Rapid Responses to:
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Rapid Responses: Rapid Responses published:
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This is not how I saw the programme
- Gavin Bullock (8 October 2004)
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Customer-led Care Era
- Adrian S. Blaj (8 October 2004)
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Open letter to Mr Waller
- Roger A Cleghorn (9 October 2004)
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Welcome to a modern 'Hystory'
- Alan N Wear, So 40 4 wu (10 October 2004)
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Reaction in Germany
- Linda C Best (10 October 2004)
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Panorama succeeded where the regulators failed
- Charles Medawar (11 October 2004)
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Perplexing...is this earth?
- Ricardo M. Gusmão (13 October 2004)
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Author's reply
- Patrick C Waller (14 October 2004)
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Give The SSRI's Some Credit!
- Craig Wheelans (14 October 2004)
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Gavin Bullock, retired GP N/A
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Patrick Waller says that the Panorama programme was one- sided. That is one way of putting it but I rather saw it as a championing of the little people's cause - that is, the ones swallowing the tablets, the ones who suffer when things go wrong. Shelly Jofre might be harrassing to those at the wrong end of her tongue but her questions to Alasdair Breckenridge were incisive and, to me, went straight to the weakness of his position at times. She was aghast, as was I, that he thought it justifiable to delay informing doctors about serious unwanted effects of Seroxat until he knew the exact per centages involved. What does it matter (from the point of view of warning doctors) whether 25 per cent or 1 per cent have difficulty in withdrawing from the drug? Those figures can wait but the warning should not. A simple, short letter or e-mail would do. Jofre was quite right to be appalled at the many patients who would become 'addicted' because Prof. Breckenridge wanted to dot his i's and cross his t's. The suicide business has been going on for a decade and gradually the awkward squad are being proved right. Dr Healey was unable to take up a new position at a Canadian university some years ago for daring to say what he thought. Why? The university thought his views would upset the drugs companies (too right!) that gave them substantial financial support. Yet his research has been vindicated (except in patients over the age of 30: and exactly 30, according to Prof Breckenridge). Finally, there is the question of the analysis - or lack of it - of the valuable Yellow Card scheme. The two experts who went through the Seroxat -related cards found evidence strongly suggestive of a link with suicide and dependence but the Medicines and Healthcare products Regulatory Agency (MHRA) - what a mouthful! - had apparently missed these links. Is this incompetence or mere neglect? One suspects that these cards were just put in a drawer and forgotten, like the old annual practice reports. "Regulators must expect criticism", writes Patrick Waller, as if a tweak here and a jiggle there is all the MHRA needs. He answers none of the main criticisms, stating that 'there are some problems with paroxetine, the jury is out,...". The point is that the patient should be given the benefit of any doubt, not the drug. To my eyes, the MHRA requires a major shake up to rid itself of its ridiculous secrecy, apparent complacency and laziness in examining clinical trial evidence. Accepting 'summaries' from drug companies is plainly improper and open to abuse. Do not forget that there were a number of distinguished clinicians who thought the same. Competing interests: None declared |
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Adrian S. Blaj, Psychiatrist Chase Farm Hospital, The Ridgeway, Enfield, EN2 8JL
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Patrick rightly feels disappointed that the programme makers effectively wasted his time. Rightly so - he worked very hard and has high moral standards. Patrick forgets one important thing: media and journalism have their own goals which not necessarily coincide with those of the honest Hippocratic followers. As everyone knows, the television programmes are heavily dependant on the interest of the viewers and therefore the sensational-seeking behaviour is almost the rule. If Patrick doesn’t mind a basic advice, I would tell him to follow in my steps and simply take the television set in the garden, place a flower pot on the top of it and take care the flowers do not die of lack of water:) Patrick also wonders ‘how many patients would inappropriately stop treatment and how many unnecessary consultations there would be in the coming weeks.’ I would say to Patrick that although it would not be in the best interest of the patient to ad-hoc stop their treatment, the ‘unnecessary’ consultations would prove a very welcome interactive exercise and an opportunity to enhance the patient-doctor therapeutic alliance! After all, not everything which prima facie appears damaging is really so. The law of unexpected consequences works both ways. By the way, are we somehow witnessing the dawn of the customer-led care era? Competing interests: None declared |
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Roger A Cleghorn, N/A SW14
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Mr Waller I read with interest your “Personal view” in the BMJ. I see a table in front of me and so here are my cards. I have been taking Seroxat for 7 years. 30mg a day. For the last six months I have been trying to stop taking the drug. I am now down to 8mls of the liquid (16mg equivalent in tablet form). I can see how you might be “offended” by the messages of the programme. However, speaking from my point of view I don’t really care if you happen to be offended. I have been seriously damaged by this drug and my family and I suffer every day at the moment as I try to reduce my dosage. A lot of real people have real problems with this drug – the evidence is clear. And yes - I feel do let down by the MHRA and GSK. You will surely understand that Mr Breckenridge is the person who is best placed to balance matters (hence your own contribution ending up on the digital equivalent of the cutting room floor). You must surely agree that his performance was poor. He was evasive, weak and squirming. Maybe you might have the better person after all, although I would take issue with your ‘balanced messages’. there are some problems with paroxetine, the jury is out, and the issues are being, and have been, taken seriously I have to say that this first statement sums up all that is wrong with the regulators/medical profession.... It’s glib, dismissive and shows no real understanding of the issue or concern for patients who are suffering. the surveillance system is not perfect but people are trying to improve it I should hope so – I think that the MHRA’s income is around £70 million a year - say things aren’t right but don’t worry we’re ‘trying’ to improve is not simply good enough. How much will it cost to get it right? the regulatory system is not perfect either but the people working within it do their best to balance risks and benefits and are solely driven by public health and patient considerations Well, their best is not good enough then. I understand a little of how the Pharmas work and I think this is part of a much wider discussion about truly new drug discovery, product pipelines, patents & patients, marketing spend and of course the all important PROFIT. The revolving door between the Pharmas and the MHRA needs to be locked shut. there is a need to consider what other bodies are doing internationally (less and more slowly than the MRHA). Ah ha – using a negative to prove a positive... flawed logic there, I’m afraid Now – I put my cards on the table – can I see yours please? What’s your angle as they say? Could I ask what links or connections of any kind you have with any drug companies now (or in the past)? I’m sorry if you think that’s a little personal, but I know PR and spin inside out and as such I tend to read between the lines and trust very little. While on that matter I’d like to ask about this line in particular: A multitude of plausible sounding experts and commentators had been assembled... Damning with faint praise indeed. That’s the classic Pharma line when confronted by experts who are ‘off message’ – and it seems somehow out of place with the rest of your article. I wonder why you felt the need to have a go at the people who were on the programme? In fact, on reflection the introduction of your article could almost have written by a person other than yourself as it seems so different in style and language from the rest of your piece. Best regards Roger Cleghorn Competing interests: I'm a patient reducing Seroxat |
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Alan N Wear, consultant Psychiatrist Marchwood Priory Southampton, So 40 4 wu
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Thank you for publishing Dr Wallers' article, it does reveal an aspect of media reporting that we all know but rarely hear about. I am sorry to hear those harrowing accounts that a program like this will collect and pass on, where the attribution of the problem is to the putative drug.What we never hear is the full background history that was taken before the drug was supplied or what consideration went in to the decision to take the drug by either the patient or the prescriber.And we don't hear these things because they simply are not that interesting. What we have is a new Modern Hystory.Modern Hystories were described by Elaine Showalter(1).The essence of a Hystory is that the dialogue about the condition is more influencial than the facts.It builds on the simple but really not that suprising fundemental that there are simply things in the world that that remain unknown. Showalter states that the essential ingredients of the condition are 1)A group of physician/enthusiasts (Dr Healy's name comes to mind) 2) Unhappy vulnerable patients and 3) A supportive cultural environment - Something Panorama is doing to its best to generate. The real tragedy of the condition is that those engaged in it have a compelling belief in the rightness of their own position and the more that an attempt is made to argue to the contrary the more convinced indivuals become of the truth of their view.Similar conditions include Chronic fatigue,recovered memories and Alien Abduction. The only truth that I can discern is that the Specific Serotonin Reuptake Inhibitor (SSRI) story is set to run and run. alan wear 1) Elaine Showalter.Hystories Hysterical epidemics and Modern Culture.(Picador 1997) Competing interests: I do from time to time prescribe antidepressant drugs including SSRI's |
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Linda C Best, Translator Freelance
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Sir: I am the founder of an Internet information and self-help group in Germany for people who have suffered adverse reactions to SSRIs. After 14 months we now have over 300 registered members from all German-speaking countries. My 18-year-old daughter became suicidal while taking and stopping various SSRIs. Her symptoms were not recognised by doctors in Germany and our concerns as to the negative effects of the drugs were dismissed. Luckily, being English, I was able to find support in the UK and the US, as public awareness that these drugs can cause severe reactions in some patients is much greater there. The BBC Panorama reports on Seroxat have played a major role in creating this awareness, and their importance should not be underestimated. It is extremely difficult - or impossible - for patients and their families to gain the credence of doctors. I personally was regarded as hysterical by the doctors concerned. Any attempts to convey the agony and suffering that these drugs can cause are unfortunately swept aside with exactly the same words as those of Mr Waller; " … the putative effect ("suicidality") is a consequence of the illness for which the drug is prescribed." He apparently fails to perceive that a large number of patients are prescribed these drugs for an astonishing array of symptoms other than those of depression. Both patients and doctors are ultimately victims in this situation. Even doctors who are willing to take their patient's concerns seriously (which are unfortunately few and far between) are completely at sea when faced with withdrawal symptoms - one even prescribed antibiotics as a seemingly desperate measure. This topic has only been prominent in German medical and media circles due to its abysmal lack of coverage. Only now in recent weeks, as a direct consequence of the actions of the UK and US authorities, has public discussion been sparked. I agree with Mr Waller that the MHRA is taking up a forerunner position in that it is at least reacting to the concerns voiced. Unfortunately here in Germany leading doctors are even refusing to accept the possibility that these drugs can be harmful to some people. The members of our group for one are jubilant that a media representative with such a weighty reputation as the BBC's flagship documentary programme has focused on this topic. To date our efforts to contact the heads of various competent institutions in Germany have been futile. No response is forthcoming. This is all the more ironic in light of the fact that Germany initially refused to approve Prozac at all as there were already concerns at the time that it can cause suicidality. While understanding that Mr Waller feels unjustly attacked, I can only applaud the laudable efforts of the Panorama team to bring these problems to light. We are thankful that the UK and US authorities are finally responding and hope that future intensified actions will at last persuade German and other European authorities to react accordingly. Linda Best Dip Trans IoL MIL BDÜ Founder of the Antidepressiva-Forum Deutschland (ADFD) www.adfd.de linda@adfd.de Competing interests: None declared |
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Charles Medawar, Director Social Audit Ltd, P.O. Box 111, London NW1 8XG
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Sir: I also rather regret that Patrick Waller’s filmed interview for Panorama was not broadcast (BMJ 2004;329:865). This denied him the opportunity to explain his pivotal role in the 1996 review of Yellow Cards that led the regulators to conclude that, “overall, symptoms due to stopping an SSRI are rare … The withdrawal symptoms observed do not appear to be severe. ” (1) When regulators say “rare”, they specifically imply a frequency of between one case per thousand and one in ten thousand (0.1% to 0.01%). This was the order of risk assumed by the Medicines Control Agency (MCA) and Committee on Safety of Medicines (CSM) until quite recently, in spite of mounting evidence of harm. (2) Responding to the first of the three Panorama programmes (13 October 2002), the MCA advised, “there have been isolated reports of more serious symptoms on withdrawal such as severe electric shock sensations, vertigo and manic reactions.” Within six weeks of the second Panorama programme (11 May 2003), an otherwise unannounced small print warning was inserted into the Seroxat (paroxetine) ‘Summary of Product Characteristics’, with approval from the new Medicines and Healthcare products Regulatory Agency (MHRA). This admitted that 25% of patients experienced withdrawal reactions, and that “in the majority of patients” (>50%), “these events are generally non- serious.” For over decade, the regulators had failed to detect an adverse drug reaction that affected one-quarter of users of the drugs. Dr. Waller would be on safer ground had he dissociated himself from a paper that not only greatly under-estimated the true incidence of paroxetine withdrawal reactions, but which also helped to refute suggestions that there was a problem. The terms of Dr Waller’s attack on Panorama and his defence of the regulators nicely illustrate what the public is up against. Beyond regulatory arrogance and ineptitude, there is also fearsome denial – sustained by a lack of either insight or accountability, that present serious health hazards. (3) Dr Waller “was staggered by how one sided the programme was”; he then rights himself to advise that, “neither the drug nor the regulator is lilywhite” He suggests that problems might compare to the odd molehill on an otherwise even lawn: “the surveillance system is not perfect … and the regulatory system is not perfect either”. These assessments seem astonishingly optimistic and imprecise. The importance of this third Panorama (3 October 2004) is underlined by the regulators’ continuing insistence that the programme’s earlier criticism, of the regulatory failure to follow up Yellow Card reports of suspected drug-induced suicidality (4), was “unfounded” (5). Finally, last week, after six months badgering, The MHRA revealed the basis of this dismissive assessment (6). The MHRA now admit they followed up fewer than half (42%) of the Yellow Cards received, even after four specific reviews of the risk of SSRI-induced suicidality, in 1991, 2000, 2001 and 2002. Some reports were hard to follow up, but whether other cases should have been investigated or not is, says the MHRA, “a matter of judgment”. Dr Waller complains that, in the latest Panorama programme, “a multitude of plausible sounding experts and commentators had been assembled to impart some clear messages — there are big problems with paroxetine and the regulators have messed up big time.” These experts included, notably, the President of the Royal College of Psychiatrists, the Editor of the British Journal of Psychiatry, and Co-Director, Mental Health Guidelines for National institute for Clinical Excellence & Co- Director, National Collaborating Centre for Mental Health. I should disclose competing interests, beyond co-authorship of a book on the history and implications of this regulatory fiasco. (3) I appeared in the second and third Panorama programme and helped a bit (unpaid) with some of the programme development. I was impressed beyond envy with the depth and quality of the research that went into the programme – if rather dismayed that the programme makers felt obliged to sidestep some issues, even when their evidence was compelling. They had established, for example, that the key member of the CSM involved in the licensing of SSRIs was secretly colluding with one of the major manufacturers. (7) Of course the programme gave a ‘balancing’ rather than ‘balanced’ account, but that seems all the more appropriate when the regulators and the companies involved have dominated the information flow; they resisted disturbing evidence and dissenting views, for many years. I fear Dr Waller may have missed the point of the programme, in concluding that he and his colleagues were accused of not wanting to do better than they did: “To be told on national television that I and many colleagues do not care is galling beyond measure.” This was nothing personal; the failures are institutional and systemic. Panorama’s message, surely, was that no evidence of risk does not equal evidence of no risk, and that ‘caring’ does not guarantee ‘effectiveness’. Meaning well should not be confused with doing good. Yours faithfully Charles Medawar 1. Price JS, Waller PC, Wood SM, (Medicines Control Agency), Mackay AVP, (Committee on Safety of Medicines), A comparison of the post- marketing safety of four selective serotonin reuptake inhibitors including the investigation of symptoms occurring on withdrawal, Br. J. Clin. Pharmacol., 1996, 42, 757-763. 2. Medawar C, The Antidepressant Web – Marketing depression and making medicines work, Int. J. Risk & Safety in Medicine, 10, 1997, 75 -126. See also www.socialaudit.org.uk (1998-2004). 3. Medawar C, Hardon A: Medicines out of Control? – Antidepressants and the Conspiracy of Goodwill (Amsterdam: Aksant, 2004). 4. Medawar C, Herxheimer A, Bell A, Jofre S, Paroxetine, Panorama and user reporting of ADRs: consumer intelligence matters in clinical practice and post-marketing drug surveillance, Int. J. Risk & Safety in Medicine 2002; 15, 161-169. 5.MHRA - http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/yellowcard/ycreviewqa.pdf - accessed 10 October 2004. 6. Raine J, Medicines and Healthcare products Regulatory Agency, letter to Social Audit Ltd., 30 September 2004. 7. Boseley S, Drug licensing flaws exposed. Guardian, 4 October 2004 Competing interests: See text |
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Ricardo M. Gusmão, Psychiatrist Lisbon 1000-007
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What is a medical journal doing when empowering an epidemic even though a behavioural one? Promoting nocebo-like effects? It simply does not seem to be true, the whole matter. In these RCT ages let me tell you about old fashioned clinical experience. I have treated hundreds of people with SSRI. And with tryciclics. I do not recall ANY patient where leaving the drug was not feasible if indicated. I know this, because if I had that experience it's exceptionality would have striked me. It doesn't take more than 1 to 4 weeks, depending on several clinical variables. The abstinence syndrome is real, undoubtely for some cases, but on remission of the psychiatric disorder it simply is not impeditive of taking the drug off! Many patients do benefit of long maintenance dosage; this was a major advantage these drugs allowed due the low side effects profile. And many people, unfortunately, do not have a good prognosis or do need high dosage to get better. Many people shouldn't be taking antidepressants continuously in the first place! Bipolar spectrum disordered patients for instance, do get irritated with them and unpleasant. No drug, natural or synthetic, psychoactive or not, is completely devoid of secondary effects or idiosyncrasic ones. Goodness, even the therapeuthic relation might be iatrogenic. I have been told yoga, tai-chi, and hypericum can be! (I know they can!) But all this unbelievable discussion seems so unethically flawed when we know so many patients -- perhaps as many as those that are being treated -- are really depressed and suffering and not having someone to acknowledge the situation, talking about it, getting antidepressants prescribed if needed and managed adequately... This is where clinical experience and evidence are really congruent. I have been blessed in 15 years of career: I never experienced one of my patients committing suicide. Though they complain a lot about it. I usually prescribe my hearing. Maybe a drug. Whatever works. One day it probably won't. PS to the editor: My advice is for you to close the BMJ universal access and get tougher with some of the reporters. No SSRI prescription. Competing interests: None declared |
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Patrick C Waller, Consultant in Pharmacoepidemiology Southampton SO30 2NY
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I thank Drs. Bullock, Blaj, Wear and Gusmão, Mr. Cleghorn and Mr. Medawar, and Ms. Best for their responses to my article. As Dr. Wear implies, television programmes such as this one are likely to be very effective in influencing many people, and more so than the underlying “facts”. The title of Dr. Bullock’s response is salutary. I do not doubt that many more viewers of the programme saw it his way than saw it mine. In my “huff”, I was quite tempted to take Dr. Blaj’s advice regarding the television. In response to Mr. Cleghorn’s “open letter”, I should first answer his question about my links with drug companies. During the period 1990- 2002, as an employee of the Medicines Control Agency (MCA), I had none. It is practically impossible to work in this field and not have any links with the pharmaceutical industry at some stage in one’s career. Previously I held various research posts which were funded by the industry but I would not accept that this means that I am biased in favour of the companies concerned or the industry in general. For example, during one of my research fellowships, I published two papers highlighting important adverse effects of a drug made by the company providing the funding [1, 2]. Since 2002 I have earned my living as a consultant in this field by focusing on regulatory and academic (primarily educational) work. What little work I have done for industry does not relate to specific safety issues for marketed drugs and has been declared in the European Medicines Agency’s public register of interests. I am sorry that Mr. Cleghorn has had difficulty coming off Seroxat. There are a lot of issues on which we would disagree but I do take his point relating to the regulators/medical profession appearing to be glib, dismissive or showing no real concern. If that is how we appear, then I regret it. I can only say that we have to deal with some very sad events but have a duty to remain objective. My article was intended for an audience of doctors and constrained by space considerations, but perhaps I could have been more sensitive to it also being read by patients. As highlighted by Ms. Best, the international aspects of this matter deserve some consideration. In this respect, Mr. Cleghorn suggested that I was “using a negative to prove a positive” but he has misunderstood my intention. Seroxat is used widely around the world and, if it is true that the safety issues with this drug are evidence of major regulatory failure, then, clearly, every regulatory body in the world has failed. The implication, to move on to a point from Mr. Medawar’s letter, would be a general failure of the system rather than particular institutions. And that would be quite fundamental to what might be done about it. If anyone wishes to know more about the attempts which are being made to improve the surveillance system, I would refer them to a published paper describing a project initiated by the Medicines Control Agency in 2001 [3]. Improving the wider regulatory system is a rather different challenge since it will be necessary to convince the European Commission, which is currently in the process of implementing some tweaks from a review which began in 2001. The UK government now has few autonomous powers in this field and I found it surprising that this last point was not considered worth mentioning on Panorama. Mr. Medawar’s fourth paragraph illustrates well the tone and nature of the criticisms faced by regulators. And when, in the few words available to me, I made it explicit that, in my opinion, the surveillance and regulatory systems are imperfect, I am then accused of “optimism and imprecision” ! Mr. Medawar cites the 1996 publication on withdrawal reactions and SSRIs of which I was a co-author [4]. That paper demonstrates that this problem was anything but missed or ignored by the MCA, and that follow-up of yellow cards was performed. Spontaneous adverse reaction reporting data may change markedly over time and the publication was a snapshot of the picture more than 10 years ago. I accept that the conclusions of the paper have since been superseded. I am grateful for Mr. Medawar’s reassurance that his criticisms were not personal. However, when a claim is made that patients are “the last priority” of an organization (Richard Brook’s words on the programme), this must surely reflect on the people involved. In my experience (twelve years working on a very wide range of issues, compared to Mr. Brook’s brief and hardly “unique” [Panorama’s word] involvement in this specific matter), people working at the Agency are committed to doing their best for patients using the resources and tools they have available, and to optimizing their systems. If it is true (as suggested by Mr. Cleghorn), that their best is not good enough, then the focus should be on improving their resources and tools. In this respect, realistic and constructive criticism based on balanced inputs from various perspectives would be much more effective in influencing those who do have some power to change things. That it is what Panorama so conspicuously lacked. Looking to the future, having responded to the main issues so far raised, I see little point in (and do not intend to contribute to) “to-ing and fro-ing” arguments of the point-scoring type that are reproduced elsewhere on the internet in relation to some of these issues. Much more appropriate would be some constructive debate about how to improve these systems in the interests of patients and public health. References 1. Waller P.C., Cameron H.A. & Ramsay L.E. Profound hypotension after the first dose of ketanserin. Postgrad. Med. J., 1987; 63: 305-307. 2. Cameron H.A., Waller P.C. & Ramsay L.E. Prolongation of the QT interval by ketanserin. Postgrad. Med. J., 1988; 64: 112-117. 3. Waller P.C. & Evans S.J.W. A model for the future conduct of pharmacovigilance. Pharmacoepidemiology and Drug Safety, 2003 ; 12 : 17- 29. 4. Price J.S., Waller P.C., Wood S.M. & Mackay A.V.P. A comparison of the post-marketing safety of 4 selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal. Br. J. clin. Pharmac., 1996; 42: 757-763. Competing interests: I was previously employed at the Medicines Control Agency and currently hold a contract to consult for the MHRA. |
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Craig Wheelans, Ships Doctor & Locum GP TSS Pacific Sky, South Pacific
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As a General Practitioner I can only sing the praises of the SSRI's. I have seen many people who have genuinely benefited from these medications and I at present continue to prescribe these medications daily. I have seen people benefit from the medications in that although their side effect profile is different from TCA's they allow people to work, worry less and return to some quality of life. As a GP I have had patients from both the Medical & Nursing professions on the brink of suicide return to a normal life and thankfully back to work without suffering the god awful feeling of 'hangover' that the TCA's give. Not one of those writing before has discussed how dangerous the TCA's are in overdose. The SSRI's are not a pancetta for all ills but I personally feel that depression is now far more recognised and treated than ever before and much of this may have been because SSRI's made depression 'trendy'. The stresses of society, long term unemployment, deprivation, drug abuse and chronic mental illness and the downright lack of disregard to takling these ills contribute more to the risk of suicide than any sham allegation of dishonesty regarding the regulation of these medications. I am not a staunch Socialist or political activist but on this occassion feel that I have to stand united with my collegues to suggest that based upon the limited tools available to us we all do a great job at looking after those suffering from the dispair that depression brings to each individual patient and their family. Competing interests: General Practitioner Using SSRI's Regularly |
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