Pharmacosis: trigger algorithm

The first descriptions of a drug causing suicide came in 1955. A few years later in 1958 and again in 1959 the problem was described with imipramine. Treatment induced suicide became a prominent media issue in 1990 with a paper by Teicher and Cole. But it was not until 2004 that regulators and companies conceded that these drugs can cause a problem. There are now 38 drugs listed as causing suicide, including drugs for asthma, obesity and skin conditions in addition to antidepressants, anticonvulsants and antipsychotics.

The first descriptions of risk-taking behavior on l-dopa were described in 1981. Similar problems were described shortly afterward for dopamine agonists given for Parkinson’s disease. Dopamine agonists are now also given for minor conditions like restless leg syndrome. The problems were serious – judges and clergymen were arrested for gambling, prostitution and other risk seeking behaviors (see DBM Dopamine & Parkinson’s Disease). But it was not until 2008 that regulators finally conceded that these drugs given for Parkinson’s disease could cause these risk-taking behaviors.

When it comes to side effects, doctors are Flat-Earthers

The moral of the story is that it can be decades from the time that a problem is first described to the point your doctor gets to hear about it and even then he may not be likely to believe it. When it comes to side effects, most doctors are Flat-Earthers, partly because it’s not a cause for concern for them in the way that it is for those they put on treatment.

There are a number of steps we take you through at Rxisk.org to establish whether your drug is causing your problem – whether you are suffering from Pharmacosis or not. This will work for problems known to be caused by the drug but also for problems not yet linked to treatment. These are the steps that any expert would take you through before deciding there was a linkage. These are the steps pharmaceutical companies routinely work through, based on which they often decide their drug has caused a problem, while still denying in public that it does so.

These are the kinds of questions that need to be asked even when it is known that a drug does cause suicide, gambling, heart attacks or some other problem. Just because someone has begun to gamble or been violent and is on a drug that can cause violence or gambling does not mean the drug has caused the problem. A judgment is still needed as to whether the drug is likely to have played a part or not. Ideally this will be a team judgment – involving the person affected and as many others as possible.

Some of the steps outlined here can be found in other algorithms of which the most famous is the Naranjo algorithm but we ask more questions and score things differently.

Pharmacosis Trigger Algorithm

    1. When did you start the drug? When did the problem start?
    2. Did the problem start or get worse after a dose increase?
    3. If you lowered the dose, did the problem clear up?
    4. If you stopped the dose, did the problem clear?
    5. If you used any other treatment as an antidote, did the problem clear up?
    6. If you restarted the drug or increased the dose, did the problem reappear or get worse?
    7. Have you ever had this reaction before on another drug? Was it the same type of drug?
    8. Have you had other drugs of the same type as this? Did you have a similar effect on them?
    9. Have you ever had this happen to you before when not on a drug?
    10. Could anything else be causing this problem?
    11. Have you ever been told you are a poor metabolizer of drugs and need lower doses, or do you have a history of sensitivity to drugs?
    12. Could you have taken too high a dose?
    13. Has a doctor or a pharmacist reviewed your problem? Do they see a link?
    14. If a name has been put to your condition is it rare off drugs?
    15. Are there previous reports of this reaction in the Rxisk or FDA database or on Google?

  Rxisk Score

Rxisk Score:

9 +

points strongly to a link – bring to your doctor/pharmacist

5-8

points to a likely link – bring to your doctor/pharmacist

0-4

needs information or input from your doctor/pharmacist (Qs 13, 14, & 15 in particular)

 

Rxisk Team

No simple score can tell whether  a drug has caused a problem. It needs a team and research and judgment. The person on the drug is critical – no-one knows what is going on quite the way the person on the drug does (see Unbearable lightness of being), and as history shows people on the drugs often get it decades before the experts. But there are many side effects that need judgment calls from doctors or pharmacists or increasingly anyone armed with Google and prepared to research things (see Out of my mind).

Birth defects in general like the phocomelia caused by thalidomide cannot be tested by challenge, dechallenge or rechallenge. Babies had been born limbless and deformed like this before thalidomide but it suddenly became a lot more frequent.

Just like phocomelia on thalidomide, conditions that looked like tardive dyskinesia happened before the antipsychotics, but were a lot more common after the antipsychotics were introduced. In this case though the tardive dyskinesia that appeared on the drug cleared up if the dose of the drug was increased – could this be caused by the drug? Scoring on the Rxisk Trigger algorithm might not point to a link but scoring on the Rxisk Terminator algorithm in the next post might have helped to bring out the link.

Ultimately the more reports shared among the greatest number of people the more likely we all are to find an answer (see Unbearable lightness of being).

Rxisk.org has gone live in Beta for feedback as of today June 18th

 


RxISK: Research and report prescription drug side effects on RxISK.org.

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You and your meds. Give the real story. Get the real story.

Pharmageddon

Pharmaceutical companies have hijacked healthcare in America, and the results are life-threatening.

 

Dr. David Healy documents a riveting and terrifying story that affects us all.

 

University of California Press (2012)

 

Available on Amazon.com

 

Comments

  1. May I suggest that you ask if the person is over 65 years of age because of the increased likelihood of too large a dosage and rapid overdosage?

  2. Bernard Carroll says:

    One reason why average clinicians are flat earthers about such risks is that an individual clinician may never see an uncommon side effect. I like to illustrate this point with some of the data on suicide: In the months following a diagnosis of cancer, the rate of suicide increases 16-fold from around 13/100,000 per year to around 200/100,000 per year. This large effect has plausibility on its face. Yet most clinicians are unaware of the issue because even at the higher rate they would see it only once in 500 cases. Nothing could better illustrate the difference between the perspective of the epidemiologist and that of the individual clinician.

    That said, I agree with your observation about cognitive resistance. The cognitive resistance arises from cognitive dissonance – we want to think of medications in positive terms as achievements to be proud of, so we are inclined to discount the associated risks.

  3. Admittedly painting with a broad brush here, but from patient reports it seems when it comes to psychiatric drugs, clinicians cannot even recognize common side effects listed in the package inserts.

    It took years for them to admit that SSRIs cause sexual dysfunction (at a rate of 30%-50%) and many still don’t include it in advice leading to informed consent.

    Yes, overlooking adverse effects must be cognitive resistance and cognitive dissonance, plus avoiding anything that might cause guilt or legal liability.

    Dr. Healy, congratulations on the launch of RxISK.org. I hope this leads to much clearer information for clinicians.

  4. The Doctors in my local clinic still believe SSRI’s help depression by correcting an imbalance of serotonin, are very safe and effective and that the side effects I reported were not be caused by the drugs. (despite them being listed in the PIL). My GP then said with complete confidence, that she could lift the phone to any psychiatrist in the country and they would tell her the same thing. But yet the same GP says is highly skeptical of the statin drugs. Why one drug and not the other? It seems the general public have this perception problem too.

    While eating my breakfast a few weeks ago, I was treated to the headlines on BBC News that according to Oxford researchers, everyone over 50yrs old should be taking a Statin.

    I decided to check out what the papers were saying about it all. The story was covered by all the main papers.
    http://www.dailymail.co.uk/health/article-2145558/Why-EVERYONE-50-needs-taking-statins-Cholesterol-busting-pills-cut-risk-heart-attack-stroke.html

    I was really interested to see that going by the comments, the public were not impressed at all by this piece of research. The top comments under the articles were all about dangerous side effects, bad experiences and dodgy science.

    For example the top rated comment with 350 thumbs up was…
    “This is the worst piece of advice I have ever seen . These drugs can effect certain people so badly , that a heart attack would be a good thing . Please do your research before offering such bad advice.”

    The worst rated comment with 122 thumbs down was…
    “Love it. For all rose sceptics eat your ‘heart’ out!!! Long live the pharma companies that deliver such wonderful drugs that extend peoples’ lives.”

    Compare this to a recent story about antidepressants in the same newspaper (Anti-depressants ‘may do more harm than good’ ) and how the public reacted to it compared to the stain article….
    http://www.dailymail.co.uk/health/article-2134863/Anti-depressants-harm-good.html

    Top rated comment with 297 thumbs up
    “I take anti-depressants- I’m not a nut job- I’m normal. Intelligent and most importantly happy! I love life- I make others happy. I’m a good mummy to my daughter. Nobody would guess! If I don’t take anti-depressants- I find life hard, I waste my life, I bring others down and cause them worry. What would you do? :)”

    Next with 222 thumbs up
    If it wasn’t for Prozac i without any doubt would be dead. Medications are not for every one but for those of us who do get the benifit of the drugs they are life changing , unless you have been in mental health hell dont pass comment on the use of these drugs.

    Worst rated comment with 242 thumbs down.
    NOBODY needs anti-depressants. What people need is to simplify their lives, eat healthily, do more exercise, and most importantly… get some good sleep. (No need for TVs in bedrooms)

    Even this more moderate comment was at 7 thumbs down
    I’m honestly surprised at the number of comments on here saying that anti-depressants actually did help them. Thankfully, I have never suffered, but I know many people who have and not one of them has gotten better due to pills. For my neighbor, it was running – a natural source of serotonin and other feel-good hormones that eventually helped her, for my two best friends it was therapy and my aunt after 15 years finally resorted to electro shock therapy which sounds horrible but actually helped her. The others I know are sadly still in a very dark place. But all of these ladies have had severe side effects: My aunt gained 50 pounds and her doctor told her it would be about 7 years before her body would begin processing food in the same way it did before the drugs. My best friends got a lot worse once they were on the drugs and one of them actually tried to commit suicide. Apparently, it does work for some but I wished docs would be a little slower in handing out these drugs.

    Yet, if you Google ‘Statins’ for News, there is a mix of positive and minor negative stories on the first page. A bit about fatigue, a bit about helping cancer patients etc… .

    Try the same thing with ‘antidepressants’ and Google News. The first page is nearly entirely negative with headlines like “Do Antidepressants Increase Your Risk of Death?” or “Anti depressants are merely another addiction – for doctors as well”, “More Bad News On Antidepressants And Pregnancy”…etc What is it that determines the public mind-set on these issues?

    Can anyone shed any light on why this. Why do so many see the problems with statins, yet ignore the problems with psychotropics?

  5. Well..could be a combination of things. Huge PR by Big Pharma, denial, the pecking order…(lets drug those with emotional and psych distress but take great care with those with a physical issue), the single minded belief by psychiatrists (most) in the medical model and all the lies and half truths that accompany it. One cd go on!
    There is lots of evidence that psychotropics do huge amounts of harm and lessen life span and cause heart problems and strokes yet they are blithely dished out in millions.

  6. There seems to be a different, (lower) standards for people who have a psychiatric diagnosis, or are perceived to have ‘mental health issues.’ This is evident to me in the scenario you describe, Neil. It is even more evident in the manner that my son and people with a diagnosis of schizophrenia are medically neglected as a matter of course by mental health and other medical professionals. My son was put on a statin, and it caused severe cramping in his legs–to where he could barely walk. When I took him to his GP, the fact that the drug is known to cause muscle cramps and to actually cause Rhabdomyolysis for some people was not considered as a potential cause for his muscle cramps. His case manager told me that muscle cramps are a negative effect of statins, so I called his doctor and asked if it could be the statin causing the muscle cramps. His doctor advised us to stop the drug, which we did, and the muscle cramps went away. http://en.wikipedia.org/wiki/Rhabdomyolysis

    The attitude that you describe Neil, seems to me to be due to the stigma associated with having a psychiatric diagnosis. People, including medical professionals, have lower standards for people with a diagnosis. For example, people with a psychiatric diagnosis are often told that a negative effect of a drug is tolerable, when obviously, this is a determination that must be made by the patient who is actually the one experiencing the effect; not a judgement that is made for the patient, ignoring the patient’s input.

    • Becky – Neil seems to be saying almost the opposite to you here. For some reason antidepressants seem to get below the radar and all kinds of people endorse them. The issues may lie in the way the two articles were written

  7. Neil, you follow my own thoughts exactly. I, too, read the Daily Mail and I am always thinking that this is a newspaper, it is not somewhere to go when you need medical advice. The articles they print are mostly nonsense.
    Statins were originally designed to help with cholesterol for those who had had a heart attack and were at risk of another.

    It is another attempt to say to the public, why don’t you all take one and then you are safe from heart attacks, high cholesterol, etc. etc.

    It is pure propoganda from pharma, just like the whole ssri debacle.
    I really don’t think newspapers should write any articles about these drugs.
    They do not have a clue what they are talking about and it is extremely misleading to the public who begin to get just a little bit confused.

    Many will fall for it. How could they not. They are advised to take it because the good old doc said so.

    When yet another gp said to me recently I should take a statin, not having high cholesterol or having had a heart attack, I said to him you must be joking. After the havoc caused to my life by Seroxat.

    Come on!

  8. Johanna says:

    Neil, I can think of a few reasons why articles on statins attract so many comments from skeptics and folks with a bad personal experience … while articles on anti-depressants tend to get comments rushing to their defense.

    1. First, almost no one subjectively “feels better” on a statin – better blood tests are your only direct feedback. However, some people really do feel better on an SSRI. Others simply know that they feel horrible whenever they try to stop, and are told that’s proof of their biological need for the stuff.

    2. Second, there’s been a relentless campaign (at least in the States) to convince us that all objections to psych drugs are due to a stigma against mental illness – to criticize the drug is to criticize the people on it. So people who do feel they are benefiting from antidepressants are encouraged to feel violated whenever someone expresses skepticism about the drug – as if they and their problems are being trivialized or discounted. You often see posts saying in effect, “I know what real clinical depression is like. It’s not the blues, or everyday stress. So if you don’t know, don’t judge.”

    3. Third – many corporations employ people working from home to post positive online messages about their products. It’s done for music CD’s, books, cars, cosmetics – and it is damn-sure done by the drug companies, which also monitor online chat rooms about drugs and disease. It is hard to tell which posts come from paid “sock puppetry” of this sort … but some of them do. I’d bet a lot more of this activity goes on re: psychotropic drugs than blood pressure or cholesterol meds.

  9. Anne-Marie says:

    Johanna you are so right about people employed to put in positive comments, Ive been on forums where people are talking about a negative side effect and along comes someone who will try to change the subject by putting in a positive comment, which to me seemed strange because their comment just did not fit in with the subject.

  10. In relationship cardiovascular events other than suggestions for use of statins for everyone over a certain age (incredible!) there has just been published an interesting study conducted in Denmark that gives us yet another major adverse event to add to the list:
    Antidepressant Use and Risk of Out-of-Hospital Cardiac Arrest: A Nationwide Case-Time-Control Study; Weeke P, Jensen A, Folke F, Gislason GH, Olesen JB, Andersson C, Fosbøl EL, Larsen JK, Lippert FK, Nielsen SL, Gerds T, Andersen PK, Kanters JK, Poulsen HE, Pehrson S, Køber L, Torp-Pedersen C; Clinical Pharmacology & Therapeutics (May 2012)
    All patients in Denmark with an out-of-hospital cardiac arrest (OHCA) were identified (2001-2007). Association between treatment with specific antidepressants and OHCA was examined by conditional logistic regression in case-time-control models. We identified 19,110 patients with an OHCA; 2,913 (15.2%) were receiving antidepressant treatment at the time of OHCA, with citalopram being the most frequently used type of antidepressant (50.8%). Tricyclic antidepressants and selective serotonin reuptake inhibitors were both associated with comparable increases in risk of OHCA, whereas no association was found for serotonin-norepinephrine reuptake inhibitors/noradrenergic and specific serotonergic antidepressants An association between cardiac arrest and antidepressant use could be documented in both the SSRI and TCA classes of drugs.

  11. Some excellent points already mentioned. But could it also be related to Professional suicide as previously explained by Prof Healy?

    The psychotropic drugs have a champion to fight their corner in (most) psychiatrists, and a champion who has tied their professional survival to the perceived safety and success of these drugs. I might be way off mark here, but I don’t see Cardiologists as champions of statins and I don’t see them protesting evidence that questions their safety or efficacy.

    If statins were taken off the market tomorrow, what would really change for the Cardiologist and his profession? If antidepressants were taken off the market tomorrow what would happen to psychiatry?

    When it comes to the public view, I think the reaction to the Statin article might show a healthy skepticism of big pharma and its sensational claims, even when the claims come from ‘researchers at Oxford’. The reaction was similar in the Guardian and the Telegraph. The problem is, even with this healthy skepticism of pharma and wonder drugs, most people still trust their doc and more importantly their specialists.

    A pattern I see in both articles is the public comments are following the authority, rather than pharma or the scientists. It just so happens that with antidepressants, pharma and the ultimate authority (psychiatrists) are both saying the same thing, which in this case happens to disagree with the news article.

    The statin article is most likely taken by the informed public for what it likely is… Stealth direct-to-consumer advertising. And the antidepressant article probably taken as scare mongering by those expensive talk therapy advocates.

    The public read about these things on many different levels of understanding and a good few will take the weakest form of evidence there is ‘Authority’ as gospel. And more often than not, despite the evidence, when that authority is in the shape of a psychiatrist or organisations like the APA, then the message is ‘OUR drugs are awesome’.

    I highlighted the news searches in the last post because I was trying to show that in this case at least, public opinion was not exactly linked to the evidence or even how much good or bad press there was about each drug. The Champion of antidepressants is busy deflecting all the criticism it can, while the statins have no apparent champion (as it should be) and their defence is left to the drug companies, their tricks and the resulting evidence.

    Until psychiatry changes its mind, or the rest of the medical profession changes it for them, the people who accept the truth about psychiatric drugs will remain limited to the best of the medical profession and the patients and their loved ones who have suffered severe adverse reactions.

    If this public perception of antidepressants is even partly true, will it have an effect on the reports submitted to RxISK for this particular class of drugs? Is it possible that psychotropic drugs could have a much lower report rate than they should, if the public are less skeptical of them and the authority less open to problems in the first place? Especially when you combine this with all the other very valid reasons highlighted by Johanna above.

  12. I fear that we may be missing a large number of patients who are not being treated primarily for “depression”. General practitioners, anesthesiologists who work with chronic pain sufferers and neurologists treating various neuralgias appear to have fallen into the habit of adding TCAs, SSRIs and anticonvulsants to opiates, anti-inflammatories and other pain relieving medications. I imagine it would be difficult to find these patients if the emphasis is only on those being treated by psychiatrists or for mood disorders.
    Then we have residents of long term care of whom it is claimed that a significant number with “dementia” (type unspecified) are depressed. I imagine that data with respect to adverse reactions in the latter group would be difficult to find because of polypharmacy and one may assume that they are not in a position to self report. I remain highly skeptical of the “depression” in patients with dementing diseases.
    The chronic pain group tend not to think of themselves as being treated with antidepressants but primarily for pain and the confounding variables of pain medications increase the problem. The third group consists of those who have taken antidepressants without knowing it. I mean those on Zyban to quit smoking who have no idea that it is Wellbutrin one of the SSRIs most likely to cause adverse reactions including suicide and self-harm. The manufacturers publish the following: “ Bupropion is a pill you take to reduce your craving for tobacco. The way it does this is not entirely known….. Doctors also prescribe bupropion (under the brand name Wellbutrin) to treat depression. But bupropion’s ability to help people quit smoking is not related to its antidepressant action. It can help you stop smoking even if you do not have depression.” Really? Although we don’t know how it works? Hmmmmmm.

  13. Correction: Wellbutrin. I am so accustomed to writing of the SSRIs that I just plunged ahead with bupropion. Of course its pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition. It binds selectively to the dopamine transporter which may be the explanation for the extrapyramidal effects many suffer.

  14. If anti-depressants were taken off the market what would happen to psychiatry?

    A very good question, Neil.

    It is a fact that people get over their grief, anxiety, depression, etc., given time and caring and understanding.

    Along come ssris, and despite suicidal tendencies from trycyclics, they are pushed down the throats of the public without any attempt to ‘do psychiatry’.

    What is psychiatry?

    My psychiatrist used to draw me little diagrams on a sheet of paper. He drew a circle – anxiety at the top, depression at the bottom. He said I was going round and round this circle and that the only thing that would stop it, would be to take a pill.

    I understand his logic to a point – he was trained to ‘short circuit’ the circular pattern and he grew up with drugs, being a young consultant in a mental hospital where drugs for serious mental illness are the norm.

    But when this young, enthusiastic guy is so enthralled with Paroxetine ‘a new and exciting drug on the market’ which will change my life, he could not have been more right!

    And when things go wrong and he is facing me in his consultancy room telling me that he doesn’t know whether my traumatic experience is down to the drug or down to me, I am as David Healy says, ‘decades ahead of him’ with my opinion.

  15. We shouldn’t forget that some of the older antidepressants, such as the MAOIs are extremely effective for melancholia in well selected patients but few psychiatrists today seem to understand them and/or are dissuaded from prescribing them by the overstated warnings about dietary restrictions. A few years ago, the manufacturer was planning to stop production until the screams of those patients who responded to them and benefited from them got through. Having said that, my own experience is that if the SSRIs in particular, were taken off the market today, a significant number of psychiatrists would have no idea of what to do. Therapeutic skills have been lost in the same way as the clinical skills of other physicians are disappearing in favour of the use of new toys such as MRI, PET scans etc. believed to be diagnostic when they are no more than diagnostic tools. Try telling a young physician that one can’t diagnose anything from an xray and one is met with incredulity. Certainly, I can know when I’m looking at a mass in a lung but I have no way of knowing what it is or what caused it and, until I do, I can’t know how to treat it. In the same way telling a psychiatrist to examine the social environment of the patient, determine the existence of supportive and caring individuals in the patient’s life, find the possible causes of the present distress (reactive or other) and the same puzzlement appears. It seems that they have forgotten, if they were ever taught it, that their job is not to make the patient better but to help her to acquire the tools to be able to function as well as possible. But, of course, that takes time, expertise and the ability really to listen.

  16. A friend in the US just posed an interesting question. What might the effects/advantage to Big Pharm be as a result of the recent Supreme Court decision? It seems to be, potentially, a whole new wider market.

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