Seroxat Litigation Chronicles - Tuesday1st

Seroxat Litigation – The CSM Expert Working Group on SSRIs – Hugh James Solicitors, the “Judicial Review” and Seroxat User Groups

2011-01-02T23:59:00.002Z

UK Seroxat Litigation Lead Lawyer Mark Harvey of Hugh James Solicitors, Cardiff, used the threat of “judicial review” and complaints made by the Seroxat User Groups (SUG) to facilitate unseating members of a Committee on Safety of Medicines (CSM) expert group investigating the safety and efficacy of the SSRI, SNRI drug class. As shown by the following quote from the CSM new Expert Working Group (EWG) report On the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants published December 2004 -

“On 21 November 2002, a group of CSM and external experts was called together to hear Dr (now Professor) David Healy present his research in relation to suicidal behaviour, including a reanalysis of human volunteer studies on fluoxetine

The conclusions of this meeting were that:

• the evidence presented did not justify a change to the regulatory position;

• changes to the UK Seroxat PIL were required to clarify warnings on withdrawal reactions

The meeting recommended the following further work to investigate suicidal behaviour:

• a study using the GPRD;

• reanalysis of clinical trial data on fluoxetine.

A further meeting of this expert group had been planned for March 2003. However, the Seroxat User Group, a group of 4,000 patients and former patients, called into question the independence of the members of the group in view of declarations of interest in the pharmaceutical industry by two members. Following legal advice, the meeting in March was cancelled and the group dissolved. It was important that this work was continued, and in May 2003 the CSM established its Expert Working Group on the Safety of SSRIs.”

the remit of the CSM and expert group did not change – sidestepping the problem without further delay to allow what they considered “important” work on the SSRI, SNRI issues started in 1998 to continue.

The new Expert Working Group was formed due to complaints raised against two members of the original expert group by the SUG groups, whose influence is evident in the CSM EWG final report published December 2004 - but not exclusively in the above statement.

The “Membership of the Expert Working Group on the safety of SSRIs“ (section 1.5 of the report copied below) details not only the members of the group, but all who participated including experts “Visiting” for the meeting of June 4th 2003, “Invited experts who presented evidence to the EWG” and “Patients, relatives and their representatives who gave evidence to the EWG”.

Although as it’s name implies, the investigation of the “CSM EWG on the safety of SSRI Antidepressants” encompassed all drugs in the SSRI, SNRI class, it appears that representation from the prescribed population or their representatives was restricted to members of SUG groups and those involved due to a direct link to the drug Seroxat.

“Patients, relatives and their representatives who gave evidence to the EWG

Seroxat User Group

Online Seroxat Support Group

Mr Graham Aldred”

With regard ADRs, side effects, discontinuation problems, aggressive and suicidal behaviour suffered by patients who had or were taking SSRI, SNRI drugs other than Seroxat - there was no personally delivered advocacy or representation by or on their behalf - despite Mark Harvey, the Invited expert witnesses and the CSM having previously liaised with established UK action groups concerned with prescription drug adverse reactions and addiction who were collating information and patient experiences caused by various SSRI, SNRIs from the 1990s.

There are a great number of prescription drug support groups, many dedicated to SSRIs, most Internet and American based, started by individuals in the 1990’s when the drug class ADR problems became apparent and litigation's against manufacturers were instigated, firstly in the USA and then the UK. In this realm the “Seroxat User Groups” are relatively new as they were not formed until 2002, after the Seroxat Litigation had been preannounced by Hugh James’ Mark Harvey in December 2001 on behalf of 30 to 40 who came forward following news of a USA legal case filed on August 24th 2001.

When the threat of “Judicial Review” was used against the original expert group in late 2002 the Seroxat User Group.org reported to represent “4,000” people, at the SUG MIND MHRA demonstration in May 2003 they reported representing “5,500” and at the meeting with “The European Agency for the Evaluation of Medicinal Products” (EMEA) held April 2004 they reported representing over “10,000” people – yet late last year there was an announced that the number of people being represented at court in 2011 is only about 350.

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“Online Seroxat Support Group” (OSSG)

The original and first UK Yahoo Group then called the “Seroxat-SeroxatUserGroup” (SUG) set up in April 2002 and owned by Anti-Seroxat and Glaxo Smith Kline (GSK) campaigner Derek Scott, a ‘supposed’ support group and additional SUG discussion forum, later abandoned and replaced with another Seroxat OSSG website.

Derek Scott actively encouraged group members to join the Seroxat litigation, supplying Solicitors contact details in “Welcome to group” letter, whilst he also actively discouraged and disallowed drug related -unless adverse and Seroxat orientated- information or withdrawal advice and help being posted, kept the group locked down for members only (non Seroxat prescribed members not tolerated) and banned members for inter group posting.

In about 2004 Derek Scott wiped the groups early post archives, renamed the group OSSG and in 2006 culled and banned most of his members without notice, the group has had little traffic since. It is believed Derek Scott moved to the blogs in 2006, along with several of his most ferociously outspoken activist group members, all Anti-Seroxat and GSK campaigners, including litigant Bob Fiddaman, fiddaman.blogspot.com under the title “SEROXAT SUFFERERS” who was a SUG group moderator and claims to be a self appointed “patient advocate” - Roger Cleghorn, seroxatsecrets.wordpress.com - Mathew Holford, itsquiteanexperience.blogspot.com.

The correspondence lobbying Derek Scott and this select activist group have subjected members of the UK government and government drug regulatory authorities to - has been at times relentless, engineered to monopolise the officials and authorities time, rude, often derogatory and ongoing until 2009, and appears to have alienated many of those in authority who were at least willing to listen - quite possibly to the detriment of all efforts by others to get the SSRI, SNRI issue and other drug problems addressed.

Sarah Venn was a member of this SUG group before becoming involved with the Lawyer set up SeroxatUserGroup.org (SUG.org) of which she was made a Committee Member and started up the second and successive SUG support forum and groups. Derek Scott was involved with the 2002 lawyer led formation of SUG.org but did not take up his offered seat on the committee.

- - - - -

“SeroxatUserGroup.org” (SUG.org) and “Seroxat User Group” (SUG)

Owned by Sarah Venn (Barrister), whose father Ernest Venn had alerted her to a problem with Seroxat in 2000, although run by Janice Simmons and Andrew Issac (then Medical Student) since 2004. Set up in June 2002 by Mark Harvey of Hugh James Solicitors, for the Seroxat Group Litigation litigants. According to Issue 1 of the “Seroxat User Group Newsletter” published September 2002 on Hugh James headed paper, Mark Harvey, presumably on Hugh James’ behalf, undertook to continue with IT support, newsletter production and, again presumably, funding for the SUG.org website which is still running.

“Hugh James will prime the Group and continue to support it, for instance with IT support and production of the newsletter.”

In the SUG newsletter Issue 1 Mark Harvey states strategy’s for future action by himself and those involved with the Litigation and all SUG Groups including in the case of changes not being made to the patient information and data sheet.

“the possibility of Judicial Review of the Medicines Control Agency if it continues to decline to act in response to the substantial evidence of dependency.”

Directing all group members to take the following action

“At the first meeting of the Group it was decided that all members should write to their local MP's along the lines of the letter attached at the end of this newsletter (It need not be copied exactly). The MP has an obligation to respond to the letter within 14 days and should be directing their constituents' concerns to the Department of Social Security and then the Medicines Control Agency (MCA).

Those Group members who have not written are encouraged to do so. Hugh James has written to the MCA inviting it to take the evidence offered by its clients of the withdrawal problem. To date the MCA has only ever accepted Adverse Drug Reaction reports from doctors.”

Along with the dictate that

“Mark Harvey of Hugh James continues to invoke media interest wherever possible to generate public pressure on GSK and the government. If any Group members have any links with any media would they please let Mark know through his secretary, Marlene.

It would be helpful however to ensure consistency of approach and efficiency of useage if interviews could be channelled through Hugh James, who can offer the use of a Public Relations company to manage the media effectively and with as little intrusion to members as possible.”

Mark Harvey, Hugh James and their Media and Public Relations Company "Good Relations" were actively generating publicity in their own right, also promoting and in total control of both SUG group members who were in contact with the press and what they said. The SUG.org committee reiterated the need to keep all communications centralised, professional and through them in the March 2003 Seroxat User Group Newsletter issue 2,

"It is in the interests of the Group that communication with the media, Seroxat experts and related organisations is channelled through the committee. Please forward your views to a member of the committee and help us maintain a uniform and professional approach.”

both SUG support groups owners, Derek Scott and Sarah Venn, openly encouraged group members to go to their local press, any approaches by the mainstream press and media for people to be interviewed were published on the SUG groups message boards and all resulting contact channelled through them or the SUG.org committee back to Hugh James Solicitors and “GoodRelations”.

In the March 2003 SUG Newsletter issue 2 the SUG.org committee congratulated themselves and SUG members for their successful achievements in the “MP letter campaign” and the resulting “intense review of Seroxat”,

“The Group’s first achievement is an intense review of Seroxat by the government, which follows the MP letter campaign. The review was prompted by a well supported Motion in the House of Commons (thanks to your letters) calling on the Department of Health to look into the labelling and availability of Seroxat. The committee is in communication with the MCA, CSM and Professor Mackay, who is leading the Review, and will be meeting with them shortly.”

which is a little confusing and misleading - as the only “Review” being lead by Angus Mackay whom they were in communication with along with the MCA and CSM – was the original and ongoing 1998 expert group investigation instigated, which following Mark Harvey’s 2002 threat of “Judicial Review” and SUG complaints - became the newly formed “CSM EWG into the safety of SSRI Antidepressants” – who planned to meet May 2003.

Other than numerous articles in papers and magazines, two of the candidates for the SUG.org committee Paula Boddington (Research Associate, HeLEX , Senior Researcher in Ethics and Genetics, Ethox, Oxford University) and Sarah Venn took part in TV programs.

Paula Boddington appeared along side Dr David Healy and Mark Harvey in the first program about the SSRI, SNRI drug class, BBC Wales’ “Week In Week Out” program “Mind Games” which aired May 28th 2002. Paula Boddington’s manifesto submission for a place on the SUG.org Committee was not successful and she subsequently disappeared from active campaigning.

The BBC’s Panorama aired the first Seroxat program “The secrets of seroxat”, October 13th 2002, under the helm of their newest reporter Shelley Jofre – who self reported liaising where the production took place in London, with UK Lawyers throughout the eight months of production. The airing was preceded by a BBC Panorama article “Anti-depressant can be addictive”, announcing the forthcoming program, detailing the worse discontinuation withdrawal ADR symptoms, the American Attorney’s involved with the Tobin v SKB (GSK) Schell case including the amount of compensation awarded, although the amount actually paid at appeal has not been disclosed.

BBC Panorama’s “The secrets of seroxat” program and announcement was strangely void of any mention of the UK based Lawyers, the 2001 preannounced UK Seroxat litigation, SUG.org, SUG groups, Charles Medawar’s Social Audit or the mental health charity MIND - although following the programs airing viewers who contacted the program were given their details and asked to fill out ADR reports by way of a “special version of the Yellow Card designed for Panorama by MIND” - as reported in the SUG.org March 2003 Newsletter Issue 2,

“BBC Panorama is planning to broadcast a follow up to the ‘Secrets of Seroxat’ documentary in May. Many of you who contacted the programme will have been asked by the producer to fill in a special version of the Yellow Card designed for Panorama by MIND. The Yellow Card system is used by GPs to report drug safety issues to the Medicine’s Control Agency. If your GP has not already filled in a Yellow Card about Seroxat, please ask them to do so.”

these exceptional Yellow Cards formed an integral and “substantial” part of the SUG.org and SUG groups representatives evidence presented to the CSM EWG. According to SUG Newsletter Issue 1 Hugh James Solicitors’ Mark Harvey had, in mid 2002, “invited” the MCA to take SUG and 800 clients evidence of dependency / withdrawal as “official reports” (without medical accreditation), at this , at this time he also highlighted the possibility of “Judicial Review” if it continued to decline.

The MCA / MHRA did eventually accept the SUG evidence along with the Panorama generated Yellow Card reports and included all in the MHRA Pharmacovigilance Services Yellow Card Data and Drug Analysis Prints (DAPs).

Sarah Venn appeared on day time TV interviewed with GSKs Dr Alistair Benbow and was featured in the BBC Panorama’s third Seroxat program “Taken on trust” with Dr David Healy, Charles Medawar, Richard Brook of MIND and Graham Aldred, the program aired October 3rd 2004 shortly before the CSM EWG report was published. Although Sarah Venn became one of the four SUG.org Committee members, she resigned to resume her legal career in late 2003.

The SUG Newsletter Issue 1 detailed formation of a committee to run the organisation and associated meta-linked Internet “support” group and contained the “manifesto’s” of nine prospective members, from which four members were chosen and instated - although there appears to have been no formal election. After the initial two meetings and publication of SUG.org Newsletters Issue 1 and Issue 2 in March 2003, there also appears to have been no further formal committee activity, annual general meetings, minutes or donation / funds bank account published, and Charity status although announced has not been acquired from the Charity Commissioners.

The Seroxat User Group.org validity was called into question by Lord Hunt who, after meeting SUG representative Janice Simmons who was seeking funding, June 18th 2007, reported in Hansard that “he would look into it, but there must be some sort of formal structure to the Seroxat User Group in order to qualify for funding”. It appears no funds were received by the SUG.org group, presumable it would be safe to assume the SUG group had no “formal structure” or legitimacy.

Janice Simmons and her husband John also attended meetings with –

April 19th 2004, EMEA, a decentralised body of the European Union, also attended by John Janyga (SUG), Derek Scott (OSSG), Faye & Peter Elliott (OSSG) and Millie Kieve (APRIL.org.uk), experts Dr Andrew Herxheimer (Emeritus Fellow at the UK Cochrane Centre in Oxford) and Richard Brook (MIND)

March 2nd 2006, Jane Kennedy MP the Public Health Minister, Charles Walker MP and as reported unnamed SUG colleagues

November 29th 2007 - her MP Jonathan Djanogly and the then Prime Minister Gordon Brown

Earlier SUG Campaign activities included a May 2003 demonstration with members of mental health charity MIND at the MHRA London offices. When their chairperson Sarah Venn reported representing “5,500” SUG members, also that the intention was to “put pressure on the agency” to disallow new Seroxat prescriptions until after the “review” involving their evidence of peoples experiences with drug finished and unsubstantiated opinion “that there have been more than 30 suicides within days of people starting to take Seroxat”.

The SUG.org website was set up meta-linked to the Hugh James website. To gain access to the SUG.org website, make enquiries, ask for advice, information or to access the SUG Discussion Forum and two further Yahoo SUG (SUG) support Groups for support - all enquirers were redirected to the Hugh James website; once there a registration form asking for personal details including full name, address, telephone numbers and medical questionnaire was required to be filled out and submitted prior to gaining access to the SUG groups website. Presumably all who registered will have been logged and counted as members.

- - - - -

Meta-linked - “Seroxat User Groups”

The SeroxatUserGroup (SUG) Discussion Forum and two further Yahoo SUG support Groups were all set up in succession by Sarah Venn, and run independently of, but in competition for the highest membership numbers with Derek Scott’s original SUG Group, although posting drug related information was not restricted, inter group posting was frowned on.

Due to the obvious link to the Lawyers website, pertinent questions were asked of the Committee members with regard group members not being given important and relevant information. Especially as to how any successful claim and payout would affect the many dependant on state benefits because of health problems – most in the wake of the Tobin v SKB (GSK) Schell case seemed to have been given the false impression that more realistic but still substantial life changing compensation sums would be paid.

In all probability, in the UK for the “no fault liability to GSK” on a “defective product” claim any payouts for a “withdrawal” problem will not be life changing amounts, those dependant on benefits would possibly find their benefits stopped completely leaving them in a worse situation. The government also have in place a “Compensation Recovery Unit” (CRU) a supplementary agency of the Department of Social Security, whereby any benefits paid to claimants on the grounds of the drug caused incapacity - can be clawed back from the any lump sum compensation paid to individuals in receipt of benefits.

Despite these questions being asked of the committee, along with requests that direction or advice be sought from Mark Harvey and Hugh James on the members’ behalf - no answers, directions or advice was forthcoming at the time or to current knowledge - since. The only action taken was that Sarah Venn, the group owner and SUG.org committee member, closed the original meta-linked SUG Discussion Forum without notice to the members, moved it to Yahoo Groups, when the same type of questions were asked this group was also closed, a third group was set up but was closed after the post archives were deleted, 2003/4.

- - - - -

Mr Graham Aldred

The only person from the “Patients, relatives and their representatives” contingency independent of the SUG Groups to give evidence to the CSM EWG was Graham Aldred, a colleague of Dr David Healy, his personal link and interest in Seroxat is through his late wife Rhona who sadly took her own life in 2001, eleven days after starting treatment with the drug.

Graham Aldred, a research associate at North Wales Department of Psychological Medicine, Hergest Unit, Ysbyty Gwynedd, Bangor, North Wales carried out a statistical research study on the prescribing trends of Seroxat resulting in the paper “The Decline of use of Paroxetine in England” being published May 17th 2004.

The study concentrated on the suicide issue, above all else clarifying that the problem affected all age groups not just under-18’s and shows a gradual decline in Seroxat total prescription numbers 2001 to 2002, this gradual decline as a result of adverse publicity given to the drug went into a virtual freefall 2002 to 2003, resulting in a 36% decline for the period 2001 to 2003 and highlights the relevant publicised events which obviously influenced the decline through public and prescribing medical professional awareness being raised.

Graham Aldred appeared with Dr David Healy, Charles Medawar and Richard Brook in the second BBC Panorama Seroxat program “Seroxat: e-mails from the edge” aired May 11th 2003, and the third BBC Panorama Seroxat program “Taken on Trust” which aired October 3rd 2004. Both programs airing appears to have been timed to pre-empt CSM events – the second program days before the new CSM EWG inaugural meeting and the third just prior to the publishing of the final report early December 2004.

The published Aldred Study paper is a damning document to the reputation of both Seroxat and its manufacturer GSK; in conclusion Graham Aldred also pays tribute to the Public Service Broadcasting and Internet communication that triggered awareness of the SSRI issues and highlights the efforts of some medical professionals and those pursuing legal recourse.

“6.0 Conclusions.

Chart 5 demonstrates the immense value to Society of free and independent Public Service Broadcasting and Internet communication. This combination has triggered the growth of awareness of SSRI danger. It has united the many thousands of victims of SSRIs across the world with some professionals who have laboured so long in a cause for saving lives, seeking justice and exposing dysfunctional drug regulation. Chart 5 shows that the tide has turned in the UK. Great encouragement should be taken from this life saving victory. However efforts must continue both to expose the known risks of paroxetine (Seroxat, Paxil) and all the other ill validated SSRIs and to call for the establishment an effective independent Drug Safety Regulator in every country, the absence of which is the root cause of this ongoing officially supported tragedy.”

Although their have been other suicides in the UK attributed to drugs in the SSRI, SNRI class - the devastating loss of his wife Rhona, his understanding of the core issues with the SSRI, SNRI drug class, his courage and willingness to speak out despite his grief placed Graham Aldred, as an accredited academic, and his evidence in an exceptionally powerful position at the first new CSM EWG meeting in May 2003, with the ability to - besides the obviously incriminating involvement of GSKs Seroxat - make a difference to the whole drug class suicide and ADR situation.

Undoubtedly Graham Aldred’s evidence, along with that of the “Invited” experts Dr David Healy, Dr Andrew Herxheimer and Charles Medawar, of Social Audit, raised awareness of the suicide issue in all age groups and facilitated recommended changes to the treatment of depression and unmonitored, ever increasing, over prescribing trend of the SSRI, SNRI drug class at primary care level as highlighted in the CSM EWG group report and the simultaneously published National Institute for health and Clinical Excellence (NICE) new Clinical Guidelines for the Treatment of Depression in adults.

- - - - -

For reason that would not become apparent until 2009 when Seroxat Group Litigation Order No:68 was discovered - the SUG group members, Anti-Seroxat and GSK campaigners, Mark Harvey and Hugh James’ PR Company “Good Relations” made considerable efforts to take and keep control of the ongoing SSRI, SNRI drug class investigation, to dominate media coverage, concentrate and keep the drug class issues focused solely on Seroxat –

effectively excluding other UK based independent campaigners, groups and organisations, some who had been liaising and working with Dr Healy and Charles Medawar since the 1990’s on behalf of those taking specific or any SSRI, SNRI drug, antidepressants and other psychotropic drugs from giving representation to the CSM EWG.

The same excluded independent campaigners, group and organisation owners - had been working to support those affected by drug ADRs and raise awareness along side the experts with the MCA, CSM and NICE - and had been instrumental in attaining the original expert group investigation into SSRI, SNRI class drugs.

Including but not limited to -

Pam Armstrong, “Back to Life” website and with Peter Ritson the “Council for Information on Tranquillisers” (CITA) set up in 1987, additionally now encompassing information and withdrawal of “Antidepressants, and Painkillers”.

Millie Kieve, who started investigating ADRS and side effects of psychoactive medication following the untimely and devastating death of her daughter in 1995, going on to set up APRIL.org.uk a registered Charity working to raise awareness about drug dangers and their responsible safer use on behalf of patients.

Ramo (Ramzia) Kabbani, who set up the first UK based SSRI, SNRI support group the “Prozac Survivors’ Support Group” in 1999. [Link broken group no longer open]

Ray Nimmo, campaigner and Web Master of Benzo.org.uk, set up in 2000, again another website that encompasses SSRI, SNRI information and has related archived information from 1999 onwards.

Paula, “SSRI Withdrawal Support Site” UK based SSRI, SNRI support site started 2001, Info Board and Discussion Forum, referred to by Seroxat Campaigners as “network54”, an uncompromising neutral group dedicated to exposing the truth about all psychoactive drugs, psychiatry and the misdemeanours of the pharmaceutical industry. Derek Scott and Sarah Venn were both members prior to opening their SUG group.

It appears Millie Keive was the only non SUG patient representative to attend the 2004 EMEA meeting - or any meeting arranged by SUG groups with authorities and government officials.

They all had an immense amount of knowledge, information, articles and personal stories of those adversely affected by the SSRI, SNRI drug class archived on their websites that could have been utilized by the CSM EWG. However, it appears it was not considered relevant, useful or needed by the SUG group members, Anti-Seroxat, GSK and pro Litigation Campaigners, Mark Harvey and Hugh James’ PR Company “Good Relations” - either then or since –

and although the excluded independent campaigners, group and organization owners have unquestioningly supported the SUG Seroxat Litigation Campaign - that support does not appear to have been reciprocated.

Since its publication neither Graham Aldreds’ damning anti Seroxat and GSK study or his later work on Baseline Suicide Rates (BSR) and Investigative Medication Routine (IMR) models have featured in or been used by SUG campaigners to raise awareness of either the Seroxat or SSRI, SNRI drug class issues.

Similarly the Report of the CSM EWG in finding all SSRI, SNRIs including Seroxat, lacking in safety and efficacy and causing discontinuation, withdrawal problems - effectively proved the Seroxat Litigation case being brought under Consumer protection Law for a Faulty Product on the caused discontinuation withdrawal problems, but has - aside from the initial furore of claiming credit for the report and hypothetical under-18’s SSRI’s “banning” – not featured in the ongoing SUG and Seroxat Litigation campaign.

Although the Aldred study was focused on Seroxat and the CSM EWG report named Seroxat more times than any other SSRI, SNRI drug - in their conclusions, recommendations and in the case of the CSM report actions taken neither actually singled out or categorically stated that Seroxat was worse than any other drug in the class. Likewise the excluded independent campaigners, group and organization owners although supportive of the SUG and Litigation campaign, raised awareness of the whole SSRI, SNRI drug class problem - not just Seroxat’s.

It appears the neutrally written supportive evidence that suicide, aggressive behaviour, ADRs and discontinuation problems appertain to Seroxat and all drugs in the SSRI, SNRI class – was and still is superfluous as it undermines the ultimate aim of the in SUG and Seroxat Litigation campaigners - to prove Mark Harvey’s Seroxat Litigation Order No: 68’s Defining Issue “stipulation” - that any adverse effects and discontinuation, withdrawal difficulties suffered by the Seroxat “user” has to be

“…to a greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”

HM Courts Service: Queens Bench Division: Seroxat Group Litigation Order no: 68.

Other than instigating the re-formation of the CSM EWG, the investigation into GSK and inflating the number of Yellow Card reports for Seroxat - unfortunately - it appears the one real achievement of the SUG, Seroxat litigation campaign thus far, is the welcome 57% decline in annual total Seroxat prescriptions issued - from it’s 2001 3.78m peak to it’s 2009 total of just 1.63m -

all be it at the expense of those now possibly unable to discontinue taking one of the 24.31m other brand SSRI, SNRI prescriptions issued in 2009 - over and above that decline.

Indeed the SUG and Seroxat Litigation campaign “orchestrated” by Mark Harvey appears to have been detrimental to progress being made by others in raising awareness of or just trying to help those affected by the problems and issues with any psychiatric medication and the whole SSRI, SNRI drug class - whose prescriptions are still escalating.

As the prescription total decline detailed in the Graham Aldred study shows it is not impossible to stop taking Seroxat – have the SUG group members, Anti-Seroxat and GSK Campaigners, Mark Harvey, Hugh James and their PR Company “Good Relations” - ultimately become victims of their own propaganda and campaigns success?

And at whose expense?

The CSM Expert Working Group (EWG) report On the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants - published December 2004.

“1.5 Membership of the Expert Working Group on the safety of SSRIs

Professor Ian V D Weller MD FRCP - Chairman

Professor of Sexually Transmitted Diseases and Director of Centre of Sexual Health and HIV Research, Royal Free and University College Medical School, University College, London

Professor Deborah Ashby BSc MSc PhD CStat Hon MFPH Hon MRCR

Professor of Medical Statistics, St Bartholomew’s and the London, Queen Mary’s School of Medicines and Dentistry, University of London

Mr Richard Brook (from May 2003 to March 2004)

Chief Executive of MIND

Professor Mary G A Chambers Bed (Hons) DPhil RN DN (Lond) RNT

Chief Nurse and Professor of Mental Health Nursing at South West London and St George’s Mental Health NHS Trust

Dr Jonathan D Chick MA MB ChB MPhil FRCPsych FRCP (Ed)

Consultant Psychiatrist, Alcohol Problems Service, Royal Edinburgh Hospital, and part-time Senior Lecturer at Edinburgh University

Professor Colin Drummond MD FRCPsych

Professor of Addiction Psychiatry, St George’s Hospital Medical School, London

Professor Klaus P Ebmeier MD

Professor of Psychiatry, University of Edinburgh

Professor David J Gunnell MB ChB MRCGP FFPH MSc PhD

Professor of Epidemiology, Department of Social Medicine, Bristol University

Ms Hilary Hawking (from October 2004 to date)

Clinical Governance User representative for South West London and St George’s Mental Health NHS Trust

Dr Elizabeta Mukaetova-Ladinska MD PhD MRCPsych

Consultant Psychiatrist, Newcastle General Hospital, and Senior Lecturer in Old Age Psychiatry, Newcastle University

Mr Eamon O’Tierney MA (Cantab) ASA (from May 2003 to September 2003)

Member of the Royal College of Psychiatry’s Committee for Patients and Carers

Dr Ross J Taylor MD FRCP (Edin) FRCGP DCH

Senior Lecturer in General Practice, University of Aberdeen

Dr Ann York MB BS MRCPsych

Consultant and Honorary Senior Lecturer in Child and Adolescent Psychiatry, Child and Family Consultation Centre, Richmond Hospital, Surrey

Dr Morris Zwi MBBCH FRCPsych

Consultant Child and Adolescent Psychiatrist, South West London and St George’s Mental Health NHS Trust

Visiting experts for the meeting of 4 June 2003

Dr Santosh Paramala

Consultant Child and Adolescent Psychiatry, Guy’s Hospital, London

Professor Peter Hill

Professor of Child and Adolescent Psychiatry, Great Ormond Street Hospital for Sick Children, London

Professor Eric Taylor

Professor of Child and Adolescent Psychiatry, Institute of Psychiatry, King’s College, London

Invited experts who presented evidence to the EWG

Professor David Healy

Professor of Psychological Medicine, Hergest Unit, University of Wales, Bangor

Dr Andrew Herxheimer

Emeritus Fellow at the UK Cochrane Centre in Oxford

Mr Charles Medawar

Social Audit

Professor Munir Pirmohamed

Professor of Clinical Pharmacology, Liverpool University

Patients, relatives and their representatives who gave evidence to the EWG

Seroxat User Group

Online Seroxat Support Group

Mr Graham Aldred”

Seroxat Litigation - Report of the Committee on Safety of Medicines Expert Working Group on SSRI Antidepressants, 2004 - ‘Suicidal Behaviour in association with SSRI’

2010-12-18T13:25:00.006Z

The previous and following excerpt of the Committee on Safety of Medicines (CSM) Expert Working Group (EWG) report “On the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants” published December 2004 shows that the issue of withdrawal, dependence, suicidal and aggressive behaviour in associated with SSRI fluoxetine (Prozac) was under review with some gravity by the UK Medicine Control Agency (MCA) and CSM from 1990, referenced in MCA / CSM 'Current Problems in Pharmacovigilance', June 1992.

The review widened encompassing newer SSRI drugs when approved and licensed, close monitoring of spontaneous adverse drug reports (ADRs) lead to “a UK exercise in 1998 -2000 to develop harmonised safety information for all SSRIs”, acknowledging that all drugs in the class induced similar ADRs and side effects, and Dr David Healy’s 1999 publication ‘A Failure to Warn’ raised the level of concern in the issue of suicide and introduced SSRI induced akathisia - the now acknowledged precursor to suicidal ideation and action.

Dr David Healy was in correspondence with the MCA by November 4th 1999 about the suicide issue and voicing concerns about the number of SSRIs being prescribed to children and adolescence,

“Both of these points, it seems to me, must be of concern to you. The issues are quite different to any problems that were ever raised in relation to benzodiazepine or SSRI dependence, where there is considerable ambiguity involved in deciding what constitutes dependence. In this case there are very clear internal company documents and a pattern of behaviour, possibly stemming from legal advice, that is inconsistent with prescription only arrangements.

Based on RCT evidence from a number of companies, epidemiological studies and other sources, at a conservative estimate I believe one person per week has killed themselves in the UK for every week that Prozac has been available over and above the number that would have done so if the same patients had been left untreated and one person per day has attempted suicide with unknown consequences for their future risk of suicide. I would be happy to go through this evidence with you, if this would help and indeed I would be happy to have the error of my ways pointed out if anyone can see a problem with my figures or logic.

Against the background outlined above, I feet particularly impelled to act as I am doing now in writing to you having been the convenor and author of a report on childhood psychopharmacology for the British Association for Psychopharmacology, which supported the prescription of psychotropic drugs to children and teenagers in appropriate circumstances and with appropriate monitoring. This document has not led directly to increased rates -of prescribing of SSRIs to adolescents in this country but it has done nothing to put a brake on what has been a dramatic increase in' recent years. Unfortunately, I now find my in-tray filling with files on teenagers committing suicide within a week or two of commencing Prozac. It is this that makes the problem difficult to walk away from.”

one of his most cited studies “Emergence of antidepressant induced suicidality” was published March 1st 2000 in the International Journal of Psychiatry in Clinical Practice, Volume 6, Number 1.

In June 2000, although the CSM concluded it was “impossible to answer the question of whether SSRIs caused suicidal behaviour in a small subpopulation of patients”, they advised updating all SSRI and antidepressant patient information leaflets (PILs) adding “a warning that suicidal thoughts may occur or increase in the early stages of treatment”. In 2000 the UK SSRI suicide assessment was also presented to the EU Pharmacovigilance Working Party (PhVWP), where all members agreed with the scientific conclusions.

The CSM reviewed the suicidal behaviour, aggression and akathisia issue, December 2001, concluding the possibility of this affecting “a small high-risk population could not be ruled out”, and advised the risk of akathisia occurring be added to all SSRI Summaries of Product Characteristics (SPC). The UK assessment report was discussed at the PhVWP which agreed, but considered further discussion was required to clarify definition of the term akathisia.

November 21st 2002, Dr David Healy presented research relating to suicidal behaviour, including reanalysis of studies on fluoxetine, to a group of CSM and external experts who concluded, no change in regulatory position in relation to suicide issue, but advised changes to UK Seroxat PIL to clarify withdrawal reactions – also recommended a suicidal behaviour study using the General Practice Research Database (GPRD) and reanalysis of fluoxetine clinical trial data. Further expert group meeting planned for March 2003.

By March 17th 2003 the planned CSM meeting was intercepted, the expert group was dissolved.

The ‘expert group’ was dissolved following the November 21st 2002 meeting due to objections raised by Seroxat Litigation Lead Lawyer Mark Harvey and Seroxat User Groups (SUG) against two members of the panel Dr Michael Donaghy, a reader in clinical neurology from Oxford University, and David Nutt, professor of psychopharmacology at Bristol University who both disclosed holding shares in Glaxo Smith Kline (GSK) - the formation of a new CSM Expert Working Group was agreed by the end of January 2003.

Mark Harvey and the reported by Hugh James Solicitors and their Media and PR company GoodRelations, 4000 SUG group members were said to be “unhappy” that the CSM review panel had not agreed an undertaking to consider the groups evidence of side effects they said they have suffered - although it had invited representatives of the group to the planned meeting, whilst excluding representation of patients taking other SSRI SNRI class drugs.

Although according to watchdog organization Social Audit Charles Medawar’s February 26th 2003 complaint letter to the Rt Hon Frank Dobson PC MP, House of Commons and The Guardian health editor Sarah Bosely’s March 17th 2003 article – Charles Medawar was also “unhappy” about the choice of chairman, Angus Mackay, director of mental health services in Lomond and Argyle, Scotland, one signatory to the CSM 1996 paper which concluded SSRI withdrawal symptoms were rare, relatively mild and not meeting the World Health Organization (WHO) dependency criteria,

and drew attention to inconsistencies in CSM member Professor David Nutt’s personal interest disclosures, that according to the CSM website he had listed current personal interests in two other companies that make SSRIs Lundbeck: Citalopram Cipramil Celexa, Escitalopram Cipralex Lexapro and Wyeth, Pfizer: Venlafaxine Efexor Effexor, Medawar made no reference to three others which he disclosed at the November 21st 2002 meeting, Pfizer: Sertraline Lustral Zoloft, Eli Lilly: Fluoxetine Prozac Sarafem - Duloxetine Cymbalta Yentreve, and Solvay.

It was also revealed that in the minutes of the CSM November 2002 meeting another expert witness, Dr David Baldwin, now Reader in Psychiatry in the Clinical Neuroscience Division, University of Southampton School of Medicine declared a personal interest in Lundbeck, manufacturers of the drugs Escitalopram (Cipralex Lexapro) and Citalopram (Cipramil Celexa), now UK’s most prescribed SSRI

however, it appears that Mark Harvey and the SUG group members lodged no objections to his or Angus Mackay's involvement with the expert group.

It was later discovered Dr Baldwin had connections with five other companies all manufactures of SSRIs - Bristol-Myers Squibb (it’s SSRI Serzone Nefazodone was taken off market April 2004, for causing liver damage in dozens of patients, and linked to the deaths of 20 people), Wyeth (Venlafaxine Efexor Effexor), Eli Lilly (Fluoxetine Prozac Sarafem, Duloxetine Yentreve) , Organon (Merck Sharp & Dohme Limited: Mirtazapine Zispin), Pharmacia (owned by Pfizer Inc. Sertraline Lustral Zoloft) and SmithKline Beecham (Paroxetine Seroxat Paxil).

The Medicines and Healthcare products Regulatory Agency report “MHRA Investigation into Glaxosmithkline/Seroxat” published March 6th 2008, outlines the situation with regard prescribing antidepressants to children and adolescents, and the efforts of the CSM in gaining information from SmithKline Beecham plc (SKB), subsequently GSK .

October 13th 2002 the first BBC Panorama Shelley Jofre Seroxat program aired - at this point no antidepressants were specifically authorised (licensed) for treatment of depression in children and adolescents, until the mid-1990 clinical trials to investigate the safety and effectiveness of medicines in children were not encouraged. All drugs, including Seroxat, unlicensed or studied for use in children carry the following standard statement in the SPC in relation to use, the warning reads

“Children: The use of [drug name] in children is not recommended as safety and efficacy have not been established in this population”.

In preparation for the November 21st 2002 ad hoc expert group meeting into the safety of SSRIs and in the wake of the first BBC Panorama Seroxat program, the CSM called a meeting with GSK on November 14th 2002 with the focus of implementing further changes required to the Seroxat product information in relation to withdrawal. At this meeting the agency - obviously aware that GSK had carried out trials in the use of Seroxat in the paediatric population - asked about the status of clinical trials in children.

GSK provided an overview with regard the nine paediatric studies carried out between April 1994 and September 2002, declaring their proposal to submit a license application for the use of Seroxat for paediatric indications in late June 2003, although they did not raise concern about the lack of efficacy or adverse reactions; until licence was sought for paediatric use there was no requirement to submit paediatric study results.

The November 21st 2002 ad hoc CSM meeting with MHRA representatives and independent experts including Dr David Healy was planned to discuss issues relating to the SSRI drug class withdrawal reactions, although suicide and related events were also discussed, and recommendations made in relation to available safety data on adult use – as until this point the safe use in the paediatric population had not been officially raised.

January 2003, by this time the two members of the expert group panel had been singled out and the panel was under threat of a judicial review by the Seroxat Litigation lead lawyer Mark Harvey of Hugh James Solicitors. The MHRA presented recommendations to the CSM and they agreed further work on the SSRI issues was required, they formally agreed to establish a new Expert Working Group to Investigate the Safety of SSRIs in February 2003, the CSM expert group meeting planned for March 2003 was abandoned.

On February 28th 2003 - pre-empting the planned March 2003 CSM expert group meeting - GSK voluntarily sent the MHRA an update on clinical trial data in relation to suicidal behaviour, the submission included two sets of data analyses, both dated October 25th 2002. The submission included both adult and paediatric study data, but did not differentiate between the two – as the paediatric participant numbers were far less than the adults, their data and the relevance of the evident safety signal was lost in final evaluation.

Unfortunately, the enforced delay and formation of the new and ‘acceptable’ Expert Working Group to Investigate the Safety of SSRIs postponed the requested clarification and separation of GSK’s information until May 21st 2003, at a second meeting the CSM called with them in advance of the planned first new Expert Working Group meeting on May 23rd 2003.

The new Expert Working Group called the second meeting with GSK - in the wake of the second BBC Panorama Seroxat program which aired May 11th 2003 - wanting to ensure all data relevant to Seroxat’s safety had been supplied and to discuss communications GSK may make with prescribing professionals. At this meeting GSK proffered briefing document relating to their intended application to extend indications for Seroxat to include use in children and drew the Agency’s attention to a safety issue which GSK had identified.

The significance of the GSK briefing document data provided robust evidence from controlled studies of a causal association between an SSRI and suicidal behaviour, previously refuted by some manufacturers. The safety concern GSK highlighted was indication of an increased rate of events relating to suicidal behaviour among paediatric patients with depressive illness treated with Seroxat, compared to placebo; GSK also stated the Agency might wish to bear this information in mind when considering the application for use in children.

In response to requests from the Agency GSK urgently submitted full clinical trial data in children on May 27th 2003, the increased risk of suicidal behaviour was drawn from pooled analysis of all the trials (a meta-analysis) and also failed to demonstrate that Seroxat was effective in the treatment of depressive illness in children and adolescents. The overall benefit-risk balance was not positive for treatment of depressive illness in under-18s, the CSM advised prompt communication and a letter issued June 10th 2003 to UK health professionals stating Seroxat should not be used for this indication.

The agency also advised GSK to submit a variation to UK marketing authorisations for Seroxat (Paroxetine Paxil) ‘contraindicating’ use for children and under-18’s. Following this all other SSRIs were reviewed for safety and effectiveness in the treatment of depressive illness in children under 18 and adults, further advice statements were issued by the end of December 2003, first Fluvoxamine (Faverin Luvox) and then Citalopram (Cipramil Celexa), Escitalopram (Cipralex Lexapro) and Sertraline (Lustral Zoloft) were also ‘contraindicated’ for under-18s.

The Report of the CSM Expert Working Group published December 6th 2004 found all drugs in the SSRI class lacking efficacy and safety, simultaneously the National Institute for health and Clinical Excellence (NICE) published new Clinical Guidelines for the Treatment of Depression in adults, talking therapy, not drug therapy recommended for treatment of mild to moderate depression after a ‘watchful waiting’ period to facilitate possible self resolution.

The CSM Expert Working Group singled out Venlafaxine (Efexor Effexor) for its cardio toxicity, recommending cardiac monitoring for patients taking the drug and psychiatric practice prescription only - although this was discretely rescinded in 2006.

The CSM Expert Working Group also authorised Fluoxetine (Prozac Sarafem) -

a drug strongly indicated in many child and adult deaths by suicide and reported as causing similar side effects, adverse drug reactions and withdrawal symptoms as all other SSRI, SNRI drugs,
the drug Dr David Healy had corresponded with the MCA on November 4th 1999 with regard the suicide and paediatric increased prescription number issues -

for use in children and adolescents.

Until this point no antidepressant had been authorised or licensed for use in children, all prescribing of drugs of this type was off list and at the prescribing practitioners’ discretion.

Ironically - although it was widely reported that all drugs in the SSRI class bar Prozac were “banned” for children and under-18’s - in reality no SSRI is “banned” - to the contrary the investigation has resulted in one SSRI antidepressant drug being approved for paediatric use.

A drug has to be authorised and licensed for use before it can be “banned” - as no SSRI was approved, authorised or licensed for paediatric use in children and under-18’s, no SSRI has been “banned” - only ‘contraindicated' for use in treatment of depressive illness, and this is at the prescribing practitioners discretion as are most drugs – if they consider use of an SSRI drug would be beneficial to the patient, they can still prescribe any SSRI for the treatment of depression and any other indication - for any age group.

Clarified in the following quote from the MHRA website question and answers dated June 10th 2003,

ADVICE ON SEROXAT FROM THE COMMITTEE ON SAFETY OF MEDICINES

“ Q5. Is Seroxat licensed for the treatment of children and adolescents?

Seroxat has never been licensed for use in children and adolescents, however it is used in this age group outside its licence. Doctors may prescribe a medicine off licence if this is considered to be in the best interests of the patient.

Q6. My child is taking Seroxat for a condition other than depression – what should I do?

Seroxat has never been approved for use in children under the age of 18, however your child may have been prescribed Seroxat outside of its licence if their doctor considers it is the best treatment for their condition. If your child has been prescribed Seroxat for a reason other than depressive illness – e.g. obsessive compulsive disorder or an anxiety disorder, and you are concerned about their treatment, you should contact your doctor and discuss your concerns.”

Following GSK’s May 21st and 27th 2003 voluntary document disclosures and their highlighting of safety concerns, on October 1st 2003 the Pharmacovigilance Group of the Agency referred the matter to the their Enforcement Group for a criminal investigation, reportedly because GSK had been accused of withholding information, the investigation according to Social Audits’ Charles Medawar took up to a reported “30 man years” of MHRA time to complete – resulting in the report dated March 6th 2008 and the finding - no case to answer.

Presumably as other drugs in the SSRI class were also subjected to the hypothetical under-18’s “banning” during the CSM Expert Working Group investigation and all also found in the end report to be lacking in efficacy and safety in treatment of mild to moderate depression in adults - similar documentation with safety and efficacy anomalies appertaining to those drugs must have been found lodged with the Agency or newly disclosed by their manufacturers and reviewed - yet no other manufacturer was indicated or investigated for withholding information or not raising concerns about safety issues - only GSK.

The Seroxat litigation lawyer Mark Harvey of Hugh James Solicitors, BBC Panorama's Shelley Jofre and SUG Groups have claimed credit for the investigation into GSK, the hypothetical SSRI “banning” for under-18’s and the investigation by the CSM Expert Working Group into the Safety of SSRIs (Seroxat) as victories of their campaign against GSK and Seroxat – although any victory could be considered ineffectual and hollow.

Unfortunately, to my knowledge, the GSK full trail documents not being submitted to the CSM EWG review until May 27th 2003 and the ‘hypothetical’ Seroxat “ban” for under-18’s announcement not being made by the MHRA until June 10th 2003 has been blamed for being “to late” to avert at least one adolescent’s suicide in late May 2003. Could this death possibly have been avoided?

It would not be unreasonable to consider that had the planned March 2003 meeting not been intercepted and delayed by the Seroxat Litigation Lead Lawyer Mark Harvey and the SUG Groups - the May 2003 Expert Working Groups request for GSK's full paediatric trial results made on the same evidence initially presented in meetings between the CSM expert group , MHRA and GSK in November 2002 would have been made earlier – likewise the decision to contraindicate Seroxat for under-18’s and the June 2003 announcement could have been made in April 2003 and the late May 2003 suicide possibly averted.

Undoubtedly the first Panorama program brought focus to the SSRI issue and the November 21st 2002 CSM ad hoc meeting in its wake considered the class wide issue with the seriousness it deserved – however, the program effectively facilitated the hijacking of a drug class problem - which, according to UK National Prescription Cost Analysis statistics is ongoing and increasing - making it appear to be solely a problem with Seroxat.

This impression was reinforced by the second BBC Panorama Seroxat programs May11th 2003 airing, timed to precede the first meeting of the new CSM Expert Working Group and by Solicitors Hugh James’ Mark Harvey using the threat of a “judicial review” to attain compliance to their demands that the original expert group review panel be dissolved and GSK investigated.

This takeover and disregarding of the established ongoing 1998 investigation into the SSRI drug class - along with the efforts of the original expert group, Dr David Healy and others in raising awareness about the SSRI, SNRI drug class and their achievements in getting the withdrawal and suicide issues recognised and acknowledged by the UK MCA and CSM, and the EU PhVWP, all whom acted to implement amendments to both SPCs and PILs to include warning clarification with regard both issues by December 2001 – has, it appears, achieved little to address the drug class problems or stem the perpetually escalating numbers of SSRI, SNRI drug class prescriptions being issued.

Was the investigation into GSK instigated solely on complaints from the anti GSK, Seroxat litigation contingency and for what purpose - and could the MHRA’s “30 man years” have been better spent?

“On the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants” published December 2004

“2.2 Suicidal behaviour in association with SSRIs

In the UK, this issue was first reviewed by the CSM following publication of a case series by Teicher et al (1990)[7] which stimulated scientific debate and intense media interest. In 1992, following further review, an article was published in the 'Current Problems in Pharmacovigilance' which stated "there is little to support the suggestion that fluoxetine induces suicidal or aggressive behaviour"[8].

Following close monitoring of spontaneous suspected adverse drug reaction reports, there was a UK exercise in 1998-2000 to develop harmonised safety information for all SSRIs. During this process, the CSM advised that the summary of product characteristics (SPC) should reflect the general clinical experience that suicidal behaviour may increase in the early stages of treatment with any antidepressant.

Dr (now Professor) David Healy raised the issue of suicidal behaviour with SSRIs in his publication ‘A Failure to Warn’ in 1999[9]. Concerns were also raised that SSRIs may be associated with the development of psychomotor restlessness/akathisia-like restlessness, which in turn may precipitate agitation and suicidal behaviour[10].

The CSM considered the available data in June 2000 and concluded that it was impossible to answer the question of whether SSRIs caused suicidal behaviour in a small subpopulation of patients. It was decided that the issue should be kept under review and formally reviewed every two to three years.

The CSM advised that patient information leaflets for the SSRIs, as with any antidepressants, should be updated to include a warning that suicidal thoughts may occur or increase in the early stages of treatment and that urgent medical advice should be sought in the event of such symptoms.

The UK presented the assessment on suicidal behaviour with SSRIs to the Pharmacovigilance Working Party (PhVWP) in 2000. All EU member states agreed with the scientific conclusions of the UK assessment.

The CSM considered data relating to suicidal behaviour, aggression and akathisia in December 2001 and concluded that:
• the evidence was not sufficient to confirm a causal association between SSRIs and suicidal behaviour, although an effect in a small high-risk population could not be ruled out;
• the risk of akathisia occurring in association with treatment should be added to the SPCs of all SSRIs.
This assessment report was then discussed at the PhVWP which agreed with the conclusions of the UK assessment report but considered that further discussion was required about the definition of the term akathisia.

On 21 November 2002, a group of CSM and external experts was called together to hear Dr (now Professor) David Healy present his research in relation to suicidal behaviour, including a reanalysis of human volunteer studies on fluoxetine.

The conclusions of this meeting were that:
• the evidence presented did not justify a change to the regulatory position;
• changes to the UK Seroxat PIL were required to clarify warnings on withdrawal reactions.
The meeting recommended the following further work to investigate suicidal behaviour:
• a study using the GPRD;
• reanalysis of clinical trial data on fluoxetine.

A further meeting of this expert group had been planned for March 2003. However, the Seroxat User Group, a group of 4,000 patients and former patients, called into question the independence of the members of the group in view of declarations of interest in the pharmaceutical industry by two members. Following legal advice, the meeting in March was cancelled and the group dissolved. It was important that this work was continued, and in May 2003 the CSM established its Expert Working Group on the Safety of SSRIs.”

CMS EWG Quote References
1 - Lejoyeux M et al (1996) ‘Antidepressant withdrawal syndromes’ CNS Drugs 5: 278-292.
2 - Stoukides J A & Stoukides C A (1991) ‘Extrapyramidal symptoms upon discontinuation of fluoxetine (letter).’ Am J Psychiatry 148(9): 1263.
3 - MCA/CSM (1993) Current Problems in Pharmacovigilance 19.
4 - Medawar C (1997) ‘The Antidepressant Web.’ Int J Risk Safety Med 10: 75-126.
5 - http://www.emea.eu.int/pdfs/human/press/pp/277599en.pdf
6 - MCA/CSM (2000) Current Problems in Pharmacovigilance 26
7 - Teicher MH et al (1990) ‘Emergence of intense suicidal preoccupation during fluoxetine treatment.’ Am J Psychiatry 147:207-210
8 - MCA/CSM (1992) Current Problems in Pharmacovigilance 18.
9 - Healy D (1999): ‘A Failure to Warn [editorial].’ Int J Risk Safety Med 12: 151-6
10 - Lane RM (1998). ‘SSRI-induced extrapyramidal side effects and akathisia: implications for treatment.’ J
Psychopharmacology. 12: 192-214.

Seroxat Litigation - Report of the Committee on Safety of Medicines Expert Working Group on SSRI Antidepressants, 2004 - ‘Regulatory History’

2010-11-14T16:43:00.002Z

The much publicised Committee on Safety of Medicines (CSM) Expert Working Group (EWG) report “On the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants” published December 2004 has been haled as a victory in raising awareness about the problems associated with the drug class – which it was.

Mark Harvey of Hugh James, BBC Panorama’s Shelley Jofre, the Seroxat User Groups and Campaigners have laid claim to this as their achievement - although the drug regulatory and safety authorities were aware of, and investigating the issues of the drug class’ safety, propensity to cause suicide, dependency and withdrawal problems from the early 1990’s.

The issue of dependency associated with the SSRIs had already been discussed at European level by the Committee on Proprietary Medicinal Products (CPMP) and its Pharmacovigilance Working Party (PhVWP), in December 1998 the PhVWP decided France and Germany should further evaluate this issue resulting in a CPMP position paper published April 2000;

“The conclusion of the CSM and the CPMP was that all SSRIs are associated with withdrawal reactions; however, they are not drugs of dependence.”

on completion of the review on SSRIs drug class safety profile in relation to the dependence, withdrawal reactions and review of suicidal behaviour with SSRIs issue, a further article covering both aspects was published in 'Current Problems in Pharmacovigilance' September 2000.

As a result of the CPMP position paper (2000) product information for all SSRIs throughout Europe were changed in relation to inclusion of withdrawal reactions, UK product information for all SSRI, SNRIs were updated accordingly.

The following excerpt from the CSM EWG report briefly explains the history of the concerns, investigations and actions, early 1990’s to date of it’s publication December 2004

“2 REGULATORY HISTORY

This chapter outlines the regulatory history of SSRIs in the UK with particular referenceto the two mains areas of concern - withdrawal reactions and suicidal behaviour.

2.1 Withdrawal reactions in association with SSRIs

It has been known for many years that symptoms can occur on the withdrawal of antidepressants. Syndromes occurring on the withdrawal of tricyclic antidepressants (TCAs) have been defined and severe reactions have been noted on the withdrawal of monoamine oxidase inhibitors (MAOIs)[1]. Since the early 1990s, it has become clear that the SSRIs can also be associated with withdrawal reactions, although different SSRIs appear to cause withdrawal reactions to different extents[2]. The greatest number of spontaneous reports of withdrawal reactions have been associated with paroxetine. An article in 'Current Problems in Pharmacovigilance' in 1993 highlighted the risk of withdrawal reactions associated with paroxetine[3].

In late 1997, an article entitled 'The Antidepressant Web' by Charles Medawar raised concern that some people may become dependent on SSRIs[4]; this prompted a review of withdrawal reactions and dependence with these drugs. The related antidepressants venlafaxine and nefazodone (which is no longer marketed within Europe) were also included in the review. The CSM considered this issue in early 1998.

The issue was also discussed at European level by the Committee on Proprietary Medicinal Products (CPMP) and its Pharmacovigilance Working Party (PhVWP). At the December 1998 meeting of the PhVWP it was decided that France and Germany should carry out further evaluation of the issue of dependence associated with the SSRIs. The outcome of this review was a CPMP position paper which was published in April 2000[5].
The conclusion of the CSM and the CPMP was that all SSRIs are associated with withdrawal reactions; however, they are not drugs of dependence. Following the completion of a class review of the safety profile of SSRIs and a review of suicidal behaviour with SSRIs, a further article covering these aspects and the issue of withdrawal reactions was published in 'Current Problems in Pharmacovigilance' in September 2000[6].

The CPMP position paper (2000) contained key principles in relation to withdrawal reactions for inclusion in the product information for all SSRIs throughout Europe. The UK product information for all SSRIs and venlafaxine was updated accordingly.

Concern about withdrawal reactions with SSRIs continued and more recently has focused primarily on paroxetine. The BBC's Panorama programmes in October 2002 and May 2003 highlighted the level of public concern.”

The issue of all drugs in the SSRI, SNRI class causing dependency or being addictive had been addressed in the UK and Europe, both the CSM and CPMP had opined that the drugs including Seroxat did not meet the World Health Organisation (WHO) criteria for addiction by April 2000.

This opinion was not changed by the CSM EWG investigation as described in the earlier post “The "Addiction” Issue & Hugh James’ need to change the Patient Information Leaflet (PIL)” that can be found here.

The closing paragraph of the above excerpt draws attention to the recent (2002 to 2004) primary focus being placed on paroxetine (Seroxat) and the “BBC's Panorama programmes in October 2002 and May 2003 highlighted the level of public concern”.

Although the CSM EWG report is quite explicitly centred on all SSRIs and venlafaxine (Efexor) - the media, Hugh James’ Mark Harvey, the Seroxat User Group and Seroxat Campaigners’ selective interpretation of this statement is that Seroxat is the worse drug in the class because recent (2002 to 2004) concern about all drugs had shifted and “focused primarily on paroxetine”; However, would it be more reasonable to say the drug Seroxats’ notoriety was generated by the “level” of adverse media coverage and the BBC Panorama’s two Seroxat focused programs?

CMS EWG Quote References

1 - Lejoyeux M et al (1996) ‘Antidepressant withdrawal syndromes’ CNS Drugs 5: 278-292.

2 - Stoukides J A & Stoukides C A (1991) ‘Extrapyramidal symptoms upon discontinuation of fluoxetine (letter).’ Am J Psychiatry 148(9): 1263.

3 - MCA/CSM (1993) Current Problems in Pharmacovigilance 19

4 - Medawar C (1997) ‘The Antidepressant Web.’ Int J Risk Safety Med 10: 75-126.

5 - http://www.emea.eu.int/pdfs/human/press/pp/277599en.pdf

6 - MCA/CSM (2000) Current Problems in Pharmacovigilance 26

7 - Teicher MH et al (1990) ‘Emergence of intense suicidal preoccupation during fluoxetine treatment.’ Am J Psychiatry 147:207-210

8 - MCA/CSM (1992) Current Problems in Pharmacovigilance 18.

9 - Healy D (1999): ‘A Failure to Warn [editorial].’ Int J Risk Safety Med 12: 151-6

10 - Lane RM (1998). ‘SSRI-induced extrapyramidal side effects and akathisia: implications for treatment.’ J Psychopharmacology. 12: 192-214.

Mad Pride Welfare Benefits & Services Protest "24 Hour Medication Strike" Caution Warning - October 25th - 26th 2010 - madpride.org.uk

2010-10-25T12:53:00.001+01:00

Reposting the following Caution Warning - anyone considering supporting this protest by joining the "24 hour medication strike" please think very carefully - no psychiatric medications should be stopped abruptly, missing doses is putting you, your health, safety and possibly liberty at risk. Please support the protest, but not this way -

thanks Tues

****
Saturday, 9 October 2010

Mad Pride Welfare Benefits & Services Protest Warning madpride.org.uk

Slightly off topic – but It has come to my attention that MadPride.org.uk are organising a protest at Speaker’s Corner, Hyde Park, London on Tuesday October 26th 2010 at 1 pm –

“A Public Execution and Assorted Horrors"
"A Demonstration against Cuts to Benefits and Services”

Promoted in their press release asincluding the promotion of

“A day of action to appose welfare benefit cuts for people labelled mentally ill”

including the promotion of

“A 24 hour nationwide medication strike!”

Whilst the sentiments of the protest against cuts to welfare benefit for the mentally ill is commendable, this suggested action –

given the nature of both the side effects caused by missed doses and the consequences of rapid withdrawal associated with powerful psychiatric drugs that all, including severely mentally ill patients, will be taking –

is irresponsible and possibly dangerous.

For years a few members of Yahoo group UKSurvivors have made great efforts to raise awareness of the dangers psychiatric drugs pose in relation to side effects, missed doses and withdrawal –

which Mark Roberts the groups owner, madpride.org.uk’s founder member, protest and “24 hour medication strike” promoter - has consciously and deliberately chosen to ignore,

whilst putting in place the following Blog, Forum and Twitter accounts to promote his protest campaign and “The 24 hour medication strike”

http://madpride.org.uk/blogs/madprideblog/

http://madpride.org.uk/forum/index.php

http://twitter.com/madpridemark

Please, by all means support the protest – BUT please, under NO circumstances follow the promoted course of action or encourage others on medication to join “the 24 hour medication strike“ - as it may have dire and possibly tragic consequences.

Tuesday
---

Is the Seroxat Group Action Litigation Order no: 68 Compromised by its Own Defining Issue?

2010-10-18T16:12:00.004+01:00

The UK Seroxat Group Action Litigation, Order No:68, is being brought under the Consumer Protection Act 1987 (CPA)

“A product is defective if, at the time of circulation, it is not as "safe as persons generally are entitled to expect," taking account of a number of factors including any instructions or warnings provided with the product and the manner in which it has been marketed.”

In proving a case of a “defective product” the only need is to show the product – in this case GlaxoSmithKline’s (GSK) drug Seroxat (Seroxat UK, Paxil USA) - was not up to consumers’ expectations.

However, lead Lawyer Mark Harvey of Hugh James Solicitors, Cardiff has chosen to include a Defining Issue stipulation that any adverse effects and discontinuation, withdrawal difficulties suffered by the Seroxat “user” has to be

“to a greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”
HM Courts Service: Seroxat Group Litigation Order no: 68.

The report of the Committee on Safety of Medicines (CSM), Expert Working Group (EWG) on SSRI Antidepressants, published December 2004, found all drugs in the class lacking in safety, efficacy and causing discontinuation problems in up to 80% of consumers.

It’s unclear why the “stipulation” has been included, as The CSM Expert Working Group report on all SSRI Antidepressants effectively proved the Group Action litigants case against GSK by finding their product Seroxat not being as "safe as persons generally are entitled to expect,".

December 2004, Seroxat Group Action Litigation case proved and won -

baring lead lawyer Mark Harvey’s inclusion of the apparently unnecessary and possibly untenable Defining Issue “stipulation”.

To prove the Seroxat Group Action by justifying the included “stipulation” raises the need to examine criteria that differentiate the drugs in the SSRI, SNRI class within the restricted Defining Issue of discontinuation, withdrawal and drug classification.

This depends on the two theories of what causes discontinuation and withdrawal and the issues of selectivity nature, affinity and potency; dose related drug action classification; definition by acronym classification; and external evidence.

All interrelate, and other than the issue of selectivity nature, affinity and potency, focus on two drugs in the class the SSRI paroxetine (Seroxat) and SNRI venlafaxine (Wyeth, Efexor UK, Effexor USA).

The CSM EWG into SSRI Antidepressants used pharmacological characteristics and the 1999 Tatsumi et al study to compare Half-life and the Potency and Affinity of the drugs on the central nervous system neurotransmitters. Finding all drugs have binding affinities to different monoamine transporters, primary effects on different receptors and cause secondary changes in receptor numbers and receptor function at the synapse.

1 - The issue of selectivity nature, affinity and potency is the most complicated – defining whether Seroxat is worse than any other drug in the class by comparing drugs with different intrinsic values that despite their acronym name classification titles i.e. SSRI, SNRI etc - are not “pharmacologically “clean”” or defined in action of selectivity “to the Serotonin system”, all also affecting to varying degrees noradrenalin and dopamine. This aspect is covered in more detail here.

The Tatsumi et al study results are valued using Kd or dissociated constant – as explained on the table the lower the Kd the higher the affinity to the transporter.

Affinity Kd ratings show –
Paroxetine (Seroxat) has the highest affinity to Serotonin at 0.1 - just point 0.2 higher that Sertraline (Pfizer, Lustral UK, Zoloft USA) the second highest at 0.3.

Potency findings published by CSM, EWG are not clear because they have not stated whether they are rating Potency on the Affinity to Serotonin alone or Serotonin (5HT), Noradrenalin (NA) and dopamine (DA).

Potency rating show –
Paroxetine (Seroxat) is the “most potent” with the “lowest selectivity” and Sertraline (Lustral) the “second most potent”.

However, when comparing the Affinity and Potency with other drugs in the class - that all to varying degrees effect 5HT, NA and DA and as Paroxetine (Seroxat) is the least selective and only has a negligible 0.2 higher Affinity to Serotonin than Sertraline (Lustral), total Affinity and Potency Kd values to 5HT, NA and DA could be used to assess this point.

Combined Kd Affinity and Potency values to Serotonin (5HT), Noradrenalin (NA) and Dopamine (DA) show –
Sertraline (Lustral) has the highest combined Affinity and Potency with a Kd 445.3 and the least selective Paroxetine (Seroxat) is second highest with a combined Kd of 530.1.

2 - The two theories of what causes discontinuation and withdrawal is explained by Dr David Healy in the “HALTING SSRIs” document, one theory is the shorter half-life of paroxetine (Seroxat) and venlafaxine (Efexor) makes these drugs more problematic, the second theory is regarding the potency of paroxetine and venlafaxine. This aspect is covered in more detail here.

If according to the first theory - which includes a switch to fluoxetine (Ely Lilly Prozac UK and USA) Half-life 1 to 4 days - the cause of discontinuation and withdrawal is dependant on the shortness of Half-life - venlafaxine (Efexor) has the shortest Half-life of 5 hours - paroxetine (Seroxat) is considerably longer at 20 hours.

The second theory - which includes a switch to citalopram (Lundbeck, Cipramil, Celexa) Kd 1.2 - with regard paroxetine (Seroxat) and venlafaxine (Efexor) being “relatively more potent serotonin reuptake inhibitors” is possibly itself called into question by the findings of the CSM, EWG and Tatsumi et al study as venlafaxine has a Kd value of 152 making it, other than mirtazapine, the least “potent serotonin reuptake inhibitor” of the drugs studied.

This possibly places the whole onus of discontinuation and withdrawal problems inherent with all drugs in the SSRI, SNRI class back on a drugs Half-life as citalopram’s Half-life at 36 hours, is longer than both paroxetine (Seroxat) and venlafaxine (Efexor) – and would possibly benefit some as with the fluoxetine switch.

3 - The dose related drug action classification issue, Wyeth are the only manufacturer of those drugs studied to have specified that their drug works on more than one neurotransmitter, however it is the opinion of Dr David Healy in the “HALTING SSRIs” document and the MHRA that although Venlafaxine is named by the acronym SNRI it’s mode of action is that of an SSRI up to doses of 150 mg, over this it has an additional mode of action to become a serotonin and noradrenalin reuptake inhibitor. This aspect is covered in more detail here

4 - The drug definition by acronym classification title by definition the difference between an SSRI and an SNRI should be dependant on selectivity and potency of action i.e. to serotonin or noradrenalin. In the case of the SSRI, SNRI drug class no drug is “selective” to one monoamine transporter, all drugs effect serotonin and noradrenalin, paroxetine (Seroxat) with Kd of 40 to the noradrenalin transporter has a considerably higher affinity than venlafaxine at a NA of Kd 9400. This aspect is covered in more detail here.

5 - The issue of external evidence, as covered briefly here, is dependant on the MHRA, Yellow Card Scheme adverse drug reports and media coverage that has influenced those reports. The MHRA has received considerably more adverse event reports for paroxetine (Seroxat) than any other drug in the class, however, the December 2004 CSM). EWG Report drew attention to the influence of the media coverage and a number of obviously duplicated reports made with regard paroxetine (Seroxat) and it has been noted that BBC Panorama published and issued it’s own Yellow Cards that were accepted by the MHRA.

I will return to the influence of media coverage, the BBC, Panorama, UK Government officials and departments, the Seroxat User Group.org and Hugh James Solicitors in more depth in future posts - but the media coverage has had a profound influence on this aspect, as the Richard M Martin, Margaret May, and David Gunnell, Department of Social Medicine, University of Bristol study “Did intense adverse media publicity impact on prescribing of paroxetine and the notification of suspected adverse drug reactions? Analysis of routine databases, 2001–2004” shows.

Is the UK Seroxat Group Action Litigation, Order No:68 compromised by Lead Lawyer of Hugh James, Cardiff, Mark Harvey’s included Defining Issue “stipulation”?

1 - Does an Affinity and Potency to serotonin of Kd 0.2 higher than Sertraline (Lustral) make Paroxetine (Seroxat) the worst drug in the class …. or does the highest combined Affinity and Potency Kd to serotonin, noradrenalin and dopamine make Sertraline (Lustral) a worse drug than the least selective Paroxetine (Seroxat)?

2 - If the theory is that discontinuation and withdrawal is caused by the drugs short Half-life …. does SNRI venlafaxine’s (Efexor) half-life of 5 hours make it more difficult to withdraw from than the SSRI Paroxetine’s (Seroxat)?

3 - Is Wyeth’s honest mode of action classification of venlafaxine (Efexor) being an Serotonin Noradrenalin Reuptake Inhibitor (SNRI), although acting as an Selective Serotonin Reuptake Inhibitor (SSRI) in doses up to 150 mg, likely to be disregarded as the SSRI Paroxetine’s (Seroxat) has the highest Affinity and Potency Kd to noradrenalin of any SSRI, SNRI studied?

4 - Can a drugs classification be defined by a catchy marketing tool or will the acronym SNRI be overruled by the scientific facts?

5 – Has the unprecedented media coverage and in particular the BBC’s Panorama issued Yellow Cards damaged the integrity of the MHRA, the system and the case dependant adverse events report evidence?

Seroxat Venlafaxine SSRI v SNRI, Dr David Healy’s “Halting SSRIs” – Freedom of Information, MHRA Official Opinion email

2010-08-04T12:24:00.000+01:00

The Medicines and Healthcare products Regulatory Agency (MHRA), an executive agency of the UK Governments Department of Health (DH) took receipt of the Dr David Healy “Halting SSRIs” document in June 2009.

Dr Healy and members of the MHRA met on 26 June 2009, the meetings purpose was to “discuss awareness and management of withdrawal reactions with SSRIs and related antidepressants”. The MHRA, Dr David Healy meetings minutes can be downloaded here.

Following the MHRAs receipt of and the documents eventual publication on the internet, it was found to include the statement that “Venlafaxine in doses up to 150 mg is an SSRI.”. Clarification of venlafxines’ SSRI v SNRI classification was sought by way of a Freedom of Information (FoI) question and request sent to Simon Gregor, the MHRAs Director of Communications.

The FoI request for clarification was made because of concerns that the Defining Issue of the Seroxat Group Litigation Order No: 68, lodged at the High Courts by the Litigations Lead Solicitors Hugh James -

“Does Seroxat have a capacity to cause asverse effects consequent upon or following discontinuance (withdrawl) such as prevent or make more difficult the ability of users to discontinue, withdraw from or remain free from taking Seroxat to a greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”

.…….. NB - spelling errors as per original document.

HM Courts Service: Seroxat Group Litigation Order no: 68.

is quite clear in it’s specification that it has to be proven that the discontinuation (withdrawal) and remaining free from Seroxat is worse and more difficult than any other “SSRI” in the drug class.

With a certain amount of knowledge and the suspicion that the MHRA were not mandated to receive or facilitate a patient treatment protocol -- which would more likely fall under the sphere of influence of the National Institute for Clinical Excellence (NICE) -- an additional questions were asked to clarify if the MHRA were in a position, or intending, to authorise the Dr David Healy “Halting SSRIs” document as an official withdrawal protocol.

According the emailed reply (copy below) with regard the MHRA’s ability to facilitate utilising the Dr David Healy “Halting SSRIs” document the MHRA spokesperson states -

“As you are aware it is not within our remit to endorse guidelines for the management of patients.”

With regard clarification of the venlafaxine SSRI v SNRI classification, the MHRA don’t appear to hold relatively basic information concerning the drugs dose related action on noradrenalin and serotonin –

although they had approved the “Summery of Product Characteristics, which is produced by the marketing authorisation holder” which presumably would have included the products name and category i.e. SSRI, SNRI, significance as such and dosage information.

The MHRA spokesperson did however quote from the official NICE “Guidance” on “treatment of depression” which states ‘At standard dose of 75 mg, venlafaxine is an SSRI. At doses of 150 mg/day and above it also inhibits the reuptake of noradrenaline and, to a lesser extent dopamine’ – adding the endorsement that they “have no reason to doubt” this.

Click here to enlarge

Published with permission of the recipient, original document here.

It would appear that the official view of the UK Governments Medicines and Healthcare products Regulatory Agency (MHRA), Department of Health (DH), National Health Service (NHS) and National Institute for Clinical Excellence (NICE) is that venlafaxine (Wyeth, Efexor UK, Effexor USA) , at standard doses up to 150 mg, is classified as an SSRI.

Seroxat Venlafaxine SSRI v SNRI Issue – Dr David Healy, CSM Expert Working Group Report and Tatsumi et al Study

2010-08-02T14:26:00.013+01:00

The Defining Issue of Seroxat Group Litigation Order No: 68, lodged at the High Courts by Lead Solicitors Hugh James, as follows -

“Does Seroxat have a capacity to cause asverse effects consequent upon or following discontinuance (withdrawl) such as prevent or make more difficult the ability of users to discontinue, withdraw from or remain free from taking Seroxat to a greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”

........... NB - spelling errors as per original document.

HM Courts Service: Seroxat Group Litigation Order no: 68.

specifying that the adverse effects of Seroxat are or have to be proven to be

“greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”

it appears the deciding factor of the Seroxat litigation – given venlafaxines’ shortest 5 hour half life– is dependant on each drugs classification.

In the “Halting SSRIs” document Dr David Healy opines (excerpt below) that venlafaxine is an SSRI up to doses of 150 mg.

He also states that although these drugs are called "Selective Serotonin Reuptake Inhibitor" (SSRIs) they are not “selective to the Serotonin system”, neither are they “pharmacologically “clean”” – meaning all drugs in the class to varying degrees also affect serotonin, noradrenalin and dopamine.

Click here to enlarge

The work by the Committee on Safety of Medicines (CSM), Expert Working Group (EWG) on SSRI Antidepressants, who’s report was published December 2004 confirms this aspect

“……When compared with tricyclic antidepressants, they are certainly more selective but still affect neurotransmitters other than serotonin in the central nervous system 8. This can be illustrated with reference to their binding affinities to the different monoamine transporters (table 5.1) 9. Furthermore, their effect is not limited to uptake inhibition. They have primary effects on many different receptors (see table 5.2), and also cause secondary changes in receptor numbers and receptor function at the synapse 8 10 11. The same principles also apply to the related antidepressants venlafaxine (which is mixed serotonin and noradrenaline reuptake inhibitor) and mirtazapine (which acts as an antagonist at the α2, 5HT2, 5HT3 and H1 receptors).”

The CSM EWG report Table 5.2 (below) shows the “Affinity” of each drug included in their investigation with reference to the “selective” nature and potency.

Click here to enlarge
………NB – The CSM Report was carried out prior to the SNRI duloxetine (Eli Lilly, Yentreve, Cymbalta – part developed by Boehringer Ingelheim) being licensed.

The findings show

citalopram (Lundbeck, Cipramil, Celexa) -- was - “highly selective”
sertraline (Pfizer, Lustral Zoloft) -- was the - “Second most potent”
paroxetine (GSK, Seroxat Paxil) -- was the - “Most potent, Lowest selectivity”
venlafaxine (Wyeth, Efexor Effexor) -- is listed as a - “re-uptake blocker” of NA = Noradrenaline and 5HT = 5-hydroxytryptamine = Serotonin

The CSM EWG report Table 5.1 (below) adapted from Tatsumi et al “Pharmacological profile of neuroleptics at human monoamine transporters” study paper originally published in the European Journal of Pharmacology 1999;368(2-3):277-83 shows the “Affinity” of each drug included in their investigation with reference to the potency of effects on three monoamine transporters, 5HT = serotonin, NA = noradrenaline and DA = dopamine.

Click here to enlarge
………NB – The CSM Report was carried out prior to the SNRI duloxetine (Eli Lilly, Yentreve, Cymbalta – part developed by Boehringer Ingelheim) being licensed.

The findings are valued using Kd or dissociated constant – as explained on the table the lower the Kd the higher the affinity to the transporter. Ignoring the tricyclic antidepressant comparator Amitriptyline and Norfluoxetine the drug Seproxetine which was investigated by Eli Lilly as an antidepressant, development was never completed and the drug as yet not marketed.

The findings -- Affinity Kd and (potency rating) -- show

citalopram - 1.2 Serotonin (Fourth) – 4070 Noradrenaline (Fifth) – 28100 Dopamine (Sixth)
sertaline - 0.3 serotonin (Second) – 420 noradrenaline (Third) - 25 Dopamine (First)
paroxetine - 0.1 serotonin (First) – 40 noradrenaline (First) - 490 Dopamine (Second)
venlafaxine - 152 serotonin (Sixth) – 9400 noradrenaline (Seventh) – 11700 Dopamine (Fifth)

In terms of classification and license applications it appears that Wyeth (now part of Pfizer) and Eli Lilly with their drugs venlafaxine, (Efexor Effexor) and duloxetine, (Yentreve, Cymbalta) are the only manufacturers to have been open in declaring the drugs additional action on noradrenaline (NA), in the case of Wyeth’s venlafaxine noradrenaline (NA) and dopamine (DA).

Venlafaxine is the only drug included in the CSM EWG investigation classified as an SNRI - however, according to the Tatsumi et al study accepted by the CSM EWG of the drugs classified as SSRIs – five have a higher Affinity and Potency to serotonin (5HT) – but six have a higher Affinity and Potency to noradrenalin (NA) - and four a higher Affinity and Potency to dopamine (DA).

Both SSRIs, Sertraline (Lustral, Zoloft) and paroxetine (Seroxat, Paxil), have considerably higher Affinity and Potency to all three transporters than the SNRI venlafaxine (Efexor, Effexor).

The SSRI Sertraline (Lustral, Zoloft) has at, Kd 0.3 the second highest Affinity and Potency to serotonin (5HT) and at Kd of 25 the highest Affinity and Potency to dopamine (DA), higher than all other drugs in the class.

The SSRI paroxetine (Seroxat, Paxil), at Kd 0.1 has the highest Affinity and Potency to Serotonin (5HT) and is the highest in Affinity and Potency, at Kd 40, to noradrenaline (NA) higher than all other drugs in the class.

The word “selective” seems to be an ambiguous descriptor of little or no value - all drugs in the SSRI, SNRI class, because they are not “pharmacologically “clean””, appear to have clear and unmistakable claim to being Serotonin, Noradrenaline and Dopamine Re-uptake Inhibitors.

With regard the SSRI v SNRI Issue – it appears the question is not whether venlafaxine can be considered an SSRI – but possibly whether paroxetine is actually an SNRI?

Seroxat the Discontinuation (Withdrawal) Issue - “Halting SSRIs” document by Dr David Healy

2010-07-31T14:09:00.026+01:00

The Defining Issue of Seroxat Group Litigation Order No: 68, lodged at the High Courts by Lead Solicitors Hugh James, as follows -

“Does Seroxat have a capacity to cause asverse effects consequent upon or following discontinuance (withdrawl) such as prevent or make more difficult the ability of users to discontinue, withdraw from or remain free from taking Seroxat to a greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”

……….. NB - spelling errors as per original document.

HM Courts Service: Seroxat Group Litigation Order no: 68.

appears to be solely based on Seroxats’ discontinuation problem being worse “than all other” SSRIs raises several questions with regard the propagation, collection, presentation and analysis of adverse drug reaction (ADR) reports; and the Medicines and Healthcare products Regulatory Agency (MHRA) the executive agency of the UK Governments Department of Health responsible for interpretation of the Yellow Card Scheme generated statistical drug analysis data and their ethics in accepting media (BBC Panorama) generated Yellow Card documentation - some collected through the Seroxat User Group.org website and support group, set up by Solicitor Hugh James for litigants.

It also raises the question of what the experts consider the cause of the discontinuation problem to be in relation to the pharmacokinetics of each drug in the class and which drugs are included in the SSRI class.

The “Halting SSRIs” document was prepared by Dr David Healy at the request of the MHRA, following their personal meeting in September 2008 with Seroxat campaigner Bob Fiddaman (SEROXAT SUFFERERS blog) who brought up the matter of an SSRI Withdrawal Protocol and suggested they liaise with the UK’s Leading Authority on the SSRI, SNRI drug class to facilitate its production. The document was presented to the MHRA in June 2009.

The David Healy document “Halting SSRIs” states -

"There are 2 theories about what leads to dependence and withdrawal that dictate slightly differing management plans.

One theory is that the relatively short half life of paroxetine and venlafaxine make these two drugs more problematic. This leads to a withdrawal strategy that advocates switching from paroxetine or other drugs to fluoxetine.

The second is that paroxetine and venlafaxine are relatively more potent serotonin reuptake inhibitors and this theory leads to a switch to less potent serotonin reuptake inhibitors such as citalopram.”

The theories highlight two problems - the drugs shortness of half-life and the drugs potency as a serotonin re-uptake inhibitor.

A drugs half-life is the average period of time the drug takes to reduce to or by half its original concentration once ingested - i.e. from 50mg to 25 mg, then from 25mg to 12.5 mg etc.

If the discontinuation problems are due to the short half-life of the drug - the December 2004 Committee on Safety of Medicines (CSM), Expert Working Group (EWG) on SSRI Antidepressants Report table 5.2 (below), shows that venlafaxine (Wyeth, Efexor UK, Effexor USA) has the shortest half-life at 5 hours, followed by paroxetine (GSK, Seroxat UK, Paxil USA) at 20 hours and sertraline (Pfizer, Lustral UK, Zoloft USA) at 26 hours.

Click here to enlarge

………NB – The CSM Report was carried out prior to the SNRI duloxetine (Eli Lilly, Yentreve, Cymbalta) being licensed.

The CSM, EWG report table 5.2 also indicates the drugs potency as serotonin re-uptake inhibitor and their affinity to monoamine transporters (MAT) – the selectivity of which has a bearing on the of the drugs classification.

Venlafaxine is classified by some as an SNRI, although in 1998 venlafaxine was listed in the Prescription Cost Analysis (PCA) statistics and British National Formulary, BNF: 4 . 3 . 3 . 0 SSRI section, in 1999 it was moved to PCA, BNF : 4 . 3 . 4 . 0 “Other Antidepressant Drugs” section where it remains. It’s unclear whether this was at Wyeth, the manufacturers, request or a licensing classification decision.

In the “HALTING SSRIs” document Dr David Healy explains the following –

““SSRI stands for selective Serotonin reuptake inhibitor. This does not mean these drugs are selective to the serotonin system or that they are in some sense pharmacologically “clean”. It means they have little effects on the norepinephrine/noradrenaline system.”

In the same document he also explains the following –

“Venlafaxine in doses up to 150 mg is an SSRI. Over 150 mg it also inhibits noradrenaline reuptake. Duloxetine is a potent serotonin reuptake inhibitor but not selective to the serotonin system.”

Venlafaxine is the only drug in the SSRI, SNRI class with a recognised additional mode of action that is dose specific -- > 150 mg Selective Serotonin RI – 150 mg > Serotonin Noradrenaline RI - 300 mg > Serotonin Noradrenaline Dopamine RI.

It would appear that if the Discontinuation Issue were solely dependant on the individual drugs half-life, venlafaxine with a 5 hour half-life would be considered the worst drug. However, the Seroxat Group Litigation Order No: 68 Defining Issue wording specifically states -

“than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”

all drug in the class are classified Re-uptake Inhibitors (RI) - can the SNRI venlafaxine with it's recognised mode of Selective Serotonin RI action in doses up 150 mg be considered an SSRI? Are other SSRIs in the drug class, including Seroxat, which also have affinities to Noradrenaline and Dopamine correctly classified?

Is Seroxat the Worst Drug in the SSRI, SNRI Class - Chronic Long Term and Intermittent Repeat Prescribing ?

2010-07-27T15:45:00.007+01:00

The following research study “Explaining the rise in antidepressant prescribing: a descriptive study using the general practice research database” was led by Tony Kendrick, professor in Primary Medical Care at University of Southampton’s School of Medicine and investigates the chronic long term and intermittent repeat prescribing which accounts for 90% of increases in SSRI, SNRI prescriptions.

The study centred on the UK Government, Prescriptions Cost Analysis (PCA) Statistics and the General Practice Research Database (GPRD) anonymous computerised records, the research team analysed all new cases of depression between 1993 and 2005 from 170 GP general practice surgeries and 1.7 million registered patients.

In the British Medical Journal (BMJ) published paper, scientists found the continual annual increases in GP issued antidepressant prescriptions was caused by a number of people taking the drugs on a long term basis.

The research scientists also found that despite a drop in new patient diagnoses of depression over eleven years antidepressant prescription numbers doubled, estimating more than 2 million people are now taking antidepressants long term or repeat intermittent course treatment to patients with multiple episodes of depression.

The researcher’s state data from the Prescription Cost Analysis (PCA) statistics shows that antidepressant prescribing in England between 2000 and 2005 increased by 36% to 7.3 million items per quarter, during this period prescribing of selective serotonin reuptake inhibitors increased by 45% and accounted for half of all prescriptions.

The following is from the Science Daily review of the study published Oct. 23, 2009, “Increase In Long-Term Antidepressant Drug Use, UK Study Reveals”

“………. Researchers at the University of Southampton found 90 per cent of people diagnosed with depression are now taking SSRIs either continuously or as repeated courses over several years.

Professor Kendrick adds: "Our previous research found that although these drugs are said not to be addictive, many patients found it difficult to come off them, due to withdrawal symptoms including anxiety. Many wanted more help from their GP to come off the drugs. We don't know how many really need them and whether long-term use is harmful. This has similarities to the situation with Valium in the past." “

http://www.sciencedaily.com/releases/2009/10/091022114359.htm

The following information, chart and conclusion are from the University of Southampton Study.

“To address our study questions and examine more closely trends occurring within the cohort, we divided patients into five pre-defined treatment pattern groups on the basis of treatment in the five years following first diagnosis (five year follow-up was possible only for those diagnosed between 1993 and 2001).”

“Table 1 + shows an overall increase in prescription duration from just under 2.9 million days in the patients studied between 1993 and 1997 to more than 4.3 million days in the those studied between 2001 and 2005. Chronic and intermittent prescribing together accounted for approximately 90% of the total prescriptions (for example, 270 005/288 249 in 1993). Although the number of prescription days increased over time for all treatment groups, small changes in the constitution of the chronic treatment and intermittent treatment groups were responsible for most of the increase in antidepressant prescribing over the duration of the study.”

“Total prescription days for each of the five treatment pattern groups is summarised in figure 7 . The volume of prescriptions attributed to long term prescribing (that is, the proportion of prescriptions in the chronic and intermittent groups) contributed the majority of the change in overall prescribing volume.

http://farm5.static.flickr.com/4140/4826430362_545d6e5c18_o.jpg

".........There was also an increase in the average number of prescriptions per patient in the chronic treatment group: from 34 over five years to 36 over five years in the period studied which equates to approximately 60 days more treatment over the five year period in 2001-5 compared to 1993-7. Bearing in mind the increase in the proportion of patients in this group (from 8.4% to 10.2%), the increase in the duration of prescriptions in the chronic treatment group is responsible for a substantial increase in the overall prescribing volume. A similar pattern was seen in the other treatment groups, but with a smaller impact on overall volumes."

"Conclusions
Antidepressant prescribing is much higher compared with 10 years ago. This increase is not because of an increase in the incidence of new cases of depression, a lower threshold for treatment, an increase in the proportion of new cases of depression for whom antidepressants are prescribed, or an increase in the duration of the prescriptions written for new cases of depression. Rather, the dramatic changes in antidepressant prescribing volumes between 1993 and 2005 seem to be largely because more patients are on long term medication and this group consumes the most drugs. In order to better understand the rise in antidepressant prescribing, research needs to focus on chronic prescribing and policy needs to focus on encouraging appropriate high quality monitoring and review of those patients who become established on long term prescriptions,”

http://www.bmj.com/cgi/content/abstract/339/oct15_2/b3999

Other than the issue of discontinuation problems, no other reason appears to have been found or proffered by the study researchers to explain the consistent and continual increase in Antidepressant, SSRI, SNRI drug class prescriptions. Although there will also be a percentage of patients content with the treatment they are receiving - whether encompassed by the chronic and intermittent treatment groups or not.

The study concluded in 2005, and found no anomaly –favourable or otherwise-- associated with the decline of Seroxat prescriptions. Since 2005 total annual SSRI, SNRI drug class prescriptions have increased from 18.88 to 26.94 million, an increase of 8.5 million or 43% before taking into account the negative Seroxat increase of 402.5 thousands of prescriptions for the same period. Seroxats’ total prescription decline of 1.74 million during the period 2001 to 2005 does not appear to be reflected in the overall prescription increase trend or numbers in the chronic and intermittent treatment groups.

Impartially, the discontinuation phenomenon is known and acknowledged to affect the whole drug class - this does not reflect negatively or otherwise on anyone being treated with any SSRI, SNRI drug – including those who have had or are having problems withdrawing from Seroxat, those still being issued prescriptions for the drug and the percentage who will have swapped or been swapped from Seroxat to other brands of SSRI, SNRIs only to find they have similar and in the case of Efexor -- because of its shorter half life -- worse problems associated with discontinuation.

This research study does and should officially raise concerns over the recognised possibility of iatrogenic illness caused by short, intermittent and long term treatment with the SSRI, SNRI drug class. The suggestion for a policy focusing on high quality --more stringent-- monitoring and review of long term patients established on antidepressant prescriptions and reference to similarities to the past situation with Benzodiazepines does indicate how serious the SSRI, SNRI drug class problem is .... and is Seroxat worse than any other drug in that class?

Seroxat Prescriptions Decline 2001 to 2003 – An Analytical Study by Graham Aldred

2010-07-27T10:15:00.004+01:00

The following chart is from statistical study “The Decline of use of Paroxetine in England” by Graham Aldred, a research associate at North Wales Department of Psychological Medicine, Hergest Unit, Ysbyty Gwynedd, Bangor, North Wales.

Graham Aldred, a colleague of Dr David Healy, has a personal interest in Seroxat as his late wife Rhona sadly took her own life in 2001, eleven days after starting treatment with the drug.

The paper discusses the UK 2001 to 2003 decline of GSKs paroxetine (Seroxat UK, Paxil USA, Aropax AU & NZ) in market standing and value due to licence end, and of trade name Seroxat and generic prescriptions due to generated adverse publicity about the drug.

The research study shows a gradual decline in Seroxat total prescription numbers 2001 to 2002, this decline went into a virtual freefall 2002 to 2003 resulting in a 36% decline for the period 2001 to 2003. The decline in Seroxat total prescriptions has continued in an exponential decay resulting in totals decline for the period 2001 to 2009 of 56%.

“The Decline of use of Paroxetine in England
http://farm5.static.flickr.com/4074/4830672772_5e1bd86c3d_o.jpg

Chart 2 (above) shows the accumulation for paroxetine in England and Illustrates the life saving decline in this ill validated drug”

“IMR uses the common medication unit called TWS, (Two Weeks Supply), this enables the medication to be accumulated under one universal label regardless of form or concentration. Chart 2 was plotted using annual data, rather than quarterly data. It shows that the annual consumption of paroxetine in all its forms grew by more than 1.15 million units per year for 7 years up to 2001, then it fell by 2.7 M units i.e. 25% from 2001 to 2003. In fact this decline is much worse if the higher precision quarterly data is used; from the peak at Q4 2001 to Q4 2003 the fall was 36%. Annual totals can disguise higher rates of change defined by the quarters within the years (frequently exploited in financial marketing.)"

http://www.antidepressantsfacts.com/the-decline-of-paxil-seroxat.pdf

Given the relatively quick decline of 2.7 million or 25% of Seroxat prescription totals over a 24 month period, 2001 to 2003, and on balance of the increase in total drug class prescriptions of 23.2% for the same period - can Seroxat be considered worse than any other drug in that class?

(The blog will return a little later to the media coverage - in particular the role of the BBC’s program Panorama, the production team and lead journalist Shelley Jofre, the position taken by UK politicians in taking the SSRI, SNRI issue to parliament … and the legacy of ignorance left to millions of patients consuming or who went on to consume SSRI, SNRI brands other than GSK’s Seroxat.)

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Data collection reference:
http://www.antidepressantsfacts.com/the-decline-of-paxil-seroxat.pdf

What the Prescription Cost Analysis (PCA) Statistics Inadvertently Indicate ….

2010-07-23T20:52:00.111+01:00

The following graph shows that prescriptions for Seroxat (paroxetine, Paxil USA, Aropax AU & NZ) decline from 2001 when the American Paxil Class Action Litigation and associated Paxil campaign engendered the initial adverse publicity about the drug.

Following the 2002 preannouncement of the Seroxat Group Litigation, the associated Seroxat Campaigns initiation and the generated unprecedented adverse publicity in the UK media the decline in Seroxat prescriptions accelerated - this decline has followed an exponential decay and continues to date.

http://farm5.static.flickr.com/4075/4821075378_797a0f2c84_b.jpg

The total reduction of 2.14 million Seroxat prescriptions for the period 2001 to 2009 unfortunately indicates it is not impossible to discontinue treatment, withdraw and remain free from Seroxat.

Whilst the increase in total SSRI, SNRI drug class annual prescriptions of 12.92 million, over and above that reduction and the actual increase of 15.07 million for the same period, strongly indicates there is a discontinuation problem with the whole drug class.

If drugs are safe and efficacious, following an initial surge in prescriptions when a drug class is first licensed, total prescription numbers should normally plateau - as new patients are prescribed for - recovering patients are completing treatment and coming off – induction and cessation of treatments should reach a point where they approximately balance each other out.

During the period 1998 to 2009 the SSRI, SNRI drug class UK statistics show a continual median annual increases of 1.69 million in total prescriptions – adjusting this figure by omitting year 2004 with the 402 thousand increase anomaly and the addition of Seroxat prescriptions negative increase - the adjusted continual median annual increases of 2.08million in total prescriptions.

The continual median annual increases for the SSRI, SNRI drug class for the period 1998 to 2009 indicate two possible problems - either the drugs do not work and patients are not recovering … or whether they worked or not … patients are unable to discontinue the drug treatment.

In market percentage terms – market rises for the SSRI, SNRI drug class 2001 to 2009 were 92% - in 2001, Seroxats’ 3.78m share of the 14.01m total prescriptions market holding 27% - by 2009, Seroxats’ 1.63m share of the 26.94m total prescription market accounts for only 6.07%.

The official drug statistics used for these charts were sourced from the UK Government, Office for National Statistics, Department of Health, Publications and Statistics, Health care, Pharmacies and Prescriptions, Prescription Cost Analysis Statistics for England only - not the whole UK.

The inclusion of comparable data from Wales, Scotland and Northern Ireland, which collectively accounts for approximately 16.2% of the total UK population of approximately 61 million, could -- as Northern Ireland antidepressant prescription rates are twice the English per capita -- possibly increase these figures accordingly or by more than 16.2%.

(The blog will return a little later to the media coverage - in particular the role of the BBC’s program Panorama, the production team and lead journalist Shelley Jofre, the position taken by UK politicians in taking the SSRI, SNRI issue to parliament … and the legacy of ignorance left to millions of patients consuming or who went on to consume SSRI, SNRI brands other than GSK’s Seroxat.)

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Data collection reference:
Department of Health; NHS; Prescription Cost Analysis (PCA) - England.
http://www.dh.gov.uk/en/PublicationsAndStatistics/Statistics/StatisticalWorkAreas/StatisticalHealthCare/DH_4086488

The Seroxat Group Litigation “Defining Issue” …..

2010-07-22T23:12:00.006+01:00

appears to state, that the whole Seroxat Group Litigation is dependant on Seroxat being worse to withdraw from than any and all other drug in the SSRI class - there is however wide-ranging evidence to the contrary.

“Does Seroxat have a capacity to cause asverse effects consequent upon or following discontinuance (withdrawl) such as prevent or make more difficult the ability of users to discontinue, withdraw from or remain free from taking Seroxat to a greater extent than all other Selective Serotonin Re-uptake Inhibitors (SSRIs)”
……….. NB - spelling errors as per original document.

HM Courts Service: Seroxat Group Litigation Order no: 68.

It would also appear that if this case continues and is settled either in or out of court - it will affectively block those on the other seven drugs in the SSRI drug class from any possible legal redress or claim for compensation for the same problems.

The case seems to have been contrived to fit a loophole made available in the consumer documentation by the law – rather than the case being brought for the benefit of the litigants, to affect change in pharmaceutical regulation or make the pharmaceutical companies, in this case GSK, accountable – significantly this litigation has no social purpose, and will achieve nothing of true value.

(The blog will return to the merits and pitfalls of group litigations, their dubious success rates and pitiful litigant benefit records and the part the Legal Services Commission (LSC) and Solicitors play in the process at a later date.)

The “Addiction” Issue & Hugh James’ need to change the Patient Information Leaflet (PIL)

2010-02-08T11:02:00.004Z

Patient safety, accurate honest comprehensive information, instructions and warnings to enable patients to make informed choices about treatment is and should be paramount in any discussions with regard literature issued to patients and primary health care providers.

"A product is defective if, at the time of circulation, it is not as "safe as persons generally are entitled to expect," taking account of a number of factors including any instructions or warnings provided with the product and the manner in which it has been marketed. “

Access my Library: Mass tort treatment pharmaceutical

"Mark Harvey, solicitor for the Seroxat Users Group, told BBC News Online: "We would welcome the removal of the suggestion that the drug is not addictive."

BBC: Seroxat safety advice to be changed

"Message from Mark Harvey, Hugh James Solicitors ………
c) For the first time in the 13 years of this drug, the manufacturers have agreed to change the Patient warning sheets to deal with the question of addiction."

Hugh James Solicitors

The Seroxat Patient Information Leaflets (PIL) was predominant in the Seroxat Group Litigation Solicitors and Seroxat User Groups discussions and media coverage, as Mark Harvey of Hugh James Solicitors confirms in the above quotes.

The first of two changes to the SSRI PILs only related to the GSKs Seroxat, the addiction issue and the sentence 'Remember that you cannot become addicted to Seroxat' which was removed from the document in 2003 – an action that Mark Harvey of Hugh James and the Seroxat User Groups took and deserved full credit for – although an empty platitude.

Removal of the Seroxat “addiction” sentence from the PIL was not an admission of guilt – i.e. by doing this GSK were not saying that you could become addicted to Seroxat - although this was the inference in any reports made by or on behalf of those accredited for the action.

Unfortunately bringing the “addiction” issue to the notice of the UK licensing authorities the MHRA in 2002 brought no change to The World Health Organization’s (WHO) criterion for addiction, therefore Seroxat and all SSRI, SNRIs remain outside that ruling - despite considerable discontinuation problems.

Had the “addiction” issue been upheld and / or the WHO criterion for addiction changed to encompass any discontinuation problems – the Seroxat Group Litigation would have been proved on “Failure to Warn” in marketing “instructions and warnings” provided with the product.

In real terms the GSK statement 'Remember that you cannot become addicted to Seroxat' although removed from the PIL - still stands – however, GSK, the MHRA and WHO have all been seen to listen to patients complaints & concerns - and have been seen to act promptly on their behalf in a professional & responsible manner.

Mass Tort: Pharmaceutical Product Liability England

2010-02-06T00:23:00.013Z

“Mass tort treatment of pharmaceutical product liability cases in England.

Defense Counsel Journal: July 01, 2006: Wilkinson, David: Copyright"

"II. Causes of Action/Remedies

There are three potential causes of actions in product liability cases. Product liability claims may be made under the Consumer Protection Act 1987 ("CPA"), in negligence, or in breach of contract.

A. Consumer Protection Act 1987 The CPA, which implements the Product Liability Directive 85/374/EEC (3) in the UK, imposes liability on the producer of defective products for damage caused by the defect. A "product" is defined as any good that includes "any natural or artificial substance." (4) A product is defective if, at the time of circulation, it is not as "safe as persons generally are entitled to expect," taking account of a number of factors including any instructions or warnings provided with the product and the manner in which it has been marketed. (5) A product cannot be deemed defective solely because an improved product has become available. Liability under the CPA is strict: it is not necessary to prove that the producer was at fault in causing the defect. Producers have strict liability for distributing a product that is "unreasonably dangerous," regardless of whether they are at fault. The claimant need only prove a defect and causal relationship between the defect and the injury; courts will distinguish between products that fail and defective products.”

Access my Library: Mass tort treatment pharmaceutical

It would appear the Seroxat litigation being brought under the CPA, is solely dependant on the personal expectation of the consumer on safety and withdrawal.

Although producers’ liability under the CPA is strict, successful litigation is not dependant on the producer being found at fault for causing the defect – therefore this case will hold no fault liability to GSK as the producer.

The lead solicitor Mark Harvey of Hugh James confirms the withdrawal and no fault criteria on his website.

“The seroxat group action claims which are being led by Hugh James are being pursued under the Consumer Protection Act (CPA) 1987. The CPA provides for a non-fault based liability if the product is found to be defective and to have caused injury as a result. The Claimants allege difficulties in withdrawing from the drug.”

Hugh James: Seroxat group action claim

Consumer Law: Consumer Protection Act 1987: Defective Product

2010-02-04T23:09:00.012Z

There is provision within the 1987 Consumer Protection Acts’ “Meaning of defect” and product “safety” criterion to facilitate action being taken for the risk of death or personal injury.

Although the lead solicitors, Hugh James, in the Seroxat Group Litigation seem to have chosen to limit the action solely to withdrawal, ignoring reports of serious injury such as stroke, dystonia, SSRI induced parkinsonism, tardive dyskinesia, suicidal ideation, suicidal action and suicide completed - why?

“Consumer Protection Act 1987

Part I: Product Liability: Meaning of defect.

3.—( I) Subject to the following provisions of this section, there is a defect in a product for the purposes of this Part if the safety of the product is not such as persons generally are entitled to expect; and for those purposes "safety", in relation to a product, shall include safety with respect to products comprised in that product and safety in the context of risks of damage to property, as well as in the context of risks of death or personal injury.”

Consumer Protection Act 1987

Seroxat Group Litigation: Order no: 68

2010-02-01T08:02:00.007Z

2001 - the UK litigations lead lawyer Mark Harvey of Hugh James Solicitors (Harmful Products Department), Cardiff, then Hugh James Ford Simey Solicitors, announced in the UK press that there was an *unidentified* problem with Seroxat and the possibility of a UK Group litigation against GSK the manufacturer - he called it “shaking the tree”.

2008, October 29th - the UK Seroxat Group Litigation was lodged in the Royal Courts of Justice – but not publicized in the media or by the Seroxat campaigners.

HM Courts Service: Seroxat Group Litigation Order no:68.

The litigation is being brought under *harmful product* consumer legislation - not under any medical law or legislation.

Although the discontinuation problems, side effects, adverse drug reactions, long term persistent & enduring residual symptoms and suicidal ideation & action are of a medical nature - encompassing psychological, physiological & neurological symptoms and in some cases permanent damage.

(The blog will return to the processes of harvesting litigants, the litigant support groups and the campaign a little later.)

Concerns over the Seroxat Group Litigation

2010-01-30T10:55:00.003Z

I’m taking time out from statistics and associated issues - as yet unpublished - to facilitate publishing information appertaining to the UK Seroxat Litigation which, having been in the public domain since it was preannounced in 2001/2, is going to court this year.

The information encompasses the UK Government Prescription Cost Analysis (PCA) statistics - although at the time of publication of my UK: SSRI / SNRI Antidepressant Statistical Politics Blog - I was unaware of one significant fact and therefore revelations were unintentional.

However, a few weeks after my blogs publication, on first sight of the Seroxat Group Litigation Order no: 68 it became glaringly obvious that inadvertently, the statistics – not me – undermine the Litigation.

Seroxat, a prescription medication, is a one of class of eight drugs known as Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Noradrenalin Reuptake Inhibitors (SNRIs).

Since becoming aware of and involved with the SSRI prescription drug forums in 2001, I have spoken out - not against the litigation - but in concern for those involved and anyone taking SSRI, SNRI drugs, especially those choosing to or being swapped without consideration from Seroxat to other drugs in the class including Prozac, Lustral and Efexor.

The statistics are, unfortunately, not the only jeopardy to the frail legal case being successful - Seroxat has a certain notoriety for being “the worst drug” in the class - but is that notoriety well-substantiated or solely due to outside influences? Do the experts agree?

Have the UK population been let down by the government, medicines authorities and the media?

This blog will hopefully extricate the distinct facts, clarify, assemble and publicise each in context - to let the readers decide for them selves.

The following will possibly adversely impact on the few hundred people who have not been culled from the originally quoted 10.000 prospective litigants ...... but the full ramifications of not speaking out will possibly impact on thousands or even millions.

I have no conflicting interests.