Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Why I don't believe in the placebo effect, published by transhumanist atom understander on June 10, 2024 on LessWrong.
Have you heard this before? In clinical trials, medicines have to be compared to a placebo to separate the effect of the medicine from the psychological effect of taking the drug. The patient's belief in the power of the medicine has a strong effect on its own. In fact, for some drugs such as antidepressants, the psychological effect of taking a pill is larger than the effect of the drug. It may even be worth it to give a patient an ineffective medicine just to benefit from the placebo effect.
This is the conventional wisdom that I took for granted until recently.
I no longer believe any of it, and the short answer as to why is that big meta-analysis on the placebo effect. That meta-analysis collected all the studies they could find that did "direct" measurements of the placebo effect. In addition to a placebo group that could, for all they know, be getting the real treatment, these studies also included a group of patients that didn't receive a placebo.
But even after looking at the meta-analysis I still found the situation confusing. The only reason I ever believed in the placebo effect was because I understood it to be a scientific finding. This may put me in a different position than people who believe in it from personal experience. But personally, I thought it was just a well-known scientific fact that was important to the design of clinical trials.
How did it come to be conventional wisdom, if direct measurement doesn't back it up? And what do the studies collected in that meta-analysis actually look like?
I did a lot of reading to answer these questions, and that's what I want to share with you. I'm only going to discuss a handful of studies. I can't match the force of evidence of the meta-analysis, which aggregated over two hundred studies. But this is how I came to understand what kind of evidence created the impression of a strong placebo effect, and what kind of evidence indicates that it's actually small.
Examples: Depression
The observation that created the impression of a placebo effect is that patients in the placebo group tend to get better during the trial. Here's an example from a trial of the first antidepressant that came to mind, which was Prozac. The paper is called "A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression".
In this test, high scores are bad. So we see both the drug group and the placebo group getting better in the beginning of at the beginning of the trial. By the end of the trial, the scores in those two groups are different, but that difference is not as big as the drop right at the beginning. I can see how someone could look at this and say that most of the effect of the drug is the placebo effect.
In fact, the 1950s study that originally popularized the placebo effect consisted mainly of these kind of before-and-after comparisons.
Another explanation is simply that depression comes in months-long episodes. Patients will tend to be in a depressive episode when they're enrolled in a trial, and by the end many of them will have come out of it. If that's all there is to it, we would expect that a "no-pill" group (no drug, no placebo) would have the same drop.
I looked through the depression studies cited in that big meta-analysis, but I didn't manage to find a graph precisely like the Prozac graph but with an additional no-pill group. Here's the closest that I found, from a paper called "Effects of maintenance amitriptyline and psychotherapy on symptoms of depression". Before I get into all the reasons why this isn't directly comparable, note that the placebo and no-pill curves look the same, both on top:
The big difference is that this is trial is testing ...

063: Crash and Learn: Lise Kuecker