Making medicines safer for all of us

Adverse drug events are now the fourth leading cause of death in hospitals.

It’s a reasonable bet they are an even greater cause of death in non-hospital settings where there is no one to monitor things going wrong and no one to intervene to save a life. In mental health, for instance, drug-induced problems are the leading cause of death — and these deaths happen in community rather than hospital settings.

There is also another drug crisis — we are failing to discover new drugs. [Read more...]

Archive for March 2012

Margaret’s Story

(The story outlined below is authored by ‘Margaret’. Since this was first written there have been a number of developments and an update to ‘Margaret’s Story’ will follow – DH).

Our son went to his GP with poor sleep because of worries at work. His doctor said he was depressed and put him on a combination of Cipramil (SSRI antidepressant) and Temazepam (a sleeping pill). A week later he took his own life. We now question both the diagnosis and the combination of medications – a mixture of uppers and downers.

Many of those who take their lives have recently attended the doctor. It must be important to see if there are any links between the use of medication and death. In the time since his death we have had a steady correspondence with the Department of Health and MHRA in an attempt to clarify how anyone can come to be placed at risk of suicide from their treatment. We would consider ourselves to be well-informed but we had no idea that mind-altering drugs are prescribed so widely with negligible safeguards.

The system… is deemed to be adequate

Early on we discovered enough about Cipramil and other SSRIs to give us cause for concern. This has been the driving force behind our enquiries since. We have written to a succession of Ministers of Health and received replies from the offices of Andy Burnham and Mike O’Brien saying in effect that the current system, with regard to maintaining the best practice in the use of SSRI antidepressants, is regularly reviewed and is deemed to be adequate.

We were directed to the regulator, the MHRA, and this led to a back and forth between the MHRA and Department of Health and ourselves. We have been sent an abundance of correspondence that invariably buries whatever issue we address in a welter of references to complying with the European Union and the CSM Working Group, along with directions to seek further information at the NICE website or MHRA’s own website etc.

This is not acceptable for someone seeking advice in plain English to find that it isn’t readily available. There is no apparent will to put information about SSRIs in the public domain. It has to be sought out and cannot easily be found. Updated information, it seems, gets posted to locations not easily accessible to the public at large.

The unalienable right for all patients and their carers to know about risks

Virtually every time I have corresponded with the Department of Health or MHRA I have referred to the BNF guidance that:

“the use of antidepressants has been linked with suicidal thoughts and behaviour. Where necessary patients should be monitored for suicidal behaviour, self-harm or hostility, particularly at the beginning of treatment or if the dose is changed”.

This two-sentence warning, and what I feel is the unalienable right for all patients and their carers to know about risks, has been at the heart of my enquiries. But it has never been addressed. The MHRA drew my attention to the NICE advice:

“Depression and anxiety commonly co-exist, and insomnia is a core symptom of depression. Whereas antidepressants usually take two to four weeks to take effect, benzodiazepines are effective anxiolytic and hypnotic drugs with an immediate onset of action. Therefore benzodiazepines could be expected to produce early improvement in some symptoms of depression, although they do not have an antidepressant effect.”

This advice ties together depression, anxiety and insomnia. It seems to direct the physician towards the use of antidepressants as a cure-all. The implication is that a benzodiazepine could help the patient initially until the antidepressant reaches a “therapeutic” level. But NICE does not recommend long term augmentation of antidepressants with benzodiazepines. As ever, the message is confused.

If the drugs take two weeks and more to work for good, then they take the same time to harm

The NICE advice, it seems to me, is being used as a fig-leaf to cover the failure to address the more dangerous period of early uptake or dosage amendment (which the MHRA choose to interpret as ‘at the point of increase’, not the dreadful time of withdrawal experienced by those with long-term repeat prescriptions who wish to stop, or those who do not sustain regular dosage). Significantly, NICE does not address the question of whether there are critical points in usage. It seems that so many interpret their advice as meaning that if the drugs take two weeks or more to work for good, then they take the same time to harm.

When, on the day he died, our son presented at an A&E unit, he saw a doctor who was not a psychiatrist. He was informed of our son’s medication details and has since stated that, although he was aware of the suicide risk of Cipramil he did not alert our son to this. Part of the hospital’s explanation for this lapse was adherence to the “two weeks to improve therefore two weeks to deteriorate” mantra embodied in the NICE advice.

Where this originally comes from is still a mystery. Our son was left without hope or insight that would have told him he was in a temporary state of crisis that could be addressed with proper medical assistance. The NICE advice is at odds with the BNF warning, and so conflicting messages are being sent to those seeking guidance.

All leaflets should contain a suicide risk warning

Much of our correspondence has centred on the failure of the PIL – the patient information leaflet – as a means of communicating risk. The MHRA assured me that all leaflets should contain a suicide risk warning, combined with the advice to appoint a relative or friend to read the leaflet and monitor the patient. I found that the Cipramil leaflet in my possession did not have the combined message. The suicide risk was mentioned, though not at all well highlighted. The advice to appoint a monitor was not there.

I received a grudging reply that steps were “being taken by the MHRA to ensure the PIL for this particular Citalopram [Cipramil] product is updated to include the full warning”. No acceptance that the current system fails and no wish to revise existing practices. I had wrongfully assumed that all PILs had to replicate a master produced by the MHRA for each drug – not so. There is no apparent will to raise the level of the suicide warning in the PILs for antidepressants.

When I asked why the two sentence advice from the BNF could not be in the public domain I was told that “it is not feasible to have a public campaign to inform all patients about the side effects associated with all of the medicines on the UK market”. I replied that SSRIs could be classed as a group and are used by so many patients that it was well worth circulating vital information about potential risks. I received no reply to this comment.

According to the Office of National Statistics, 39 million prescriptions were issued for antidepressants in 2009. Even factoring in a calculation for repeat prescriptions, the number of patients using antidepressants runs into millions. This establishes them as a considerable proportion of patients who need to be as well-informed as possible, given the suicide risk their medication can give rise to.

Who decides who lives and who dies?

I wrote to Anne Milton, Under Secretary of State for Public Health, expressing my concerns and dissatisfaction with the response of the MHRA and also copied the current Minister for Health, Andrew Lansley, into a letter I wrote to the MHRA. I was then switched to the Department of Health and I was told that the

“Department believes a balance has to be reached between raising awareness and deterring people from taking antidepressants which can and do prove to be very effective treatments …..”

This “effective treatment”, if it exists, is being achieved at the cost of the lives of a vulnerable minority, no reference to this of course. Who decides who lives and who dies – shouldn’t we know about these risks, especially when knowing about them means that more might live?

The Department believes that my concerns over public awareness have been well covered in the press and the scientific media. Really? The Department has deemed that

“the PIL is a patient aid and does not replace the discussion between the prescriber and the patient. It is good clinical practice to discuss the potential risks as well as the benefits of a treatment, prior to issuing a prescription”.

Plainly, nobody has told the prescribers this. It appears to me that ill-informed and pressurized GPs are just as much victims of the current failing system as the patients. The emphasis on targets has led to foreshortened consultation time and quick-fix prescription of medication.

In a bizarre twist I was directed towards the General Medical Council

Then in a bizarre twist I was directed towards the General Medical Council (GMC) by Department staff as “….the training and development of medical professionals is the role of the GMC.”  The Department says it does not investigate the conduct of doctors but

“the GMC seeks to promote high standards and ensure that medical education and training reflects the needs of patients, the service, students and trainees. Your concerns about the lack of knowledge regarding antidepressants should also be directed to the GMC”.

I approached the GMC. They did not respond to my query as to whether or not the seemingly counteractive combination of antidepressant and sleeping medication is deemed to be accepted practice. They have chosen to deal with this as a fitness to practise issue and gave me a deadline by which time they wished to receive the names of the GP and A & E doctor involved in our son’s case. Otherwise they would assume that I wish no further investigation. I have refused to comply, as I don’t see the doctors as being to blame.

As a result the GMC now consider that they are not the best agency to deal with my concerns. I have been told that they “are not a part of the NHS or Department of Health and have no powers to affect generalized policies. Concerns about the system, that is NHS procedures or the way that medics are trained, does not generally fall within our remit.”

This seems to be a complete contradiction to the promise of the Department of Health that training and development of medics is in the remit of the GMC – they are talking totally at cross purposes.

The Department will be unable to enter into further correspondence with you on this matter

The GMC directed me to the Parliamentary and Health Services Ombudsman, our local MP and, ironically, back to the MHRA. Exasperating to say the least. The Department of Health meanwhile now tells me that

“unless there are any subsequent developments surrounding the labelling of UK prescription medications, the Department will be unable to enter into further correspondence with you on this matter.”

The authorities refuse to listen or respond. At a time when the situation is fluid and changing as more information emerges about adverse drug reactions, the authorities are set in concrete or stagnant. If you are not satisfied with their reply, then it is your fault and you are not to bother them again. This institutional heedlessness parallels the stance of the pharmaceutical companies when a patient is not responding well to their drug – it must be down to the patient and not the drug.

The system is failing patients and doctors. Doctors are not trained to look out for or to deal with adverse drug reactions. Medication is not accompanied by adequate patient information and the doctor is not instructed to outline clearly the potential dangers to the patient. We can’t improve the system unless we recognize the inadequacies.

Out in the real world, precious lives are being lost to horrific avoidable deaths.

If Pharma Made Cars

generic car

If Pharma made cars, the seat-belt warning signs would be removed, and the beeping noise if you moved without a seat-belt on would be silenced, as the start of a gradual process that would result in seat-belts being removed or made non-functional. The safety-bags would be removed or made ornamental. The car would be turbo-charged. The accelerator would be re-engineered so that the only options were travel at the upper end of the speed limit or faster.

The car would come with a Driver (Dr.). You could not get one without this option. The law would be adjusted so that in the case of any untoward event, legal liability falls on the Dr. rather than the manufacturer.

There are four types of ‘Dr.’

You would have no real choice of car, your Dr. would choose it for you. There are 4 types of Dr. but depending on the country you were living in you might have little or no choice of type of Dr.

One type of Dr. is the Speedy Gonzalez model, who is programmed/trained to put experience over adherence to speed-limits and other regulations, who is likely to attempt exciting maneuvers in the course of travel, and who is imbued with what you might regard either as confidence or foolhardiness. If you voice nervousness at the driving this Dr. is likely to increase speed.

A second type is the Standard Model, who is most concerned with keeping things uncomplicated. Driving is a matter of getting from A to B – she is less interested in the onboard gadgets. She keeps an eye on the routes her colleagues take and follows these rather than taking short-cuts or other off-piste options in the face of traffic snarl-ups. This is not done with an eye to liability but it makes her legally invulnerable should anything go wrong.

A third type is the Guidelines-Based Dr. This Dr. has become more popular lately as cars have come with GPS installed to offer the Dr. advice on standardized driving. These computers are supposed to have Ruse Controls installed to manage the “tricks” that Pharma get up to but the computers are programmed by Pharma. Rigid adherence to the GPS often leads these Drs the wrong way up one way streets – once you start paying heed to the onboard voice it’s difficult to stop.

Finally there is the Traditional Model but this is being phased out, despite being celebrated in Dr. textbooks and routinely invoked by politicians and others.

A Dr. is no good without the latest car

The key personnel in terms of sales at the Trade Fairs, or in the showrooms, have more extensive training than the Drs. These are highly professorial staff whose brief it is to cover different company products but never mention any other form of transport such as bicycles or walking, even though their earlier training included exposure to these other forms of transport. They are central to company efforts to get over two messages – one that cars are the way to go – what other form of transport comes with a Dr? And at the same time a Dr. is no good without the latest car.

Companies are legally obliged to answer the question “Can cars kill?” with a “Yes”. They can usually evade this by answering instead the question “Will this car kill me?” or “Did it kill him?” with a “No – absolutely not – if things went wrong it was the Dr’s fault”. But ultimately they depend on their professors (who are carefully managed independent contractors under no legal obligation) to deliver the message “Cars Cannot Kill”.

If Philip Morris made drugs…

If Philip Morris made medicines, all available drugs would come with prominent Black Box warnings that this product can kill consistent with the traditional medical view that Every Drug is a Poison, and the Art of Medicine lies in finding the right dose.

There would be a ban on all advertising including Direct to Consumer Adverts. The use of drugs for children would be severely restricted, and exceptional rather than common.

As company products are available over-the-counter rather than on prescription-only, doctors would be openly skeptical of the claimed benefits and would fully support ongoing research to demonstrate the risks. Somewhat more puritanically perhaps some doctors might be expected to attempt to get Philip Morris sponsorship of university activities banned.

 If American Airlines made drugs…

Unlike doctors, pilots have to take the same flight that those in their care take. As a result safety is a real issue for them; if the passenger is injured, the pilot is likely to be also. If American Airlines made medicines, doctors would have to sample all of the medicines they gave to patients. More generally doctors would need extensive retraining on safety issues.

Doctors would have to liaise with colleagues regarding near misses and other events that happen ‘in therapy’. The current Adverse Event Reporting System (AERS) would be replaced by something closer to the Airline Safety Reporting System (ASRS). Not such a big change in reporting – but a world of difference in the way the reports are handled by regulators. AERS reports now dismissed as anecdotes would, like ASRS reports, be taken seriously by regulators – “Often, such lower-bound estimates are all that decision makers need to determine that a problem exists and requires attention.”

If the case of a drug disaster, the regulatory agency responsible for letting a drug on the market would not be one charged with investigating the problem. An independent Drug Safety Board would be set up.

The emphasis placed at present on the efficacy of drugs would be replaced by a focus on their safety. Airlines do not compete on the basis of who can get me to Kansas 30 minutes earlier. If an airline is perceived as being less likely to get me to Kansas safely – it goes out of business.

Odysseus Come Home

prison

Odysseus was in his 70s. Coming up to the 50th anniversary of a very happy marriage. He had formerly been a respected professional, a longtime member of the bowling and social clubs – a pillar of the community.

He had had minor episodes of anxiety primarily since retirement but no diagnosis of nervous problems. He went to his primary care doctor and was given a sleeping pill for poor sleep but stopped it after the first pill knocked him out. A few weeks later he was brought back to the clinic by his wife and ended up on Cipramil (citalopram) for anxiety. In the following 9 days he had 3 nose-bleeds – an SSRI side effect not recognized by his doctor.

The medical records pointed to a deteriorating situation… but no risk was noted

He kept a diary while he was on Cipramil, which recorded that he was feeling worse and worse, and becoming concerned that he might be going mad. He returned to the doctor and complained about his antidepressant but was persuaded to continue the pills – “these drugs take several weeks to work”. No risk of suicide was noted. The medical notes record his concerns about the stress he was causing his wife.

The medical records, the later testimony of acquaintances and family members all point to a deteriorating situation. His anxieties about trivial matters were escalating rapidly. He began voicing doubts about his wife’s commitment to him. This was exacerbated by a new anxiety about driving that led him to ask her to drive him everywhere which she would not do. He described himself as a fly in a jam jar and his diary records a fear that he might be committed to an asylum.

His son found him pacing restlessly and scratching himself furiously – the 10th day since starting citalopram

He mentioned suicide to neighbors but said he would never have the nerve. A daughter thought of flying home. A son came to visit, and found his father pacing restlessly, scratching himself furiously and unable to hold a coherent conversation. His son left the following morning for a work engagement – the 10th day since his father started Cipramil.

Shortly afterwards, Odysseus got a blunt instrument, went into the bedroom where his wife was sleeping and battered her to death. The transcript of his interview with the police later that day – after calling them to tell them what had happened – shows a man who was incoherent. Several weeks later, after Cipramil was stopped, when interviewed in hospital he was quite different.

A clear cut case of SSRI induced violence

This was one of the most clear cut cases of SSRI induced violence that I’ve seen. His children were happy for him to come home to live with them if he were acquitted. I wrote a report supporting a not guilty by virtue of insanity case. In comparable cases elsewhere, such as David Hawkins in Sydney in 2001, people have walked out of Court effectively free (see Healy et al 2006).

Did Odysseus’s lawyers bottle it? Neither Odysseus nor his family saw my report. He was in prison, isolated from almost all contact and unable to test their view or intentions. He accepted their advice to plead guilty, which gave him 2 years in prison. No one it seemed had any incentive to help Odysseus get home. For the police, he kept their conviction rate up. For the lawyers, he was on legal aid and so they stood to make the same amount of money from a quiet day in the office. I wrote to the Judge but was blocked from sending the letter by advice that I would be in contempt of Court.

All of the biases outlined in these posts come into play when it comes to the issue of violence on prescription medication. We have no difficulty in believing that illegal drugs like cocaine or amphetamines, or over-the-counter drugs like alcohol can lead to violence, but extraordinary difficulties in believing that prescription drugs can do so.

The original insanity defense

Drugs formed the basis for the original insanity defense outlined by Chief Justice Matthew Hale in 1743 who stated that:

“if a person by the unskillfulness of his physician or the contrivance of his enemies, eat or drinketh such a thing as causeth such a temporary or permanent frenzy, as aconitum or nux vomica, this puts him into the same condition, in reference to crimes as any other frenzy, and equally excuseth him”[1].

The frenzy Hale refers to here means delirious states, stemming from physical or other disorders, and only secondarily to what later came to be termed not guilty by virtue of insanity or psychiatric illness. Delirium refers to states induced by a fever, or toxic metabolism, or by a toxic agent such as a drug. Delirious states as instanced by the disordered mental states accompanying a high fever or delirium tremens offer an absolute defense against murder and provide a basis for a not guilty verdict because the capacity to form intent to kill could not have been present.

But 260 years later we have much greater difficulties with these issues than Hale had. In the Pittman case in South Carolina, a 12 year old boy who had murdered his grandparents several days after starting Zoloft, Judge Pieper was much less clear than Hale before him:

“There is no case in South Carolina that addresses involuntary intoxication by prescription drugs… It seems to turn the whole medical system on its side if you can’t rely on the medication your doctor prescribes… It potentially forces you into a situation of lifetime commitment if that drug induces an effect of which you are unaware. There’s something disconcerting about that, albeit probably of a legal nature that is troubling me”.

The idea that a doctor might have poisoned a person is close to unconscionable

Treatment induced violence may be the most neglected treatment related problem in all of medicine, despite an abundance of the most convincing data. How could something be so Evidence in the 18th century and cause such problems now?

This is one of the two places where the tensions in prescription only arrangements become most acute (the other is pregnancy). No doctors intend harm, and certainly not harm to an innocent third party. The idea that a doctor might have poisoned a person is close to unconscionable. The idea that the most poisonous aspect of what happened was the doctor’s advice to continue taking the pills or double the dose leads many doctors and lawyers to something close to a psychotic breakdown when it comes to violence on prescription drugs.

Easier boycott Odysseus than Lundbeck’s drugs

And so in the face of mass school shootings where the great majority of the perpetrators are on antidepressants, we stay silent. Odysseus only got two years – a small price to pay many will think for ensuring the guilty don’t walk free.

But Odysseus didn’t just get two years. Back in Ithaca, his friends who had once been willing to testify on his behalf in the belief he was not guilty now refuse to have anything to do with a guilty man. The social club and bowling club turned down his applications to rejoin. For medical care he has to go back to the same doctor. The people he now has most contact with are the checkout girls at a supermarket some miles away.

Dare he risk an appeal? The judicial system might opt to re-imprison him.

And of course Penelope is dead. Who was responsible for her death? Lundbeck? Easier boycott Odysseus than Lundbeck’s drug. The gods seem more likely to listen and bring Odysseus home than Lundbeck.

[1] Hale M (1736/2003) Historia Placitorum Coronae. Vol 1 Lawbook Exchange. Clark New Jersey, Chapter 4, Concerning the Defect of idiocy, madness and lunacy, in reference to criminal offences and punishments. page 30

The Dram of Eale

They told me the 80 year old man who’d had a stroke must be depressed – he wasn’t rehabilitating properly. Could I see him and look at whether the citalopram he’d been started on a week before needed tweaking?

Jeff was solidly middle class, professional. He had never been ill before his stroke and never ever been mentally ill. He had a large loving close-knit family who came to see him every day. He didn’t seem depressed to me. I stopped his SSRI and said I would come back in a week to see how things looked – perhaps his depression would be more obvious then.

A week later, Jeff seemed much better than he had been on citalopram. He clearly didn’t need an antidepressant – if he wasn’t rehabilitating it was because of where his stroke had struck.

‘While on those pills I had a terrible urge to get up and strangle him. I’ve never seen him before.’

I got up to leave just as his family came in. He grabbed my arm. ‘I’ve something to tell you before you go. You see the man across the room’. There was another older man confined to his bed.

‘Well while on those pills you know I had a terrible urge to get up from my bed in the night and go over and strangle him. I don’t know why. I’ve never seen him before. Those feelings have gone since you stopped my pills.’

This makes it about as Evident as you can get that SSRIs cause violence. The only thing possibly more convincing would be data from healthy volunteer studies where aggressive episodes have been relatively common (see Mystery in Leeds).

Homeland Security

In the latest hit series Homeland Claire Danes plays Carrie Mathison a CIA agent with bipolar disorder taking Clozapine. She takes the drug to prevent herself tipping over into frank paranoia in a world where being paranoid is necessary for survival.

Anyone who knows anything about Clozapine knows Claire Danes is definitely not on it – she would not be as slim and svelte as she is if she were taking it. Weight gain is something Evident about Clozapine that stands in contrast to the Evidence showing no weight gain that companies have gone out of their way to produce for Clozapine and related drugs like Zyprexa and Seroquel (see False Friends).

Should Claire Danes get paranoid?

The question is what does Claire Danes know about Clozapine and should she get paranoid rather than just play the paranoid? As an actress is she killing people playing the part she plays? Is there anything else Evident about Clozapine being hidden by the Evidence?

Clozapine began life in 1958. It was given to the world’s leading psychopharmacologist Pierre Deniker to assess. At the time the neuroleptic/antipsychotic group of drugs was regarded as very safe. Several of Deniker’s patients died on Clozapine and startled by the number and range of deaths he said it was Evident that it should not be developed.

Deniker said Clozapine was too dangerous to be developed

The company who made Clozapine (Wander) paid no heed to him; business and clinical evidence are two different things. Clozapine’s development continued even after Wander was taken over by Sandoz. Then in 1975 a series of deaths on Clozapine following drops in white blood cell counts happened in Finland. Clozapine was removed from markets in Europe and never made it to the US – Homeland Security (aka the FDA) intervened.

But it re-emerged in 1988 in the United States, in part because of efforts within Homeland Security. The history of Clozapine’s return has been spun and respun – see The Creation of Psychopharmacology – in the course of which a myth has been created that Clozapine is more effective than other antipsychotics (very important for someone on whose wits the fate of America depends) even though head to head trials in first episode psychoses show Clozapine to be no better than older drugs like chlorpromazine.

Recently the Lancet published a large study by Jouko Tiihonen and colleagues, ironically from Finland, which has thrown the cat among the safety pigeons. In line with expectations, Tiihonen showed that patients treated with antipsychotics had higher mortality rates than patients not on antipsychotics. Except for Clozapine. Clozapine had a lower mortality rate than all other antipsychotics, lower even than non-treatment.

Did Deniker get it badly wrong?

So did Deniker get it badly wrong? Have the Lancet redressed an historical error and are they helping Homeland Security by getting Claire Danes on Clozapine – or has the Lancet been turned and is it also now a threat to the American people if not to US business?

Having spent several posts pointing up the limitations of randomized controlled trials (RCTs), and before going on to labor them further, this Finnish study offers a wonderful example of where RCTs really are needed. The need for an RCT in this case should have been very apparent to the Lancet and its reviewers, and probably should have led to the Tiihonen paper being turned down – other than as a marvelous illustration of how badly wrong cross-sectional outcome studies can get things.

Here’s the problem. Outcome studies like the Finnish one are not randomized. The investigators in a study like this just look at what happens in patients taking older antipsychotics like haloperidol, newer drugs like Zyprexa (olanzapine) or Clozapine. Given that thousands of patients may be on each drug and they were followed up over longer periods of time than the usual clinical trial would follow them up, is randomization we might ask a big deal? Does the accumulation of lots of patients not ultimately manage the bias that randomization helps us manage? If Clozapine is dangerous could it conceivably show up in a study like this as the safest drug in town?

Outcome studies can get things this badly wrong. Here’s how it can happen. Patients never get Clozapine first line. They have to have taken several other antipsychotics first. This means they will never get Clozapine in their first year of treatment and perhaps not in the first three to five years. The significance of this is that by far the greatest cause of mortality in patients on antipsychotics, over 50% of the mortality, comes from suicide, primarily in the first year of treatment.

The next biggest source of mortality comes from heart attacks and strokes. But these happen for the most part in older patients given antipsychotics for acute and transient psychoses or delusional disorders. These older patients are at some risk of heart attacks or strokes even before treatment. Again these are patients who rarely if ever get Clozapine. There were deaths in the group of patients who were not on any antipsychotic and these most likely came primarily from older patients with acute and transient psychoses.

This is how the most lethal drug in town can appear the safest

Add these two exclusions together and it becomes clear why there could be fewer deaths on Clozapine in Finland but how at the same time it can be the most lethal antipsychotic. Clozapine causes problems of unparalleled severity in every body system with deaths from myocarditis, interstitial nephritis, cardiomyopathy, diabetes, neuroleptic malignant syndrome and a range of other causes, including suicide, much more than other antipsychotics, but it is not ordinarily been given to the patients at greatest risk.

Clozapine is a wonderful drug – to have in reserve. It is not the drug that is going to help Danes keep the Homeland more secure than others.

But when even the most lethal of the antipsychotics, with a range of cautions like no other, can be billed as the safest, it’s clear we have a system that can induce paranoia. Here’s a question for Danes – is the Lancet one of our heroes or has it in some way been turned? A series of Lancet articles touting the benefits of Agomelatin, and the work of Robert Gibbons, and a more general track-record embracing the latest treatments would make anyone wonder.

The reality is more likely to be as Homeland Security might say that the price of security is eternal vigilance. The issues are tricky and expertise is needed. Beyond expertise we also need to shift orientation back to the future – away from the current adoption of the latest chemical as a wonder fertilizer to be spread as widely as possible, and back to a traditional medical view of chemicals as poisons to be used judiciously.

Clozapine really does deserve a poison sign

We used to have a poison sign on most medicines (see We need to talk about doctors). Among antipsychotics Clozapine is the most deserving of such a symbol still.

Medicines are chemicals that used to come with information about their use in people. The drugs are still poisonous and the art of medicine should still involve balancing the risks of the poison against the risks of the illness, but the information that comes with the drugs that portrays them as free of risks is increasingly poisonous in its own right. Is it time to introduce a poison symbol with articles touting the benefits of pharmaceuticals? Pharmaceutical companies campaign actively against any references to their chemicals as poisons. Medical journals would most likely be equally resistant to the use of such symbols on their articles.

For some of us having a poison symbol on articles might feel like the best way to avoid tipping over into paranoia. But this was tried with quality marking controlled trials and when this was done pharmaceutical company articles garnered all the best quality marks. It’s likely in just the same way that company articles touting the benefits of treatment would end up festooned with symbols of purity while other studies pointing to the risks of drugs would have a poison symbol. Time to reach for the Clozapine.

We Need To Talk About Doctors

doctor with a stethoscope

Randomized controlled trials (RCTs) came into favor in the wake of thalidomide as a method to evaluate drugs and their risks.

They were supposed to keep ineffective drugs off the market, but companies have learned that you can do any number of trials and if even some show a marginal benefit they can get their drug on the market and the others can be suppressed so no one has a true picture of the effects of the drug. Once on the market, the favorable RCTs are turned into a turbo-charger to boost sales even for debatably effective drugs. The risks get written out of the script by ghostwriters and creative publication strategies.

Once on the market, the favorable RCTs are turned into a turbo-charger to boost sales even for debatably effective drugs

RCTs in turn underpin the era of guidelines we are now in. As trials became more common, sooner or later, someone was bound to get the idea that all the “scientific evidence” accumulating could be assembled to show which treatments should be used first, which second, etc. This looked like another good way to control pharmaceutical companies and the risks of drugs but it soon became just the opposite. Neither managers nor pharmaceutical companies like the idea of doctors having clinical discretion, and guidelines based on the (published) evidence have become a way to standardize clinical practice and manage risks. What risks?

The formerly healthy tree of medicine is sapped by the ever more vigorous pharmaceutical ivy growing on it

The irony is that a method introduced to manage the risks of drugs has become one that has been used to shift the blame for things going wrong over to doctors.  If the drugs work well and are safe, if anything then goes wrong, it must be the prescriber’s fault. The marketing of today’s drugs always spins them as safer and safer – if so, given that things still go wrong and in fact treatment induced injury is now a leading cause of death and disability, doctors must be becoming riskier and riskier. The effects of a prescription-only embrace has been to leave the formerly healthy tree of medicine sapped by the ever more vigorous pharmaceutical ivy growing on it — at risk of being brought down by the next storm.

If the drugs are becoming safer and safer, doctors must be becoming riskier and riskier

Three symbols tell the story.

First there is the now ubiquitous seatbelt symbol. Over the last 30 years, safety features to help manage the risks of driving have become ever more common, from seatbelts to airbags, to cars engineered not to start if the driver is not belted up. In every area of life, except prescription-only medications,  there is an increasing emphasis on safety warnings; even in sports and war.

seatbelt

Second is the poison symbol that used to feature on many medicines, particularly those that were dangerous in overdose. It is now all but illegal to refer to a drug as a poison — see The spin that no data can overcome. These symbols have completely vanished. Ironically perhaps, one of the first drugs to advertise itself as not poisonous in this sense was thalidomide. Adverts for commonly showed it being taken accidentally by a child who, we were told, would not die as a result of taking it where they would likely have died if they had taken the alternate sleeping pill — a barbiturate.

poison

The third symbol comes from Gideon Koren, a researcher at Motherisk in Toronto, who has advocated putting a symbol featuring a pregnant woman on medications like the antidepressants in an attempt to overcome the reluctance of women to take these drugs in pregnancy.

Gideon Koren pregnancy image

This last symbol seems almost redundant, as despite increasing evidence that antidepressants double rates of birth defects and miscarriages and may cause mental handicap in the children born to mothers who have taken them through pregnancy, prescriptions for these drugs are escalating and they are now among the most common drugs taken in pregnancy.

Despite increasing evidence that antidepressants double rates of birth defects and miscarriages and may cause mental handicap, they are now among the most common drugs taken in pregnancy

Medicine used to balance the risks of a poison against the risks from an illness, but now illnesses have become the unique source of risk. Drugs, which are prescription-only because their hazards are unknown and quite liable to exceed the risks of over-the-counter or illegal drugs, in contrast are portrayed as wonderfully safe, fertilizers rather than poisons.

We can hear the desperate plea from the doctor in the Woodley inquest (see Model doctors?), “If we left her untreated and things went wrong what would you say then?”

Doctors have regressed to childhood. They look to a father figure, in particular FDA, when things go wrong. But when they do they find they are not the pet child anymore. The pharmaceutical companies are. And companies are adept at smiling sweetly at Daddy and protesting their innocence.

Put another way, in controlled trials companies have found a Philosopher’s Stone to transform base metals into gold. These trials began as a means to manage clinical uncertainty, but now deliver commercial certainty instead. And under the spell of the Stone the magic that used to lie in Doctors like Dr Kildare and Marcus Welby has migrated into pills like Prozac, Lipitor and Fosamax, while the risks have moved in the opposite direction into doctors. We need to talk about doctors before Lionel Shriver writes a book about their involvement in a school shooting.

Out of My Mind. Driven to Drink

alcohol

Author: Anne-Marie

(This story epitomizes what RxISK.org is all about. It shows one woman extraordinarily getting to grips with a problem she has on treatment. The hope when RxISK is up and running is that we will be able to make it easier for people like Anne-Marie to engage with their doctors to solve problems like this. Unfortunately even though clearly a drug-induced problem Anne-Marie does not want to be identified – DH).

I have been asked to write this story to raise awareness about a strange side effect of treatment and my efforts to get to the bottom of it.

Before my problems began I had been working as a health care assistant at my local hospital in Surrey for five years. I enjoyed my job. I had a stable life. I owned my own home and car.

Following the sudden and devastating death of my father I became anxious and over a period of a year developed a fear of choking which got worse to the point that I was avoiding food and losing weight. I realized I needed help.

I went to my GP and was prescribed paroxetine 20mg in liquid form because I couldn’t swallow the tablets. I had nausea, dizziness, felt spaced out and detached but was assured by my doctor that these symptoms would settle down.

After a few months things did start to improve. I noticed my eating had returned to normal. I felt much more energized and more confident and was able to complete a day’s work without feeling drained and exhausted. I started socializing again.

The warning reassured me it was safe enough to have a few drinks with friends

To begin with I was concerned about drinking alcohol on the medication. I checked the patient information leaflet which gave, what seemed to me, to be a mild warning that “although it is always advisable to avoid alcohol whilst taking medication there is no known interactions with Paroxetine and alcohol”. This reassured me that it was safe enough to have a few drinks with friends.

At first I was only having a few glasses of wine but slowly over time I drank more and more. I began saying and doing things I had no memory of later. I got banned from restaurants and bars in my local town and became an embarrassment to my friends. Eventually some of my close friends and family distanced themselves from me. I was losing everyone around me and losing control of my life but I just didn’t care. I felt like I was in a dream and that none of this was real.

I became verbally aggressive and my behavior was reckless. On one occasion I climbed out of a velux window and onto my roof. I was not trying to kill myself. I didn’t even consider the dangers of what I was doing.

I began to get into trouble with the police, in the main for continual nuisance phone calls to the police station. This happened on a regular basis when I was drinking. Sometimes I would ring them 20 to 30 times a night on their non-emergency number with only a very vague memory of doing so. It resulted in me getting arrested on numerous occasions.

I began to feel that something was very wrong

After getting arrested several times I began to feel that something was wrong. I started taking time off work. I got cravings for alcohol that were so intense I felt I was possessed. I would start drinking and couldn’t stop. I’d continue until I was either arrested or I collapsed into a coma. Things were getting very out of hand. I felt alone with my problem and couldn’t understand why I was behaving like this. I felt that no one understood what was happening to me or cared.

I began to research on the internet to find an answer and I found other people reporting cravings for alcohol on SSRI medication on many websites. This really shocked me. Yet no one in the medical profession seemed to be taking any notice of it. Why? The first time I saw a psychiatrist I was told that it was due to my drinking problem.

Terrible overwhelming uncontrollable cravings

I knew I was drinking too much but I also had terrible overwhelming uncontrollable cravings for alcohol. I printed some of the information from the internet out and gave this to my doctor and tried to explain that I thought the medication was giving me intense cravings for alcohol.

My doctor was very sympathetic but not convinced. Again I was told that I had a drink problem and was in denial. He did however agree to change my medication and prescribed me 20mg of citalopram. I was referred to my local drug and alcohol clinic.

Following the switch to citalopram over the course of a couple of months, I felt less aggressive. However my cravings for alcohol were as strong as ever and I still couldn’t stop drinking. Things spiraled further out of control. I spent time in prison, was suspended and eventually sacked from the job I loved. Even a couple of alcohol free months in rehab, where I was provided with overwhelming help and support, wasn’t enough to stop the pattern continuing as soon as I returned home.

By now I had given up on the experts… who accused me of denial

By now I had given up on trying to tell my medical team that I thought it was my medication that was causing the problems. I was accused of being in denial over the alcoholism but I was certain that these intense cravings for alcohol were being induced by the SSRI.

Before I had searched for others with similar problems, now I began searching for answers. First I googled alcohol cravings induced by paroxetine and then by citalopram. The first web pages I came across were from the depression forums and similar websites where people where sharing their stories about the same alcohol cravings and looking for answers. I came across the International Coalition for Drug Awareness, the Seroxat Users Support Group and the Seroxat Secrets website where many people were reporting the same thing.

I decided to start looking at research papers but I couldn’t find any on SSRIs and alcohol cravings. I then read a message on one of the forums that mentioned a Yale study from 1994 that had a link to serotonin. This pointed me toward reading about alcoholism and the serotonin system.

There were no easy answers to this

I read many papers that I only vaguely understood. I had to learn all about serotonin receptors, transporters and neurons to understand the research papers I was reading. I had to leave it several times and go back to it as my head was hurting trying to understand it. I nearly gave up looking several times but couldn’t because I knew the answer was there somewhere. I learnt that there were seven serotonin receptors and was very disappointed to learn that there were even more receptors connected to these receptors. There was also only one receptor though that had a gateway to dopamine which was the S-3 receptor. I now needed to learn what all these different receptors did and to see if any were connected to cravings for alcohol. There were no easy answers to this.

Had I really been like this for ten years?

I wanted to wean myself off citalopram. I knew it was ruining my life. In the first month I couldn’t believe the change in me. I felt as if I had been given back my sight and hearing again. I felt in awe of everything around me. Had I really been like this for ten years and hadn’t realized it? Almost immediately the cravings for alcohol reduced by about 50%.

But withdrawal wasn’t easy and I went through two months of distress with extreme mood swings, panic attacks, sensitivity to noise, feeling like I had the flu with aches and pains. I couldn’t cope with this so went back to my GP and was put on mirtazapine 15mg, which was later upped to 30mg as I was experiencing restless leg syndrome at the lower dose. (I had seen on the internet that another woman had a similar experience as me on 15mg mirtazapine which disappeared at 30mg).

I realized that mirtazapine may have the answer

My cravings went completely. I realized that mirtazapine may have the answer. I knew it worked differently to the SSRIs.

I looked up medications for alcoholism and came across a drug called ondansetron, which works by blocking the S3 receptor and eliminating cravings. I discovered that mirtazapine also blocked S3 receptors.

I searched for alcoholism and S3 receptors and found that the S3 was the only serotonin receptor that had a gateway to dopamine and a paper ‘Functional Genetic Variants That Increase Synaptic Serotonin And 5HT3 Receptor Sensitivity Predict Alcohol And Drug Dependence’. I was amazed. It makes sense that if some people have a genetic link to alcoholism mediated through the serotonin system that SSRIs might increase this sensitivity and mirtazapine block it.

I have also just found another research article that was carried out on mice back in 1990’s that also found that if S3 was blocked in mice it stopped the mice from drinking alcohol.

I now know what happened to me

It’s taken me a lot of time, reading and learning but I now have understanding of why I had such intense cravings for alcohol whilst taking SSRIs.

It makes me angry that we never had warnings like they do in the United States. Why were we not being protected here in the UK with appropriate warnings in the same way? If my GP had known that SSRIs could cause cravings for alcohol in some people he would have taken me off these drugs at the very first signs of drinking.

This would have saved me years of suffering and maybe helped many other people too. I’m sure that this is a problem that is more common than people realize. In addition to all the people I have come across reporting these effects on various internet websites, I have met many people who have had similar problems or who know of people who have also had problems on these drugs.

People on these drugs are vulnerable anyway and it is worrying to think how many could be drinking to excess across the country because of a craving for alcohol caused by treatment. It’s absurd to give the impression these drugs are relatively safe with alcohol if the tablets cause some people to experience intense cravings. It’s worrying also that both the drug and alcohol can independently cause confusion, disorientation, hypomania, aggression, and obsessional and bizarre thoughts and behaviors and that the combination in some people can make this much worse.

It has now made me look to other people’s experiences for information regarding drugs as they seem to be more accurate and honest in their findings than companies, regulators or doctors.

It’s crazy that patients have to get together on the internet to compare their side effects and discuss their problems because there is nowhere else to go. It has made me look to other people’s experiences for information now regarding drugs as they seem to be more accurate and honest in their findings than companies, regulators or doctors.

I didn’t realize until I came off the medication how bad I was. I feel ashamed and guilty for what I put people through. I have lost my job, had to move home, have a criminal record and lost the respect of family and friends. This could all have been avoided if there had been proper warnings in place and effective communications between different authorities.

I saw my retired GP in Asda recently and he asked me if I was back in Nursing. I told him no, I will never be able to go back now after what has happened to me. He said nothing and walked off. I didn’t mean to sound as if I was blaming him but I think he felt that was what I was doing. I felt guilty afterwards. I don’t blame my GP at all, I blame the drug companies and MHRA. What annoys me is that even the Department of Health wrote back to my MP basically laying the blame on the GP who they said should have noticed any changes in my behavior.

I want to tell my story as a warning to anyone who may be craving alcohol on SSRIs. I also want to tell people that sometimes it’s a mistake to leave it to the experts. And finally I want to tell doctors that your patients can often see that the information you are getting is wrong — we don’t blame you for this, we just want you to listen to us.

(The extraordinary twist in the tail here is how the regulator manages both to deny the existence of this problem and blame the doctor at the same time. This is becoming ever more common in modern healthcare systems — DH).

Since posting this it has become clear there are hundreds of people who have experienced something similar – if you have been one of them could you add your experience to this thread.

Watch where you wave that Wand

magic wand

It was a white wand — the kind a little girl might have. White ribbon wound round a long straw, at the top of which a double pair of white wings was set. Another more delicate white ribbon looped around the wings, to the front of which was fixed a downy feather, and behind which the ribbon was tied in a bow.

Crusoe was facing her most difficult patient. A man with manic-depressive illness who, when depressed, posed a serious risk of suicide. She had tried all possible medications but none had helped. They seemed, if anything, to make things worse and to prolong the condition. The only thing that had helped in the past was electroconvulsive therapy (ECT) but he was resistant to this. Contemplating what to do, she idly picked up the wand and waved it.

She realized her mistake before he did. She should of course have sought his consent before exposing her patient to any risk. She apologized. He was perplexed; if he wished to get better or she wished to get him better — where was the problem?

“Look what happened to Macbeth”

“Well,” she said, “It might seem straightforward, but look what happened to Macbeth.”

“But what would I consent to?” he replied. “Do I consent to believing in magic or to your believing in magic or simply to having you wave the wand around?”

“Well in this case,” she said, “simply having me wave the wand around. Look I don’t know whether having the bow or the pom-pom facing you makes a difference, or even whether holding it the right way up or upside down makes a difference. I didn’t chant spells, invoke powers, or connect this manipulation to any belief system, but a wand is a wand. It’s not like reading a horoscope, where your eye might accidentally catch sight of some words but there is no one on the far end of them, and most of us can take or leave these things. I’m on the far end of this.”

“Well,” he said, “whose karma is it that might come back to haunt me — mine or yours? Was Macbeth the victim of the witches or did he undo himself? Makes a difference to any consent form. Actually, you say you didn’t tap into any belief system when waving the wand, but hasn’t mentioning informed consent created the need for informed consent, so that in a sense even before asking me to consent you’d have had to get my consent to having the idea of informed consent raised — but how could you do this?

“If I were elsewhere and you had been idly waving the wand and thinking about me, would you have needed informed consent then or is it just the fact that now that I’ve seen you do it that you need me to indemnify you, as it were?

“if you’re going to muck around with reality like this, surely you need to get the consent of everyone?”

“And if you’re going to muck around with reality like this, maybe change the structure of the universe, surely you need to get the consent of everyone?”

Crusoe thought about this.

“We’re not talking about turning you into a white rabbit,” she said, “so I can’t see a need to get your wife and family to agree to this. But these days if my employers knew what was going on here, they almost certainly wouldn’t consent — so in this sense getting you to sign a consent form might make my position worse.

“But while you’re most unlikely to end up as a white rabbit, life goes on after this wand is waved, things continue to happen, and waving it just may affect your perception of the sequence of things afterwards. If they go well, fine. But if they go badly, will you begin to wonder about what effect the wand may have had.”

“Why haven’t you gotten my consent for all the pills you’ve put me on over the years?”

“Now that you’ve mentioned it, I get most of the side effects that are listed in the package inserts. Why haven’t you gotten my consent for all the pills you’ve put me on over the years?” he asked.

“Is there any difference between the way the witches ‘paltered with’ Macbeth ‘in a double sense’ and the way drug companies do with me, or rather with you?  At least the witches showed him all the data which is more you can say for the drug companies.”

“I have — I told you about likely problems. You may not have signed a form but by taking them you showed that you agreed.”

“Ah, no you didn’t. You didn’t get me to face the prospect of something going seriously wrong. We both just assumed things would go right, or that we’d be able to manage whatever went wrong. We’re nervous now because we’re not sure we could manage what would happen if the wand went wrong, but it is much more likely that things will go wrong with the pills. All the things that may have been going to happen anyway — things that you’re now worried I might attribute to the wand — would still have happened after the pills, and I’m even more likely to think that they were caused by the pills than by the wand.

“Waving these pills around you really do change the fabric of the universe…”

“And I don’t just mean things going wrong for me, but waving these pills around you really do produce changes in the fabric of the universe that we can see happening as a consequence of growing pharmaceutical company profits and power — all the women who are going to be persuaded their lives will make sense once their sexual dysfunction is sorted out. Did you get my consent for that?

“And what do I tell my wife about this wand? After all, things only started happening to Macbeth once he told his wife. Will the fact that you’re a woman make a difference to how she views things?”

Notes on a Scandal

In 1996 Zoe Heller, the author of Notes on a Scandal, took part in a widely reported debate with Roy Porter about Prozac. She defended the drug. It had restored her to life. He said today’s miracle invariably ended up in tomorrow’s tragedy and asked, Why is it that we never learn?

The story of a schoolteacher who seduced one of her male pupils

In 2003, Notes on a Scandal came out. It was made into a stunning movie in 2006 starring Cate Blanchett. This was the story of a schoolteacher who had seduced and was having continuing sexual relations with one of her male pupils.

In 2006, Rosie Meysenburg started up SSRI Stories, a website for cases of violence triggered by SSRI drugs (see The story of SSRI Stories). To collect the material she posted, Rosie had to review reports of criminal and other legal cases in which media reports mentioned SSRIs. To her astonishment, she began to notice that she had a series of cases involving women teachers convicted for inappropriate sexual behavior toward male pupils — with the women typically taking an SSRI. For one woman, the Courts decided her drug had caused the problem. This was the plot of Notes on a Scandal.

The most obvious thing SSRIs do is change sexual functioning — almost all people on an SSRI will notice some change within hours of having had it. Ian Hindmarch’s women volunteers in Leeds in 1983 almost certainly all had changes in their sexuality or sexual behavior. Delayed orgasm is extraordinarily common to begin with; reduced libido comes later. In many cases, things return to normal when the drug is stopped. In a not inconsiderable number of cases the changes are permanent — we don’t know how often this happens.

Curing homosexuals?

At the start of the antidepressant story, Roland Kuhn celebrated the fact that imipramine, an SSRI, had cured some homosexuals he had seen (discussed in greater length in The Antidepressant Era). Thirty years later Peter Kramer celebrated in the same way for Prozac. No one argued this was impossible. There are good grounds to accept that SSRIs can shift some of us along the axis of our sexual orientation.

But it’s not reasonable to think the shifts are likely to be only one way — in the direction some would view as normalizing. For every one whose change in orientation the Catholic Church might celebrate, there is likely to be another whose change would pose problems for the bastions of morality. There won’t be one without the other.

In 1999, 13-year-old Matt Miller was taken by his parents to see a doctor, as he was unsettled in a new school. The doctor, who was on Pfizer’s speakers’ bureau, put him on Zoloft. Matt became restless on Zoloft. A week later he hung himself in the bathroom between his and his parents’ bedroom.

Auto-erotic asphyxiation gone wrong

Pfizer argued Matt’s death wasn’t caused by Zoloft; it was a case of auto-erotic asphyxiation gone wrong. To argue their case, they wheeled in Parke Dietz, an expert who had offered the view that Anita Hill’s claims that she had been harassed by Supreme Court Judge Clarence Thomas were just fantasy. But Dietz didn’t come up with this idea of auto-erotic aphyxiation first — Pfizer did. Where did they get it from?

The idea almost certainly came from their studies, whether healthy volunteer trials like the Leeds study (see Mystery in Leeds), or in one of their trials for other purposes or in convincing reports to the company. This idea didn’t come from anyone’s understanding of what 13-year-old boys normally do.

Would Zoloft-induced impulses to auto-erotic asphyxiation be more or less plausible than a 13 year old spontaneously turning to this sexual expression? If it seems more plausible that Zoloft had induced auto-erotic asphyxiation, then whose fault would this death have been given the volume of data on Zoloft and sex that Pfizer had?

If Matt had practiced auto-erotic asphyxiation regularly (before starting Zoloft), another set of complications opens up. Zoloft inhibits orgasm. Could Zoloft have changed things, leading him to go too far? If so, whose fault would his death have been then, given that Pfizer had not warned about this? Knowing what they knew, Pfizer should have been honor-bound to warn anyone else who engages in auto-erotic sexual play or any form of sexual play, about this possibility.

Pfizer really should have told us what they knew about sex

It was one thing for Pfizer to argue for auto-erotic asphyxiation gone wrong, but they really should have told the court of the range of sexual changes they knew about.

In the Miller case, Pfizer flew Ian Hindmarch over to a pre-trial hearing. At this he claimed that the volunteers in his Zoloft study in Leeds (see Mystery in Leeds) were just suggestible. Nothing much had happened to any of these women. But the study remained unpublished, and its full details have probably never been seen by any regulator.

Four years later, the FDA put a Black Box warning of the risk of suicide in children taking Zoloft and other SSRIs. It’s difficult to believe that many people will have ever thought that Matt Miller died because of auto-erotic asphyxiation rather than a straightforward Zoloft-induced suicide. This warning should drive a stake through the heart of Pfizer’s argument.

Professional auto-erotic asphyxiation?

For most people, the only remaining unanswered question of interest is likely to be where Pfizer got the auto-erotic asphyxiation idea from in the first place. The only remaining question for most people, that is, except the American Psychiatric Association, who after the Black Box warning rushed out a statement that the APA believes Antidepressants save lives. As outlined in Professional Suicide, this is an extraordinary example of a professional suicide note.

But perhaps what the APA, and more recently the Irish College of Psychiatrists, has been doing is not suicide after all — perhaps it is auto-erotic asphyxiation? Let’s hope it doesn’t go wrong.

Model Doctors?

Another inquest may bring out the risks to doctors from their professional associations behaving as the American Psychiatric Association (APA) or the Irish College of Psychiatry has done (see Professional suicide – the Clancy case).

She posed no suicide risk. She was put on citalopram

Yvonne Woodley, a 42-year-old woman with two young daughters, ran into difficulties with her husband. They began talking of separation. Under stress, she visited her primary care doctor who noted that she was not depressed, and that she posed no suicide risk. She was put on 10mg of citalopram.

A week later she was noted by the doctor who saw her to be more anxious and for the first time as having voiced thoughts of harming herself, but she was still viewed as being at no risk of suicide. The dose of citalopram was increased after which she talked about suicidal impulses to her mother and made a suicide gesture — taking 100 analgesics to a remote place from which she phoned her husband and told him she was thinking about overdosing. He came to get her, brought her to the doctors, and from there she was referred to a mental health team.

Yvonne hung herself with her daughters downstairs watching television

A further assessment concluded that she was at minimal or no risk of suicide. She dropped her contact with the mental health team and went back to her primary care doctor who doubled the dose of citalopram yet again. A few days later, Yvonne hung herself in the attic of her house with her daughters downstairs watching television.

Lundbeck, the makers of citalopram in Europe, sent a former medical director from their UK division to the inquest, Dr Chris Muldoon. The coroner, Aiden Cotter (AC), heard testimony from the family, from me, from Chris Muldoon, from one of the primary care doctors, and from the consultant psychiatrist linked to the mental health team.

Each of the doctors was asked two questions in common: “Can citalopram cause someone to commit suicide?” and “Did it cause Yvonne Woodley to commit suicide?” I answered that it can cause suicide and that Yvonne Woodley’s case bore the classic fingerprint of a treatment-induced death.

It was then Chris Muldoon’s turn:

AC: I would like you to answer the next two questions either yes, no or I don’t know. Then you can talk for as long as you wish as to why you’ve reached those decisions. But let’s just try to have yes, no, or don’t know.

CM: Ok.

AC: Do you believe that citalopram can cause somebody who would not otherwise take their own life to do so?

CM: Yes.

AC: And is that what you think happened to Yvonne Woodley?

CM: No.

He then went on to outline that there had been debate about the issue that had led to a range of warnings and he cited the National Institute for Healthcare and Clinical Excellence (NICE) guidance, which said:

NICE Guideline

Monitoring risk (page 8):

Monitor for signs of akathisia, suicidal ideas, and increased anxiety and agitation, particularly in the early stages of treatment with an SSRI.

Advise patients of the risk of these symptoms, and that they should seek help promptly if these are at all distressing.

If a patient develops marked and/or prolonged akathisia or agitation while taking an antidepressant, review the use of the drug.

Choice of antidepressant (page 9):

If increased agitation develops early in treatment with an SSRI, provide appropriate information and, if the patient prefers, either change to a different antidepressant or consider a brief period of concomitant treatment with a benzodiazepine followed by a clinical review within 2 weeks.

The doctors to blame?

The effect of this being read out in court was of a company saying we’ve done all we can in terms of warnings. If something went wrong therefore it must have been the doctor’s fault.

Having listened to themselves being put in the frame for blame and in particular having heard the company say their drug can cause suicide, what was the response from the doctors?

Here is the primary care doctor:

AC: And do you believe Citalopram does make people take their own life?

Doc 1: No actually. I think I’m going to say that, because we prescribed her Citalopram in the hope to make her feel better. That was the whole point of her taking it as an antidepressant, to help her to feel better. This is the risk that is reported by BNF and NICE. That is not to say that we’re actually prescribing somebody something that is going to make them kill themselves. I think if we had not prescribed her anything what would be the conclusion then if she’d hung herself? That she hadn’t been treated?

And here the psychiatrist:

AC: Let me ask the same questions I have previously asked the doctors. First do you believe that citalopram can make somebody who would not otherwise take their own life, do so?

Doc 2: I don’t.

AC: You don’t believe it?

Doc 2: No.

AC: So it follows from that that you don’t think that’s what happened to Yvonne?

Doc 2: No.

This exchange makes a number of things clear.

In the Clancy and Woodley cases and in other cases, if asked if their drug has caused this person to commit suicide or homicide, Lundbeck and other companies will always answer No. If asked can your drug cause suicide, they will always contrive to answer the question as though it refers to a particular person and give the impression that there have been no cases where their drug has caused a problem. In a previous post (Psychotic doubt) we have seen Ian Hudson do this.

Companies are legally obliged to say that their drug “can” cause suicide. But doctors are under no such obligation — even under oath.

But if asked up front under oath, they are legally obliged to say that their drug can cause suicide. This is like Philip Morris agreeing smoking can cause lung cancer but denying that it has caused this death or that death from lung cancer.

But an academic, such as an Irish Professor of Psychiatry, or a professional body, like the Irish College of Psychiatrists, are under no such obligation, and they can state even under oath that these drugs do not and cannot cause someone to take their own or another’s life.

The dictionary definition of a model is “a shrunken replica of the real thing”.

So if stuck with a tricky question, other than in court, Lundbeck and other companies can and do defer the questioner to an academic — or to the APA or the Irish College of Psychiatry. They don’t even have to lift the phone. It’s all part of a complete doctoring service.

As the response from Tom Fahy in Professional suicide – the Clancy case shows, this is a new service. One question for those of us who have not retired is whether we want to be represented in this way.

Why call these new doctors “model doctors”? Well, the dictionary definition of a model is “a shrunken replica of the real thing.”

For doctors this is a matter of professional politics.

There are some doctors for whom academics defending drugs like the APA or Irish College have done might be morally distasteful, but for all doctors it is a matter of professional politics. If medications are perfectly safe and very effective, there are much cheaper prescribers, who are much more likely to stick to guidelines than doctors.