If you look at the adverse events section of the sertraline – Zoloft – label you will see in small print that sertraline has been linked to psychosis, hallucinations and aggressive reactions. Its there in small print. These links have been there since the mid-1990s.
Vanishingly few doctors understand what is going on here. They see a label saying something like “there have been reports of violence and psychosis on our drug so we are including these here”. They read this as – look at this wonderfully transparent and responsible company who are putting in the label even whacko reports from nutters and scientologists – am I going to believe this? Don’t be ridiculous.
In fact what is going on is Pfizer and other companies have reports that no matter what way they spin it they cannot explain in any other way but that our drug has probably caused this.
Our Drug Causes
From internal Pfizer documents:
“As of 15 March 1994, 13 cases coded… “psychosis” in sertraline treated patients patients were identified… One case was poorly documented and contained insufficient information to be properly evaluated. Four cases could have been related to the underlying disease, two other cases to concomitant medication (unspecified sleeping pill or alprazolam) and one case to a mutiple drug overdose. These eight cases are excluded from further discussion.
“All of the five remaining cases were spontaneously reported to Pfizer. These cases are summarised in the attached table. In three cases, the psychosis either improved or resolved after either discontinuation of sertraline therapy or a decrease in sertraline dosage. In one case the event continued and in one other case the patient died.
“In summary, a review of Pfizer’s early alert safety database identified cases… five of which were sufficiently detailed to evaluate and had no other obvious cause. Therefore it is recommended that “psychosis” be added to the Adverse Reactions section of the sertraline International Product Document (Core Data Sheet)”.
It was the same for aggression, agitation and hallucinations.
In 1952, Parke-Davis were faced with cases of aplastic anemia on Chloromycetin. This was their best-seller. It had made the company the biggest pharmaceutical company in the world – at a time when Pfizer were a minnow in the market.
Faced with this threat, the company created an Anything But the Company Drug playbook. This involved digging deep into the medical records, and circumstances, of the person reporting a problem in order to find the ingrown toenail at the age of two that was possibly the cause of the problem. And of course if something else was possibly the cause – like the unnamed sleeping pill above (better unnamed than named) – then we can’t conclude our drug did it.
Part of the problem for Pfizer – who swallowed up Parke-Davis decades ago – is that in some of their cases the problems cleared up when sertraline was stopped. This evidence of challenge-dechallenge is still the best evidence for cause and effect there is. (RCTs are the gold standard way to hide adverse effects). Parke-Davis were in a handy position with aplastic anemia – the problem doesn’t clear up when you stop the drug. The patient, child, adult, black, white, stays fucked.
Skin in the Game
Quite aside from any large print saying our drug can cause aggression or psychosis, the adverse reaction sections of the label of over hundred drugs says they can cause psychosis – and this is without checking all the others that say they can cause hallucinations or delusions or paranoid reactions.
The adverse reaction section in heading toward a hundred other drugs say they can cause violence, aggression, hostility or homicidal ideation. Again there may be multiple other terms under which these reactions may be hidden. I have to thank Julie Wood for putting in the leg work to track these references down.
The drugs involved include the skin drug isotretinoin. This comes in tens of different trade names so for it alone there may be close to what might seem like fifty different drugs causing both violence and psychosis.
The other skin drugs recently released Siliq, Taltz, Otezla and others will almost certainly have similar reactions soon – or should do.
Other drugs include a host of antibiotics including the fluoroquinolones and many others, steroids, drugs like Advair (salmeterol) as Singulair – montelukast – and Accolate – zafirlukast – for respiratory problems, most of the retrovirals and other anti-viral drugs, as well as Mefloquine (Lariam) obviously.
The dopamine agonists are on the list. They are for parkinson’s disease – or for just little ol’ restless legs syndrome.
It may be little surprise to find the stimulants on the list but remember these drugs are being given hand over fist to children. Everyone recognizes the link between street amphetamines and violence but somehow once the same drugs are channeled through a prescription pad this recognition seems to be laundered away.
The list includes pretty well all antidepressants, and anticonvulsants and in addition a bunch of antipsychotics. Antipsychotics note causing psychosis and hallucinations and violence. It also includes the choline-esterase inhibitors giving for dementing disorders.
All these cases are interesting because the companies have the chance to in most cases to blame the problem on the disease but there is something about at least some of the cases reported to them that blocks off this easy escape route.
Or Should Do
A few lines up, the phrase “or should do” occurs. Many years ago a number of us had a shock seeing a memo from a Forest lawyer telling staff they should never make causal determinations in the case of any reports in to the company of adverse reactions happening on citalopram and escitalopram.
The rough basis for something like this – a strategy first adopted by GSK – is as follows. Even if by all the conventional rules of cause and effect, by the Federal Judicial Manual sanctioned rules which hinge on challenge and dechallenge – not RCTs – there is no way out of assigning causality, we can still claim that unless RCTs have shown drug A causes problem B there is no way for sure to know the drug has caused the problem.
So you dudes who work for Forest or GSK, despite all logic you guys have to refrain from assigning causality until the RCTs proving the point get done. The fact that they will never get done, that it would be unethical to do them, is irrelevant. Come to think of it there are no RCTs of anyone ever dying from Zyklon B – maybe time to rewrite that bit of history.
The above scenario is for real. It is not a nightmare. The first person I heard push it was Ian Hudson, then of GSK, now head of Britains MHRA (FDA). But it may be the case that at least some people in what Iain Chalmers and Ben Goldacre continue to laud as the most ethical outfit in the universe and in other companies have recognized the lunacy of this and are quietly doing something else.
Difficult to know. But it pays to read the small print and maybe translate it for your doctor – or lawyer.
There are unquestionably many people now in jail who possibly should not be because of a drug they were on, dead who should not be because of drugs someone else was on, or who will not get a fair trial because when it comes to the small print vanishingly few people realize what is being said.