Making medicines safer for all of us

There has been a fascination recently with watching the orchestrated demonstrations of flag-waving enthusiasm for the regime that emanate from North Korea – the waves of people moving in synchrony like a shoal of fish. It’s difficult to know whether it is scarier to have the population behave this way and not believe in their leaders or have them behave this way because they do believe in their leaders.

Nothing like that could happen here

North Korea seems unique. Having something like that happening here is unimaginable.

Over a year ago I attempted to bring the issues of violence on antidepressants and other psychotropic drugs to the attention of the American Civil Liberties Union (ACLU). ACLU has a distinguished record in helping vulnerable and marginalized groups cope with the power of vested interests. I thought they might be interested to get to grips with the certainty that there are people ending up in the criminal justice system at huge public expense who are innocent. People who are not guilty of the crime they are accused or convicted of by virtue of a prescription-drug induced intoxication. My phone calls and emails went unanswered.

ACLU it seems only want to hear about access to treatment. They want to ensure that everyone within the criminal justice system who could conceivably be deemed in need of mental health treatment gets access to psychotropic drugs.

ACLU and the feminist movement just say yes to drugs

Around the same time I had been lecturing on the issues of Antidepressants and birth defects. Antidepressants double the risk of major birth defects, double the rate of miscarriages (one of the biggest predictors of a woman’s future mental health), cause all kinds of other problems and now appear linked to learning disabilities/mental handicap/autistic spectrum disorder in the children born to women who take them during pregnancy. I thought the issues would be of interest to the women’s mental health movement and to feminist groups.

But the response from the women’s mental health movement, and in particular feminists, has been hostile. All they want to hear about it seems is a woman’s right to access treatment and getting as many women as possible on a psychotropic drug.

The only thing that unites both sides of Congress

This is less surprising than it might seem when you take into account that pretty well the only issue that unites the most divided American legislature ever is agreement that consumers need to be able to access the latest drugs and medical devices at the earliest possible opportunity.

It’s difficult to avoid the impression that we are all North Korean now.

A new McCarthyism

It’s harder to work out whether we are jiving in unison because we all hear the same tune and love it, or whether many of us keep step because we are scared. Listening to colleagues, especially from America, confess their fear to having their name put on documents questioning the benefits or noting the hazards of treatment, there is clearly a great deal of fear, almost – to pursue the North Korean theme – a new McCarthyism.

But it’s also easy to see where enthusiasm for the flag-waving comes from. The rallying cry is we want to Beat Cancer or Beat Schizophrenia. It would be un-American not to want to beat Cancer or Disease. This is exactly what pharmaceutical companies trade on – what makes them so profitable and what gives them such an inside political track. Beating Cancer or Disease means getting the latest high tech weaponry and deploying it with as much Shock and Awe as possible.

The latest drugs are like North Korean rockets

The latest doesn’t mean the best. It used to be the American way to put Men on the Moon and to produce the drugs that got people off their death beds and back to work before anyone else. But rather like the recent North Korean rocket that crashed soon after take-off Western drugs are increasingly more likely to kill than cure but we take them it seems in part because they create jobs (see Pills and the Man).

Who wants to be a cheese eating surrender monkey

Philippe Pinel’s famous claim (see Pharmageddon) that “the art of medicine lies in knowing how to administer medicines properly, but that it is an art of much greater and more difficult acquisition to know when not to treat” increasingly to Western ears sounds very like Jacques Chirac the French President (aka the cheese eating surrender monkey) at the time of the Second Gulf War suggesting it might be wiser not to go to war. This is not the American way.

A new credo for Pinellistas

Pinel came up with his famous dictum in 1800 and like North Korea he seems slightly anachronistic now. It sounds paternalistic to have a doctor decide for you and distinctly un-American to have a doctor decide not to treat you. But what if we were to update Pinel to – ‘If I have to live with a disease there is an art in knowing how and when to use potentially helpful drugs but probably an even greater art in knowing when not to use them’.

From this point of view things look different. It looks like there might be more than one way to Beat Cancer. Launching into an all-out assault with the latest cocktail of poisons is one way to go about it – a way that also makes a profit for drug companies and might give the public health authorities better cancer figures but may not be the way for me to beat my Cancer. A way that’s good for the North Koreans out there who are happy to strip all individuality out of medicine in favor of a national 5-year plan but not a way that fits Yankee individualism.

You have to feel that professional discretion is not much more welcome in the West these days than it would be in North Korea. This is a world in which the skepticism that gave rise to Evidence Based Medicine is to be treasured but is vanishing fast. Except when it shows drugs don’t work, Evidence Based Medicine can never tell me when it would be wise not to treat – paradoxically it always pushes toward treatment.

For me to beat my Cancer or Schizophrenia might mean focusing my energies on completing the projects closest to my heart rather than having my attention consumed by a project that suits Cancer, drug companies and other interest groups. Treatments will be helpful in so far as they help me meet my goals and harmful if I get bent out of shape to fit the goals of treatment.

Disease in its Ur-form

It’s difficult to know whether what we are faced with at this juncture is Disease in its Ur-form co-opting companies and societies using the most sophisticated brain-washing to all but forcibly administer ever more chemicals to the population so that treatment induced death and disability has likely overtaken death and disability from Cancer or other major diseases. Americans are now falling down world life expectancy tables. Cuba overtook America in this league some time ago; will North Korea be next?

… or modern robber barons

If we are not being stalked by Disease, the alternative seems even more problematic. In this case, companies are using the specter of disease to take as much money from us and from the public purse as they can possibly manage – with no regard for whether we might benefit. If they had some compunction and did not extend their rapacity to our children they might get away with it but Moloch-like they demand everything.

The most effective company propaganda, the line that has enabled them to body-snatch 10,000 doctors has been – “It’s the disease not the drug”.

Faced with the new leading killer – pharmacosis (see forthcoming blogs) – do modern Pinellistas need to say – “It’s the company not the disease”.

North Korea is an anachronism that can’t survive, so maybe there’s nothing to worry about. We will wake up from dystopia and normal service will resume. Or have we woken up from the 1950s and 1960s, which gave us a cornucopia of real cures and North Korea, to find normal service has resumed?

There are a number of features of the American Woman story that are emblematic. My original post said she contacted GSK and GSK replied but a closer reading of the emails makes all this less clear. I will continue the convention of referring to contact with GSK, as ultimately it would seem the company must be responsible for the handling of the event. There is probably nothing specific to GSK about this however – other companies will handle events the same way.

A case study of the barriers put in the way of “consumers”

AW’s email (see all AW Paxil emails) “was received by one of our external websites and Glenna at CRC”. CRC usually means Customer Response Center, which at that time was for Over-the-Counter drugs. Why go this route? Well as we shall see this is a case study of the barriers a consumer has to overcome to get an adverse event reported directly to a pharmaceutical company.

The report says the initial email came in on May 31, 2001 from an external website. It is responded to by the call center within hours of being received. AW had a response on May 31, 2001 at 12:59pm, and the safety department at two minutes prior at 12:57pm. Yet, the second time AW e-mails, this time directly to the CRC on Friday, June 1 instead of through the external website (in response to the CRC’s May 31 outgoing e-mail), it takes 2 business days for CRC to take action. The CRC notifies the safety department about it on Wed, June 6, 11:32am while also notifying them that they have not responded to AW. Why the delay in forwarding the data and responding? In fact we don’t know when Glenna at CRC or their external site first received AW’s e-mail, which leaves the 15-day FDA notification up in the air.

External website?

What external website did AW contact? The Paxil website at that time did not have an e-mail submission page, but only a brochure request page that did not include a “questions/comments” line for data entry. It was simply a submission page of personal information in order to get mailed a brochure.

The Paxil website did not have a “contact us” link at the bottom of the page or instructions on how to specifically report an adverse event. Who did she e-mail then? There simply was not a way to e-mail GSK through the website. The only instruction about reporting adverse events was after many clicks in one paragraph about side effects where the consumer read this line “If you should experience any side effects, be sure to report them to your doctor”.

GSK has many phone numbers… but it’s not clear how many connect to GSK

The company has several phone numbers. There is the Medical Information number listed in the response letter. There are also phone numbers on all the Paxil DTC ads. But it’s not clear that any connect directly to the company. Even professional journal ads whose audience is doctors did not at this time have a number that would reach the company directly. In the case of Paxil DTC adverts, the company subcontracted a call center to provide information to consumers – this is neither a medical information center, nor the GSK Customer Response Center call center, although it provides information of the type a manufacturer’s Medical Information department would provide. They can be mail-houses for brochures.

Some of the Paxil numbers have been recycled. For example, Paxil CR’s toll free number is now a program called Neevo Plus for an entirely different company, or the Paxil’s DTC numbers just ring and hang up. They do not reach the company. The advert numbers were not an internal company phone number. So if a woman like this called the numbers on the Paxil DTC ads, even if she left a voice message, it is almost certain that no one called her back as she had not reached GSK. This may have led to her efforts to email GSK and her pleas for someone to respond.

What are FDA doing about these call centers?

This begs a question – Do the call centers hosting prescription drug ad toll free numbers have an adverse events channel? They may not, which raises an interesting issue for FDA.

Companies now have FDA’s Medwatch reporting mechanism on their print ads and a line stating “talk to your doctor”. But whereas manufacturers have to follow up on adverse event reports they are notified of, and because of this Direct-to-Company communication from patients could lead to changes to their label’s warnings, if they find the adverse event could be caused by the drug, Medwatch does not have to follow up on incoming adverse events. Having the reports go straight to Medwatch paradoxically makes it less likely there will be action on any reported adverse events.

Is this saying “please don’t call us, it would cause us problems?”

The message “talk to your doctor” instead of call our Medical Information Center also stops reporting of adverse events to the manufacturer. As the email to our American woman says “Because patient care is individualized, we encourage patients to direct questions about their medical condition and treatment to their physician.” Is this really saying “please don’t call us, it would cause us problems”?

Ironically, the origin of “Talk to your doctor” seems to lie in negotiations around OTC labels 1997. The FDA set up the “talk to your doctor” message to give consumers someone to talk to before taking the OTC drug. Then FDA requested OTC labels to carry a number directly to the manufacturer, for any questions after they took the OTC drug. But while this was seen as good for OTC drugs and OTCs list a toll free number directly to the manufacturer, it was never set up in this fashion for a prescription drug print ad, package insert or commercial.

The DTC ads from 1999 had 800 numbers that were not direct to the manufacturer and were not set up to report adverse events. The number offered in the AW letter is not the same as the numbers listed in any of the Paxil DTC print or TV ads. How many adverse events were not reported because consumers could not reach GSK directly and just gave up?

If Medwatch and talk to your doctor didn’t exist, companies would have had to invent them

Since 2007 the package insert for prescription drugs mentions reporting adverse events to Medwatch and gives the manufacturer’s direct toll free number. While on the package insert, the direct manufacturer adverse event toll free number is not readily available on a prescription medication manufacturer’s website, while the Medwatch info is. The argument may be that the package insert is geared to doctors and not consumers, therefore it is more appropriate to have the manufacturer’s direct number solely in the package insert. But, given how few doctors submit adverse events that argument seems somewhat hollow.

Making reference to the Medwatch scheme, and urging patients to Talk to your Doctor makes companies look good but if in fact companies can divert patients down one or other of these routes they have an almost perfect way to hide problems. Win-win.

Why are GSK acting like they could not reach this woman?

Ultimately we know from the correspondence a letter was sent to an address, but it is not clear it went to the woman. The zip code on the return certified letter suggests it went to Hudsonville, Michigan. The 4 digit code at the end of a zip code may mean a Post Office Box location.

The message has “other” marked off and “undeliverable” stamped, so it appears that she did not come in to pick up her mail and the post office, or whoever was holding the letter, sent it back.

The company sent a Medwatch report to FDA on this case. On this they indicate they sent one follow up letter “X1 letter unclaimed.” Yet, this woman communicated well via email. Why was she not sent an email asking for the doctor’s info? Why are GSK acting like they could not reach this woman?

The company reports “mother’s concurrent medications and medical conditions were not specified” as though she was on other meds but did not disclose specifically which ones. This is not supported by the woman’s statement which was she was on Paxil for Panic Disorder. Leaving other meds or conditions unknown means the company do not have to assign causality.

She was married in October 2000… in Hudsonville?

In her email, the woman said she was married in October 2000. If this was in Hudsonville, and in Church these could be checked. The town hall may contain her marriage certificate.

Can anyone help us trace this woman?

On Thursday, May 31, 2001, a woman whose name is known only to GlaxoSmithKline emailed the company:

I was absolutely distraught

“My name is… I was diagnosed with panic disorder about four-and-a-half years ago. Since that time I’ve been taking Paxil, which is truly a miracle drug. I’ve been panic-free with this drug and have been able to go on with a normal life.

“I was married in October of 2000. My husband and I found out we were pregnant at Christmas time. I was so excited. I love children. The only problem is that I carried the baby to six months gestation and then had to have a termination.

“The doctors diagnosed my son with Truncus arteriosis. They said he would not lead a normal childhood and would most likely not make it through the open heart surgery that he would need as soon as he was delivered (if he was able to make it to that time). To say the least, I was absolutely distraught with this news. I thought this was something that I did, was because I stayed on the Paxil for selfish reasons.

“I wanted to know if you could direct me to any information you might have of any woman that has taken Paxil and still had healthy babies. My husband and I are ready to try again to get pregnant in the next month or two. I am so nervous. I don’t want to stop taking my miracle pill. But, then again, if there is a chance that this might hurt or affect the baby I want to know upfront. And I will somehow stop taking it for the time being.

“Please contact me as soon as possible. I love everything this drug has done for me. I am so thankful that your company had this available for me. I just want to continue to have a normal life and have the child that I always wanted. Please contact me as soon as possible.

“Please don’t forget about me, Thank you.”

We are attaching a copy of our product information leaflet

GSK responded on Thursday May 31st:

“Thank you for your inquiry. We are attaching a copy of our current product information for Paxil. Please review the section on use during pregnancy. Further questions about your treatment should be directed to the physician, pharmacist or healthcare provider who has the most complete information about your medical condition. Because patient care is individualized, we encourage patients to direct questions about their medical condition and treatment to their physician. We believe that because your physician knows your medical history, he or she is best suited to answer your questions.

“Our drug information department is available to answer any questions your physician or pharmacist may have about our products. Your healthcare professional can call our drug information department at 1-888…”.

[As of 2001 the label for Paxil made no mention of the number of reports of congenital abnormalities associated with Paxil. Company policy at the time was not to tell doctors or patients or pharmacists how many reports of congenital abnormalities had been reported with Paxil usage].

I do not want to put my unborn child through anything that would hurt him/her

On Friday, June 1, 2001, the unknown woman wrote again:

“This response is in regards to an e-mail that I had sent you previously. I was asking to see if you have any or are in the process of any clinical trials for women who are currently on Paxil and pregnant. I wanted to find out information to see how many women were on Paxil during pregnancy and if they were able to successfully have healthy babies.

“I am in no way insinuating your product did this to my child. I love the product, and I don’t think I could have gotten through my panic attacks without the wonderful help of this miracle drug. I just want to start to try and get pregnant again soon. I do not want to put my unborn child through anything that would hurt him/her.

“Please, if you do not have this information, where is this information held? Does anyone do studies like this? Please, any information you may give me would be great. Thanks again for your help.”

Almost certain

On June 13, 2001, an internal division within GSK monitoring adverse event reports looked at this congenital abnormality and made a judgment about the link to medication. Their judgment was that it was “almost certain”.

Who is this woman? Can you help us find her?

At a meeting of the Royal College of Psychiatrists in Brighton in June 2011, Dave Nutt, a professor of psychiatry at Imperial College London issued a call to arms to his audience at a plenary lecture to defend psychiatry which in Dave’s view meant defending psychopharmacology. On a slide entitled ‘No Psychiatry Without Psychopharmacology’ he outlined the threats from treatment deniers like Irving Kirsch and Joanna Moncrieff whom he claimed argued drugs don’t work. Psychiatry is also apparently threatened by illness deniers who claim that addiction or shyness are just lifestyle options.

Then labeling and libeling me a Scaremongerer, he claimed psychiatry was threatened by me. The first point to note is that I was not held to deny the reality of illness nor held to say that treatments don’t work.

The only risks of an on-patent drug that can be mongered are ones that are real

As regards the risks of drugs, pharmaceutical companies are quick to sue people who claim that treatments have risks if they cannot back up their claims with evidence. As we have seen in the first post in this series almost everything I write or say at meetings is scrutinized with a view to suing me. Calling someone a Scaremongerer, as a matter of logic, should be all but an oxymoron – such a beast cannot exist. The only risks that can be mongered are one’s that are real. If these risks are real, should they be regarded as scares?

If the argument is that it is fear that is being mongered, pharmaceutical companies monger fear the whole time. Leave your child’s depression untreated and she will grow up to be alcoholic, drug abuser, will have a failed career and marriage and ultimately commit suicide. Leaving your anxiety or depression untreated while pregnant and your child is likely to be born with a birth defect.

Doctors are there to quarry information out of pharmaceutical companies

If medicine is going to save itself, if it is going to remain a profession, it is time to embrace the duties given it in 1951 and again in 1962 when drugs were made available on prescription-only (See Pharmageddon). Doctors warn people about the risks of over-the-counter products – like patent medicines or tobacco. Prescription-only medicines are prescription only precisely because they are riskier than over-the-counter drugs. If they are no riskier than alcohol or nicotine, which people can manage on their own, why have them on prescription-only. Doctors are there to quarry information out of pharmaceutical companies about these risks – not to be a risk-denying conduit for drugs.

Dave, who I used to think of as a friend or at least a colleague, has form in this area. He has instigated investigations of me by the General Medical Council (see Academic Stalking), aimed it would seem at getting me debarred from practice.

After this lecture, I sent an email asking for the slide branding me a scaremonger – it’s one to treasure – but he didn’t respond.

Dave has another role which is agitating on behalf of the pharmaceutical industry – making regulations less onerous and the environment more company friendly so companies don’t move jobs elsewhere. Mickey Nardo has commented on this http://1boringoldman.com/index.php/2012/03/24/21579/#comment-220767. The only quibble I have with this portrayal of Dave and others is as some Greek chorus; I can think of better analogies.

Should doctors be scaremongerers?

But if Dave as a spokesperson for Pharma has taken one line, the question is has he inadvertently crystallized what doctors should be doing? The thrust of a series of recent posts here (Pills and the Man, If Pharma made cars, We need to talk about doctors, Professional suicide) is that if doctors cannot be identified as the people who know about the risks of drugs, they are likely to go out of business. They should be scaremongerers in other words.

It’s time to come out of the closet

Now is the time for doctors to come out of the closet. We urgently need to develop Scaremonger Pride to match Black, Gay and Mad Pride.

I’m open to nominations for a Dave Nutt Prize for most effective Scaremongering of the Year for 2011 and would urge everyone to keep track of possible nominees for 2012. You can nominate the person who in your opinion did the most to alert others to a hitherto unknown or poorly recognized substantial risk from some treatment. Anne-Marie or Rosie Meysenburg would be good candidates for 2011.

(also see DN slide).

When she sent Margaret’s Story to us, M had already written to Britain’s Suicide Czar, Louis Appleby. She got the following response:

Dear Mrs

Thank you for taking the trouble to contact me. I am so sorry to hear about the death of your son. Those of us who work in suicide prevention are always aware of the individual tragedies that lie behind our figures.

The problem of agitation in the early period of treatment with SSRIs has been known for several years, at least to psychiatrists. I think you are commenting on front-line A&E staff and if so, I suspect you are right, that many will be unfamiliar with the side-effects of SSRIs as they are not specialists in mental health. I have forwarded your note to my Department of Health colleagues who are preparing the final suicide prevention strategy – analysing the consultation responses has taken a lot of time and they are still working on this. I will also raise it when I meet the College of Emergency Medicine shortly.

As you will appreciate, one of our biggest concerns in preventing suicide is still the under-treatment of depression in primary care. One reason for this has been the reluctance of many depressed patients to take antidepressants. SSRIs have helped here because in general their side-effect profile is more acceptable than that of the older tricyclic drugs, and because taking them is usually a matter of only one tablet a day. However, SSRIs are not without their own risks.

Thank you again for writing.

With best wishes

Louis Appleby

But there is no evidence that suicide rates would be reduced

The argument that we can’t warn because it will deter others from seeking help first surfaced at FDA hearings on Prozac and suicide in 1991 (See Pharmageddon). If there were any evidence that anyone’s life was being saved this might be one thing, but there is no evidence that suicide rates would be reduced if we got everyone who could be treated with SSRIs and related antidepressants onto them.

The data shows a net harm, even when FDA stripped the suicides and suicidal acts linked to withdrawal out of the picture in 2006. Adding withdrawal suicides back in makes the risk of treatment look even worse.

It’s difficult to see how Dr Appleby or others expect to get many more people on antidepressants than we now have. We have had 20 years of perhaps the most successful marketing campaign in history, a campaign that has even managed to persuade parents and doctors that pre-school children are depressed and in need of antidepressants. The vast majority of these and of anyone else who might be likely to end up on antidepressants are at a vanishingly small or no risk of suicide.

The biggest single reason people might not end up on an antidepressant in recent years is down to pharmaceutical company marketing of bipolar disorder and efforts to persuade doctors to prescribe anticonvulsants or antipsychotics rather than antidepressants.

What is an antidepressant?

Let’s step back and ask what an antidepressant is. An antidepressant is a drug that gets through current testing procedures put in place by regulators like FDA. The current testing procedures are such that if two glasses of good red wine per day were put through the kinds of trials in the kind of patients that brought SSRIs on the market, the wine would show up as being just as “antidepressant” as SSRIs do. There might even be less evidence of suicide risk with wine compared to SSRIs, but whether less than or the same as SSRIs, if the argument were put forward that we must avoid warning about the risks of alcohol because we don’t want to deter others from getting started on it, what would we think was going on?

A covert vaccination program..?

If there was a good reason to think that SSRIs could somehow reduce rates of suicide, despite the evidence, the failure to warn about the risks in order to increase the numbers likely to be put on the drugs comes close to a covert vaccination program. All will be treated in the expectation that more will be saved than lost as a result.

A curious vaccination program in that with a vaccine while some lose everyone stands to gain but in this case a majority of those being vaccinated have little or no conceivable gain. A curious vaccination program in that doctors aren’t actively on board with it. They are as much in the dark as to what is going on as everyone else, maybe even more so. They haven’t been told there is a good case to warn but we aren’t going to warn for fear of deterring you from putting as many people on pills as you can.

This under the radar “policy” appears to have come out of meetings between a few bureaucrats in FDA and company people in Lilly, over 20 years ago.

A standard bureaucratic dismissal

Louis Appleby’s letter to Margaret seems like a standard bureaucratic dismissal. Over 10 years ago, aware of some of the individual tragedies behind the figures and of company documents conceding the drugs caused suicide, I tried to engage with MHRA – the entire correspondence was posted on socialaudit.com and part is on healyprozac.com. I asked them to show me where I was wrong as I would feel a moral obligation to stop talking about the risks of SSRIs if there was evidence they did more good than harm. I met MHRA on several occasions but despite an open invitation to them to tell me where I was wrong was never given any information.

It makes no difference to a bureaucratic machine if Margaret and others write forever.

A Platonic Lie is when a ruler decides to keep the truth from his subjects in what he determines to be their best interests.