Another Mechanism for the Placebo Effect?
The placebo effect (benefit in groups receiving fake pills) and nocebo effect (detriment in those same groups) have frequently been the bane of medical research. They are usually explained in terms of psychology: because people receiving placebos believe they have been treated, they get psychosomatic effects that cure symptoms and create side effects. This explanation is supported by the fact that the placebo effect is strongest when the effect being studied is subjective—eg, tests of painkillers and antidepressants. This explanation is neat, tidy, and in my opinion, altogether unsatisfying.
I have an alternative theory. Most people in medical studies take more than one medication; in addition to the drug being studied, they take unrelated drugs and supplements, usually including a multivitamin and often including other things they were prescribed. However, many people take their pills inconsistently; they miss or mistime some fraction of their doses. This is especially true of depressed people. Prescribing a placebo, however, fixes this; when they take their placebo pill in the morning, they are reminded to take everything else they should be taking. In addition to making pill-taking more salient, being prescribed a placebo may also cause some people to fix the organization and affordances they have for taking pills.
I suspect that many of the benefits attributed from placebos may in fact be due to increased compliance with unrelated prescriptions and correction of vitamin and mineral deficiencies. Arranging a study to test this should be fairly straightforward; simply measure the rate at which unrelated prescriptions are refilled in two groups, one of which receives sugar pills and one of which does not.
One of the strongest cases for placebo effect is IV morphine, whose powerful painkilling effects can in many cases be simulated by IV saline which someone says is morphine. Finding the placebo effect with a professionally-administered IV drug usually given in hospital suggests it’s not just an issue of compliance.
Would appreciate some citations...
The famous story here is that of Henry Beecher, usually considered discoverer of the placebo. From the Telegraph:
Or for a more formal study, see Analgesic responses to morphine and placebo in individuals with postoperative pain
This abstract frustrates me. How effective was the placebo compared to the iv morphine? Are they saying that it’s as effective till 4-6mg of IV morphine? Any other studies with complementary or contrasting evidence? Thanks for the share by the way.
Something else to keep in mind:
A very small fraction of studies actually publish the ingredients to their placebo. Thus, the assumption that the placebo can have no chemical effect on participants is not the most reliable. In one case an AIDS treatment was tested against a placebo that contain dairy. A fraction of the control group was lactose intolerant (AIDS patients are at increased risk). Long story short: the drug looked great because the placebo was killing the control group. In cholesterol medication studies some meds were tested against placebos that contained corn or olive oil which may have cholesterol reducing properties, understating the effectiveness of the drug.
Jeez, is this true? It seems such an obvious precaution to take. I mean, what’s wrong with simple saline, anyway?
It’s mainly an issue with pills where they try to make them look and taste similar to the drug.
If you say so, though I don’t understand why that would be necessary—capsules look and taste the same no matter what’s in them.
Edit: I was interested, so I looked it up. The claims likely come from this Reuters article, which references this research paper, which seems legit. Depressing.
The nocebo effect is evidence against this hypothesis.
I strongly suspect you are wrong since the placebo effect has been around since well before multivitamins and similar things were at all common. But the hypothesis seems worth testing.
Wasn’t there some research indicating that the placebo effect has gotten stronger recently? Perhaps this effect, combined with the increased prevalence of vitamins and higher fraction of patients with unrelated prescriptions, could explain the increase.
Is this your source for the claim that the placebo effect has gotten stronger?
It merely claims that the gap between a placebo and real drug has gotten smaller, while your theory predicts that they would both grow, the gap unchanged. And the evidence is that lots of new drugs don’t work, which is easy to explain other ways. It does claim that placebo response to antidepressants is larger than it used to be, but depression is difficult to measure and it is easy to believe that this is a different population that wouldn’t have been treated earlier.
I believe that a less specific version of your hypothesis is commonly accepted: being part of a medical trial gets people better health care. I’m pretty sure that it has been repeatedly measured that compliance is higher in studies than in nature, the usual explanation being attention. I don’t know if compliance for medicine outside of the study has been measured.
It got stronger in anti-depressant trials after successful anti-depressant drugs were heavily marketed. The traditional theory explains this readily.
This is a good point. It drastically increases my estimate probability of your hypothesis being correct.
I would have guessed that the primary reason why the placebo effect has gotten stronger is that people believe in medicine more. There have been studies that show a stronger placebo effect if things feel more medical, such as making the sugar pills not taste good or the like. This suggests that the belief level can be quite malleable. But this now makes me extremely interested in your hypothesis.
Agreed—I was all set to vote it down, but it’s a clever enough idea that I voted it up.
You are correct that compliance (sorry, don’t know how to fix the missing parenthesis) is a major issue in many situations. This book discusses, among other things, the effects of compliance and concludes that high-compliant patients do better on placebo as well as on real drugs vs low-compliant patients. This is one of the studies they discuss. Whether this is due to the patients being more conscientious about taking other drugs apparently has not been specifically tested, unlike the physiological effects of taking a placebo, which have been measured with fMRI.
To post a link containing a close-parenthese), put a backslash in front of it, like this:
To save everyone some time).
Following Help → More Help on the comment box would lead you to this page that has the answer.
The conventional wisdom in medicine is almost the opposite: more pills leads to lower compliance. This has been studied and will be studied more the future, since it is an easy source of patents. The term to search for is “fixed-dose combination,” putting two drugs in one pill. Really, how could it be otherwise? It could: adding an “important” drug to a regime of “unimportant” drugs could increase compliance of the “unimportant” drugs. But I think this is most plausible with vitamins. Being in a study might cause that particular drug to get labeled “important,” but I doubt it.
As I said elsewhere on the thread, it is well-known that medical studies increase compliance. The conventional wisdom is a more specific hypothesis that proximity in time to an appointment increases compliance with all drugs, a claim that has consequences outside of clinical trials. I was not able to find any studies of this, perhaps because I don’t know the correct terminology. Compliance is a booming field, especially outside of clinical trials, and I expect that this will be well-studied in the future if not yet.
In other words, it is important to distinguish between the placebo effect and the effect of being in the placebo arm of a clinical trial. The pure placebo effect of placebo vs no drug is very rarely studied.
There are certainly psychological effects that can be quite significant. There’s a ton of literature on placebos and related psychology. They’ve done brain scans. At this point, it is tied to too much other psychology and too many every day experiences for it to be wrong. It’d be like learning that the laws of physics apply except for on prime days of leap years, when physics like human intuition says it should.
There is no reason to posit another mechanism unless you’d expect it to be significant a priori.
(Note to self: replicate double-slit experiment on January 3 of next year.)
(Note to self: replicate double-slit experiment on January 3 of next year.)
Edit: An upvote, really? I immediately thought no, that’s way too silly, it’ll be downvoted to oblivion.
Wait, you can edit retracted comments?
This is a funny, interesting, and a bit profane video about the placebo/nocebo effect. In the studies he references the effects are basically immediate, with no time for what you are describing to interfere. At the very least this makes me think that the placebo/nocebo effect does exist, and it seems reasonable to accept it as the cause both for immediate effects and more long term ones.
The cause? Why should there be only one?
shugs There’s no reason for there only to be one but with one perfectly good reason and not much evidence for a second I don’t think we need to put much confidence on your hypothesis just yet. It’s probably worth looking into though. I really don’t know.
Do you know whether he was accurate about the effects of placebos and nocebos?
I didn’t spend too much time looking but here’s a link to the full text of the study involving muscle relaxants. The talk is by the guy who writes badscience.com, so generally I trust him.
P.S. That was a good question. I hadn’t looked into it at all until you asked.
As Yvain said, the original example of the placebo effect is immediate and does not involve pills. A long-term pill-less example is that sham acupuncture beats conventional treatment for back pain. (real does not beat sham)