Date: Fri, 12 May 2006 17:29:59 -0400
Subject: GlaxoSmithKline Reverses Decade of Denial: in Clinical Trials Paxil Triggered Significantly More Suicide Attempts in Adults than Placebo
ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)
Promoting Openness, Full Disclosure, and Accountability
A faith-based belief system masquerading as science is collapsing under the weight of evidence that has, for so long been denied by drug manufacturers, by the FDA, and by psychiatry: the best selling, most profitable antidepressants pose an increased risk of suicide for children and adolescents, for young adultsin fact, no age group is exempt. 
1. GlaxoSmithKline (GSK) has submitted documents to the FDA and other regulatory agencies, contradicting its decade long denial that its antidepressant drug, paroxetine (Paxil / Seroxat) increased the risk of suicidal behavior in the companys controlled clinical trials,. http://www.gsk.com/media/paroxetine_adult.htm
2. In a letter to healthcare professionals this week, GSK warned about the increased suicide risk stating:
"There is a possibility of an increased risk of suicide related behavior in young adults ages 18-29" -- whether the drug is prescribed for depression or for other conditions not associated with suicide. http://www.gsk.com/media/paroxetine/adult_hcp_letter.pdf
3.GSK is the first of the SSRI drug manufacturers to acknowledge in the Paxil label that the drug may trigger more than suicidal thoughts. The drug increases the risk of suicide attempts. The Paxil CR label now includes the following warning:
young adults, are at an increased risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
GSK added warnings acknowledging that patients on the drug may experience persistently worse depression, or may experience emergent suicidality or symptoms that might be precursors to worsening depression or suicidality and these symptoms may be severe, abrupt in onset, or were not part of the patients presenting symptoms."
The company advises doctors: "Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication.
When was the link between SSRI antidepressants to suicide first reported?
In 1990 by Dr. Martin Teicher warned that Prozac (the first SSRI antidepressant) could cause suicidal behavior: At the present time we recommend that this drug be used cautiously and that the practitioner be attentive to the possible emergence of suicidal ideation, even in those patients without a previous history of suicidal thoughts or actions. 
In 1991 Dr. Robert King reported that the same phenomenon happens in children.  Yet, for more than a decade, drug companies indignantly denied any suggestion of such a risk, attacking those who were able to see the risk and dare to disagree.
In 1991, the FDA convened an advisory committee whose financial ties to Eli Lilly, allowed them to equivocate enough for the FDA to conclude there is no credible evidence that Prozac increases the risk of suicide
This imprimatur became the watchword of the industry and the new antidepressants skyrocketed to a $17 billion dollar market.
But the human casualties who had been prescribed Paxil and other SSRIs mounted, and in October, 2002, the BBC-Panorama aired an investigative report whose after-effects still reverberate on both sides of the Atlantic, as well as in Australia. BBC not only introduced the public to victims of irresponsible prescribing of the drug, and GSKs drug marketing tactics, making visible the collision between patients' physical and mental well-being and corporate marketing tactics, but the program laid bare the indifference of regulatory agency officials to a serious threat to public health safety.
In May, 2003, a BBC follow-up report provided the opportunity for two expert psychiatrists to express their opposing views publicly. Dr. David Healy, psychopharmacologist, medical historian, and Director, North Wales Department of Psychological Medicine, cited evidence of a suicide risk, and Dr. Alastair Benbow, GSKs Head of European Psychiatry, defended the drug and denied the risk. 
Dr. Healy: The evidence is that roughly one person in sixty that goes on this drug makes a suicide attempt. Now you have to contrast that with the people going on placebo or sugar pill, and the rate there is one person in five hundred and fifty. That's nine or ten times less. The risk on the drug is nine or ten times greater than the risk on sugar pill.
Dr. Benbow: We have been asked by the regulatory authorities to provide all our information related to suicides and I can tell you the data that we provide to them clearly shows no link between Seroxat and an increased risk of suicide no link.
BBC reporter asked Dr. Benbow if he was absolutely confident that Dr. Healy is wrong on this issue and will be shown to be wrong?
Dr. Benbow replied:
Yes, absolutely. Not only that but Doctor Healy has made the same claims about a range of other medicines. He made the same claims about Prozac
he made the same claims about a range of other SSRIs. On every occasion he has been found to be wrong.
In September, 2004, Alan Metz, GSK North American medical director told the Wall Street Journal: Each time it has been looked at, there is no suggestion of an association with suicidal tendencies in adults, with relation to SSRIs.
For more than a decade, they claimed that depression causes suicide, not the drugs. Since then, the backtracking of the naysayers has taken on an almost comedic air. In 2004, they acknowledged "suicidality" in kids, but not suicide, and certainly not adults. Now, GSK admits the drug is associated with increased risk of suicide attempts in adults, but only in young adults. Well, okay, the fine print states the higher frequency observed in the younger adult population may extend beyond the age of 24. But it is difficult to conclude a causal relationship.
No its not difficult to conclude a causal relationship. This double speak is reminiscent of comedian Steve Martins admission to smoking marijuana:
"I used to smoke marijuana. But I'll tell you something: I would only smoke it in the late evening..... Oh, occasionally the early evening, but usually the late evening - or the mid-evening...... Just the early evening, midevening and late evening. Occasionally, early afternoon, early midafternoon, or perhaps the late-midafternoon. Oh, sometimes the early-mid-late-early morning. . . . But never at dusk.."
This week's GSK acknowledgements put to rest the hackneyed defenses:
its the disease not the drug and no evidence of a drug-induced suicide risk in adults.
The simple truth is this: these drugs can cause violent suicidal behavior and death: in kids and in adults, in depressed people and in nondepressed people. The data do not demonstrate that any segment of the population is not susceptible to this risk.
Industrys denials were buttressed by the FDA.
Daniel Troy, FDAs former chief counsel, intervened in judicial procedures on behalf of drug companies by invoking FDA authority which he falsely claimed pre-empts state laws protecting public health safety. In a 2002 Amicus Curiae brief, Troy wrote:
had Pfizer given a warning as to a causal relation between Zoloft and suicide, FDA would have disapproved the warning. Indeed, based on its current scientific knowledge, FDA would still do so today. 
Then, senior FDA officials tried to suppress a report by FDAs own safety officer, Dr. Andrew Mosholder, whose pediatric SSRI data analysis confirmed a twofold suicidal risk. 
Only under intense pressure (in 2004) from parents whose children became suicidal after an SSRI was prescribed; and only after Congress applied pressure on the FDA were warnings of suicidality added to these drugs label. However, complaints by drug companies led the FDA to weaken the warnings, removing the following sentence from the label: A causal role for antidepressants in inducing suicidality has been established in paediatric patients.
Even as black box warnings were being crafted senior FDA officials denied the existence of evidence the drugs increase the risk of suicide. Dr. Robert Temple testified before a Congressional committee: At the time ... it was not an issue that was prominent in our thinking," Temple testified. "We had never seen a signal for suicidality in the adult data."  And Dr. Thomas Laughren said his agency had a database of about 40,000 adult patients involved in clinical trials and that "so far, we have seen no signal" indicating the drugs might increase suicide risk.
GSKs public admission that in fact, in some cases, young adults (18-24) who take Paxil (paroxetine) are at increased risk of suicide, is based on clinical trial data that GSK and the FDA have been sitting on since the early 1990s. This acknowledgement of the evidence contradicts its repeated pronouncements and contradicts the sworn congressional testimony of these FDA officials.
Despite the acknowledged suicide risk, GSK attempts to persuade physicians (in the letter to healthcare professionals) to continue to prescribe their drug, offering the company's faith-based "belief" in the drug's benefit: "GSK continues to believe that the overall risk-benefit of paroxetine in the treatment of patients with MDD and other non-depressive disorders remains positive
But here again, the evidence does not support GSKs claim of SSRI drug efficacy. A meta-analysis of the clinical trial evidence from short and long-term clinical trials by Professor Irving Kirsch and colleagues, showed that 83% of the effect of these drugs is duplicated by placebo. 
The question is: Should drugs be approved and marketed on the basis of what the drug company believes, or what the evidence shows?
The pharmaceutical industry is regulated because drugs have the potential to cause serious harm, and industry, with its obvious financial conflict of interest cannot be relied upon to serve the public interest. This is the reason we have an FDAits mission is to protect us from harmful drugs that companies may want to market. How has this regulatory system been working?
For 15 years the FDA has stood firm in support of drug companies even as they misinformed physicians and the public with false assurances about the safety of these drugs, claiming that there is no evidence of a drug-related risk of suicide. FDAs policy allowed drug companies to market SSRIs aggressively by flooding the media with deceptive advertisements. The drugs became blockbusters and companies raked in billions of dollars in sales. All the while, both the industry and the FDA covered their eyes and ears to the human tragedies and the rising number of drug-related casualties.
GSK now reluctantly acknowledges the evidence linking the risk of suicide to its antidepressant, evidence whose existence GSK had denied for so long. That evidence is not new. Dr. Teicher, Dr. King, and all the physicians and lay people who recognized the red flags about these drugs hazards, and were courageous enough to speak out, were right all along. And the FDA was wrong all along. Even today, the FDA has not acknowledged the lethal risk that GSK has finally admitted. The evidence has been in FDAs files for years. Thus, its failure to warn to protect the lives of children and adults is either due to their incompetence or their complicity with drug manufacturers. Either way, their inaction is a dismal failure and betrayal of the public trust.
Earlier this month, the GAO issued a report about its investigation of the FDA, concluding that the FDA is broken and unable to fix itself.  The GAO suggested that new legislation is needed to correct the corruption at the current FDA that today is costing people their lives. This latest installment in the book of FDA failures confirms the GAO report. The only question now is whether congress cares more about public health or the financial interests of the pharmaceutical industry.
1. Juurlink, DN, Mamdani, MM, Kopp, A, Redelmeier, DA. The Risk of Suicide With Selective Serotonin Reuptake Inhibitors in the Elderly, The American Journal of Psychiatry (May 2006).
2. Teicher, M. H., Glod C., & Cole J. O. (1990). Emergence of intense suicidal preoccupation during fluoxetine treatment. American Journal of Psychiatry, 147, 207210. See also case report by Creaney, W, Murray, I, and Healy, D. Antidepressant Induced Suicidal Ideation, Human Psychopharmacology, 1991, Vol. 6:329-332.
3. King, R. A., Riddle, M. A., Chappell, P. B., Hardin, M. T., Anderson, G. M., & Lombroso, P. (1991). Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 171176.
4. BBC Panorama: Postcards from the Edge, 5/11/03
5. Daniel E. Troy, Chief Counsel Food and Drug Administration Amicus Brief, September 3, 2002 ; See also: Gary Young, FDA legal strategy would pre-empt tort suits National Law Journal March, 2004, vol. 128; Pg. 3 ww.law.com/jsp/nlj/PubArticleNLJ.jsp?id=1076428430132
See also, http://www.ahrp.org/infomail/05/09/30.php
6. Dr. Mosholder's embargoed report and the accompanying FDA memos are posted on the AHRP website at: http://www.ahrp.org/risks/SSRImosholder/index.php
7. Anne C. Mulkern, Panel hammers FDA on antidepressant issue Kids' suicide risk cited, Denver Post, September 24, 2004.
8.Irving Kirsch, Alan Scoboria, Thomas J. Moore, Antidepressants and Placebos: Secrets, Revelations, and Unanswered Questions, Prevention & Treatment, Volume 5, Article 33, posted July 15, 2002 http://journals.apa.org/prevention/volume5/pre0050033r.html
9. GAO Report http://www.ahrp.org/cms/content/view/148/28/
Contact: Vera Hassner Sharav
From: MEDWATCH - The FDA Safety Information and Adverse Event Reporting Program [mailto:MEDWATCH@LIST.NIH.GOV ] On Behalf Of CDER MEDWATCH LISTSERV
Sent: Friday, May 12, 2006 11:09 AM
Subject: FDA MedWatch - Paxil/Paxil CR (paroxetine HCl) and recent meta-analysis of paroxetine showed a higher frequency of suicidal behavior in young adults treated with paroxetine compared with placebo
MedWatch - The FDA Safety Information and Adverse Event Reporting Program
GlaxoSmithKline (GSK) and FDA notified healthcare professionals of changes to the Clinical Worsening and Suicide Risk subsection of the WARNINGS section in the prescribing Information for Paxil and Paxil CR.
These labeling changes relate to adult patients, particularly those who are younger adults.
A recent meta-analysis conducted of suicidal behavior and ideation in placebo-controlled clinical trials of paroxetine in adult patients with psychiatric disorders including Major Depressive Disorder (MDD), other depression and non-depression disorders. Results of this analysis showed a higher frequency of suicidal behavior in young adults treated with paroxetine compared with placebo.
Further, in the analysis of adults with MDD (all ages), the frequency of suicidal behavior was higher in patients treated with paroxetine compared with placebo. This difference was statistically significant; however, as the absolute number and incidence of events are small, these data should be interpreted with caution. All of the reported events of suicidal behavior in the adult
patients with MDD were non-fatal suicide attempts, and the majority of these attempts (8 of 11) were in younger adults aged 18-30. These MDD data suggest that the higher frequency observed in the younger adult population across psychiatric disorders may extend beyond the age of 24.
It is important that all patients, especially young adults and those who are improving, receive careful monitoring during paroxetine therapy regardless of the condition being treated.
Read the complete MedWatch 2006 Safety Summary, including links to the Dear Healthcare Professional Letter and the revised approved product labeling at: http://www.fda.gov/medwatch/safety/2006/safety06.htm#paxil
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Benbow: "...I can tell you the data that we provide to them clearly shows no link between Seroxat and an increased risk of suicide no link...
Benbow: ...Not only that but Doctor Healy has made the same claims about a range of other medicines. He made the same claims about Prozac
he made the same claims about a range of other SSRIs. On every occasion he has been found to be wrong.
PharmaPsych Alistair Benbow
GSK's Paxil/Seroxat/Aropax Ambassador to Europe,
affectionately known by people around the world as
'Mr Happy' because of his ever-cheerful demeanor,
smiles broadly for TV cameras while denying there is
any truth to nasty rumours that the Crappy Pills he
peddles can and do cause suicidality or withdrawal.