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Thursday, July 29, 2010

Placebo response without placebos

Often, I hear that the placebo response is an artifact, merely a control for the "real" treatment. Today, I'd like to blog about a paper that suggests that every treatment is partially placebo. The paper is Benedetti et al 2003, and is probably one of the most interesting papers I have read.

Essentially, the study looked at whether or not the awareness of treatment had any impact on the response to real drugs. To do this, they used (mostly) post-operative patients and looked at pain & anxiety.

Each treatment was given in two conditions: open and hidden. In the open condition, patients were given a drug by a doctor who told them what they were getting. In the hidden condition, the drug was given without the knowledge of the patients.

The study also looked at open and hidden interruptions in treatment, and the results were essentially the same (i.e. pain/anxiety levels were higher after the open interruptions). 

The results were clear for pain and anxiety. Open infusions were much more effective than hidden ones, with pain decreasing much more in the open condition than in the hidden one.  The drug given for anxiety was diazepam (Valium) and this drug was COMPLETELY ineffective in reducing anxiety in the hidden condition. One could take these results to mean that Valium is a placebo, and only works because people believe it will. Is it the cultural lore thats developed around Valium be the only reason its effective? Shocking stuff, and food for thought the next time someone argues that placebos are "just" controls or have "no clinical significance".

Now, its worth being aware of a few caveats to this study. Firstly, the open condition was actually measuring the difference between the presence of a doctor and the awareness of a treatment. This could be gotten around by using a prerecorded voice telling participants that they were about to get medication.  Unfortunately, no one appears to have done this study yet, but its an interesting question nonetheless.

Benedetti, F., Maggi, G., Lopiano, L., Lanotte, M., Rainero, I., Vighetti, S., & Pollo, A. (2003). Open versus hidden medical treatments: The patient's knowledge about a therapy affects the therapy outcome. Prevention & Treatment, 6 (1) DOI: 10.1037/1522-3736.6.0001a


  1. Great post/series! I've been reading up on the placebo effect recently and it really is shocking how great of a percentage the effects of psychotropic medications can be explained by placebo or active placebo effects. I'll bet you've probably read this, but in case you haven't, I highly recommend this book:

    Basically, the author thoroughly goes through all clinical trials that have been conducted on anti-depressants and convincingly demonstrates that they are nothing more than active placebos, and that these studies are really not double blind. I wouldn't be surprised at all if Valium was very similar.

  2. Thank you, its nice to know that someone is reading!

    I haven't read the book, but Professor Kirsch is on my board of advisors and i've read the papers he uses as source material. Good to know you're enjoying it, will try to keep up the blogging.

  3. Does Valium relieve anxiety in animal experiments? If so, I doubt that the animal knows in any meaningful way that it is being given an anti-anxiety drug. If not, then perhaps the knowledge/belief in the drug is partly or wholly responsible for its anti-anxiety effects.

  4. I first read about this study in 13 Things That Don't Make Sense by Michael brooks.

    There is a whole chapter on placebo and it is Fascinating stuff.

    The notion that we understand placebo is based on assuming that not only the existence of placebo but also that its effects can be separated out from the chemistry of the drugs being tested.

    The assumption is only relatively recently being studied. As a follow up to the topic you mention there is this information in the book.

    "It all kicks off with the pain-racked patients receiving something like a morphine drip. Later, after the patients have begun to associate the morphine with pain relief, you can subtly substitute saline solution for the morphine. The patients don’t know their “morphine” is nothing but salt water and, thanks to the placebo effect, they report that their pain medication is still working fine. That is strange in itself, but not as strange as the next twist makes things. Without saying anything to the patients, you put another drug into the drip: naloxone, which blocks the action of morphine. Even though there is no morphine going into the patients’ bodies, naloxone still stops the pain relief in its tracks; the patients, oblivious to all that has gone on, now report that they are in discomfort again.
    The only plausible explanation is that the drug that blocks morphine’s pain-relieving power also blocks the saline’s (placebo-based) pain-relieving power. Which means the saline really was doing something—it wasn’t all in the patient’s imagination. Or at least it means that imagination can have a physiological effect."

    This the notion that either drugs are placebos or "real" may well be a false dichotomy. Reality, as usual it seems, is delightfully thrashing our assumptions.

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