Washing the numbers, selling the model

January 26th, 2008 by Ben Goldacre in adverts, bad science, big pharma, medicalisation, neurostuff, regulating research | 57 Comments »

Ben Goldacre
The Guardian,
Saturday January 26 2008

If there’s one thing I love, it’s academics who take on the work of investigative journalism, because they are dogged. This has been a bad week for the SSRI antidepressants.

First there’s the stuff you already know: bad data got buried. In a cracking new analysis of the “publication bias” in the literature, a group of academics this week published a paper in the New England Journal of Medicine which listed all the trials on SSRIs that had ever been formally registered with the FDA, and then went to look for the same trials in the academic literature.

37 studies were assessed by the FDA as positive, and with one exception, every single one of those positive trials got properly written up and published. Meanwhile, 22 studies that had negative or iffy results were simply not published at all, and 11 were written up and published in a way that described them as having a positive outcome. You’re a sophisticated reader, so you understand this doesn’t mean that they’re necessarily rubbish drugs, but you also understand that this is dodgy behaviour, all the same.

That’s the easy bit.

The second paper is more interesting. Over the past few decades, we have been subjected to a relentless medicalisation of everyday life by people who want to sell us sciencey solutions. Chancers from the $56 billion international food supplement industry want you to believe that intelligence needs fish oil, and that obesity is just your body’s way of crying out for chromium pills (“to help balance sugar metabolism” etc).

Similarly, quacks from the $600 billion pharma industry sell the idea that depression is caused by low serotonin levels in the brain and so – therefore – you need drugs which raise the serotonin levels in your brain: you need SSRI antidepressants, which are “selective serotonin reuptake inhibitors”.

That’s the serotonin hypothesis. It was always shaky, and the evidence now is hugely contradictory. I’m not giving that lecture here, but as a brief illustration, there is a drug called tianeptine – a selective serotonin reuptake enhancer, not an inhibitor – and yet research shows this drug is a pretty effective treatment for depression too.

Meanwhile in popular culture the depression/serotonin theory is proven and absolute, because it was never about research, or theory, it was about marketing, and journalists who pride themselves on never pushing pills or the hegemony will still blindly push the model until the cows come home. Which brings us on to our second new study on antidepressants. Two academics, a lecturer and an associate professor of neuroanatomy, decided to chase journalists, in the style of this column – or rather, in the style of this column on crack – and fired off multiple emails, demanding unrealistic levels of referencing from doubtless irritated and baffled hacks. They proudly document their work with an excessive number of examples, and I will pick just a few.

“In the New York Times (12/31/06), Michael Kimmelman wrote about the life and work of Joseph Schildkraut, one of the founders of the chemical theory of depression. The Times reporter stated, ‘A groundbreaking paper that he published in 1965 suggested that naturally-occurring chemical imbalances in the brain must account for mood swings, which pharmaceuticals could correct, a hypothesis that proved to be right [italics added].'” The prof’s gave chase. “E-mails to the author requesting a citation to support his statement went unanswered.” A victory for the noble pedantry.

“In another New York Times article (6/19/07), ‘On the Horizon, Personalized Depression Drugs,’ Richard Friedman, the chairman of Psychopharmacology at the Weill Cornell Medical College, stated: ‘For example, some depressed patients who have abnormally low levels of serotonin respond to SSRIs, which relieve depression, in part, by flooding the brain with serotonin.'” They chased, and they give no quarter. “For his evidence he supplied a 2000 paper by Nestler titled, “Neurobiology of Depression,” which focuses on the hypothalamic pituitary system, but not on serotonin.”

The serotonin hypothesis will always be a winner in popular culture, even when it has flailed in academia, because it speaks to us of a simple, abrogating explanation, and plays into our notions of a crudely dualistic world where there can only be weak people, or uncontrollable, external, molecular pressures. As they said in the Pittsburgh Tribune Review (4/2/07) “It’s not a personal deficit, but something that needs to be looked at as a chemical imbalance.”

The real world is more complicated than this simple dichotomy. But when you probe the evidence for simple fables about serotonin stories in popular culture, you’ll find “the quote was attributed to a psychiatric nurse practitioner, the author did not respond to e-mails, and the nurse’s e-mail was not available”.

References:

Here is the NEJM paper on the missing SSRI trials.

content.nejm.org/cgi/content/abstract/358/3/252

Here is “The media and the chemical imbalance theory of depression”

www.springerlink.com/content/u37j12152n826q60/

You can read an older Leo and Lacasse paper for free here if you haven’t got an academic login (it’s ridiculous that this stuff is behind a paywall).

Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. Lacasse and Leo 2005.

The relative ropeyness of the serotonin hypothesis is nicely reviewed in this paper from Nature Reviews Neuroscience

www.nature.com/nrn/journal/v6/n3/full/nrn1629.html

Contemptibly that is behind a paywall too but there is a lay summary from my chums MindHacks here

www.mindhacks.com/blog/2005/05/is_depression_a_brai.html

And if this sort of thing interests you, then you can listen to a looong lecture from me about medicalisation called “more than molecules”, at the British Pharmacology Society meeting last year, here.

www.badscience.net/?p=602


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57 Responses



  1. muscleman said,

    January 26, 2008 at 9:20 am

    In the open Leo and Lacasse paper they try and rubbish the chemical imbalance theory by reference to the actions of cannabis, LSD and psylocibin. However their assumption that if these substances work the chemical imbalance theory is wrong is just bollocks.

    The problem with the SSRIs is not that they don’t work as anti depressants, they clearly do, but with the story of HOW they work. Criticising people for providing what other people want, credible narratives is a bit perverse. Is it strictly scientific? partly, the SSRIs do raise serotonin levels and they do treat depression.

    All you are basically complaining about is that proving direct causation in the brain is very, very difficult. For eg we know that the SSRIs also enhance neurogenesis, they make more neurons. However I know of no research that says this is not due to long term raising of the serotonin levels.

    The main beef of Leo and Lacasse seems to be about dose regimes, yes cannabis, LSD and magic ‘shrooms make you feel good, man. But indulging in them every day is likely to make the side effects of SSRIs look extremely mild in comparison.

    Cognitive Behavioural Therapy works, yes (though didn’t I see one paper where they showed it raised serotonin levels?). But what is wrong with there being more than one way to achieve an end result? IOW there need be no conflict between CBT and SSRIs, take your pick.

  2. Bob O'H said,

    January 26, 2008 at 9:24 am

    What fun! Although I’m surprised the academics managed to get away with this:
    “For instance, if a critic were to argue that neurosyphillis was not a disease, an infectious disease specialist could locate and cite the paper which proves this incorrect—and the debate would be over.”

    I think we should all email them and ask for the reference.

    Bob

  3. davimack said,

    January 26, 2008 at 10:06 am

    “…the side effects of SSRIs look extremely mild in comparison.”

    Umm… that’s rather a subjective assertion, given that there’s no support for it, and the side effects of SSRIs are particularly heinous. Also, there is a difference in kind: the drugs mentioned are clearly illegal, whereas the SSRIs are pushed via every media outlet, for every ill, up to and including menstrual pain and bowel dysfunction.

    The fact that drug trials have been suppressed is perhaps one of the key reasons behind these drugs’ repeated visits to the law courts, as they are obviously not all they’re marketed to be.

  4. DanielRoberts said,

    January 26, 2008 at 11:18 am

    I am agreed with davimack.

  5. walden said,

    January 26, 2008 at 11:34 am

    I’ve always thought it a bit odd that we treat mental illnesses with drugs anyway.

  6. stever said,

    January 26, 2008 at 11:48 am

    I find that whole concept a bit depressing. Is there a pill for me?

  7. guvno0or said,

    January 26, 2008 at 12:13 pm

    I can see why there are concerns about the efficacy of anti depressant and other drugs. But as a person who takes them for depression and panic disorder it makes me wonder where I truly stand on the subject. I am pretty sure that they have helped take the ‘edge’ off my panic attacks and my dips into depression often last days rather than weeks-months. In combination with practices learnt through CBT, I’d say I approach my problems in a better way but the medication has helped on some level: it hasn’t cured me, but I live a pretty good life with my “problems”.

    Does the worry about the influence of big pharma and misleading published results impact me as a patient? Should I chuck away my meds and be prepared to have panic attacks on the tube, walking down the street, or at work/in the lab? Do they work at all or is it all placebo?

  8. trickcyclist said,

    January 26, 2008 at 12:26 pm

    Actually Muscleman, for those of us trying to treat people with mental illnesses, the problem is that it is increasingly unclear whether antidepressants do work that well after all, and the sneaky tricks of the PharmaCos help no-one.
    If you look at the NEJM paper above, the effect size quoted for the published papers is 0.37, which isn’t bad, but for the unpublished it’s 0.15, which isn’t quite so thrilling.
    Another factor that makes me less certain of the seeming efficacy of antidepressants is the issue of ‘active placebos’ – placebos whose side effects mimic those of the active drug. If, as is the case in depression, there is a significant placebo response, being unblinded to one’s treatment in a trial would inflate the apparent efficacy of the drug, and that is shown in a Cochrane review here.
    Unlike Walden, I have no problem with certain mental illnesses being treated with drugs, but we need to know that the ones we have available actually WORK.

  9. trickcyclist said,

    January 26, 2008 at 12:30 pm

    Dammit! Here.

  10. Jamie Horder said,

    January 26, 2008 at 12:55 pm

    On the topic of the NEJM paper, Peter Kramer (of “Listening to Prozac” fame) has something to say about this

    www.slate.com/id/2182585

    Basically he’s saying that all of these antidepressants do work, and that many of the negative trials are probably actually “failed” trials which only show no difference between drug and placebo response rates because the placebo response rates were so high. This he attributes to the fact that pharma conducts shoddy studies, recruiting people who aren’t really depressed, and who recover spontaneously. He never explains why they would keep spending so much time and money on trials which wrongly show their own drugs not to work, but I think there’s something in this; antidepressants are prescribed for people who don’t really need them, it’s only to be expected that they’re trialled on them as well.

    On the serotonin hypothesis: I blame the American Psychiatric Association. The serotonin theory is clearly inadequate as an explanation for all cases of depression – tianeptine being but one example of this – but who says that there has to be one single explanation for depression? Depression is a symptom, or perhaps a syndrome, not a disease – except if you’re working with the APA’s diagnostic system (DSM-IV), when all depressed people have Major Depressive Disorder, a terminology encourages a belief in the One Cause. There’s actually a lot of evidence that serotonin is causally associated with mood in some depressed people – just not in all of them.

    Certainly the serotonin hypothesis has been as much a marketing as a scientific phenomenon. It might not be all wrong, though.

  11. RS said,

    January 26, 2008 at 1:13 pm

    Not impressed by the Castrén paper (what a false dichomoty in the brain, networks versus chemicals!) – while he is right that the monoamine theory is woefully oversimplistic and not that well supported his objections (to do with lack of immediate effect on mood) seem to take a deliberately unsophisticated approach to the monoamine theory ignoring the sorts of explanations monoamine theory advocates would use to explain it (like receptor down regulation, raphe nucleus autoreceptors etc).

    As for his alternative explanation, this sort of ‘neural network’ ‘information processing’ theory is so fundamentally empty of explanatory power as to be useless. The grab bag of studies he cites are just a cherry picked selection that fits in with his narrative.

    Currently there is so much research out there in the field of psychiatric neurobiology and neuropathology that no one can truly claim to have any idea what is really going on. None of these theories is a satisfying account of what causes depression (and research in other psychiatric disorders is similarly affected), it is possible that some of the genetic research might reveal some causal pathways, but the current small effect sizes being thrown up suggest that they might not.

  12. PhilEdwards said,

    January 26, 2008 at 3:26 pm

    What about MDMA, then? I thought that worked by triggering a kind of serotonin binge.

  13. Fralen said,

    January 26, 2008 at 3:33 pm

    Some drugs which increase serotonin levels in the brain can improve mood.

    This doesn’t mean that depression is caused by low serotonin, as the journalists being rightly criticised in the article have claimed, and as most of the world’s population seem to believe.

  14. PlanetaryGear said,

    January 26, 2008 at 5:50 pm

    so… the problem is that we dont fully understand how these drugs work? Or that we’ve overestimated how well they work? Or that the public has accepted a drastically simplified or possibly just wrong mechanism by which they work?

    How is that different from anything else we do every day ;)

    They DO work for some folks, and dramatically so. I’ve seen it among my own small circle of friends a couple of people pulling their life back from the brink. Of course others have tried it with no effect at all. But for the folks that actually have whatever it is that is treated in whatever manner successfully by these SSRI’s it’s certainly better to have a mysteriously active drug than no drug at all.

  15. Anon_Acad_3000 said,

    January 26, 2008 at 6:59 pm

    The Leo & Lacasse paper on “Chemical Imbalance and the Media” is available full-text free at tinyurl.com/24exct – no login needed for this particular article.

    [Although it's hard to see why a magazine charging for its articles is 'ridiculous'...?]

  16. JLE said,

    January 26, 2008 at 7:14 pm

    There is a simple solution for depression: MDMA.

    The “studies” deeming it harmful are all fabricated and flawed.

    It works.

  17. trickcyclist said,

    January 26, 2008 at 11:13 pm

    JLE, I’m not sure a night out raving is the perfect depression cure you think it is!
    MDMA causes a large release of serotonin, which makes you feel great … for about 4 hours. However once it’s all gone it’s all gone, and you have to wait for the synapses to re-charge, hence the diminishing returns of repeat doses, and the ‘tuesday blues’ (or so I’ve been told!).

  18. muscleman said,

    January 26, 2008 at 11:34 pm

    It is just that the studies of the efficacy of CBT that I have seen have measured against SSRIs and been found to be about as effective as them. So if SSRIs don’t work for depression, though one certainly helped my wife, then neither does CBT.

    So does that mean that the best treatments for depression that we seem to have don’t work at all? I find that a bit hard to accept. I accept that one treatment fits all is unlikely and it will depend on the person. My wife tried two before one both worked and had tolerable side effects. I have tried to suggest CBT but the closest we have come is she bought a self help book based on CBT but it is apparently me who has to read it…

  19. muscleman said,

    January 26, 2008 at 11:48 pm

    Also nobody has mentioned the short serotonin receptor allele linked to life events triggered depression paper. That alone is prima facie evidence that the serotoninergic pathways are involved in mood. That the story is not simple does not mean serotonin is playing no role at all. That paper also suggests that genotype probably underlies how people will react to SSRIs which would in part explain relatively low response rates. The solution to this is not to ditch or diss SSRIs but to discover how to tell which people will benefit.

    The problem is the companies aren’t into funding such studies since they think it will shrink the prescribing base.

  20. Jamie Horder said,

    January 27, 2008 at 12:04 am

    Muscleman : You’re referring to Caspi 2003, which is indeed a classic paper; it hasn’t been consistently replicated, although it’s been supported often enough that I think only the hardest-nosed skeptic could believe that there’s nothing in it. Either it’s true or there’s some truly outrageous publication bias going on.

    Problem is, the polymorphism which (in vitro anyway) makes you have less of the serotonin transporter protein – in other words, the one which approximates the effect of SSRIs which block that protein – is the one which protects against depression. The gene effect appears to be the wrong way round – which is bad news for the simple “serotonin deficiency” hypothesis, although obviously interesting in its own right.

  21. mjs said,

    January 27, 2008 at 1:04 am

    a bit off-topic…

    i agree that public access to primary research is a great idea. for any who might not have heard, NIH and HHMI are both instituting policies this year requiring it for research funded by grants (partial or in full) from their agencies.

    the NIH news release
    the Hughes announcement

    pubmed central is the FREE database available to the public. the onus is on the researchers (authors) to get this done so that they can continue to receive grant money, unless a journal is already affiliated with PMC, in which case the article is automatically posted.

    i expect a lot of people will be scrambling to get all their papers posted over the next several months. this will also influence which journals are selected to publish in, for those who want to avoid going through the process of posting it themselves.

    so, there’s a start.

  22. Robert Carnegie said,

    January 27, 2008 at 2:50 am

    Which is cheaper, pills or CBT? Data point – I’ve come out of paralysing depression twice using prescribed drugs, lofepramine first, fluoxetine (Prozac) the second time – but though presumably they should act differently, I came down with headaches and digestive upset if I was short of sleep – I’ve mentioned this before – after about a year on the pills, each time, and for a while after stopping, second time around. That isn’t an officially listed side effect as far as I know.

    I asked one GP whether brain chemistry malfunction or life in general had been getting me down, and she said it makes no difference. But, speculatively, if you aren’t sorting your life out or escaping a temporary intolerable situation, such as recent bereavement (the “recent” part goes away), a pill won’t fix everything. Indeed I’m reminded of a claim – I don’t know if it’s true – that the Davy safety lamp for miners didn’t statistically improve safety at all, and that this is thought to be because it made miners more confident about going into dangerous situations, where consequently they got killed anyway. A pill can relieve distress but it doesn’t teach you mental self-defence techniques. On its own, maybe it can stimulate you just so that you dig an even deeper hole for yourself than before.

    Where are the homeopathists? Do they have a conference this weekend or something? St John’s Wart should have come up by now.

  23. ken said,

    January 27, 2008 at 6:21 am

    Phew, that has been a rambling discussion.

    It seems to me fairly clear that SSRI’s do reduce depression in very many cases. Probably the only more effective treatment is ECT which, for many reasons – good and bad – is not often used.
    CBT is as effective as SSRI’s for mild to moderate depression. Perhaps it has not shown equal effects with severe depression because CBT requires disciplined application by the patient, which is quite difficult for someone deeply depressed.
    It is also clear that some of the drug companies have not been entirely open and frank in reports of research they have supported as well as in their and marketing.
    To me, one thing being overlooked in all this debate is that suicide numbers have been declining steadily in most developed countries for about 10 years. Suicide rates are a pretty good indication of untreated mental illness, especially depression.
    It can reasonably be inferred that the reduction in suicides is partly due to better treatment of mental illness. The group in which suicide is not declining – young men – is the group less likely to seek treatment for mental illness.

    It seems to me that something is working in our treatment of mental illness. So, at least until we understand it all better (which we might, using brain scan research) we should continue to do what we are doing, including prescribing SSRI’s.

  24. RS said,

    January 27, 2008 at 12:53 pm

    “That alone is prima facie evidence that the serotoninergic pathways are involved in mood”

    You mean the paper where the effect of the allele alone wasn’t statistically significant but throwing in some other factors lead to a significant interaction? That is a lot more dubious than the papers which have found significant associations with other serotonergic genes (e.g. tryptophan hydroxylase 2) without dodgy statistical shenanigans.

    “Which is cheaper, pills or CBT?”

    A couple of studies have suggested that the cost is similar.

    “It can reasonably be inferred that the reduction in suicides is partly due to better treatment of mental illness.”

    Can it? I doubt that. It might be due to it but we don’t have any hard evidence either way.

  25. trickcyclist said,

    January 27, 2008 at 1:02 pm

    Hang on, aren’t we falling for the same thinking errors that we criticise the homeopaths for here? Faced with the evidence that antidepressants, whilst not ineffective, are much less good than we give them credit for once the unpublished data the drug companies would rather we didn’t have access to is taken into account, we seem to be relying on conviction, anecdata or ‘clinical wisdom’ that they are effective, the enemies of evidence-based medicine.

    I too am guilty of this, as I take solace in the thought that they must be effective for some people, and we need more honest research to identify predictors of treatment response, although I have no real reason beyond the same observational data people have described above for actually believing this, and good reasons to be cynical about whether the drug companies will ever carry out such research.

    As to ken’s comments above, much as we’d love to, I don’t honestly believe mental health services can take much of the credit for declining suicide rates. Looking at the national confidential enquiry into suicide, only 27% were in current or recent mental health patients. My hunch is that declining suicide rates are more to do with a period of relative prosperity, demographic changes, low unemployment, and measures to reduce access to lethal means.

  26. woodchopper said,

    January 27, 2008 at 4:55 pm

    @trickcyclist – I agree absolutely. We shouldn’t use the “I know it works, lets find the data” argument.

    Its also possible that as there are many causes of depression, SSRIs etc could be beneficial for some people, while on others they are just a placebo.

    Reduced access to lethal means is important. In addition to your list, there are also big reporting biases concerning suicide. Coroners may well return accidental death or open verdicts even when they suspect that it may be a suicide.

    IMHO, such reporting biases cover a lot (but not all) of the international differences in suicide rates.

  27. ken said,

    January 27, 2008 at 6:27 pm

    “Looking at the national confidential enquiry into suicide, only 27% were in current or recent mental health patients.”
    Yes, but this in not inconsistent with the statement that suicide is an indicator of untreated mental illness. The figure often quoted (I have checked the source, but don’t have it to hand) is that 85% of those committing suicide have suffered mental illness.

    “My hunch is that declining suicide rates are more to do with a period of relative prosperity, demographic changes, low unemployment, and measures to reduce access to lethal means.”

    Hunch? Hmmm. In many countries the trend has continued through more than one economic cycle. I believe that reduced access to guns has been a factor in Australia but even before tighter gun control, shooting was not a major means of suicide. Men prefer hanging, women poison from drug overdose.

    It is generally believed that coroners (and police, as there is often not an inquest in clear cases) are more likely to record suicide these days. I agree that reporting bias can explain some of the international differences.

    I guess this is another of those “how convinced do we need to be?” questions. Better treatment of mental illness seems to be working. Doctors and psychiatrists give many anecdotal references to this. There is more under treatment of depression than over diagnosis – though there is certainly some of the latter.

    I use SSRI’s because I believe that they have helped manage my depression and because in my family there is a strong history of depression, with a suicide or two a generation for 80 years.
    I don’t care (in making my decision) that drug companies have exaggerated the research and that we don’t know quite why and how SSRI’s work.
    And, no, I would not come to the same conclusion about an alternative remedy if I was being treated by a homeopath or somesuch. I do not trust them, I do trust experienced psychiatrists.

  28. apricot said,

    January 27, 2008 at 8:26 pm

    Oh dear, you all sound very confused about SSRIs and whether they work or not.

    Someone asked ‘where are the homeopathists’ [although I prefer the term 'homeopath'] and ‘St Johns Wart’ [I think you mean 'St Johns Wort' which is a herbal remedy]

    Here are some remedies for depression depending on the symptoms and circumstances of the sufferer:

    Sepia- depression due to hormonal changes – PMS, after childbirth, also due to feeling burdened by family duties, becomes indifferent and irritable.

    Pulsatilla – also hormonal related depression, sufferer feels unsupported, weeps copiously.

    Natrum muriaticum – depression due to relationship breakdown or lack of mothering. Cries alone.

    Aurum – depression due to feelings of responsibility and not being able to live up to expectations. Silent depression, family unaware.

    Natrum sulphuricum and/or Arnica – remedies for depression after head injury.

    Don’t start on the vitriol, I won’t be debating any of it, just thought you might find the information useful.

  29. trickcyclist said,

    January 27, 2008 at 9:05 pm

    apricot could you provide us with some evidence from randomised controlled trials for the above?

  30. ultracrepidarian said,

    January 27, 2008 at 10:37 pm

    I’m not at all surprised to see some cold water thrown on the 5HT theory of depression. As a pharmacologist, it always seemed too simplistic; and having personally taken paroxetine for a few months, I know it’s not a wonder cure. Sure, n=1 is only anecdote, but paroxetine seemed to me to be more of an anxiolytic than an antidepressive. Having additionally experienced its side effects (including anorgasmia and short-term memory loss) and its distressing withdrawal symptoms (even on graduated withdrawal), I’m frankly surprised it’s still prescribed.

    I think there’s a great deal of interesting info yet to come out about such SSRIs; if it turns out that relevant info existed yet was suppressed, I anticipate some intriguing court cases.

  31. Robert Carnegie said,

    January 28, 2008 at 2:21 am

    Re 25, I don’t think any of us should for more than a moment consider going away thinking that Ben has proved that depression drugs don’t work. Even “much less good” seems substantial overstatement. If I follow, the voluntarily unpublished material isn’t publication peer-reviewed, a process which includes detecting and fixing errors in the work – did I get that right? And there is only one population to test on – loosely speaking; the drugs work or they don’t work, but a theory in either camp has to account for the existence of all of the experimental results, for as well as against drugs – including by recognising error. The fault that Ben is drawing attention to is the burying of unwelcome results.

    Re 26, car ownership has gone up and up, and a car is quite an efficient carbon monoxide generator and a popular suicide method, proverbially. Or you can just steer it into a wall. We also have more high-rise buildings with windows to jump from, although the very latest may not, for safety. Overall, if the suicide rate is less, it isn’t for want of the means available to determined people.

  32. ken said,

    January 28, 2008 at 3:20 am

    Let’s see what we can agree on and maybe clear out some of the undergrowth on this subject.
    1. In medicine there are no “wonder cures”, “silver bullets”, “magic solutions” or, pace some journalists, “universal panaceas”.
    Perhaps the closest is some antibiotics with some infections. Everything else may help with some patients some of the time for some complaints.
    2. Everything stated in one sentence (and most things set out in a 100,000 word PhD thesis) can be described as an “oversimplification”. To use that term is not adding much to understanding of a matter.
    3. “Depression is caused by a chemical imbalance” is not an accurate statement. It has been useful, in layman’s language, to make the point that depression can be helped by medication. Remember that until the development of medication for mental illnesses (antipsychotics and antidepressants in particular) the only thing we could offer the mentally ill that helped at all was ECT. No psychoanalysis or psychotherapy was any help at all. If some of the claims made by drug companies are misleading, the claims made by some psychoanalysts were downright fraudulent. CBT and its variants, which do help, are very modern inventions.
    Until medications for mental illnesses came along postwar, the mentally ill were locked up, laughed at or shunned.
    An aunt of mine was institutionalised most of her adult life with what we now know was depression involving psychosis. In the early 1960s I visited her and talked to a doctor who said that they were beginning to believe that mental illness was caused by a chemical imbalance and that one day there will be drugs for it. I went away thinking “Wow! So there is hope!”
    But the expression can probably be retired now.
    4.The drug companies are what an American friend of mine would call “A whole nother problem.”
    The problem has to do with patent law – the short time they have to earn a return from investments on new drugs – the cost of bringing a new drug to market and the fact that they are really in the gambling business. Big gambles, many losers, big prizes for the winners. It’s not a good way to manage any area of medicine though I can’t think of a better way. Meanwhile, as I am not a gambler, I won’t be buying shares in drug companies.

  33. pottedstu said,

    January 28, 2008 at 11:57 am

    Slightly off-topic but in response to Robert Carnegie:

    It’s much more difficult to commit suicide with the exhaust from a modern petrol car because the catalytic converter removes carbon monoxide. Evidence? www.chestjournal.org/cgi/content/full/115/2/580

    You might also consider greater safety features in cars (resulting in lowered road death figures despite increased car ownership – www.statistics.gov.uk/cci/nugget.asp?id=1208 ). Plus the replacement of highly toxic town/coal gas by natural gas (methane). You could also hypothesise reduced gun ownership, the introduction of anti-suicide measures on many public buildings, restrictions on poisons such as arsenic, and the growth of non-medical counselling services like Samaritans and Childline.

  34. Grathuln said,

    January 28, 2008 at 1:31 pm

    I bet the scientologists will be having a field day with this news. Its all about the body thetans you know; alien spirits that are attached to your body. Tom Cruise says scientologists are the experts in helping people so it must be true. Scientologists don’t like physchiatrists either.

  35. Grathuln said,

    January 28, 2008 at 1:32 pm

    I’ll get my coat…

  36. woodchopper said,

    January 28, 2008 at 8:42 pm

    pottedstu – you should also mention selling paracetamol in smaller packets.

    “Legislation restricting pack sizes of paracetamol and salicylates in the United Kingdom has had substantial beneficial effects on mortality and morbidity associated with self poisoning using these drugs.”

    From here: www.bmj.com/cgi/content/abstract/322/7296/1203

  37. guvno0or said,

    January 29, 2008 at 1:04 pm

    Good luck getting your coat, xanthrux the destroyer of worlds or whatever the hell he is called has probably eaten it (your coat)

  38. maia said,

    January 29, 2008 at 4:29 pm

    Tom Cruise just wants an excuse for not giving up his lovely lovely euphoric hypomania. At least that’s a reason for being a scientologist that makes sense, if you know what that feels like.

    SSRIs: I think the problem is that depression is a symptom, with several different underlying conditions (and probably several different “causes”/contributing factors for each of those). It’s not like an infection, where the same drug may well be the best treatment for all patients. I’ve seen very positive results in other people (and overall, the studies do seem to suggest they work – just not perfectly, and not necessarily the way we used to think). Personally, I’ve tried SSRIs (and other ADs), with very little success: either no effect at all, or (Paxil) a moderate effect that only lasted a couple of months. The side effects (nausea, anorgasmia, mild anomic aphasia, yawning all the time etc.) didn’t really bother me – if the pills had worked I would still be taking them. CBT was no alternative; I didn’t have the right kind of symptoms. The correct treatment (very effective, with no side effects worth mentioning) for me turned out to be an anticonvulsant – something that, for most depressed people, would probably have little or no effect but might have quite significant side effects.

    Another problem is that the companies want to sell as much as possible, and “These pills will help some people, but not all, to varying degrees, but won’t solve all their problems. PS. Some people may be unable to take the pills because of nasty side effects. Oh, and we’re not sure why this stuff works anyway.” – is not the best sales pitch, I’m afraid.

  39. ken said,

    January 29, 2008 at 5:51 pm

    To pottedsu, woodchopper and those giving reasons why the suicide rate is falling – why , on this subject, are people reluctant to give credit to the medical profession?
    All these action you have mentioned – including support services, gun control and so on – have probably helped and are worthwhile. But we know that a large percentage of those killing or attempting to kill themselves are mentally ill in some way. And we believe that we have now ( and for the first time in history) have better ways – medication and CBT in particular – of treating such illness.
    All that I and some others are arguing is that we should do more of what we are doing, including encouraging those who suffer depression to seek medical help. If this happens to make the shareholders of drug companies a bit richer, I am not too upset.
    There is much comment about the “medicalisation of melancholy” but it is strange that so many people – not just scientologists – seem to want the demedicalisation of mental illness.

  40. RS said,

    January 29, 2008 at 7:37 pm

    “But we know that a large percentage of those killing or attempting to kill themselves are mentally ill in some way.”

    Maybe the massive decrease in lethality (in overdose) of SSRIs over tricyclics helps. They’re certainly no more effective.

  41. LazyLabTech said,

    January 29, 2008 at 8:26 pm

    Just a wee anecdote regarding suicide and statistics: In the sixties there was a marked fall in the suicide rate amongst housewives. This was put down to the success of the women’s lib movement. Women had more opportunities than ever, were taking important steps towards equality and were happier and less suicidal, it was concluded.
    Actually the sixties also brought the introduction of North Sea gas to British households, which is much less toxic than the coal gas used up till then. So it was that the Sylvia Plath suicidal housewife’s method of choice was removed.
    Not sure how Chinese Whispered this story is (I heard it from a mate in the pub I think) but it certainly serves to make a point.
    This blog www.samizdata.net/blog/archives/007602.html quotes a version from TV’s own Raj Persaud.

  42. ken said,

    January 30, 2008 at 4:51 am

    RS said:
    Maybe the massive decrease in lethality (in overdose) of SSRIs over tricyclics helps. They’re certainly no more effective.

    Perhaps, though overdose on tricyclics was never a major method of suicide. Barbiturates, yes,and these are less easily available.

    All modern antidepressants seem to be about equally effective over the population, though not necessarily for an individual.
    The main improvements in each class have been in reduction of risks and side-effects.

  43. RS said,

    January 30, 2008 at 1:31 pm

    “This blog www.samizdata.net/blog/archives/007602.html quotes a version from TV’s own Raj Persaud.”

    I wonder where he plagiarised that from.

  44. RS said,

    January 30, 2008 at 1:47 pm

    “Perhaps, though overdose on tricyclics was never a major method of suicide. Barbiturates, yes,and these are less easily available.”

    Overdose with tricylcics is a major method of suicide even now (e.g. here).

  45. Wonko said,

    January 30, 2008 at 2:05 pm

    The serotonin myth was a product of its time – people with depression were not being taken seriously, and wanted to show that their illness was “real” (ie biochemical); politicians wanted a (relatively) cheap quick-fix for growing rates of mental distress; Big Pharma wanted to promote the new SSRI drugs as the answer to life the universe and everything.

    It is most likely myth rather than lie – something is going on with serotonin in depression, but it is more likely a symptom than a cause.

    Interestingly, a new cognition myth has grown up in opposition to the serotonin myth. But the new negative thinking = depression myth is no more valid. Again, what is being touted as a cause is most likely an effect. But hey, that isn’t going to stop a government that is looking for a quick-fix from ploughing £millions into CBT rather than improving general mental health.

  46. SleepyHead said,

    January 30, 2008 at 4:02 pm

    I’ve had bouts of depression all the way through my adult life. Fortunately for me they’re not terribly serious and mainly amount to be very crabby for a few days every now and then. However at one point when I first started getting depressed I had a great many suicidal thoughts and worried my parents sufficiently for them to convince me to see a doctor.

    The doctor initially suggested pills, but when I pointed out that this was unlikely to make my debts disappear, provide me with instant friendships, or make me feel any less alienated he relented and sent me for therapy.

    Unfortunately that didn’t work too well either as both my parents were counsellors and frankly I was sick to the back teeth of talking about my problems in the hope that just talking about them would make them go away. In the end I stopped going out of pure irritation: I reasoned that if I spent most of my therapy time visualising how I was going to punch the counsellor in the face because their simplistic causal analyses were annoying me to the point of distraction it was probably doing me more harm than good.

    So off I went and just ‘got on’ with depression and although I can’t prove it I reckon I’m at least as well off without drugs and therapy than I would have been with it. I still get the occassional bout but – after 20 or so years of having this stupid condition – I’ve come to conclusion that depression – like asthma – is something you’re likely to be saddled with for life: There isn’t a cure but this is not necessarily a problem as long as you can keep things in check.

  47. ken said,

    January 30, 2008 at 7:07 pm

    RS said:
    Overdose with tricylcics is a major method of suicide even now (e.g. here).

    I’m not sure that the source supports Tricyclics as a major method – as distinct from a significant one – and my quick mental arithmetic suggests that reduction in prescribing of T’s would not account for much of the downwards trend in suicides.
    Still, I’ll concede that it is a factor and that anything to reduce access to means is good.
    Unfortunately, we can’t ban the sale of rope, though.

  48. quietstorm said,

    January 30, 2008 at 8:57 pm

    Sorry, I’m new to the thread, so I’m going back to the beginning article, but it’s important to remember that the point being made here is not “SSRIs don’t work at all” but more that

    a) All trials of all drugs, once registered, should be adequately reported, regardless of outcome

    and, our old favourite,

    b) journalists need to be a lot more rigorous.

    We came across this before, months ago, where professional journalistic bodies talk about how their mission is to entertain, not to inform, and that journalism does not necessarily have anything to do with uncovering the truth.

    At least 37 trials had positive results. The drugs clearly do something, for some people. However, some trials had positive results, some had negative. Similarly, some posters above have mentioned that these drugs worked for them, but they didn’t work for other contributors. We have all this inconclusive evidence – so why stop now? How can we work out what the differences are if the negative/inconclusive results remain unpublished?

    It’s nice to think that once science or medicine has “an answer” then we don’t need to do anything about that problem any more. It’s unsatisfactory to those of us who like certainty, but progress must be allowed to continue. Treatments can always be improved – I would have thought it would have been in a drug company’s best interests to continue the research, make new and improved drugs which are demonstrably better than the ones which everyone now knows about and which other drug copmanies can make for themselves in a few years……

    More short-term thinking going on, I fear.

  49. Diotima said,

    February 5, 2008 at 3:45 pm

    What does Ben think of Lewis Wolpert’s ‘Malignant Sadness’ which makes a strong case for the objective effectiveness of SSRIs? Wolpert is a UCL Professor of Biology in relation to Medicine, so is unlikely to be a scientific illiterate.

  50. banshee said,

    February 10, 2008 at 10:51 pm

    The “Seven” part of the Sunday Telegraph today had a review of a book on depression by a psychoanalyst. The reviewer makes a number of the same ol, same ol assertions around SSRI, 5HT and suicidality and finishes up by saying “If you’re depressed, then, only take pills as a last resort. Get a therapist.”

    Shame about this recent research on suicidality and depression in young adults then (don’t think it’s been reported here):

    In 2003 FDA and European regulators warned that antidepressants in younger people might increase suicide thoughts and attempts. The results were a 22% reduction in SSRI use in under 20s in The Netherlands and a 30% reduction in SSRI use in under 20s in USA

    Unfortunately the suicide rate in creased in both nations – a 49% increase in under 20s in the Netherlands (from 0.86 to 1.28 per 100,000 population) and a 14% increase in under 20s in USA
    (from 2.83 to 3.23 per 100,000 population)

    This was reported as the largest annual increase in US suicide rates since the year dot (I paraphrase) and that the trends are similar in two different countries – an abrupt reversal of 20-year trend.
    (Am J Psychiatry 2007;164:1356-63)

    (Thanks to Steve Bazire for this ref)

  51. inspiros said,

    February 18, 2008 at 4:02 pm

    Add the latest publication bias to the 2002/2003 studies by Kirsch and Moncreif showing that placebo effect had been understated in the public studies.

    In 1998 Kirsch et al found placebo was 75% as effect as SSRI. In 2002 a further analysis found it to be 82% effective as SSRI.

    Add this to the concerns about most studies not including active placebos (Moncrief at el 2001) – and those that do showing NO difference between SSRI and active placebo. (www.cochrane.org/reviews/en/ab003012.html)

    Here is a somewhat dated (2003) and fairly conservative summary of the studies and media coverage (with a notable mention of the Guardian… possibly pre-Ben G?)
    www.srmhp.org/0201/media-watch.html

    Comments on comments:
    WONKO: you don’t explain the improvements people experience. I’m assuming you are saying that SSRI and CBT both are effective due to placebo. People do experience real improvement. That isn’t under question here.

    guvno0or: “Do they work or is it just placebo?” They work – there is no doubt about that. However it is likely that your belief and expectation that they are going to work may be the “active ingrediant”.
    Does knowing that weaken the “active ingredient”?
    In SSRI/drug treatment possibly. In the case of CBT acquiring a meta-belief about the effectiveness of CBT – should be part of CBT treatment anyway.
    If you undergo CBT and persist in the belief that CBT doesn’t work then I would predict lower outcomes.

    The real question here is whether a complex mix of poor trial design, media hype, desperate GPs and patients, and unpublished studies have allowed GPs to prescribe substances where there is a very high expectation of positive outcome (with matching side effects) in an area where self-fulfilling prophecies hold sway (our psyche). It has worked and helped millions. But perhaps we can do better.

  52. banshee said,

    February 21, 2008 at 7:47 pm

    And the latest studies from the UK cast doubt on any relationship between SSRI use and suicide rates – at least in the UK. (See my previous entry)

    www.ukmicentral.nhs.uk/
    headline/database/story.asp?NewsID=6834

    Joanna Moncrieff has published some good material and we certainly need questioning professionals but her work attracts a lot of valid critiscism.

    The Cochrane report quoted by inspiros was on TCA’s vs placebo – although I wouldn’t discount the validity entirely it wasn’t on SSRI’s – and the data they looked at looks very incomplete – 1966-2000 but only including 9 studies with 751 participants? Very curious.

    I’m very impressed with the SMHP page – thanks inspiros! – very well balanced and making the point borne out in many trials that the more severely ill you are with depression the more difference the medicines make.

    Consent to trials in mental health tends to lead to milder illness being trialled more commonly – somebody with really serious psychomotor retardation can’t consent to anything!

    CBT and other talking therapies are not tested to anywhere near the same degree as medication.

  53. Robert Carnegie said,

    February 26, 2008 at 10:52 pm

    Y’know, you’d expect an important issue like this to get more news coverage.

    Or, to put it another way, Boom!

    I -thought- I’d just -been- reading about this at BadScience… deja vu.

  54. chewywater said,

    May 24, 2008 at 7:33 pm

    I once took part in a study to see if zoloft would cure night hunger (I can’t remember exactly but I’m pretty sure it was funded by pfizer). When my data showed that zoloft did not have any effect, they sent me more forms to fill out and I was asked to continue taking the medication. If I said no I would be counted as someone who dropped out of the study. In this way they could string people along and wind up with the data they really wanted. I finally took an online poll of most of those involved in the study and found that the actual number of people who claimed zoloft helped with night eating was no better than placebo. Here is the study:
    www.ncbi.nlm.nih.gov/pubmed/16648332

    I now have very little faith in corporate funded science, unless the studies are replicated by people with opposing interests.

  55. NeilHoskins said,

    September 18, 2008 at 10:19 am

    Is there such a thing as an anti-placebo? No, really. Has anybody ever run a trial in which a drug with known, measurable, beneficial properties, is given to patients who are told, “This one’s not very effective and won’t do you much good”?

    All I know is that I’ve been leading a normal life for ten years on fluoxetine, and since you bastards started publicly slagging off SSRIs I’ve been feeling like shit. Causation or coincidence?

    Another, separate question: if placebos are so effective, why do you – apparently – want them removed from the GP’s toolbox?

  56. Paul Murray said,

    July 13, 2009 at 4:54 am

    “The serotonin hypothesis will always be a winner in popular culture … because it … plays into our notions of a crudely dualistic world where there can only be weak people, or uncontrollable, external, molecular pressures.”

    Or demons. It wasn’t me – the devil made me do it. It was witches. It was caused by the moon being in Mars.

    Part of the problem is that “self” is a bit of an illusion. We have these competing drives, and people want to know, which is “me” and which is other. The answer is that they are all “me” – me is precisely the interplay of these parts. My hormones, my self. No excuses.

  57. Astonmartin said,

    January 2, 2011 at 4:14 pm

    Anti-depressants has helped alot of people to help them function in everyday life I agree, but im just woundering if I offered any scientist £5000 to give me concrete physical proof to say that depression is down to the chemical imbalance whats the chance of me keeping my money?

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