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31 Responses

1. jackpt said,

   March 1, 2008 at 3:07 am

   The placebo effect leaves me with a git-load of questions that I’m not going to attempt to answer or have too much of an opinion about. The cultural aspects of it are mind-boggling. The “An Exploration of Neurotic Patients’ Responses to Placebo When Its Inert Content Is Disclosed’” trial, where the placebo was presented as a placebo – the script was like advertising. I wonder if “the best pink placebo pill with a fizzing action” would edge out plain pink placebo pills. Until the patented Micro Targeted Pink Placebos came to market, promising they “target affected illnesses fast with best ever cultural significance”. Although, I’d take the own-brand supermarket placebos because I know they do the same thing :).

2. lawrabbit said,

   March 1, 2008 at 9:24 am

   That wouldn’t be a certain library in Euston, would it? Libraries should have Scan + Email, failing which cameras are fair game. Luckily, archives are deserted enough to not bother thinking up an excuse for holding your phone over each page of text…

3. eveningperson said,

   March 1, 2008 at 9:52 am

   For a lot of us, photocopying charges are still cheaper than getting there…

4. drunkenoaf said,

   March 1, 2008 at 10:12 am

   Academics should register multiple ATHENS accounts and post Thais spare ones on bugmenot.com… although I can see a few librarians doing their nut over that! 😉

5. grolsh said,

   March 1, 2008 at 10:45 am

   question:
   -Given that placebo works for any pill for a given condition
   -So even a pill with a working known ‘mechanical’ effect also benefits from placebo..
   -do the two effects
   (a)bolster each other or are they
   (b)’mutually redundant’

   ?

6. kim said,

   March 1, 2008 at 11:58 am

   Has anyone considered the possibility, at least in the case of the SSRIs, that it wasn’t the placebo effect that was working, but the fact that the patients would have recovered anyway? Was there a control group of patients not taking any pills at all?

7. wol said,

   March 1, 2008 at 1:11 pm

   ” Sugar pills are the future, if only there was a way to give them with integrity, and a straight face”

   How about Fair Deal Homeopathy ?
   www.fdhom.co.uk/

8. spk76 said,

   March 1, 2008 at 1:39 pm

   There seems to be a lot of confusion about the placebo effect. IMHO it’s important to understand that it’s not a real ‘effect’ at all but a misattribution of some non-specific perceptions of effect when there is in fact none.

   That is to say, the ‘placebo effect’ is equivalent to no effect at all – it isn’t some sort of magic or yet to be elucidated psychosomatic action, and it doesn’t mean that it at least has some minimal benefit and is therefore worthwhile to some people; what it actually means is that there is no measurable benefit whatsoever above giving nothing.

   The perception of an affect can be variously explained by:

   1. regression to the mean (many conditions, especially long-term chronic relapsing/remitting ones (those favoured by homeopathic and most other alternative therapists) wax and wane between periods of complete or partial remission and outbreaks of severe exacerbation, whilst mostly treading an average baseline. People go to real doctors during acute exacerbations and may turn to CAMsters in desperation after conventional therapies have failed or been thought to fail, by which time their condition has settled down again to the mean level or even gone into remission, often with the additional help of the real medicine they were taking before)

   2. fluctuation of symptoms

   3. the effect of conventional treatments taken at the same time

   4. experimental design flaws and errors

   5. observer, recall and selection bias (e.g. people retrospectively mistakenly ascribe their improved condition to their homeopathic treatment, whilst conveniently neglecting other factors contributing to the ‘cure’ and ignoring the occasions when the homeopathy failed, i.e. confusing correlation with causation)

   6. the natural history of the conditions being treated

   7. habituation (many conditions, such as hay fever, eczema and asthma, eventually remit (children are often said to ‘grow out’ of them) – what is really happening is a decrease in response to the stimuli due to repetition, i.e. the body slowly resets its thermostat, so to speak. This is why people may complain of having hay fever for years, having tried all the treatments, and then one day they no longer have it.)

   8. small sample sizes of statistical invalidity

   9. uncritical reporting of unreliable anecdotes

   10. delusion, denial, deceit and fraud

   So when the control group in a double blind RCT are given a placebo, they are being given a blank, i.e. a pill with no active ingredients (just like homeopathy).

   The effects that some people perceive from taking the fake pill are in fact just background noise, and this is why genuine medical interventions need to be proven to have an effect over and above placebo, i.e. placebo = no effect.

   If a placebo had an effect, it wouldn’t be a placebo…

   And it bears emphasising that the original quantitative claim that placebo is real (Beecher, H. K. 1955. The powerful placebo. Journal of the American Medical Association, 159:1602-1606) was subsequently thoroughly dismissed (Kienle GS, Kiene H. 1997. The powerful placebo effect: fact or fiction? J Clin Epidemiol. 50:1311-8).

   Additionally, Hrobjartsson and Gotzsche published a study in 2001 and a follow-up study in 2004, again questioning the nature of the placebo effect. (N Engl J Med. 2001 May 24;344(21):1594-602). They performed two meta-analyses involving 156 clinical trials in which an experimental drug or treatment protocol was compared to a placebo group and an untreated group, and specifically asked whether the placebo group improved compared to the untreated group. They found that in studies with a binary outcome, meaning patients were classified as improved or not improved, the placebo group had no statistically significant improvement over the no-treatment group.

   Similarly, there was no significant placebo effect in studies in which objective outcomes (such as blood pressure) were measured by an independent observer. The placebo effect could only be documented in studies in which the outcomes (improvement or failure to improve) were reported by the subjects themselves. The authors concluded that the placebo effect does not have ‘powerful clinical effects’ (objective effects) and that patient-reported improvements (subjective effects) in pain were small and could not be clearly distinguished from bias.

   These results suggest that the placebo effect is largely subjective. This would help explain why the placebo effect is easiest to demonstrate in conditions where subjective factors are very prominent or significant parts of the problem. Some of these conditions are headache, stomach ache, asthma, allergy, tension, depression, and the experience of pain, which is often a significant part of many mild and serious illnesses.

9. Jamie Horder said,

   March 1, 2008 at 1:47 pm

   Kim : Good point. All of the studies in question used placebo pill vs. antidepressant pills. Everyone got some kind of pill.

   It’s hard to study what happens to depressed people with no treatment at all because as soon as they’re diagnosed they generally want to be treated. However it’s generally believed that most depressive episodes will remit of their own accord after a few months, usually less than 1 year, although some can go on for much longer.

   On the other hand, it’s also known that relapse rates are very high – many people who suffer from one episode of depression will suffer more. In that respect, it might be that a good measure of antidepressant usefulness is not whether they can end a depressive episode a few weeks faster, but whether they can prevent them from reoccurring.

   A meta-analysis (Geddes et. al. 2003 Lancet) concluded that antidepressants do prevent relapse : “The average rate of relapse on placebo was 41% compared with 18% on active treatment [in people who had responded to antidepressants initially]…The treatment effect seemed to persist for up to 36 months, although most trials were of 12 months’ duration”.

   So antidepressants seem to have a powerful protective effect if they are taken for long periods of time. Whether the effect size would be diminished if unpublished data were included is another question…

10. muscleman said,

    March 1, 2008 at 2:55 pm

    I had forgotten that bit Steve. For the record, I have never knowingly* received funding or support from the pharmaceutical industry in my work or in a personal capacity. i am not currently employed.

    *there was one short term contract where I never did find out the source of the funds I was employed with. The Dept did have a large amount of regular money from a consortium of pharma/biotech companies to give them first access to results and these moneys could well have been used to fund my salary. I simply do not know. The work involved no pharmaceutical studies and was purely analysing phenotype in genetically manipulated mouse embryos.

    Here endeth my statement of involvements/interests.

11. inspiros said,

    March 1, 2008 at 3:02 pm

    Ben – thank you for the link to The Onion article… that was a hoot! Hope you don’t mind me posting an excerpt from everyone’s delight

    “Yes, placebo has benefits, but studies link it to a hundred different side effects, from lower-back pain to erectile dysfunction to nausea,” drug researcher Patrick Wheeler said. “Placebo wreaked havoc all over the body, with no rhyme or reason. Basically, whichever side effects were included on the questionnaire, we found in research subjects.”

    GlaxoSmithKline expects to have two versions of placebo on the shelves in late December. One, a 40-milligram pill called Appeasor, will be marketed to patients 55 and over, while the other, Inertra, designed for middle-aged women, is a liquid that comes in a 355-milliliter can, and is cola-flavored. Eli Lilly plans a $3 million marketing campaign for its 400-milligram tablet, Pacifex.

    “All placebos are not the same,” Eli Lilly spokesman Giles French said. “Pacifex is the only placebo that’s green and shaped like a triangle. Pacifex: A doctor gave it to you.”
    www.theonion.com/content/node/39082

    A couple of points:
    first is that we fail to describe and remember that the body/mind is a remarkable self-maintaining and self-healing system. We need to keep this in the forefront of our minds at all times – despite the fact that clinicians will generally only see that small fraction where the self-maintenance and self-healing has broken down in some way.

    It seems a small step to make to accept that triggering an expectancy of improvement will allow this self-healing system to bring about an improved state of health. (Particularly if the symptoms are psychological/subjective nature)

    It is only when the mental model that we hold of the body is reductionist – and clinicians see themselves as engineers fixing cars – that placebo (improvement & healing through increased expectancy of positive outcome) seems strange or weird.

    Secondly, there is a real difference between symptom reduction – which we know can be achieved through suggestion (aka hypnosis) as perception can be altered through suggestion (see the studies on pain, color perception etc.)
    compared with actual healing where there was an organic cause.

    For patients with disorders where there is no clear organic cause – and it is really defined by subjective reporting of symptoms (no-one gets any of these right?) – then change in perception of symptoms would be entirely consistent with people getting better – and we know this can be achieved across many modalities through suggestion (which is simply increasing expectancy).

    Again I’d refer you to the work on expectancy and placebo by Irving Kirsch – the lead researcher on the recent anti-depressant study.

12. Idlethought said,

    March 1, 2008 at 5:26 pm

    Here is a possibly painful thought.

    The vast marketing budgets of the Pharma companies should be boosting the apparent effectiveness of their drugs significantly.

    Since the marketing rules are geographically limited, then the placebo effect should be measurably different in different places.

    If this is true I would expect trials in the UK to demonstrate consistently less effect than trials in the US (where every third advert is about how some pill is going to solve all your problems)

    This ‘advertising placebo’ difference should show on both placebo and real-drug numbers.

    Has anyone ever looked at this?

    –

    (On the plus side, if we tell everyone how wonderful the NHS is, they’ll get sick less)

13. pv said,

    March 1, 2008 at 5:39 pm

    It’s just a shame that if you start pointing out the flaws in the PLoS study, you give the impression that you’re a PR man for Big Pharma.

    Only to dyed in the wool sCAMpers.
    Anyone hear Phil Hammond’s comments on the News Quiz (R4, 29th Feb)?
    www.bbc.co.uk/radio4/comedy/newsquiz.shtml

14. le canard noir said,

    March 1, 2008 at 6:56 pm

    Share tipping, Ben? Homeopathic companies? I hope you have made a full disclosure and don’t have any interests in such businesses.

15. HypnoSynthesis said,

    March 1, 2008 at 9:09 pm

    Addendum:

    Here’s a passage from Braid’s later work about placebo and suggestion,

    “One draws several important conclusions from the consideration of the phenomena which take place in consequence of the power of primary impressions, lively faith, and attention concentrated on dominant ideas, causes which contribute to modifying physical action […] It is possible for us today not only to understand the cause and treatment of many diseases on which no specific external influence, nor internal drugs have any effect, but also to explain a great number of phenomena which were attributed to demonology and magic, ghosts and enchantments, for the power of witches who abused and killed their gullible victims by means of hexes and their harmful influence, so readily accepted.

    “Nowadays [by reference to hypnotic suggestion] we grasp the power of the methods of enchantment, magic formulas and amulets, […] the bread crumb [placebo] pills and the infinitesimal [homoeopathic] amounts of powerful drugs which can [i.e., without suggestion] affect a living being neither for good nor ill.”

    Don Robertson

16. muscleman said,

    March 1, 2008 at 11:53 pm

    Hypnosynthesis, the heroin addicts were not so deluded as you make out. The body has no real way of knowing what is injected, what the body knows and reacts to is the act of injection. So when injected intravenously a high is indeed produced, possibly by release of endogenous opiods or simply by stimulus caused activation of the relevant neural pathways, like Pavlov’s dogs in fact.

    ‘knowing’ it is only saline does nothing to stop that pathway.

17. diogenes said,

    March 2, 2008 at 12:09 am

    @spk76:

    You seem to know what you are talking about, and i am in no position to claim superior knowledge. But what you have said seems to flatly contradict what Moerman says on the subject, which of course is intended to be warrented by extensive empirical research. Is your disagrement based on a different reading of the same or similar evidence, or based on different research? Or perhaps easier to answer, is it the case that a serious debate exists within the relevent circles as to the existence of the placebo affect (understood as meaning a ‘meaning response’), or are either one of you somewhat maverick?

    (BTW, I bought the Moerman book on Ben’s advice a while back; I read it in an evening and thought about it for many more. I recommend it throughly, even to scientifically semi-literates like myself. Thanks for the tip Ben)

18. Robert Carnegie said,

    March 2, 2008 at 12:28 am

    The placebo effect is not the effect of nothing. There is no “nothing” in a clinical encounter. In a simple and non-comprehensive model, the patient turns up with a perceived problem. The doctor initiates or continues a “treatment”, which could be a placebo. Or the doctor refuses to specify a treatment. Either way it matters. Null would be achieved only by the doctor walking out without explanation and not coming back, or being abducted by aliens or the Mafia, or referring the patient to a specialist. It would be easiest to measure the placebo effect of the last… But any expressed decision by the doctor in the consulting-room will influence the patient psychologically as well as by the simpler physical effect.

    A capable doctor should not let their own confidence in a drug influence the patient. Bluff them!

    As for improved placebo performance in different tests over time, how can different trials be compared? But it could represent an increasing public understanding of depression and public confidence in pills for it.

19. don_pedro said,

    March 2, 2008 at 1:26 am

    Do placebo effects matter? It seems to me in some cases they clearly don’t. Someone can be seriously ill, with objectively measureable deterioration, and yet swear that taking essence of magic moonbeams make them feel better. Or sugar pills, or whatever. This doesn’t mean the person *is* getting better, and persisting with the placebo, to the detriment of effective treatment, seems completely wrong.

    OTOH, some conditions, such as depression, are wholly or mostly about how the patient feels, subjectively. There don’t seem to be any objective measurements that could matter more than a person’s own report on the internal feelings.

    In these cases, whatever (legal) means makes someone feel better seems fine. There’s no chance of missing out on some other objectively effective treatment. You, the sufferer, are the arbiter of effectiveness.

    Someone with a better handle on study design and interpretation might speculate better than I can, about how you might unpack the ‘placebo’ effect into the ‘someone paying me attention’ effect’ as against the ‘taking positive action’ effect, as against the ‘soothing voice’ effect, & etc.

    I’d like to hope that the most effective elements will turn out not to be being lied to people pretending to hold bogus expertise.

20. diogenes said,

    March 2, 2008 at 2:24 am

    The suggestion seems to be that placebo type effects are verifiable only for ailments that are best described as subjective: e.g. depression. Insofar as the distinction between subjective and objective is really significant, I take it that placebo (or meaning response) is supposed to exist at least partly in the objective sphere. That is to say, although it is of course necessary that the subject is aware of the treatment, the criteria by which the success of the treatment is judged need not be psychological. It has been suggested above that there is no such effect; i.e. that no objective effects can be justifiably infered from the empirical evidence. I do not know that this is not true. But if this is not the case, the suggestion is that placebos actually are effective, they really do work, and work for preciely the type of things that one would expect a priori for them not to work. And this really is intereting; it really DOES matter. (Not only medically but perhaps even also philosophically: the standard metaphor of engines and pipes etc. breaks down)

21. Richard Horobin said,

    March 2, 2008 at 11:25 am

    In the column at the top of this thread, Ben noted that certain drugs appeared to “deteriorate” over time, maybe as “better” ones were marketed. And the weight of the posts above are that this is a placebo effect, and perhaps [or not] that such effects are not so likely in non-“psychiatric” arenas.

    This triggers a comment, and another interesting paper:

    COMMENT – Moerman, in his book, reviewed studies which were not “psychiatric” … including cardiac surgery!

    ANOTHER PAPER – documenting a “loss of efficacy with time” for a major anticancer drug [doxorubicin] was published a few years back. As follows:

    Does a drug do better when it is new?
    Fossati R, Confalonieri C, Apolone G, Cavuto S, Garattini S.
    2002. Annals of oncology. 13: 470-473.

22. kim said,

    March 2, 2008 at 12:53 pm

    HypnoSynthesis – thanks for a very interesting post.

    spk76 – others have pointed this out, but to be honest, it’s pretty simple – if there were no placebo effect, you’d never need a control group of patients having a placebo, would you? You’d just give the control group nothing at all, and see what happens. The group receiving the placebo is there in recognition of the fact that there will be some placebo effect attached to the active drug.

23. kim said,

    March 2, 2008 at 4:32 pm

    killary45 – yes, and that’s usually known as the Hawthorne effect, derived from a social experiment in the 1920s where factory workers improved their performance if the lights were turned up, and also improved their performance if the lights were turned down. Basically, their performance improved because they knew someone was taking an interest in them, not because they worked better in brighter or dimmer light.

    You’re right that you’ll often find this in education: someone will say “Let’s teach the kids Latin/philosophy/yoga and see what happens,” and what happens is the kids get all keen and their results improve. People put it down to the Latin/philosophy/yoga, when in fact, the children improve because they know someone’s making an effort. (I guess this is where the fish oils business comes in.)

24. Wonko said,

    March 3, 2008 at 10:14 am

    So, what we need is a new generation of antidepressants (perhaps working on melatonin and/or dopamine receptors) that we can give a zappy name to, and can spend the next 5 years aggressively marketing in order to restore our faith in pills.

    Better still, we could re-package common sense as “CBT”, aggressively market that (at huge cost to the NHS and with less benefits than pills) and spend the next 5 years believing in that.

25. HypnoSynthesis said,

    March 3, 2008 at 4:06 pm

    Wonko: I think that many researchers would dispute the idea that CBT is less effective than pills, and conclude just the opposite. CBT is not simply repackaged common sense either. It is perhaps common-sense-based, to its credit, but there’s considerable evidence to support the view that it is more effective than other talking therapies, so probably also more effective than mere common sense.

    In fact, the findings of research on psychotherapy often contradict popular opinion, and thereby refute certain aspects of “common sense.” By contrast, what people mean by good or sound “common sense” is, paradoxically, a very rare thing.

    In the non-blind placebo study cited by Ben, the researchers conclude that the effect of placebo pills which subjects were told were “sugar pills” without any active ingredients resembled that of psychotherapy. Of one subject, they write,

    “The patient indicated that she was quite suggestible, and she thought the treatment had been effective through a form of ‘hypnosis’ because she had been told so many times she would improve.” (Park & Covi, 1965)

    Perhaps this patient was right, at least her interpretation of the experiment would be consistent with the model of hypnosis developed by Braid, its founder, as I’ve mentioned above.

    Don Robertson

26. Robert Carnegie said,

    March 4, 2008 at 10:16 am

    Wasn’t there a fairly recent experiment on placebo for something or other where patients reported feeling better but demonstrably weren’t doing any better?

27. calmooney said,

    March 6, 2008 at 1:41 pm

    It appears that selling placebos cheaply may not be the best policy if a recent JAMA article is anything to go by. Unfortunately I can’t access the full text myself so can’t tell if it’s being reported accurately but apparently the placebo effect was greater in people told that their drug was expensive.

    www.bloomberg.com/apps/news?pid=20601202&sid=aAmdWrOf6gl0&refer=healthcare

    Rebecca L. Waber; Baba Shiv; Ziv Carmon; Dan Ariely.
    Commercial Features of Placebo and Therapeutic Efficacy
    JAMA, March 5, 2008;299:1016-17.

28. Universal Placebos said,

    April 2, 2008 at 4:29 am

    In Search of Placebos Online

    Fascinating thread – maybe you’d be interested in our story. Having become interested, and absorbed a lot of the online (and growing) discourse about the ‘placebo effect’, a small group of us (one a practising homeopath) set out to find how we might buy products actually branded as ‘placebos’.

    There are historical precedents for such, listed in Wikipedia and elsewhere, and there are interesting studies on the ‘informal’ (deceptive?) prescription of placebos by modern physicians – e.g. provision of antibiotics to treat a virus, provision of saline injections – with all the accompanying ethical dilemmas.

    But the closest we’ve come to a branded placebo is CEBOCAP, available through Walgreens in three strengths (!) by prescription only (!!) – see www.walgreens.com/library/finddrug/druginfo.jsp?particularDrug=Cebocap&searchChar=

    It seems that Cebocap is manufactured by Forest Pharmaceuticals (www.frx.com/products/index.aspx) but we can’t find any reference to them on the Forest site. Cebocap is also listed at www.canadacure.com/drugsearchAtoZlist.asp?Search=n,
    but that site notes that it’s “Only Available By Prescription … and Not available in Canada”.

    There are some great spoof sites around, like the article in the Onion already referred to in this thread, and we have a terrific spoof poster from a head site called Tripzine. But no REAL placebos 😉

    As adherents of homeopathy, criticised by many as one big placebo anyway, we’re fascinated by this. We’re able to source plain sugar pills, since that’s the base for many of the homeopathic remedies, but no one seems to have taken the step (had the nerve?) to come straight out and label something as a placebo. Perhaps it’s the assumption that the patient mustn’t *know* it’s a placebo s/he’s taking, but as also cited elsewhere in these pages, there are tantalising suggestions that even in such cases the placebo effect may still kick in. (And it’s not so strange anyway to imagine why ‘no blind’ placebo tests – on placebos – don’t often take place!)

    Like homeopathy and other CAMs, the value of it all seems to reside in intangibles, which makes it so problematic for materialist views of the world – values such as trust, intention, confidence, mutuality, relationship with practitioner. It’s like the placebo can offer us the affordance of ‘getting out of our own way’ and allow room for the body’s innate capacity to heal.

    So … the long and the short of it is we recently decided to set up a website as a clearinghouse for information and references to the placebo effect, and to actually package and offer placebo pills for sale online. As far as we know, we’re the only ones actually doing it, rather than just joking about it. And the content of our placebo pills? 100% sucrose. Why should anyone buy a bottle of placebos rather than, say, eat the occasional few grains of sugar from a bowl, or self-inject saline? As we say, we think it has to do with the contract, the intangible qualities involved in engaging with a formal interaction which inspires healthy somatic affects. This goes to the heart of homeopathy as well – we don’t see placebos and homeopathy as uncomplementary (to use a phrase).

    It’s early days, but so far the reaction has been good. Our intention is absolutely serious, stemming from our commitment to CAMs, but we also want to hold the information lightly, have fun with it, and take a bit of a poke at the medico-pharmaco juggernaut.

    Check us out if you like – www.placebo.com.au

    With best wishes

    Universal Placebos

29. mickjames said,

    April 12, 2008 at 3:25 pm

    I used to have bottles of vitamin pills I’d labelled Placebo and PlaceboPlus afer hearing Richard Bandler float the concept. They were OK, but I wonder if commercially prodiced placebos would work better?

30. physicistindespair said,

    June 9, 2009 at 6:52 pm

    Oh dear Ben – here we go again with round n+1 of the placebo game – however this time a government body has given some kind of legitimacy to this (as one letter back to the BMJ (found in the ‘rapid responses’ section) describes) ‘snake oil’:

    www.bmj.com/cgi/content/extract/338/may20_1/b2055

31. Dancer said,

    October 29, 2009 at 8:35 pm

    Fascinatingly, one of our local alternative therapists starts her consultations with something along the lines of “what I am going to do with you will mostly work because you believe it works and you have invested time and money on it, so you will want it to work, which makes it more likely to work, you will also find it quite relaxing, and you get to talk about you for an hour should you so wish. It has no other proven benefit.”

    I don’t suppose she publishes data, but I would be fascinated to know whether her approach works better than that of someone who believes in their particular form of therapy.

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