Make-Up of the MHRA Falls Under the Spotlight

The Daily Star, a British tabloid, today ran with a story regarding the safety of  Tamiflu and the conflict of interest that exists within the UK drugs regulator, the MHRA.

Regular readers of this blog with know how, in the past, I have corresponded and met with MHRA officials, discussing various aspects of SSRi safety, in particular the withdrawal issues concerning this class of drugs.

The article, by Jonathan Corke, shows how, when reviewing the safety of Tamiflu, the swine flu anti-viral, the MHRA had insisted that the product was not responsible for 13 deaths in the UK.

Corke writes:

We also told how the Medicines and Healthcare products Regulatory Agency (MHRA) had received reports of 2,084 suspected adverse reactions, including suicidal thoughts, convulsions and psychotic episodes.

The MHRA insisted Tamiflu handed to more than 1.1million people in 2009 is safe and was not “directly responsible” for the deaths.

But health professionals have questioned the make-up of the MHRA as many members who sit on its committees have links to drug firms.

We found at least 18 people on committees and advisory groups with links to Tamiflu makers Roche.

Some declared “personal interests” in the Swiss company, others received cash for lecturing or consultancy work and some sit on advisory boards.

Welcome to the world of reality Mr Corke, I'm surprised that you have just learned of the *revolving door at the MHRA, it's been going on for years and nobody seems in the slightest bit interested.

If you think 13 related deaths on Tamiflu is serious, check out the related deaths from SSRi type drugs.

The following from the MHRA website:

Citalopram [Cipramil] - 148

Escitalopram [Cipralex] - 28

Fluoxetine [Prozac] - 240

Paroxetine [Seroxat] - 177

Sertraline [Lustral] - 102

"Safety reviews carried out by the MHRA have seen them give each and every one a clean bill of health.

In my book, The evidence, however, is clear...the Seroxat scandal, I highlight the conflict of interest and lack of help patients have received over the years from the MHRA. They are an influential body but they influence nothing. Why would an "independent" body, wholly funded by the pharmaceutical industry, bite the hand that feeds it?

There's an ever bigger problem, the MHRA, despite being sent evidence, refuse to acknowledge that GlaxoSmithKline's wonder drug, Seroxat, is a teratogen [1]. This is putting many lives at risk. In fact their protection of Seroxat over the years hasn't gone unnoticed. Hardly surprising that a body of regulators whose Chairman, Alasdair Breckenridge, is a former employee of GlaxoSmithKline, would sway on the side of the industry. Their Head of Licensing, Dr Ian Hudson, is former World Safety Officer at GlaxoSmithKline too.

Earlier this year I was mildly surprised to learn that the UK Seroxat litigation will feature witnesses [experts] for GlaxoSmithKline. One such witness is Rashmi Shah, his former job? -Senior Medical Officer at the MHRA.

Whilst the Tamiflu deaths are poo-pooed by the MHRA they will continue backslapping each other, devoid of any conscience that they are clearly not doing their jobs properly. They've been doing it for years... and will continue to do it with pharmaceutical funding.

On September 2, 2008, I met with the MHRA to discuss the management of withdrawal on SSRi type medication [2] - During the meeting they agreed to meet with Prof David Healy, an SSRi withdrawal expert.
Both my meeting and the meeting with Healy [3] proved to be fruitless - they still bury their heads in the sand regarding the SSRi withdrawal issue and they still refuse to accept that Seroxat is a teratogenic substance, despite evidence to the contrary.

Stakeholder Analysis MHRA June 2008

In fact, it would appear that the MHRA are more concerned about their own reputation than that of the patients they are supposed to protect. In 2008 they commissioned a web consulting firm to analyse the influence and popularity of various online information sources for people interested in learning more about Seroxat and the MHRA, [4] quite why they did this still remains a mystery.

I refuse to liaise with the MHRA any more, the reasons of which are covered in my book.


*revolving door - A term coined by investigative journalist Evelyn Pringle.

1. Teratogen - any substance, organism, or process that causes malformations in a fetus.
2. Guidance on the Management of Withdrawal from Seroxat (Paroxetine) and Other SSRIs
3. Meeting to discuss awareness and management of withdrawal reactions with SSRIs and related antidepressants
4.Stakeholder Analysis MHRA June 2008


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ADHD - The Challenge

One word - Genius.

Four letters - CCHR


 


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The GSK Challenge

Are Glaxo up for the challenge?

As mentioned in a previous post, I've been trawling through thousands of clinical trials during the past few months and one thing that struck me was Glaxo's inability to run any sort of trial that proves their antidepressant, Seroxat [known as Paxil in US, Aropax in Aus] is not addictive.

Surely the world's second biggest pharmaceutical company would move Heaven and earth to prove this point, a clinical trial showing Seroxat caused no withdrawal problem would be the ace up their sleeve when faced with litigation.

Glaxo have settled over 3,000 withdrawal cases in the US, they have never used any withdrawal clinical trial as a defence...because they have never carried out any. Even if they have, they more than likely pulled the trial because signs were not favourable.

So the challenge is simple.

Would GlaxoSmithKline be prepared to conduct a challenge/re-challenge clinical trial?

Subjects can be given Seroxat, taken off it, then started on it again.

Simple really but not so for Glaxo.

"There is no proof that the drug [Seroxat] does these things and because of that there is no reason to carry out trials that might decide it one way or the other." [1]

Yeh right, instead they can settle with over 3,000 claimants and seal the evidence as part of that settlement.

The proof, as they say, is in the pudding.




[1] The evidence, however, is clear...the Seroxat scandal Pg 53



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**Breaking News...COMPLAINT: Glaxo Involved In Thalidomide Suppression

What was the role of GSK's predecessors in the  thalidomide scandal?

It never rains but it pours for British pharmaceutical giants GlaxoSmithKline. Court settlements with drugs such as Paxil and Avandia, Income Tax evasion fines, dirty plants in Puerto Rico, price fixing...the list is endless.

Here's a new one - it's just been revealed that GlaxoSmithKline, the company that wants you to do more, feel better and live longer, have been hit with a suit in a Pennsylvania court alleging that they, along with other pharmaceutical companies and their predecessors, negligently buried evidence showing the morning sickness drug thalidomide caused birth defects.

Law360 writes:

GSK predecessor Smith Kline & French “concealed from the public that it tested thalidomide on at least 875 people, including pregnant women,” in the late 1950s, plaintiffs' lawyer Steve Berman of Hagens Berman Sobol Shapiro LLP said in a statement Tuesday.

“During those trials, we believe new documents reveal that at least one baby was born with severe birth defects. If SKF had come forward then, future trials might have been stopped and many lives saved,” Berman said.

The suit, filed by 13 people born with severe birth defects, also claims thalidomide may be responsible for more birth defects than previously thought. For decades, the conventional medical wisdom has been that thalidomide only causes bilateral birth defects, which affect both sides of the body.

The NOTICE TO PLEA reveals some disturbing facts and is revealed here for the first time.

IV. STATEMENT OF FACTS A. An overview of the thalidomide tragedy.

Administering thalidomide to pregnant women has been called one of the biggest disasters in modern medicine. First sold in Germany as an over-the-counter remedy for everything from the flu to insomnia to morning sickness, the drug was advertised as ―completely harmless‖ and ―atoxic‖ during the nine years that it was distributed for human use. Far from being harmless, the ingestion of even one pill during the early stages of pregnancy caused severe birth defects, including malformed limbs, curved spines, malformed or missing internal organs, and damaged ears, eyes, and gastrointestinal systems.

The tragedy starts with Grünenthal, a German company that was a subsidiary of a large cosmetics company. Its research was unashamedly market-driven, and its corporate strategy was to penetrate the burgeoning antibiotic boom. Conditions in postwar Germany were appalling, and health authorities feared epidemics of tuberculosis and even cholera. So antibiotics were big business for German pharmaceutical companies. The director of Grünenthal‘s research and development group was Dr. Heinrich Mückter.

Two years before he joined Grünenthal, Mückter was a medical scientist for the army of the Third Reich. Specifically, he was Medical Officer (Stabsarzt) to the Superior Command of the German Occupation Forces occupying Krakau, Poland, with the additional, ominous title of "Director for the Institute of Spotted Fever and Virus Research." Given the role that military medicine played in the objectives and methods of the Nazi occupation of Krakau, Mückter‘s work there involved the science of killing rather than healing.

So what is the role of Glaxo in this?

The complaint filed continues...

Each Defendant participated in the effort to hide the facts as to its distribution and marketing of thalidomide in this country. Smith, Kline & French, the predecessor to SmithKline Beecham Corporation and the Glaxo Defendants, has been portrayed for decades as a company that refused to market thalidomide for Grünenthal, based on tests on mice in the 1950s that showed that thalidomide was "useless" as a sedative.

But SKF concealed for more than fifty years that it had conducted a clinical trial on at least 875 people in 1956 and 1957 in the United States, including pregnant women. Its President lied to Congress about the fact that at least one, if not more, malformed babies were born to women participating in this trial by 1958. Although Grünenthal knew that SKF had conducted human experiments and Merrell should have (and must have) known it, both companies cooperated in the concealment of SKF‘s early use of the drug with pregnant women in the United States, a use that resulted in the births of malformed babies.

SKF did not disclose that it had experimented on pregnant women with thalidomide supplied by Grünenthal, save in a single unreported letter to Congress on August 27, 1962, so there was no publicly available information linking SKF to Grünenthal and thalidomide.

Does this shock you, are you surprised that yet again the name of GlaxoSmithKline [albeit their predecessors] appears in a lawsuit that alleges harm to children?

Anyone remember the Paxil 329 studies?

Children

Anyone remember how hundreds of Irish children used for "Medical Science"...even in death?

Or what about the thousands of babies in the UK that were inoculated with a batch of toxic whooping cough vaccines in the 1970s?

We have children and teenagers who have killed themselves whilst on GSK's Paxil [Seroxat], Sara Carlin, Sharise Gatchell and Adrian Keegan are three such children.

Not forgetting how New York City used children to test experimental AIDS drugs

What is it with GlaxoSmithKline, their predecessors and children?

Where is the love?

Full complaint, dated Oct. 25, 2011, can be read HERE [PDF]

GlaxoSmithKline are currently pushing the boat out in third world countries, offering vaccines to children. Is it just me or does anyone else think that this company should be stopped handing out vaccines until, at the very least, their part in the thalidomide cover-up has been answered?

I'm left scratching my head at the preposterous law that exists. The morals of this company are abhorrent if this recent complaint is anything go by.

**Updated - Reason Magazine Perpetuates False Information About Safety and Efficacy of Antidepressants

Republished with the kind permission of Baum, Hedlund, Aristei & Goldman, P.C

Reason Magazine Perpetuates False Information About Safety and Efficacy of Antidepressants

The September 27, 2011 edition of Reason Magazine reported on a “new working paper” from the National Bureau of Economic Research (NBER), suggesting that the FDA’s 2005 black box warnings concerning antidepressants and the risk of suicidal behavior in adolescents and teenagers caused a dramatic drop in antidepressant use and, consequently, a rise in teen suicides, not to mention a host of other maladies such as declining grades, binge drinking, use of illegal drugs, fighting, etc.  Attributing any of these “consequences” to a lack of antidepressant use is erroneous (to say the least) for a number of reasons.  

The article, written by Katherine Mangu-Ward, the managing editor for Reason Magazine, recycles unwarranted conclusions by pharma-funded academics which have been debunked by other scientists and by the authors themselves. 

The view that lack of antidepressant use has contributed to an increase in youth suicides is an old argument put forward by pharma-funded “key opinion leaders” (or “KOLs”) such as Gibbons, Keller, Nemeroff, etc. (who figure prominently in the NBER’s working paper). [ i ] The unwarranted conclusions from the underlying “studies” on which the “working paper” authors rely have resoundingly been debunked by other scientists, the FDA, CDC and, in some instances, by the authors themselves. 

A.  Antidepressants Are Not Effective In Treating Adolescent Depression  

The most glaring problem with NBER’s working paper is its presumption that antidepressants are effective at treating adolescent depression. Yet, antidepressants as a class have not been shown in clinical trials to be effective at treating adolescent depression [ ii ] Indeed, of the 36 antidepressants subject to the black-box warning, only two antidepressants – Prozac and Lexapro – have been approved for adolescent [ iii ]  The other 34 antidepressants, which form the bulk of the market, have failed to show efficacy.  NBER’s working paper fails to make any mention of this important fact and simply presumes that all antidepressants are effective at treating adolescent depression. 

Exaggerated expectations of the efficacy of antidepressants have been fueled in part by selective publication of positive studies while negative studies remain hidden or misreported.  Many failed clinical trials are never made public because they undermine the drug’s commercial profitability.  For example, GlaxoSmithKline (“GSK”), the manufacturer of Paxil, conducted various clinical trials, all of which showed that Paxil was not effective at treating adolescent depression.  When GSK became aware of the negative results, it made a concrete decision to conceal the information and, in an October 1998 internal memo (uncovered during litigation), an executive concluded “it would be commercially unacceptable to include a statement that efficacy has not been demonstrated as this would undermine the profile of [Paxil]. [ iv ] Years later, a Pennsylvania federal judge overseeing a case involving the suicide of a 16-year old boy cited the internal memo and other GSK documents concluding that the evidence showed that “GSK knew of the risk of pediatric suicidality as of 1998” and that “GSK documents suggest that [GSK] acted with a wanton and willful disregard for the safety of its consumers.”  

Unfortunately, the concealment of negative clinical trial data is not unique to GSK.  Rather, pharmaceutical manufacturers have for decades, through selective and biased publication of clinical trial data, managed to dupe the medical community into believing the efficacy and safety of their respective elixirs.  As Jon Jureidini, a professor of psychiatry at Adelaide University and colleagues pointed out, “efficacy of newer antidepressants in childhood depression have exaggerated their benefits”; “adverse effects have been downplayed,” and; “antidepressant drugs cannot confidently be recommended as a treatment option for childhood depression. [ v ]

Eric H. Turner, an assistant professor in the psychiatry department at the Oregon Health and Science University and colleagues, in their analysis of antidepressant clinical trials, found “bias toward the publication of positive results” and “studies that were not positive ... were often published in a way that conveyed a positive outcome.”  Turner concluded that “the efficacy of this drug class is less than would be gleaned from an examination of the published literature alone,” which “can lead doctors to make inappropriate prescribing decisions that may not be in the best interest of their patients and, thus, the public health.” 

B.  NBER’s Contentions Regarding the Level of Prescriptions and Suicides Are Factually Flawed

Moving past the efficacy issue, NBER’s contention that youth suicides have increased following the advent of the black-box warning is also factually flawed.  The Reason article cites NBER’s fallacious working paper for the proposition that “Youth suicides had been flat or declining among 10-19 year olds in the years preceding the warnings, but in 2004, 10-19 year old girls experienced a sharp increase in suicides, of over 30 percent.”  This is simply not supported by the data, which, as outlined below, reveal that suicide rates were not only rising prior to issuance of the black box warnings, but actually went down following issuance of the black box warnings.

In 2004, the year suicides increased, “there was no significant drop in SSRI prescribing." [ vi ]  As Jureidini pointed out, Gibbons “incorrectly analyzed the relationship” between prescription rates and suicide rates among children and, when carefully examined, Gibbons’ suggestion of a clear causal association from the data analyzed “show no such association.” Id.  Like Gibbons, the NBER working paper is making erroneous “[a]larmist predictions regarding the consequences of decreased prescribing.” Id.

Gibbons, himself, has since acknowledged that his data did not support a causal link:  “We really need to see the 2005 numbers on suicide to see what happened." [ vii ] (The alleged culprit of the NBER’s “list of terribles,” i.e., the black box warning, was implemented in early 2005, and antidepressant prescriptions did decrease that year.)  The FDA’s Dr. Thomas Laughren confirmed at a 2008 hearing that antidepressant prescribing did not change until 2005 and the 2005 suicide numbers “are down from where they were in 2004." [ viii ]

Moreover, one of the studies cited by the working paper authors by Gibbons et al. was so scientifically illegitimate that it was described by the British Medical Journal as “astonishing,” “misleading” and "reckless." [ ix ] Further, one of the Gibbons study authors, Ron Herings admitted the study’s findings are “not right” and that it “doesn’t follow from the data, it is not true and serves just to scare people.  It is hard to admit this, as I am one of the authors of the article and I attached my name to it ..." [ x ]

Finally, NBER’s reliance upon ecological studies to support their arguments is methodologically flawed.  Authors of ecological “studies” universally agree you cannot conclude that increasing or decreasing suicides (or any other malady) is the result of a lack of antidepressant consumption based on these types of analyses. [ xi ] 

C.  Selling Sickness

Another important issue in this debate is the over-promotion and subsequent indiscriminate prescription of antidepressants to as many people as possible.  The marketing of depression and use of antidepressants has been called “a masterpiece of marketing." [ xii ]

Prior to antidepressants hitting the market, “depression was considered a rare disease, affecting about 1 percent of the population (as opposed to 10 to 15 percent of the population today) ...” Id. [ xiii ] According to Australian professor of psychiatry, Gordon Parker, the “[r]easons for the overdiagnosis [of depression] include ... marketing of treatments beyond their true utility in a climate of heightened expectations." [ xiv ]

Depression has “grown to epidemic proportions in modern, developed Western countries in particular.  Within two decades the percentage of the population having depression that requires treatment has risen five-fold on average: in 2009 more than 5% of the general population." [ xv ]

In his article Overprescribing Antidepressants, Christopher Lane, Ph.D., a research professor at Northwestern University, pointed to a Rand Corporation survey conducted in 2002, showing that just 20% of those surveyed who had received an antidepressant prescription “tested positive” for clinical depression.  “Fewer than 30% of those receiving the medication had any depressive symptoms at all.”  In other words, “70% of patients in the survey presented no medical need for antidepressant treatment, and a further 10% fell into a significant gray area, with an insufficient number of symptoms to warrant a DSM diagnosis.” 

D.  Conclusion

It has been said, “Every risk to public health seems to beget an equal and opposite effort at denial from the industry whose products are implicated." [ xvi ]

Like the tobacco industry, which “helped invent the strategy of using scientists as third-party advocates” in order to “create doubt” (id. at 230) about the health risks associated with tobacco, drug manufacturers and their KOLs have used a similar strategy by propagating a steady stream of “studies” to counteract the impact of strengthened warnings about their drugs’ risks.  The argument bears a remarkable resemblance to that put forward by tobacco companies in the 1960s – that deaths from respiratory and cardiac causes had been falling from 1900 through to the 1960s and life expectancy rising, all during a period when cigarette consumption was on the rise. [ xvii ]

While the NBER paper’s objective is not readily apparent, what is clear is that the presumptions and methodology are erroneous and the conclusions misleading.  Relying on NBER’s paper, an unsuspecting mother might feel the cure to her child’s poor grades is an antidepressant and insist that he/she be placed on a drug that is not only clinically ineffective, but that has some potentially very serious side effects.  Observing societal problems such as illicit drug use, violence and poor grades and working toward workable solutions is a good thing, but believing a single magic pill will somehow cure all those ills is misguided. 

                                 

Disclosure: Baum Hedlund has litigated antidepressant suicide and suicide attempt cases for approximately 20 years. As a result, the firm (in conjunction with research consultants and leading experts in psychopharmacology) have conducted a great deal of research on the issues presented in the NBER paper and, further, the firm has obtained confidential pharmaceutical company documents which shed further light on the issues. Baum Hedlund has but a handful of antidepressant suicide cases remaining in its inventory, thus, any financial motivation in responding to Reason’s article is limited. We believe, however, that it is important to continue to share our knowledge base when we become aware of research that could mislead the public.

---

i. See Paul Basken, “As He Worked to Strengthen Ethics Rules, NIMH Director Aided a Leading Transgressor” (i.e., Charles Nemeroff), The Chronicle of Higher Education, June 6, 2010,http://chronicle.com/article/While-Revising-Ethics-Rules/65800; Silverman, "Grassley Targets Brown's Keller Over Grants," Pharmalot.com, July 14th, 2008,http://www.pharmalot.com/2008/07/grassley-targets-browns-keller-over-grants/; Firestone and Kelsh, "Keller's findings on Paxil disputed by doctors, FDA,”The Brown Daily Herald, September 24, 2008, http://www.browndailyherald.com/campus-news/keller-s-findings-on-paxil-disputed-by-doctors-fda-1.1669707#.ToN-EYIa-dA; Firestone and Kelsh, "Senator targets professor's ties to big pharma," The Brown Daily Herald, September 24, 2008, http://www.browndailyherald.com/campus-news/senator-targets-professor-s-ties-to-big-pharma-1.1669703#.ToN98oIa-dA; Silverman, “Antidepressant Use And Conflicts Of Interest,” Pharmalot.com, September 7, 2007,http://www.pharmalot.com/2007/09/antidepressants-suicide-and-conflicts-of-interest/.

ii.See September 13, 2004 Psychopharmacological Drug Advisory Committee transcript, http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004 4065T1.htm, p.445; September 14, 2004 PDAC transcript, http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004 4065T2.htm, p. 83.  See also Jureidini, Doecke, Mansfield, Haby, Menkes, Tonkin, Efficacy and safety of antidepressants for children and adolescents, BMJ  2004;328:879 883 (10 April), doi:10.1136/bmj.328.7444.879 available in full at http://www.bmj.com/cgi/content/full/328/7444/879; Newman, A Black Box Warning for Antidepressants in Children? N Eng J Med, Vol. 351:1595 1598, October 14, 2004, abstract available at http://content.nejm.org/cgi/content/short/351/16/1595

iii. http://www.fda.gov/cder/drug/antidepressants/QA20070502.htm.  Even so, both Prozac’s and Lexapro’s efficacy for the treatment of children and adolescents is dubious.  As Dr. Thomas Newman, an epidemiologist from UC San Francisco and an FDA advisor, explained during the September 14, 2004 PDAC, “We have I think very strong evidence of harm and really not very good evidence of efficacy, and although I know many practitioners are convinced that these drugs work, if you look very closely at the [Prozac pediatric] trial, just as an example, ... the improvement over placebo was really very, very small, and I would say not detectable by a clinician treating individual patients. ...” See September 14, 2004 PDAC transcript at
http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004 4065T2.htm, p. 338.  With respect to Lexapro, its approval for children ages 12-17 in March 2009 came, curiously enough, amidst charges by the Department of Justice that its manufacturer, Forest Labs, illegally marketed Lexapro for children and paid pediatricians kickbacks to prescribe the drugs off-label.  Forest labs ended up paying over $313 million to settle the unlawful marketing allegations and pled guilty to felony obstruction of justice, two misdemeanor counts and paying kickbacks to doctors.  See: Department of Justice press release, "Drug Maker Forest Pleads Guilty; To Pay More Than $313 Million to Resolve Criminal Charges and False Claims Act Allegations," September 15, 2010,http://www.justice.gov/opa/pr/2010/September/10-civ-1028.html.  Another oddity about Lexapro’s approval is that it was approved based on only one favorable clinical trial of Lexapro (the FDA normally requires two well-controlled clinical trials).  The FDA accepted the company’s combination of one positive Lexapro trial and one positive trial of Lexapro’s “sister” drug Celexa, which, on its own, Forest was never able to prove effective.  Two other pediatric clinical trials (one Lexapro and one Celexa) failed.  Forest was also unable to prove that Lexapro was effective for maintaining treatment for depression in children and/or adolescents.

iv. Knipe v. GlaxoSmithKline, 583 F.Supp.2d 602, 640 (E.D.Pa. 2008).

v. Jureidini et al., Efficacy and safety of antidepressants for children and adolescents, Brit. Med. J., p. 879, 10 April 2004.

vi. See Jon Jureidini, The Black Box Warning: Decreased Prescriptions and Increased Youth Suicide?, 164 Am. J. Psychiatry 1907 (2007). 

vii. See Alex Berenson & Benedict Carey, Experts Question Study on Youth Suicide Rates, N.Y. Times, September 14, 2007.

viii.See Joint Meeting of the Peripheral and Central Nervous system drugs advisory committee and the Psychopharmacological Drugs Advisory Committee, (“PDAC”) FDA (Beltsville, Maryland) (July 10, 2008), Hearing Tr. at 52.

ix. See Tony Sheldon, Dutch Academics Criticise Suicide Claims in American Journal, 336 Brit. Med. J. 112 (2008). 

x. Interview with Ron Herings, Argos, VPRO/VARA, Radio 1 (December 7, 2007).

xi. See e.g., Jorgen Bramness et al., The sales of antidepressants and suicide rates in Norway and its counties 1980-2004, 102 Journal of Affective Disorders 1 (2007)Jorgen Bramness et al., The sales of antidepressants and suicide rates in Norway and its counties 1980-2004, 102 Journal of Affective Disorders 1, 6-7 (2007). (“Ecological studies cannot infer causality;” “the observed relationship [between declining suicide rates and antidepressant prescriptions] could be a spurious finding”); Gibbons et al., The Relationship Between Antidepressant Medication Use and Rate of Suicide, 62 Arch Gen Psych 165 (2005) Gibbons et al., The Relationship Between Antidepressant Medication Use and Rate of Suicide, 62 Arch Gen Psych 165 (2005) (“the aggregate nature of these observational data preclude direct causal interpretation of results.”)

xii. See Charles Barber, Comfortably Numb, How Psychiatry is Medicating a Nation 7 (2008). 

xiii. Spending on antidepressants rose from $5.1 billion in 1997 to $13.5 billion in 2006. Id. at 8. Pieters and Snelders, Psychotropic Drug Use: Between Healing and Enhancing the Mind, 2 Neuroethics 63 (2009).

xiv. Gordon Parker, Is Depression overdiagnosed? 335 Brit. Med. J. 328 (2007).  See also, Jureidini and Tonkin, Overuse of Antidepressant Drugs for the Treatment of Depression, 20 CNS Drugs 623 (2006); Pieters and Snelders, Psychotropic Drug Use: Between Healing and Enhancing the Mind, 2 Neuroethics 63 (2009).

xv. Pieters, Snelders, “Psychotropic Drug Use: Between Healing and Enhancing the Mind,” Neuroethics, 11 February, 2009. 

xvi. See Rampton and Stauber, Trust Us, We’re the Experts – How Industry Manipulates Science and Gambles With Your Future 229 (2001).

xvii. See Tobacco and the Health of the Nation athttp://legacy.library.ucsf.edu/cgi/getdoc?tid=dxb34f00&fmt=pdf&ref=results and Smoking and Health Proposalat http://legacy.library.ucsf.edu/tid/rgy93f00, 690010954 (“Doubt is our product since it is the best means of competing with the ‘body of facts’ that exists in the mind of the general public. It is also the means of establishing a controversy ... .”)  

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Japanese Paxil Study in Children Proves Very Little

How Glaxo recruited 7-17 year old children for their Japanese Paxil study

Back in 2009 I reported on how GlaxoSmithKline Japan were trialing out Paxil/Seroxat in children and adolescents. Over the following months I sought to find out why such a study was taking place, it seemed odd, to say the least, that GlaxoSmithKline were trying to prove their drug was safe in children and adolescents when it was blatantly obvious that it was not safe and effective.

The clinical trial, aimed at 7-17 year olds, went ahead, an 8 week trial which, it appears, was for the sole purpose of trying to prove one thing, at least that's the impression I get when reading the results.

What did Glaxo wish to push the boat out for? Well, my assumption, because I'm allowed to assume, is that Glaxo will use the results of this study to spin the suicidal ideation in kids claims that they hid in the earlier Paxil 329 study.

The 2009 study, which was completed earlier this year, shows a quite remarkable change.

You've guessed it folks.

Take a look at the following table:

You will note that the psychiatric disorders shows there were 3 reports on placebo whilst none were reported for Paxil. I't's hardly convincing seeing as there were only 29 subjects taking Paxil but I'm sure GlaxoSmithKline will use this to their advantage.

However, it would appear that the study proves nothing. Paxil was only slightly superior compared to placebo but it's all irrelevant anyhow.

Personally, I feel the only reason this study took place was to highlight the suicidal thoughts or lack of - Glaxo will no doubt spin this in future medical journals...or rather key opinion leaders handpicked by Glaxo will.

With just 29 subjects on Paxil they would have been lucky to pick up just one (3 per hundred is about 1 per 33). The low number of participants in the active treatment group pretty well ensured they most likely would not see emergent drug induced suicidality.

The study, like 329, has been manipulated, that's my opinion anyway, I'm still allowed an opinion aren't I?

If you look at the original exclusion criteria for this study you will see that it is not based on real-world prescribing. Remember just 1 subject in a hundred becoming suicidal because of the drug equates to 1000 subjects per million. And nobody knows for certain how many of those will go on to kill themselves - we do know that there have been many.

Each subject in this trial were asked a series of questions to determine if they were experiencing adverse reactions, the questions were, it appears, based on the CDRS-R rating scale

The CDRS-R is a brief rating scale based on a semi-structured interview with the child (or an adult informant who knows the child well). Designed for 6- to 12-year olds, and successfully used with adolescents, it can be administered in just 15 to 20 minutes and easily scored in a few minutes more. The interviewer rates 17 symptom areas (including those that serve as DSM-IV criteria for a diagnosis of depression): [SOURCE]

Impaired Schoolwork
Difficulty Having Fun
Social Withdrawal
Appetite Disturbance
Sleep Disturbance
Excessive Fatigue
Physical Complaints
Irritability
Excessive Guilt
Low Self-Esteem
Depressed Feelings
Morbid Ideation
Suicidal Ideation
Excessive Weeping
Depressed Facial Affect
Listless Speech
Hypoactivity

Most of these symptom areas are rated on a 7-point scale so the CDRS-R can capture slight but notable changes in a child's symptoms. This makes the scale ideal for monitoring symptoms during illness or remission. Other additions to the scale include suggested interview prompts and guidelines for integrating information from multiple informants.

Japanese Medwatch were concerned about this particular study, so concerned that they wrote the following to GSK Japan:

Click to read

The results of the trial have now been published online and can be viewed HERE

I anticipate they will appear [polished and spun] in medical journals soon.

Previous coverage of the Japanese Paxil Trials:


Monday, January 12, 2009 - GSK Just won't stop trying to push paroxetine on children!

Thursday, January 15, 2009 - Email to Japanese Embassy regarding New GSK paroxetine study in Children. ClinicalTrials.gov Identifier: NCT00812812

Friday, April 03, 2009 - Email to Ministry of Health - Japan

Friday, April 03, 2009 - Japan/GSK - 329 All Over Again!

Saturday, July 25, 2009 - Paxil Study 329 All Over Again?

Friday, May 21, 2010 - Email To GlaxoSmithKline Re; Paxil Study In Children

Friday, September 24, 2010 - HEY, GLAXO!... LEAVE THOSE KIDS ALONE

Friday, May 13, 2011 - Glaxo remain tight-lipped on new Japanese Paxil study in children.

Wednesday, May 18, 2011 - GSK JAPAN - PAXIL STUDY IN KIDS UPDATE

Monday, May 23, 2011 - Are GlaxoSmithKline Japan Putting Children At Danger With Paxil Trial?




Fid

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SSRi Use For PMS - Is It Right?

When faced with a patient who is suffering from Premenstrual syndrome [PMS] what is a doctor supposed to do? Evidence suggests that SSRi use benefits those who suffer with PMS but there are also those who have tried this therapy who have claimed that the medication has actually made them worse.

It's a given that SSRi use can bring on agitation when first starting and stopping abruptly, in some cases it can bring on feelings of suicide and also homicidal thoughts have been reported.

PMS is a subject that I, as a man, should steer clear of. What could I possibly know about PMS and how it should be treated? I pretty much know the time of the month when the need to walk on eggshells is approaching...or at least I did when I was married.

I could write a post making light of PMS, that would be wrong but most that know me personally would know that there was no malice

A week or so ago, a reader of my blog was sitting in the waiting room at her doctor's practice. To pass the time she started flicking through the array of magazines strewn around the waiting room. One such magazine was called "Healthy Magazine". The article that caught her attention was written by a doctor [male] and was about treating Premenstrual syndrome, also known as Premenstrual tension [PMT]. She was actually visiting her doctor because she was struggling to taper off Seroxat, in fact she had been struggling for over two years and was finally down to 1.5mg, a tapering process that had caused her feelings of suicide, anxiety, head zaps, profuse sweating, vivid nightmares, weight gain, plus a whole host of other adverse events.

The article, entitled, "Your PMS Action Plan", offered advice, much of which was about tweaking your lifestyle etc.

In finishing his article, Dr Nick Panay suggested that if the 'tweaking' wasn't helping then talking to your doctor may help. He went on to suggest that your GP may recommend an SSRi if it was the emotional aspects of the PMS that you were struggling with. The article made no mention of the dangers of this group of drugs, no mention of suicidal thoughts, no mention of withdrawal problems and no mention of the teratogenic effects that they cause. This bothered me, so I wrote to the editor of the magazine:

I have been sent a segment of your magazine 'Healthy'' that a reader of my blog, Seroxat Sufferers, sent me.

The article in question, "Your PMS Action Plan", offers advice, it appears, from Mr Nick Panay. [Jpeg attached]

I'd like, if I may, to draw your attention to the heading "When to seek help".

The advice about SSRi's is unbalanced and inaccurate.

Mr Panay claims that SSRi's increase levels of serotonin, suggesting that levels may be too low.

This has never been proven, it is just a theory and one that may be misleading to your readers. I'd be grateful if this section could be edited or an announcement in your next edition of 'Healthy' be made to correct this misleading statement by Mr Panay.

I am intrigued to learn what studies Mr Panay refers to in his column when he writes: "...research has shown that taking them for two weeks at the end of your cycle is as effective as using them continuously - without the risk of becoming hooked."

Two queries about the above statement by Mr Panay:

i; Could Mr Panay provide me with the research he refers to?

and

ii; Does Dr Panay claim that one can become 'hooked' on SSRi medication?

Dr Panay offers no warning about taking SSRi medication during pregnancy, in particular during first trimester where studies have shown that [in the instance of Seroxat] increases the chance of the fetus developing serious heart defects. I refer you to the recent trial of Kilker Vs GlaxoSmithKline, where GlaxoSmithKline's Seroxat was deemed responsible for the causation of Lyam Kilker being born with serious heart defects. GlaxoSmithKline have quietly settled, out of court, a further 800 cases regarding Seroxat's teratogenic properties.

A video deposition of how they [GlaxoSmithKline] knew years ago about this problem, but failed to act, can be seen here - http://fiddaman.blogspot.com/2011/09/exclusive-jane-nieman-video-testimony.html

I'd be grateful if you could pass my concerns on to Mr Panay and ask him to answer me directly as I intend to write an article about his column.

Yours sincerely

Bob Fiddaman.

I was grateful to Dr Panay for answering my query personally, many column writers or TV doctors tend to ignore opposition.

Dr Panay wrote via his editor:

Could you please forward the RCOG evidence based guidelines to the gentleman. These were developed by a group of experts including myself and ratified by the RCOG.

With regards to his numbered queries

1) If he looks at refs 13 and 14 these are two of the studies (there are others) which show that luteal phase treatment with SSRIs is as effective as continuous usage.

2) I would never personally use the term "hooked" - but, it is well recognised some women do experience withdrawal symptoms when discontinuing SSRIs abruptly - the point is that SSRIs should be withdrawn gradually to avoid these side effects.

Other points of accuracy

1) I do not suggest that there is a serotonin deficiency - the hypothesis is that women with severe PMS (possibly genetically predisposed) can respond adversely to the physiological fall in serotonin levels in the days leading up to menstruation (as estrogen levels fall)

2) As far as early pregnancy is concerned, it is a case of weighing up pros and cons, risks v benefits. Specifically, do the benefits of continuing SSRIs into early pregnancy outweigh the risks in that individual. By the way, we do prescribe Seroxat in our PMS patients.

I hope this addresses all his concerns - I am sure that he is aware of how underestimated the problem of PMS/PMDD is and would support an evidence based approach to managing this difficult problem so I thank him for his concern and critique.

The *RCOG evidence that Dr Panay sent me was attached and is available for perusal here.

It is quite clear that the evidence supplied does suggest that SSRi use for PMS is effective, quite whether we should believe this evidence is another matter. We have seen, in the past, how, for instance, GlaxoSmithKline showed how 'safe and effective' Seroxat was in children and adolescents - we now know that the study was not only deeply flawed, it was also ghostwritten. I'm not suggesting for one minute that the RCOG evidence is flawed or indeed ghostwritten but I reserve judgement as I have spoken with many women who have experienced severe withdrawal problems on the medication recommended by Dr Paney. That's me addressing the balance issue, the risk v benefits if you will. One such friend who, upon hearing about Dr Panay's advice, told me, "Talk about throwing gas on a fire!"

I disagree that medication such as Seroxat can be started then abruptly stopped [RCOG evidence - luteal phase treatment with SSRIs is as effective as continuous usage]

I also disagree with Dr Panay and his stance on the usage of the word 'hooked' - if people experience withdrawal symptoms then do we suggest that the drug is not addictive?

The article will be read by many, men, women and possibly teenage girls as they sit and wait for their names to be called out for their appointment with their GP's. My only hope is that they don't take what is written at face value, that they do their research on SSRi type medication and that they are each able to make an informed choice on all the evidence which should include anecdotal evidence of the many women who have experienced the horrific side effects that these drugs cause.

One of they key words in Dr Panay's response to me sticks out like a sore thumb. "Hypothesis"


Be it depression, shyness or indeed PMS  - The treatment of SSRi use and the diagnoses of the illness it is prescribed to treat is based purely on hypothesis. That is the risk when taking these drugs, you are taking something based on guess work and also based on clinical trials from pharmaceutical companies who have been less than forthright with trial results in the past. All I ask for is informed consent, by that I mean list every single side effect these drugs cause and not just the minor ones such as dizziness, sickness and diarrhea. Don't ever feel you may put people off receiving the medication that may or may not help them by hiding the more severe side effects. Patients have a right to know what they are putting into their bodies, be that in the form of a patient information leaflet or a column written by a doctor in a health magazine.

Would I recommend an SSRi for PMS?

No, I wouldn't.

Could I offer an alternative?

No, I couldn't.

Herein lies the problem. A problem that the pharmaceutical industry have the monopoly on.

To be honest I wouldn't give my worst enemy Seroxat, I've experienced the harm it can cause. If it can turn normal healthy people into killers then one can only imagine what it could do to a woman suffering from PMS. If drugs like Prozac and Cipramil can induce suicide and homicidal thoughts then the last thing I would recommend to somebody suffering severe tension would be drugs of this ilk.

I'd like to thank Dr Panay for his response. I don't agree with his stance and I cannot offer an alternative... that doesn't mean that I am wrong now, does it?

If you have been treated with SSRi medication for PMS and you have found the treatment to be efficacious or indeed the opposite, then please feel free to drop me a line with your story.




*Royal College of Obstetricians and Gynaecologists.




Fid

ORDER THE PAPERBACK 'THE EVIDENCE, HOWEVER, IS CLEAR...THE SEROXAT SCANDAL' By Bob Fiddaman US and CANADA HERE
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