Placebos for Migraine

Timothy C. Hain, MD • Page last modified: June 2, 2021

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Hope springs eternal in the hearts of man as the saying goes. There are an immense number of medications or regimens for migraine, some of which are probably placebos. By placebo, we mean a substance or procedure that has no net positive effect, aside from providing hope and the "placebo effect". We do not think that there is no value for this. Still, we think it might be preferable to pick a medication or procedure that has been proven to help to a greater extent than placebo, when this is available..

The placebo effect in migraine is potent -- Couch et al (1987) reported "The initial placebo effect is dramatic with 62% of 188 subjects improving by 75% after 4 weeks of placebo. The continuing effect is demonstrated by occurrence of 75% further improvement in 28% of 282 subjects in 7 studies in which comparison of results after 4-12 weeks was made with a placebo stabilization period." This seems a bit high to us - -Macedo (2008) et al pooled mutiple studies and concluded rather that "The pooled estimate of the placebo response (patients who improved) was 21%." So when a study is done without a placebo control, one is looking for a response rate > 20%, to do better than a placebo.

Some authors, e.g. Granato et al (2019) have suggested "leveraging" the placebo effect. In other words, if placebo's work, use them. Some placebos (especially those having to do with cutting or surgery) are more effective than others (such as pills). (Diener et al, 2010; Meissner et al, 2013)

So factors that seem to improve placebo response are use of needles, surgery, and presumably interventions having to do with dramatic devices such as ones that use shocks. We would also think that some health care providers might enjoy a higher placebo effect than others.

There obviously is a trade-off between positive placebo effects and negative aspects (cost of treatment, pain involved in treatment, damage to normal tissues from surgery). We are thinking particularly here about very expensive new drugs that have just a little benefit over placebo, such as the CGRP family and Botox as well. Of course, these treatments both involve needles.

This is not meant to be an exhaustive list. That would take too long - -we are just trying to pick off recent and notables.