The Empire of Humbug: Bad Pharma

April, 15, 2013 | 15 Comments


  1. Thanks for that very interesting interpretation of recent medical history.

    Have you done any research on operational definitions in psychiatry? They seemed to be part and parcel of the whole push to make psychiatry more scientific in the 1960s. As a trainee psychiatrist in Edinburgh one of my teachers wars Bob Kendell. One anecdote from him I remember related to a conference on psychiatry which had been dominated by disagreements on the major diagnoses. It seemed that every Department of Psychiatry had its own definition. Bob Kendell described how there was a visiting American philosopher who had stood up and said you will make no progress until you define your terms. From that developed the Maudsley’s romance with operational definitions which became a core part of pharmacotherapy investigation. Kendell went on to do the research that supported the unitary hypothesis of depression rather than the bimodal one based which had been based on depressive psychosis and depressive neurosis (or their pseudonyms). As I had been exposed to structuralist ideas through having a flatmate who had become a follower of Levi-Strauss I had several arguments with Bob Kendell pointing out that the results he gave flowed from the assumptions he had made. He riposted that I was a Platonist. I knew a lot more about structuralism then than now and I cannot fully recall the details. To my mind that positivist error of dividing the world by words and concepts where in truth there is no division has hampered psychiatry for the last 50 years. Anyway enough of my ramblings. You are a scholar and I wonder if this is an area that you have studied.

  2. When you write: “The rule says that it takes two positive studies to approve a drug. In law, if there were only two positive studies out of 100, the regulator would approve the drug” I assume you are referring to the FDA and therefore US law, yes? Is this the same in the UK, presumably with the EMA and/or MHRA?

    • De Facto its the same in the UK. Not certain what the wording is – would be worth an enquiry. The UK tends to approve faster than the US – so less stringent rather than more so.

  3. I could not let the week pass without mentioning a certain lady of colour and it seems relevant here.
    This is all so interesting, my favourite to date, and as a mere bit of collateral damage hanging off the edge of ssris, can I just say that Maggie T. is now considered divisive.
    I have not heard the word divisive as many times as I have this week and it is relevant here.
    Evidence and evident are divisive. not meaning the same thing at all. Effective and effect are divisive, not meaning the same thing at all.
    Divisive means two halfs, split in two, halved, etc. but the sum of the two parts equals whole is not happening.
    The War on Words and their acute meaning is a very important part of the ‘science’ behind the rct and the ssri, and where the Humbug comes in, is in the bit of paper in the ‘box’ which all doctors should stick in their bin before giving the packet to the patient……instead, for all it matters, the words to the patient could be ‘pot luck, your call, you’re on your own, I didn’t make the bloody pill’.
    I appreciate the moderator usually prefers the scholastic comments, I just like to offer the subjective, simplistic, human interest angle.
    Also, a sense of humour is pretty vital, at this moment in time, otherwise, what is left.
    As it was said: Witty A. Report to the President.
    Wish we had Spitting Image back….Maggie T. was a hoot, Witty A. would be ….not one ‘icon’ was missed out on Spitting Image….
    I am not being ‘divisive’, I am just saying Witty A. and President of the US in one breathe is a trick (y) bit of information.

  4. “Controlled trials are based on a null hypothesis.”

    I’m looking at this phrase trying to find a comment but I decided that it is not necessary.
    They create the hypothesis later.
    It that becomes theory following the peer-reviewed methodology,
    This is what they name “science”.
    Hmm… Ok…

  5. I have checked the statistical analyses reported by Davies and Shepherd and I cannot confirm a statistically significant effect of reserpine on the primary outcome measure (their global rating presented in Table 1). It’s possible that Shepherd just miscalculated… this done was before desktop calculators and desktop computers with statistical packages came along. I invite anybody else to check it for themselves. It is surely a stretch to say reserpine was equal to later antidepressant agents.

    As for the study of imipramine reported by Lasagna in 1961, it is not really appropriate to use as a benchmark for evaluating the putative antidepressant effect of reserpine. Though one has to admire the pioneering effort, reading that report by Lasagna makes clear that it was a messy piece of work, clearly underpowered, plagued by diagnostic chaos, excessive dosing with resultant toxicity of imipramine, multiple dropouts, and an overly complex design (randomized crossover sequence of 4 weeks on placebo and 4 weeks on imipramine). As the authors themselves acknowledged in presenting the Results, “this part of the report is essentially one on the methodology of antidepressive drug studies rather than a definitive assessment of imipramine.”

    • Barney – this is wonderfully helpful. Definitely worth going back over all these old reports to do just this. But I still think reserpine looks as good as if not better than Prozac and Zoloft. In the case of Zoloft for instance of the first 5 trials done only 1 struggled to be positive so that even FDA reviewers said the data was embarassing. Take a mean of the Zoloft data and reserpine looks better than that.

      In the case of Prozac of the studies that got it on the market, one that regulators critically dependence on used a facility used by Louis Fabre in Texas. FDA almost certainly knew then what it knew later which led Fabre to be debarred from doing clinical trials. The data even so are more than embarassing but it is likely that without these data the drug would not have been licensed. The company were pleading to use the separate centers of a multicenter trial as separate trials in order to claim that marginally better results from a few of these centers constituted evidence of several positive trials.

  6. A small interruption to your interesting dialogue.
    If I am ‘vaguely suicidal’ in 1988 from starting Imipramine with all the withdrawal there is in the book and an up to date psychologist takes me off it as he said himself,’Imipramine can sometimes bring on acute anxiety and emotionally labile symptoms and it will be ceased’.
    I am ill for months afterwards, not having a clue what is going on. In 1988.
    Then, in 1999, I am given Seroxat. The man does not check on previous medical history, re Imipramine. He tells the surgery to switch me to Fluoxetine, this is ignored, and six weeks later I am more than vaguely suicidal.
    The man said I had no medical history of note, I was not suicidal, I was not psychotic, I was of above average intelligence……
    I thought I almost had this man and my surgery over a barrel.
    Lax, lazy, inadequate, irresponsible; along with a fabrication re Fluoxetine.
    The fact that Imipramine caused me suicidal ideation in 1988, led my Glasgow lawyer to throw out my case re my gp lying about Fluoxetine because following on with Seroxat and suicidal ideation and acts, my experience with Imipramine then proved that I was ‘suicidal’.
    I am thankful that Imipramine and Seroxat now come out in the same breath.
    Call it bad luck, call it what you will, Imipramine and Seroxat almost did for me….
    I left the hospital of this man, who could not even be bothered to check on my medication and four days later….they got me again.
    This is the human interest story, once again…….
    The truly scary part for me is, if Prozac causes suicide, as well as Seroxat, then my case against the prescriber and surgery are dead in the water……what is the point of switching to Fluoxetine is my main query at the moment…….NICE say switch, MHRA say switch, DH says switch…but…then what might happen….
    And….if I do send in a complaint to the MHC, then whom would they refer to about Imipramine, Seroxat and Fluoxetine…to whom would they refer to for advice.
    Because if they go to NICE, MHRA, then the circle starts all over again and this becomes a total non-starter.
    Nowhere has never been so nowhere.
    Carry on with your interesting dialogue, Mr. Carroll and Prof.; just wanted to interrupt it for a second.

  7. A comment on this by Dr. Mickey Nardo from his 1 Boring Old Man blog:

    “And now for the problem that haunts us to the present. The six-week clinical trial of Reserpine showed that it was useful in a number of psychiatric dimensions, proven by a statistically significant double-blind randomized placebo-controlled clinical trial – the first in history. And that’s correct … Unfortunately, in the long term, it can cause depressions indistinguishable from naturally occurring psychotic depressions – big ones. As we well know, generalizing from the brief clinical trials now used for approving drugs misses a lot of what can happen with prolonged use.”

    Was this view of reserpine – that it could be antidepressant in the short run but cause depression in the long run – pretty well accepted in the 1950’s when it was in wide use? Did anyone claim to know what led to this? If so it could be very damned relevant to what is going on today with SSRI’s, SNRI’s etc. I have read articles by G. Fava, R. El-Mallakh and others raising this possibility and saying research is urgently needed – but they seem to be roundly ignored. (Who the hell is going to sponsor that kind of research?)

  8. David, would you possibly be able to offer any hope to someone who has had their brain ruined by psychiatric meds? It’s a long story but I used to have mild to modetate depression before starting meds and now I feel ruined after getting into the psychiatric med system. I live in the U.S. and have been trying to find any doctor anywhere that might can help what these meds did to me. I may be able to travel if I needed to.

    I appreciate the incredibly ethical approach you take to the world of psychiatry. It’s refreshing to read your articles and makes it seem their might just be hope left in this wworld for people who need help.

    • Michael

      Its not meant to be incredibly ethical. Much more a concern that doctors are going to go out of business if they don’t realise that a substantial part of their future lies in managing the kinds of problems you have rather than just acting as a conduit to get people on meds. The future lies with informed patients working together and with doctors who can manage teamwork rather than with old style medical experts whose word is law.

    • Ah don’t let him fool you Michael, it is ethical as all get-out. It has a good sound doesn’t it? Kind of gives you hope, and it’s a lot more interesting than all the prattle about finding the sixth or tenth or 14th drug to batter you with until you are “symptom-free.” But the larger point David makes is very true. We need doctors who can approach their patients as a human being among human beings, and we need to create some teamwork. Otherwise doctors just may go out of business. Of course a lot of them would be just as happy being stockbrokers … but others would not, and those are the ones we are counting on to break ranks.

      Even though this is not a mutual-aid board per se, I have to pipe up as someone who has found myself in a similar position but maybe a few years further down the road. So far, no one has an Antidote for the damage that’s been done, and there’s not even any certain diagnosis. No one can put you in an MRI machine, study the films and say “Sorry pal — your soul is gone,” or “Look, there’s hope, 65% of it is still functional.” So a great deal depends on what we choose to believe. Until proven otherwise, I gotta believe they could not engineer a chemical to “save” me so they could not destroy me either. Hope you stick around! We will need a big and diverse team to figure this out.

  9. Much more a concern that doctors are going to go out of business if they don’t realise that a substantial part of their future lies in managing the kinds of problems you have rather than just acting as a conduit to get people on meds.”

    But it doesn’t seem like there’s a way to manage many of the problems that meds can cause. Sure a doctor could prescribe Wellbutrin or some other stimulant for “post SSRI sexual dysfunction” but otherwise things like anhedonia being induced by a med like Mirapex serms untreatable in the traditional way we increase pleasure chemicals in someones brain. I’ve been in contact with someone on a forum who has this same problem I have from Mirapex. He’s referring to it as DAWS (Dopamine Agonist Withdrawal Syndrome.) I call it hell on earth.

    Too many problem meds cause seem untreatable, even if you get a psychiatris who believes you about it.

    • Michael

      Quite coincidentally, there has been a Rxisk story about DAWS just this week – see

      I agree there are some terrible problems out there, in particular withdrawal problems. I think few people have any idea of just how bad DAWS and SSRI withdrawal can be. These will be difficult to solve but are much more likely to be solved by the people affected and doctors and pharmacists working in a team to solve them.

      Can you submit a Rxisk report and get anyone you know who has DAWS to do so also? Would be good to build a HeatMap of where the problems are and a HeatMap of helpful doctors perhaps

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