Placebos for Migraine
Timothy C. Hain, MD • Page last modified:
June 2, 2021
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.
- Amitriptyline. Goncalves et al (2016) reported placebo to be superior to amitriptyline. This conclusion is not generally held however. We ourselves think amitriptyline is better than placebo.
- Botox: Solomon et al (2011) wrote " Botulinum toxin A used to treat headache evokes prominent placebo effects and it is likely that these effects are solely responsible for its apparent effectiveness." This conclusion also goes against general thought which holds that Botulinum toxin is better than placebo, from a very large trial conducted by Allergan, the drug manufacturor.
- Chiropractic manipulation (CSMT). Chaibi et al (2017) wrote "The effect of CSMT observed in our study is probably due to a placebo response." We suspect here that it depends on the provider.
- Cutting and needles. Meissner et al (2013) concluded that "Sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos." Very reasonable.
- Green light. Martin et al (2021) reported that green light was more beneficial than white light in prevention of migraine, in a study of 39 patients. Maybe true, but maybe a placebo as well. We don't see any reasonable way to "blind" this study. We would see similar issues for rose colored glasses, etc.
- Surgery for migraine: McGeeney, B. E. (2015). wrote ""Various related techniques aim to free up "trigger sites" by removal of small facial muscles or "decompressing" small facial nerves. DISCUSSION: The basis for migraine trigger site surgery is without merit. There is one positive placebo controlled study with many limitations. Natural history and placebo mechanisms explain the outcomes from migraine surgery. " This seems reasonable to us.
- Chaibi, A., et al. (2017). "Chiropractic spinal manipulative therapy for migraine: a three-armed, single-blinded, placebo, randomized controlled trial." Eur J Neurol 24(1): 143-153.
- de Craen, A. J., et al. (2000). "Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos." J Neurol 247(3): 183-188.
- Couch, J. R., Jr. (1987). "Placebo effect and clinical trials in migraine therapy." Neuroepidemiology 6(4): 178-185.
- Diener, H. C. (2010). "Placebo effects in treating migraine and other headaches." Curr Opin Investig Drugs 11(7): 735-739.
- Goncalves, A. L., et al. (2016). "Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention." J Neurol Neurosurg Psychiatry 87(10): 1127-1132.
- Granato, A., et al. (2019). "Dramatic placebo effect of high frequency repetitive TMS in treatment of chronic migraine and medication overuse headache." J Clin Neurosci 60: 96-100.
- Macedo, A., et al. (2008). "Placebo response in the prophylaxis of migraine: a meta-analysis." Eur J Pain 12(1): 68-75.
- Martin LF et al. evaluation of green light exposure on headache frequency and quality of light in migraine patients. Cephalgia. 2021 41(2) 135-137
- McGeeney, B. E. (2015). "Migraine Trigger Site Surgery is All Placebo." Headache 55(10): 1461-1463.
- Meissner, K., et al. (2013). "Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis." JAMA Intern Med 173(21): 1941-1951.
- Solomon, S. (2011). "Botulinum toxin for the treatment of chronic migraine: the placebo effect." Headache 51(6): 980-984.