These doctors treated Mr. Barbaros’ anxiety with prescriptions for a benzodiazepine tranquilizer.

Mr. Barbaros had experienced a very severe anxiety reaction to his first dose of Paxil, but it apparently never entered his mind that Paxil was causing it. From the medical record, it looks like he never told the emergency clinic or the cardiologist he had recently started taking Paxil and he never told his primary care doctor, when he returned for follow up later on, that he had been so anxious that he went to a cardiologist and received sedative tranquilizers. It is very common for individuals to fail to realize that their acute psychiatric emergencies are being caused by their psychiatric medication.  I call this phenomenon “medication spellbinding” or intoxication anosognosia.

As a medical expert in a product liability case against GlaxoSmithKline, the manufacturer of Paxil, I had discovered from the company’s secret files that Paxil frequently caused severe psychiatric adverse reactions during the first few doses. I had published an article about this in the hope of alerting people to the risk. This earlier work of mine enhanced the credibility of my discussion.

So… when I was asked at the beginning of cross-examination to explain why Mr. Barbaros would have such a bad reaction to being restarted on Paxil since he never had a bad reaction to being started many years earlier, I had an unexpected answer. I could reply and document from the medical records that, in fact, he had a drastic psychiatric reaction to the original 10 mg dose but no one recognized that it was related to the Paxil. The defense attorney was so flummoxed by my revelation that he never even asked to see the relevant medical records. The cross-examination then went on for an unexpectedly long time, requiring me to come back a second day. The defense probably was hoping that the jury would forget the revelation I had disclosed in the first few minutes.

The jury not only found that PrimeCare and several of its practitioners and staff had been negligent, they further concluded that the company and most of the individual defendants acted with deliberate indifference to Mr. Barbaros’ medical needs.

Despite a vigorous challenge by the defendants’ attorneys, the judge qualified me as an expert in psychiatry, psychopharmacology and the specific drug Paxil. In the trial, other experts testified for the plaintiffs concerning the nursing care and administrative policies of the healthcare provider, as well as the violent method of Mr. Barbaros’ death by gagging himself.

The jury award included $2.8 million for negligence, $1.06 million for federal deliberate indifference and $8 million for punitive damages. The case is Ponzini et al. v. Monroe County et al., case number 3:11-cv-00413, in the U.S. District Court for the Middle District of Pennsylvania. The attorney for the plaintiff was Brian Chacker of Philadelphia. He worked extraordinarily hard and with great diligence on the case.

I do believe that the success of this case reflects greater awareness within the public and the judicial system concerning the dangers of psychiatric drugs.

GSK’s Patrick Vallance Casually Glosses Over The Deaths Of Kids From Seroxat (Paxil/Aropax)


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Patrick Vallance: “Alltrials is not pushing for that level of data availability and neither are we”

“If I’m a shareholder, which I am, I don’t want a company to be hiding something that might come to light”…

Yesterday I posted an interview with GSK’s CEO Andrew Witty. In that interview Witty was very clearly (and visibly) uncomfortable when questioned by BBC’s Newsnight’s Evan Davis about GSK’s bribery scandal in China and their corruption of doctors.

Andrew Witty’s awkward body language said it all.

See here for more


In an interview (see Audio above) with BBC 4’s ‘Life Scientific‘ radio series today with Jim Al-Khalili, GSK’s (head of R and D and admitted GSK share-holder) Patrick Vallance, is asked about Seroxat harming kids, and his response is really very unsettling. He casually glosses over the harm to (potentially) millions of kids from GSK’s dangerous Paroxetine (Paxil/Seroxat/Aropax) over the past 15 years in a very matter of fact way, as if he was discussing a certain flavor of tooth-paste or the symptoms of a very mild head ache.

Vallance says (when asked about Seroxat killing kids)  that:

“It’s inevitable that side effects things will occur from time to time”

“I’d rather know them than not know them”

(but isn’t this the whole point Pat- we weren’t warned of the side effects such as suicide, withdrawal and self harm so many millions of people didn’t know the side effects and were harmed by Seroxat- me included- purely on the basis that we didn’t know and were not told about them).

Wow, is that really your answer to the Seroxat scandal Pat? It’s inevitable that people get killed and maimed is it? It’s inevitable that GSK push drugs like Seroxat on under 18’s (when GSK knew from its own studies that Seroxat could harm them). That’s inevitable, all above board and expected is it? Is it all just inevitable really because that’s the nature of the drugs business? Or do scandals like Seroxat happen because of human greed, profit and sociopathic corporate behavior? I’d go with the latter…

It’s inevitable that it might rain tomorrow, it is not inevitable for a drug company to push its dangerous anti-depressant on young people when it knew it might make them kill themselves… How about making sure that your drugs are safe? Now there’s a novel idea Pat…

When asked about GSK’s endorsement of Alltrials GSK’s Pat Vallance admits that the Alltrials agenda is not about access to data at all ( data is the meat of the drugs industry, without access to it we just don’t know the dangers or efficacy of the drugs we take- see study329.org for more). Vallance also spins the well worn GSK yarn that they have been always publishing their trials on the clinical trials register but the truth (and what the GSK spin machine always omits) is that GSK were forced by two separate department of justice investigations into the company which have compelled them to publish trials- they did not do this willingly).

When asked by the interviewer, Jim Al-Khalili : “Is this about making clinical trial data available to all people”?

Pat Vallance responds that: “Alltrials is not pushing for that level of availability and neither are we”

Vallance’s answer is really very telling, and it reveals why GSK were so eager to jump on board the Alltrials/Ben Goldacre bandwagon. Access to data is what is needed here, not access to drug company’s published trials. Alltrials is a red herring, it gives GSK more control, and Ben Goldacre really has a lot to answer for in this regard. However since he seems to be enamored with Witty and Vallance, I won’t hold my breath for him to challenge them anytime soon. (I’ve written about these issues here, and Dr David Healy’s been banging the drum about Alltrials on his blog too- see here).

Furthermore, one of the only ways to get access to the data, is often only through litigation or department of justice investigations etc. People shouldn’t have to wait decades before they know the harms of a drug Mr Vallance. This is not acceptable nor inevitable. Seroxat has harmed immeasurably.  The long term damage hasn’t even begun to be assessed.

Just like Andrew Witty, your attitude towards those damaged by your drugs like seroxat seems to be… “well that’s just tough”..

And your company still makes a profit on Seroxat, it’s still being sold, which means that you and Witty are still profiting directly (and knowingly) from death, human damage, addiction and child suicide…

How nice for you both..

Ugh..

Study 329: Conflicts of Interest (From Dr David Healy’s Blog)


http://davidhealy.org/study-329-conflicts-of-interest/

Study 329: Conflicts of Interest

October, 20, 2015 | Reply

GSK Fails To Warn Customers Of Contaminated Paroxetine (Seroxat/Paxil)


http://www.pharmamanufacturing.com/industrynews/2014/fda-shames-gsk-contaminated-api/

The most strongly worded portion of the March 18 FDA warning letter stated, “We are concerned that your firm does not consider the entry of pharmaceutical waste streams into your manufacturing process a significant deviation with a potential quality impact. In your response to the Form FDA-483, you acknowledged that you should have informed your customers of this incident; however, you did not describe any recent or future communication with your customers regarding the incident to rectify the prior lapse.

GlaxoSmithKline Recalls Batches of Orlistat(“alli”) & Paroxtine(Paxil & Seroxat)


http://www.fortunespharmacy.ie/2014/04/05/seroxat-recall-information-for-patients/

http://www.dailykos.com/story/2014/04/05/1289815/-GlaxoSmithKline-Recalls-Batches-of-Orlistat-alli-Paroxtine-Paxil-Seroxat#

 

may withhold approval of any new applications or supplements listing your firm as an API [active pharmaceutical ingredient] manufacturer.”

Paroxetine is an adult SSRI drug used for several forms of depression, panic, anxiety, obsessive-compulsive disorder, post-traumatic stress, some menopause-related symptoms, etc. GSK said in a statement:

“GSK acknowledges the concerns raised by the FDA and we are recommending a Class 3 recall ― that is a recall from wholesalers ― of certain batches of Paxil/Seroxat containing the paroxetine API supplied by the Cork site that are implicated in the Warning Letter. Based on a medical assessment, GSK considers that there is no increased risk of harm to patients taking finished product manufactured from the implicated batches of paroxetine API.” …The company added that it is currently “reviewing the content of the Warning Letter to assess the concerns raised, in order to develop appropriate Corrective and Preventative Actions. We will be able to comment further once we have prepared and submitted a comprehensive response to the Warning Letter to FDA by April 9.”

Two weeks earlier, Medscape reported GSK’s March 27 recall of “alli” its over-the-counterorlistat weight-loss drug, from U.S. and Puerto Rican retailers, due to customer complaints of bottles containing

“a range of tablets and capsules of various shapes and colors” [and some bottles] were missing labels and had tamper-evident seals that were not authentic. Orlistat is packaged in a labeled bottle that has an inner foil seal imprinted with the words, “Sealed for Your Protection.”
“We have received reports of about 20 bottles purchased by 12 consumers in 7 states: Alabama, Florida, Louisiana, Mississippi, New York, North Carolina, and Texas. We have had no reports of serious side effects,” Deborah Bolding, senior external communications manager, GSK Consumer Healthcare, told Medscape Medical News by email.

On March 26, GSK had issued a consumer alert for alli giving packaging lot numbers and expiration dates (see also Medscape article). The alli website was modified to prominently feature the recall warning, with slightly confusing-looking links to the company press release and to photos of the “authentic” product and the consumer alert.

GSK’s Seroxat Made Children Suidical : Seroxat Study 329 Must Be Retracted and Condemned


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From the Brown Daily Herald…

http://www.browndailyherald.com/2014/04/02/controversial-paxil-paper-still-fire-13-years-later/

SCIENCE & RESEARCH

Controversial Paxil paper still under fire 13 years later

Some say former U. professor Martin Keller’s paper was ghostwritten and should be retracted

By 
Science & Research Editor

Former University Professor Martin Keller published a 2001 paper on the drug Paxil that has allegedly been ghostwritten by GlaxoSmithKline.

Two weeks ago, Edmund Levin and George Stewart, members of the American Academy of Child and Adolescent Psychiatry, sent a letter to the editor of the Academy’s journal, requesting an explanation as to why a controversial study led by former Brown Professor Emeritus of Psychiatry and Human Behavior Martin Keller has not been retracted.

The paper — which details the findings of Study 329 and focuses on the effects of the drug Paxil on adolescent depression — has been continually criticized since its publication in 2001.

While Levin and Stewart have worked to get the paper retracted, Jon Jureidini, a professor at the University of Adelaide in Australia and a member of the nonprofit Healthy Skepticism, has been working with his team to reanalyze the original data and republish the results.

A controversial history

Since its publication, Keller’s paper, which suggests that Paxil is an effective treatment for adolescent depression, has been criticized for being ghostwritten by associates of GlaxoSmithKline — the drug company that makes Paxil.

In 2006, Keller publicly acknowledged that GSK had given him tens of thousands of dollars during and after the time the study was conducted. Keller did not respond to multiple requests for comment for this article.

A Senate investigation in response to a U.S. Department of Justice lawsuit confirmed the presence of ghostwriting in the paper, said Paul Thacker, a fellow at the Edmond J. Safra Center for Ethics at Harvard who participated in the Senate inquiry.

But Rachel Klein, one of the 22 cited authors on the Keller paper and a professor at New York University, said while she thinks GSK played a role in writing the paper, it was not ghostwritten.

Continued research in the years after the article’s publication has suggested Paxil is linked with an increase in suicidal ideation in adolescents, The Herald previously reported.

The study is continually cited in other papers as evidence of Paxil’s effectiveness, Jureidini said. That a fraudulent paper is still cited “really has to be addressed,” he added.

“I think the concern is legitimate,” Klein said. “But I think it is too bad because the paper presents everything. As long as you give the information, you’re not misleading.”

The University has declined to support any efforts to have the paper retracted, The Herald previously reported.

Leemon McHenry, a member of Healthy Skepticism, and Jureidini have written to the University administration to ask for support in having the article retracted, but administrators have refused, McHenry said.

“The University takes seriously any questions about the soundness of faculty-conducted research,” said Marisa Quinn, vice president for public affairs and University relations. “While the University cannot comment on individual personnel cases, it does take appropriate actions whenever such questions are raised… We have effective policies in place, and those policies are consistently applied, although they are confidential.”

Clinical Professor of Family Medicine David Egilman ’74 MD ’78 said though no institution has ever punished a faculty member due to ghostwriting, “It’s a social responsibility to make sure that fraudulent information is not published by faculty.”

Retracting the paper

Levin said he first became interested in Study 329 due to his association with AACAP.

Though 13 years have passed since the publication — and despite the Senate investigation finding the Keller article to be fraudulent — there “still has been no effective action in getting it retracted,” Levin said.

Levin and Stewart’s regional division of AACAP has sent two different letters to Andres Martin, the editor of the journal. In addition to the one sent two weeks ago, the group sent a first letter requesting the study’s retraction.

In response to the first letter, Martin wrote that the paper did not meet the criteria for retraction, Stewart wrote in an email to The Herald.

The group was also informed that AACAP leadership had instructed the ethics committee not to investigate the article, Stewart said, adding that he was not sure why the committee had been “muzzled.”

Martin has not yet responded to the group’s second letter, asking for an explanation, Stewart wrote.

Martin did not return The Herald’s requests for comment.

Reanalyzing the data

Jureidini, along with four team members, is currently reanalyzing the data from Study 329 to “write the paper as it should have been written,” he said.

The decision to do so came in the wake of the British Medical Journal’s Restoring Invisible and Abandoned Trials initiative, announced June 2013. The initiative “calls for third party authors to publish or republish unpublished and misreported clinical trials,” according to a document released by the BMJ.

In the document, the BMJ named Study 329 an “abandoned study” — a study no one is working on but which is “misreported” and has not been corrected or retracted.

Jureidini said he and his team have been reanalyzing the data since late last summer and hope to have a draft completed in the next month.

“What they have found is that the fraud and corruption in the Keller article is far worse than anyone ever expected,” McHenry, who has worked closely with Jureidini, said. Specifically, the paper is far worse in terms of safety and efficacy, he added.

Very few people, including Keller, ever looked at all the raw data, McHenry said, adding that most of this was done by statisticians associated with GSK.

It is “ironic” that his team has looked at the data more than any of the authors of the Keller article, Jureidini said.

Levin and Stewart both said they support the study’s reanalysis. It may “be unrecognizable when Jureidini publishes it,” Levin said.

Jureidini said he hopes the original Keller article will be retracted in the wake of the republished one.

But Klein said she does not think the new results will show the Keller article to be fraudulent.

“I’m all for the data being examined,” she said. “If it is true that the results are very different, that would be a very different situation, but I can’t imagine that that would be the case,” she said.

A clinical perspective

Despite the Keller paper’s suggestion of the efficacy of Paxil, many psychiatrists said they do not prescribe the drug to patients.

Multiple psychiatrists interviewed said Paxil has worse side effects and withdrawal symptoms than other antidepressants and should not be prescribed as a first-line drug.

Allegations of ghostwriting and the role GSK played in Study 329 raise issues related to the relationship between psychiatrists and drug companies.

Study 329 and the Keller article are “a very good soap box from which to talk about the atrociously dishonest and morally unethical things the pharmaceutical industry has done,” Levin said.

Thacker said studies like Study 329 show that psychiatry is not independent from drug companies, and pharmaceuticals have “captured and owned the field of psychiatry.”

“You can’t live with them and you can’t live without them,” said Louis Velazquez, a practicing child and adolescent psychiatrist, referencing drug companies.

Research psychiatrists also rely on pharmaceutical companies to fund their research, said John Fanton, a child and adolescent psychiatrist at Baystate Medical Center and an assistant professor of psychiatry at Tufts University School of Medicine, who was completing his residency at Brown when the allegations about Study 329 arose.

When there is an economic downturn, there is “a legitimate need to identify and access other finding streams,” he said, adding that pharmaceuticals often will provide the most money for research.

But there is an “inherent conflict” between researchers and pharmaceutical companies, because researchers are required to share both good and bad knowledge, and pharmaceutical companies may have different goals, Fanton said.

If the paper is retracted, it will create “ongoing problems” for GSK, Thacker said. “There’s a lot of egos and a lot of money at stake.”

Seroxat (Paxil) Induced Akathisia: Stewart Dolin


http://missd.co/

About MISSD

Stewart Dolin had the perfect life. He was married to his high school sweetheart for 36 years. He was the father of two grown children with whom he had a very close and meaningful relationship. He was a senior partner of a large international law firm, managing hundreds of corporate lawyers. He enjoyed his work and derived satisfaction from cultivating relationships with his clients, as well as helping them achieve the results they desired. He enjoyed travel, skiing, dining, joking around with his family and friends and an occasional cigar. He was 57 years old, and high on life.

In the summer of 2010, Stewart developed some anxiety regarding work. He was prescribed Paxil (paroxetine), a selective serotonin reuptake inhibitor (“SSRI”). Stewart’s prescription was filled with a generic version of Paxil, manufactured by Mylan. Within days, Stewart’s anxiety became worse. He felt restless, had trouble sleeping, even asked his wife to listen to a meditation tape with him (hardly typical behavior). He kept saying, “I still feel so anxious.”

On July 15, 2010, (six days after beginning the medication), following a regular lunch with a business associate, Stewart left his office and walked to a nearby train platform. A registered nurse who was also on the platform later reported seeing Stewart pacing back and forth and looking very agitated. As a train approached, Stewart took his own life. This happy, funny, loving, wealthy, dedicated husband and father who loved life left no note and no logical reason why he would suddenly want to end it all. Neither Paxil nor the generic version listed suicidal behavior as a potential side effect for men of Stewart’s age.

We did not know it then, but Stewart was suffering from akathisia.

MISSD (The Medication-Induced Suicide Education Foundation in Memory of Stewart Dolin) is a unique non-profit organization dedicated to honoring the memory of Stewart and other victims of akathisia by raising awareness and educating the public about the dangers of akathisia. MISSD aims to ensure that people suffering from akathisia’s symptoms are accurately diagnosed so that needless deaths are prevented. A website, the creation of educational materials and support of conferences such as Selling Sickness, will help to raise awareness and knowledge of akathisia and medication-induced suicides. Again, we feel it’s important to note that we are not anti-drug, and recognize that prescription drugs can be positive and life-saving for many individuals. We are for truth in disclosure, honesty in reporting and legitimate drug trials.

If this could happen to Stewart, then it could happen to anyone. MISSD will make a difference.

Akathisia

Akathisia is a disorder, induced by SSRI medications, which can cause a person to experience such intense inner restlessness that the sufferer is driven to violence and/or suicide. It has been said, “Death can be a welcome result.” For reasons related to the strong political and lobbying power of pharmaceutical companies, akathisia is rarely explained as a possible side effect of SSRIs, and medical professionals and the general public know very little of the existence of this disorder.

In fact, the drug lobby would like you to believe that akathisia is simply “restless leg syndrome.” As a result, sufferers of akathisia, as well as the medical professionals with whom they consult, are not able to recognize the symptoms of akathisia and therefore take the steps necessary to stop it. This lack of knowledge has tragically resulted in akathisia sufferers taking their own lives, and leaving behind devastated loved ones.

MISSD is not anti-drug. We know that prescription drugs have been life-saving for so many individuals who struggle with mental health issues. We are for truth in disclosure, honesty in reporting and legitimate drug trials.

What should I do?

If you or someone you know is suffering from the symptoms of akathisia, you should tell the doctor who prescribed the drugs, call 911 or go to the nearest emergency room. MISSD does not give medical advice or counsel (see disclaimer).

According to the FDA:

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms

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IN THE CIRCUIT COURT OF COOK COUNTY, ILLINOIS

http://www.baumhedlundlaw.com/pdf/dolin-paxil-complaint-filed.pdf

Plaintiff Wendy B. Dolin, wife of the deceased, Stewart Dolin, (57-year-old former partner at Reed Smith in Chicago), charges that GSK negligently failed to warn her and her husband of what it knew to be a significant risk of suicide associated with its drug. 

 

 

Hey Hey GSK: The Seroxat Hidden Data Debate Won’t Go Away


http://pharmagossip.blogspot.ie/2013/11/bmj-hidden-data-putting-glaxosmithkline.html

FRIDAY, NOVEMBER 15, 2013

BMJ – Hidden Data Putting GlaxoSmithKline to the test over paroxetine

Cite this as: BMJ 2013;347:f6754
  1. Peter Doshi, associate editor

Author Affiliations

  1. pdoshi@bmj.com

Blockbuster antidepressant paroxetine is no stranger to headlines. The drug is now back centre stage as requests for clinical data from one of its trials are testing manufacturer GlaxoSmithKline’s commitment to full transparency, Peter Doshi reports

When the Journal of the American Academy of Child and Adolescent Psychiatry(JAACAP) published study 329 in 2001,1 its editors could have had no idea that the paper would spark a controversy, not only about the use of the antidepressant paroxetine in children but also about secrecy in clinical trials. It is a controversy that rages to this day and that goes to the heart of recent campaigns to gain access to drug companies’ trial data.

By most accounts, GlaxoSmithKline is leading the pack in its efforts to liberate access to its clinical trial data. It was the first major pharmaceutical company to sign up to the international AllTrials petition calling for all trials to be registered with the full methods and the results reported.2 Whereas companies like AbbVie and InterMune have lodged lawsuits aiming to block access to clinical trial data,3 GSK has forged ahead with a new website enabling third party access to deidentified participant level data “because it is the right thing to do, both scientifically and for society.”4 GSK’s website states that five requests have been approved up to 20 September. None have been rejected. One is under review.

But one group’s request for data is testing the limits of GSK’s commitment to full transparency. Jon Jureidini, clinical professor of psychiatry at the University of Adelaide, is leading a team to reanalyse and republish the results of GSK’s study 329—a randomised, double blind, placebo controlled trial of paroxetine for the treatment of depression in adolescents. For over a decade, Jureidini has been critical of how the study was reported in JAACAP in 2001. In 2003, Jureidini and Tonkin wrote toJAACAP: “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.”5 They noted that “on neither of [the study’s two primary outcome] measures did paroxetine differ significantly from placebo”—yet the Keller et al paper concluded that “paroxetine is generally well tolerated and effective for major depression in adolescents.”1

Jureidini was subsequently contracted to provide expert advice as part of a class action lawsuit against GSK in 2004. Through this legal action, some internal company documents were released into the public domain, and Jureidini and colleagues reported that study 329 had an additional six secondary outcomes specified in the protocol.6 Paroxetine was not more effective than placebo on any of these outcomes either.

TROUBLED HISTORY

Paroxetine was a blockbuster antidepressant, known by its trade names Paxil in the United States and Seroxat in the United Kingdom, and was widely prescribed “off label” for use in children and adolescents. The drug came under heightened attention in the early 2000s, after a decade of rising antidepressant use among youths,7 over concerns about a link between paroxetine and suicidality in children.

In 2003, the UK Committee on Safety of Medicines recommended that paroxetine not be used in children and adolescents for the treatment of depressive illness because of concerns about an increased risk of self harm and potentially suicidal behaviour.  And in 2004, the US Food and Drug placed a boxed warning, its most serious type of warning, on all antidepressants, stating that they increase the risk of suicidal thinking and suicidal behaviour in these age groups.8

In 2012, GSK agreed to pay $3bn (£2bn; €2.4bn) in a fraud settlement with the United States government. In a statement connected with the lawsuit, the Department of Justice declared that “the centerpiece of GSK’s efforts to market Paxil for childhood depression was the GSK funded Study 329,” about which the published JAACAP“article distorted the study results and gave the false impression that the study’s findings were primarily positive, when they were, in fact, primarily negative.”9

Jureidini and colleagues have led a long campaign to compel the journal to correct or retract the article, which was authored by both academics and GSK employees.10Earlier this year, Jureidini presented GSK’s chief executive, Andrew Witty, with a final plea to help correct the scientific record. “Your corporation has so far failed to take responsibility for a published report that has harmed young patients who were prescribed paroxetine on the basis of this misleading article. As the CEO of GSK, you have the opportunity to correct the scientific record. I respectfully urge you to do so,” Jureidini wrote (see data supplement on bmj.com ).

But GSK defended the integrity of the 2001 publication. “GSK does not agree that the article is false, fraudulent or misleading,” John E Kraus, head of medical governance, wrote to Jureidini.

Jureidini has responded by assembling a team to reanalyse and republish study 329. In July they publicly declared their intention to produce a new journal report of study 329, written in accordance with the BMJ endorsed restoring invisible and abandoned trials (RIAT) initiative, which calls for third party authors to publish or republish unpublished and misreported clinical trials.11 The team’s starting place is a trove of over 6000 pages from a previously internal clinical study report written by SmithKline Beecham in 1998 that was forced into the public domain as a condition of a consent order GlaxoSmithKline agreed to in the settlement of a 2004 lawsuit with the New York State Attorney General.12 (SmithKline Beecham and Glaxo Wellcome merged in 2000 forming GSK.) The pages include a report of the trial, the study protocol, statistical analysis plan, blank case report forms, and numerous data tables, which Jureidini’s team will use for its analysis.

But GSK’s public posting of its internal report on study 329 is incomplete, lacking an unknown number of pages containing original case report forms from Appendix H. Jureidini and colleagues have therefore asked GSK for access to the deidentified case report forms and the corresponding deidentified electronic participant level data, “so that we can restore the publication of trial 329 in a fair, complete and publicly transparent way.”

“With regard to the electronic database,” James Shannon, GSK’s chief medical officer, wrote to Jureidini on 11 October, “I would ask that you do indeed submit an analysis plan via the website and sign a data sharing agreement.” Jureidini had initially rejected submitting an analysis plan arguing that “such a plan is irrelevant when restoring a publication where our primary focus is the original analysis plan drawn up and implemented by your own statisticians.” Nonetheless, Jureidini complied, and submitted an analysis plan—mostly a direct copy and paste from the protocol contained in the company’s 1998 clinical study report—placing GSK’s independent review panel in the unusual position of refereeing the appropriateness of the manufacturer’s own analysis plan.

As for the case report forms, GSK initially rejected Jureidini’s request, explaining, “We do not publicly disclose Case Report Forms (CRFs) and we do not provide them to other researchers. Complete CRFs are available to regulatory authorities for audit and for them to assure the integrity of the data sets and CSRs.” However, last week the company suggested a phone call with Jureidini, “to explore with you how we can help with this.”

COMMITMENT TO TRANSPARENCY

GSK’s wavering responses contrast with the many upbeat public proclamations by its executives about the company’s commitment to transparency. “Increasing transparency about our research is a critical area we’ve been pursuing at GlaxoSmithKline for almost a decade,” Shannon wrote in a September editorial in theHuffington Post.13 “We’ve also launched a new website allowing scientists to request access to the very detailed, anonymised patient-level data sitting behind the results of our clinical trials. This will mean independent researchers, with a fresh perspective, can conduct further research which could advance medical science and improve patient care.”

Transparency is “at the core of how we work,” Shannon explains. “People have asked me, ‘what if a new side effect comes to light for one of your medicines? Or what if a scientist discovers that you made a mistake in your research?’ My answer back is ‘why wouldn’t we want that to happen? Isn’t it better that we know? There is always the potential for us to find a better way to do things.’”13

Last month, Witty took it one step further in a television interview with the US Fox News. “We’re not simply going to publish data on trials still to come, but we’re going to go back, and we’re going to publish all the data for all the trials that have been done since the company was formed.”14

Witty’s phrase “all the data” sounds straightforward, but the company’s 11 October response to Jureidini implied that “all the data” would not include case report forms from study 329—or, it would seem, any other study. Nor, it seems, is GSK going to “publish” any of the deidentified patient level data on its new website, if “publish” means to make something public and freely accessible.

CAVEATS

A more careful reading of GSK’s stance is that it believes in what it calls a “closed-access system,”4 in which only approved researchers are permitted to query (but not download) data in preapproved ways. To gain access to GSK’s participant level data, requestors must first submit and have their analysis plan approved by an “independent review panel” and sign a data sharing agreement. A sample agreement posted on GSK’s website indicates that researchers are expected to run only preapproved analyses: “GSK and Researcher agree that GSK will provide the Researcher with access to patient level data from the GSK-sponsored clinical studies listed in Exhibit A for the sole purpose of analysis according to Researcher’s approved research plan (the “Analysis”) attached as Exhibit B and for no other purpose.”15

GSK suggests that such a system is necessary to protect the privacy of research participants. It is not enough to simply remove personally identifiable information from the participant level dataset. “It may be possible to combine deidentified data with other information to identify individuals. To minimize any such risk, our approach will be to provide access to anonymous patient-level data on a password-protected website that has controls in place to prevent data from being downloaded or transferred.”4

This concern is underscored in an editorial, published in the Lancet, coauthored by Patrick Vallance, GSK president of pharmaceuticals research and development, and Iain Chalmers, one of the founders of the Cochrane Collaboration and now coordinator of the James Lind Initiative.16 They write that “the protection of privacy is vital in IPD [individual participant data] analyses,” but point out that the process of deidentification can be carried out so thoroughly as to render the scientific value of the data useless. Deidentify the data insufficiently, and trial participants may be re-identified, violating their privacy. Vallance and Chalmers posit that a “controlled system” of restricted access offers a possible solution to the reidentification problem.16

It is therefore unsurprising that GSK initially refused Jureidini and colleagues access to the case report forms on grounds of protecting the privacy of trial participants. “The content of Appendix H is not posted on our website because it contains information (such as names) that can be used to readily identify the patients concerned.”

But Jureidini and company are challenging GSK. “As a group we do not accept your argument about patient confidentiality . . . The blank case report forms (CRFs) in the Clinical Study Reports (CSRs) make it clear that the only patient identifiers in any CRF not contained in the CSRs were initials. Redacting initials is the work of minutes.” Jureidini adds that reidentification of patients “is not our intention. We think anyone in our group attempting to do this would do significant damage to the data access cause. We are happy to sign agreements that there will be no effort to identify anyone and that the de-identified CRFs will not be shared with anyone outside the 329 group, with access limited to two to three designated individuals within our group.”

Jureidini also questioned GSK’s commitment to its patients: “noting the concern you expressed in your letter for the wellbeing of patients who participate in clinical trials, can we enquire as to GSK’s follow-up of patients who were in Study 329? For instance, were those who became suicidal or violent on Paxil subsequently advised of the possible role of the drug in their dangerous and distressing feelings/actions and counselled that it may be better for them to avoid SSRIs [selective serotonin reuptake inhibitors] in future?”

Perhaps most concerning, Jureidini explained to GSK that his team has concerns about how some of the adverse event data were reported in the 1998 clinical study report and therefore needs the additional requested data.

Recently, GSK has softened its position and seems willing to discuss the possibility of rethinking its previous position. “I recognize, however, that you believe you need to see the CRFs and I would like to explore with you how we can help with this,” Shannon wrote. “Please could we arrange a telephone call to discuss this more fully and agree a way forward?”

Jureidini has declined the telephone call, and requested keeping the interactions by email. “I would be grateful if you could indicate what in your opinion is the safest way of getting all CRFs from study to me, suitably de-identified, but otherwise complete with narrative elements intact.”

“RESPONSIBLE” DATA SHARING

Jureidini’s quest to access the complete participant level data for study 329 highlights some of the anxieties surrounding disclosure of clinical trial data.

Looming large are concerns about misuse of data. “We believe that there are public health risks if the proposed analyses are not scientifically robust and give rise to erroneous concerns about safety or false hopes of a potential benefit for patients,” GSK has declared.4 This fear of misleading analyses is embodied in an adjective gaining popularity among discussions over data sharing: “responsible.” The Institute of Medicine has named its ongoing consensus study on the topic “Strategies for Responsible Sharing of Clinical Trial Data” and a recent essay in the New England Journal of Medicine entitled Preparing for Responsible Sharing of Clinical Trial Data, warns that “poor-quality analyses can harm rather than advance public health, it must ensure responsible use of data.”17

IRONY OF STUDY 329

There is a certain irony in the story of study 329 and its 2001 publication in JAACAP. In a letter to Jureidini, GSK explained that the JAACAP publication “was subjected to peer review on three occasions” and “accurately reflects the honestly-held views of the clinical investigator authors.” But a more pertinent question is whether the published article accurately reflects the trial.

In their most recent letter to GSK, Jureidini and his colleagues reiterate their need for the study 329 case report forms and their intention to analyse study 329 “following the original analytic plan.” As such, Jureidini’s team’s efforts to independently analyse and publish the results of study 329 can be viewed as perhaps the most “responsible” of all analyses—and one that it seems may yet overturn the JAACAP publication that GSK continues to defend.

Story of study 329

  • 1994-98: SmithKline Beecham conducts study 329, a study of 275 adolescents with depression

  • 24 November 1998: Date of SmithKline Beecham’s internal clinical study report for study 329, which was made public by the 2004 consent order

  • July 2001: Keller et al publish study 329 in the Journal of the American Academy of Child and Adolescent Psychiatry1

  • 26 August 2004: GSK signs consent order with the New York State Attorney General, agreeing to pay $2.5m and publicly post clinical study reports for GSK sponsored trials of paroxetine in children and adolescents

  • 2 July 2012: US Department of Justice announced that GSK “agreed to plead guilty and to pay $3 billion to resolve its criminal and civil liability arising from the company’s unlawful promotion of certain prescription drugs, its failure to report certain safety data, and its civil liability for alleged false price reporting practices”18

  • 26 April 2013: Jureidini writes to GSK chief executive requesting his help in retracting the Keller et al JAACAP article

  • 3 May 2013: GSK responds that “GSK does not agree that the article is false, fraudulent or misleading”

  • 13 June 2013: BMJ publishes the restoring abandoned and invisible trials (RIAT) declaration11

  • 25 June 2013: GSK expresses support for RIAT, stating that “by making the Clinical Study Reports available we are very happy for others to publish on the records if they wish to and if journals consider the work to be of scientific merit”

  • 15 July 2013: Jureidini publicly announces his team’s intent to republish study 329 in accordance with the RIAT initiative

  • 28 October 2013: Jureidini and colleagues formally submit a request for deidentified electronic participant level data through GSK’s website. The result of their request is pending review by GSK’s independent review panel

NOTES

Cite this as: BMJ 2013;347:f6754

FOOTNOTES

  • Competing interests: I have read and understood the BMJ policy on declaration of interests and declare the following interests: I am the first author of the RIAT declaration, which was co-authored by David Healy, who is part of Jureidini’s team. I am providing the Jureidini team with unpaid advice on the RIAT process. I am also a member of a Cochrane review of neuraminidase inhibitors that is based in part on clinical study reports provided by GSK for zanamivir. I initiated an inquiry in 2012 that resulted in an additional 38 781 pages from the clinical study reports of study 329 and eight other studies to be publicly posted on GSK’s website.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

REFERENCES

  1. Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, et al. Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry2001;40:762-72.
  2. Kmietowicz Z. GSK backs campaign for disclosure of trial data. BMJ2013;346:f819.
  3. Hawkes N. Industry and drug regulators disagree on which data should remain confidential. BMJ2013;347f5390.
  4. Nisen P, Rockhold F. Access to patient-level data from GlaxoSmithKline clinical trials. N Engl J Med2013;369:475-8.
  5. Jureidini J, Tonkin A. Paroxetine in major depression. J Am Acad Child Adolesc Psychiatry2003;42:514, author reply 514-5.
  6. Jureidini JN, McHenry LB, Mansfield PR. Clinical trials and drug promotion: selective reporting of study 329. Int J Risk Saf Med2008;20:73-81.
  7. Zito JM, Safer DJ, dosReis S, Gardner JF, Soeken K, Boles M, et al. Rising prevalence of antidepressants among US youths. Pediatrics2002;109:721-7.
  8. Olfson M, Marcus SC, Druss BG. Effects of food and drug administration warnings on antidepressant use in a national sample. Arch Gen Psychiatry2008;65:94–101.
  9. United States ex rel. Greg Thorpe, et al v. GlaxoSmithKline plc, and GlaxoSmithKline llc. United States’ complaint. C.A. No. 11-10398-RWZ. 2011 www.justice.gov/opa/documents/gsk/us-complaint.pdf.
  10. Newman M. The rules of retraction. BMJ2010;341:c6985.
  11. Doshi P, Dickersin K, Healy D, Vedula SS, Jefferson T. Restoring invisible and abandoned trials: a call for people to publish the findings. BMJ2013;346:f2865.
  12. Civil Action No 04-V-5304 MGC. People of the State of New York against GlaxoSmithKline, plc and SmithKline Beecham Corporation. Consent order & judgment. 2004. www.ag.ny.gov/sites/default/files/press-releases/archived/aug26a_04_attach1.pdf.
  13. Shannon J. Unlocking access to clinical trial data— what are we afraid of? Huffington Post2013 Sep 9. www.huffingtonpost.co.uk/james-shannon/clinical-trial-data_b_3859734.html.
  14. GlaxoSmithKline CEO on increasing transparency of clinical trials. Fox Business2013 Oct 10, http://video.foxbusiness.com/v/2735629915001/glaxosmithkline-ceo-on-increasing-transparency-of-clinical-trials/.
  15. Vallance P, Chalmers I. Secure use of individual patient data from clinical trials. Lancet2013;382:1073-4.
  16. Mello MM, Francer JK, Wilenzick M, Teden P, Bierer BE, Barnes M. Preparing for responsible sharing of clinical trial data. N Engl J Med 2013;369:1651-8.
  17. US Department of Justice. GlaxoSmithKline to plead guilty and pay $3 billion to resolve fraud allegations and failure to report safety data. 2012. www.justice.gov/opa/pr/2012/July/12-civ-842.html.
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