Someone, seriously injured by a medicine he had taken, got in touch this week asking if it was possible to take an action against his doctor or in some way get compensation for his drug inflicted damage. He was sure he had not been informed of the hazards when it was prescribed. He had a mild problem that didn’t ‘need’ treatment and if he’d known the risks he wouldn’t have taken them. Something was wrong with all this, he figured, and it should be possible to hold someone to account.
Another person has just posted a comment on Silencing Safety, part of which reads:
In complete contrast, BMJJ had a recent article on new Prescribing Safeguards about the risks linked to isotretinoin that dermatologists should convey when prescribing it. The full article is HERE. A month later Andrew Affleck responded – below and HERE complete with references.
I am extremely disappointed at the new MHRA legislation around the prescription of oral isotretinoin and I suspect all UK dermatologists feel the same way. Indeed, there are a list of words that I could use to try and express my feeling including angry, let down, incredulous, undermined and dejected. It is a sad day when evidence is not used to influence clinical practice and instead disproportionate weight is given to the overvalued views of a minority of individuals with significant personal agendas and emotional bias attending a stakeholder event. The silent vast majority of patients have not been heard. Hearsay has trumped science. The opinion of dermatologists working at the coal face, who have been the only prescribers of isotretinoin for 40 years has not been heard. We know that isotretinoin is a safe and highly effective medication. The only side effect tends to be dose-dependent mucocutaneous dryness. A so-called “expert group” with no experience with isotretinoin have bowed down to pressure from stakeholders’ views that isotretinoin causes depression and sexual dysfunction despite overwhelming evidence to the contrary accrued over many years and continuing to be produced. Certain individuals who have taken isotretinoin and at the same time or months or years later (which does not fit a scientific modal of causality) developed physical or psychological symptoms and had a vendetta against isotretinoin trying to get it banned completely. The persistent symptoms are often non-specific and could be consistent with somatic symptom disorder which is common in the population. It can be human nature to try and blame an external factor and in modern life, forums on social media develop which can perpetuate overvalued beliefs in keeping with an internet meme. The MHRA yellow card reporting system is inherently flawed as one apparent adverse event can be reported multiple times.
Many side effects even those listed as “common” on isotretinoin package inserts are spurious and merely found incidentally in the normal population with levels fluctuating up and down eg anaemia, neutropenia, thrombocytopenia and thrombocytosis. Despite these abnormalities of FBC being listed as occurring in up to 1 in 10 people FBC monitoring is not recommended which causes confusion and worry for patients This shows the lack of credibility in the MHRA. Surely clinical studies of hundreds of thousands of patients is superior.
To enforce asking about sexual health at baseline and at every consultation could cause significant harm via the nocebo effect in often young sexually immature individuals.
The vast majority of patients with acne do not have a mental illness before starting isotretinoin and their emotional health is not compromised when taking it. Most patients will be a bit demoralised, frustrated and have some minor affective symptoms which may reach the threshold of social anxiety disorder with reduced self-confidence and avoidance behaviour quite common. These patients will be helped by improving and likely clearing their acne but with the new legislation they may well be harmed by dermatologists being more reluctant to prescribe. Many studies have shown that isotretinoin can improve mental health and indeed may be protective against suicide with consistent finding of reduced rates of self-harm compared to the background population and in those taking antibiotics for acne.5 Also, to enforce regular use of 2 screening questionnaires (PHQ-9 and GAD) at baseline and for every consultation as part of the drug licence is unhelpful and a step too far. Of course, prescribers should be vigilant for signs of distress or a new or evolving mental illness in all dermatology patients but an impersonal tick box questionnaire is not a substitute for skilled talking and listening and asking the appropriate questions. The proforma can then be used if clinically indicated when it can indeed be a useful adjunct to check for any trend. There will always be a tiny minority of patients who have an undiagnosed mental illness when isotretinoin is initiated eg body dysmorphic disorder, emotionally labile personality disorder or an eating disorder or develop such a disorder incidentally during or after a course of isotretinoin. These illnesses are associated with an increased life time suicide risk.
The final unprecedented new legislation which will likely cause harm is the need to have 2 doctors approve the initiation of isotretinoin in under 18s. This goes against the autonomy of a doctor and shows a lack of respect and trust in dermatologists. If a dermatologist sees a patient under age 18 with acne then we should continue to let them do their job which they are trained to do and often have many years of experience prescribing isotretinoin. Why would a colleague ever wish to disagree? Thus will become a pointless tick-box exercise with no benefit to anyone and merely worry patients and their families unnecessarily as to why a second opinion is needed. They would be quite right in thinking, “gosh this must be a very dangerous drug if a second opinion is needed!”. To add to the nocebo effect we are creating for our vulnerable patients, a recent Patient Information Leaflet on mental health and isotretinoin has a link to a resource for children and young people , “When bad things happen”. You couldn’t make it up. If that wouldn’t put you off, what would.
Some of the parents lobbying for warnings on isotretinoin made mistakes – insisting isotretinoin should be removed from the market. The point with warnings is to alert a teenager in particular to the fact the drug might be triggering some of the weird thoughts or experiences they are now having.
Dermatologists have been among some of the most humane doctors and decent people I have known. Jonathan Rees’s The Last Three Patients – will leave most readers figuring he is the kind of doctor they would like to be treated by. I’m not sure Jonathan will have registered any of patients having sexual or suicidal problems on isotretinoin that have likely come his way.
But I do know in the case of other good dermatologists – something gets in the way of them seeing what’s in front of them. I get to see to person afterwards.
Has Andrew seen and not-seen them? Likely yes. The people who have lobbied for warnings have all themselves or their children taken Isotretinoin and were absolutely normal to begin with – they did not have borderline personality or depression. What teen is going to tell Andrew, or his or her parents, about weird new thoughts or numb genitals? Weird new thoughts that kill them before Andrew gets to follow them up.
Then there is the case of my second contact above, which should give Andrew food for thought. He is nervous about even mentioning the sex of the doctor in this case – its all they – for fear of reprisals. This is a common experience among patients. The Andrews of this world see themselves and are often seen by their friends as decent and approachable but its not how things work out. People with PSSD have been detained by shrinks for mentioning their crazy ideas about what the drugs have done to them.
In this case genital numbing happens almost universally on SSRIs and this is the main feature of PSSD. So it’s difficult to understand how most psychiatrists, including the current President of the Royal College of Psychiatrists, who has a background in drugs and sex and reproductive issues, can’t see what is happening. Something gets in the way.
There are two dynamics at play here. One stems from Paul Ehrlich’s concept of A Magic Bullet – a medicinal agent that targets a disease precisely, avoiding collateral damage. Magic Bullets are the Holy Grail for pharmaceutical companies – and their marketing departments. The Basic Rule of Combat advert above riffs on this theme. Another framing is in terms of Surgical Strikes – as with Cruise Missiles.
When drug receptors were discovered, in the 1980s companies turned to combinatorial chemistry, certain this would lead to hundreds of keys to receptor locks and cures for everything. This is not how things worked out. There have been fewer life-saving drugs since 1980 than before.
When the Human Genome Project was in full swing, companies expected it would lead to more rational drugs than before. This underpins the ideas of monoclonal antibodies and mRNA vaccines – but in terms of efficacy this is not how things have worked out, and in terms of safety the best way to put it is – Drugs Err but Monoclonal Antibodies can really foul things up.
Most recently Artificial Intelligence has led to claims we can now produce the drugs we really need. But this won’t happen. A.I. is binary – we and our responses to drugs are not binary. (I will pick this up in another post soon).
As the Has Healthcare Gone Mad post medicine makes clear A Magic Bullet narrative hands control to pharmaceutical companies. The only job remaining for a doctor is to prescribe the Magic. The only job for us is to give thanks for the Sacrament and not be tempted to blasphemy by claiming it has harmed us.
Isotretinoin and SSRIs whizz to the spot and fix the problem – if anything else goes wrong, as Andrew A mentions its down to some other fragility the person has like borderline personality or depression stemming from acne or whatever.
This line of thinking is bad for doctors and for us. Bad because most medicines are not Magic Bullets – they are Therapeutic Principles that compensate for some damage by acting on another system entirely – usually inhibiting it or even damaging it, as is most obviously the case in surgery.
When Arvid Carlsson created the first SSRI, Zelmid, he was making a therapeutic principle – a drug with an anxiolytic effect that might suit some people and not others. He did not think Zelmid was putting something right. Using it was necessarily harmful, and he accepted it might even cause suicide, if it was the wrong therapeutic principle for this patient.
The constipation and laxative image above doesn’t convey the harm element but does convey the idea that there are a lot of different ways to tackle constipation, some of which will be right for one person but not another. Similarly SSRIs, TCAs, noradrenaline reuptake inhibitors, and mirtazapine offer different antidepressant principles.
The idea we are using therapeutic principles hands the narrative back to doctors and to us. We need to talk to each other in order to work out, which of the different kinds of laxatives or antidepressants is likely to be the right one for us. Just giving a drug for constipation because a company is allowed to call it a laxative, or a drug for depression because a company can call it an antidepressant is not good practice. It also risks putting doctors out of business – nurses can do and increasingly are doing this.
In a great symbol of the way things were going 30 years ago, SmithKline’s marketing department transformed SSRI Therapeutic Principles into Magic Bullets, relieving doctors of any need to furrow their handsome brows when prescribing.
With Magic Bullets, there supposedly can be no collateral damage. With Therapeutic Principles there inevitably are harms. We harm in order to help. If this is what we are doing, there is an onus on us to let our patients know.
The message that the art of medicine lies in bringing good out of the use of poison seems to be too much for our current generation of doctors or liberal intelligentsia. Pharmaceutical company lawyers petition judges to have this hallowed phrase struck out of my testimony in legal cases. (See Silent Health to work out why the intelligentsia have snuck in here).
This brings us to the second dynamic. Doctors used to figure they had skills to read our personalities and our wish to be informed about risks. In 1950s court cases, women with breast cancer and people getting ECT changed this and created the idea of Informed Consent.
Since the SSRI and suicide controversies in 1990-1991, regulators and companies have taken on the role doctors once had – deciding what it is we should be let know. They have decided not to warn about suicide in order not to deter us from seeking treatment. They have decided not to mention the genital numbing caused by SSRIs even though it is by far the commonest effect of these drugs. Over thirty years after first knowing about PSSD, FDA in the US still does not warn about it.
In these cases its not just the person who takes the treatment who is affected, its their partner also and arguable the entire nation as fertility rates plummet roughly in line with rising SSRI consumption – Pharmageddon and Fertility.
In acting in this way, in going along with company non-science, rather than helping us to use company products wisely to live the lives we want to live, regulators are de facto getting us to live the lives Pfizer, GSK and Lilly want us to live and leaving a lot of lonesome heroines and forgotten women in their wake..