Last month, JAMA published a clinical summary of treatments for the prevention of migraine, a reprint from a publication called the Medical Letter. What’s amazing about this summary is that it manages to include a mind-bogglingly diverse collection of treatments – everything from drugs to supplements to experimental head gadgets, from the virtually un-tested to treatments demonstrated to be ineffective in double-blind placebo controlled trials. And yet incredibly, this review does not mention acupuncture, one of the most thoroughly tested guideline recommended treatments of demonstrable efficacy, effectiveness and safety for the prevention of migraines.
Given that the purpose of JAMA’s review is to help inform clinicians about effective treatment options for migraines to better help their patients, my colleague Mark Bovey of the British Acupuncture Council and I felt that we’d be remiss not to draw attention to their oversight with a quick letter to the editor for publication in their next edition. Alas, we were informed today that the JAMA editorial staff didn’t feel that our letter was a ‘high enough priority’ for publication in their prestigious journal.
But it just so happens that I have a blog and can publish whatever the heck I like! So here it is, our response to Prevention of Migraines (this is a somewhat longer version that was drafted before I realised they have a 500 word limit!). It is a shame that JAMA felt that the subject of migraine prevention was important enough to cover but not important enough to cover thoroughly, omitting the treatment that according to copious clinical evidence has the potential to most benefit patients while simultaneously reducing risk. At any rate, enjoy!
“Prevention of Migraine”: Acupuncture is Conspicuous by its Unexplained Absence
We read your article on the prevention of Migraines with great interest and while not billed as a systematic review, we couldn’t quite tease out how you went about choosing recommendations for inclusion for educating clinicians. Obviously, it’s problematic to choose treatments in a completely arbitrary manner, which could leave out effective, evidence-based options while promoting treatments that have a poorer risk to benefit profile, thus undermining the entire purpose of the review. While the review mentions pharmaceutical, nutraceutical and physical approaches, both FDA approved and off-label, as well as effective and ineffective treatments, it fails to mention acupuncture, which has a stronger evidence base than most of the treatments recommended in your article. We wondered on what basis this was not included in your review informing clinicians about treatment options for migraine prophylaxis.
Initially, we thought it possible that this review was only covering pharmacological treatments. But then we noted the inclusion of butterbur, melatonin, riboflavin, and other non-drug supplements.
The review could have been focusing only on treatments taken orally, which could be why drugs and supplements, but not acupuncture, were mentioned. But the review includes a ‘transcutaneous electrical nerve stimulation device’ called Cefaly, which has undergone a single randomised placebo controlled trial consisting of 67 patients.1
It would have been logical that only FDA-approved treatments or treatments included in official clinical guidelines were considered for inclusion in the review. But most of the interventions mentioned don’t meet these criteria. Most Beta Blockers (metoprolol, nadolol and atenolol), the antidepressants (tricyclics and SNRIs), ACE inhibitors, NSAIDs, statins, and supplements, are not FDA-approved for migraine prevention and constitute off-label prescribing, as well not enjoying any official recommendation. So approval status does not seem to have weighed in to whether or not a treatment was mentioned. On the other hand, the FDA now recommends that doctors learn about acupuncture as a safe and effective pain treatment in order to reduce prescribing of opioids and acupuncture is recommended in the NICE clinical guidelines for the prevention of migraine. The only drugs recommended were topiramate, propanolol and gabapentin.2
One could approach the inclusion of treatments in such a review from a safety and tolerability perspective, but the vast majority of the treatments mentioned are poorly tolerated and frequently discontinued due to unpalatable side-effects. Likewise, many are not considered safe for use during pregnancy. On the other hand, acupuncture is considered to be a very safe treatment.
A review could be undertaken from the perspective of only including well-studied treatments. But some of the included treatments had only the flimsiest of evidence to support a recommendation. For example, the review mentions the combination of simvastin plus vitamin D in the prevention of migraine, based on a single study consisting of 57 patients, in a design that did not separate the effects of the statins from those of vitamin D, which has some evidence of effectiveness on its own. Incidentally, the lead authors of this study have applied for a patent for this treatment. On the other hand, the most recent Cochrane Systematic review of acupuncture for migraine prophylaxis includes 4,985 participants in 25 randomised controlled trials, firmly placing it amongst the most well-studied treatments for this condition.
Finally, in writing an informal review of treatments for preventing migraine, one could have approached the inclusion from the perspective of effectiveness or efficacy, focusing on the treatments that have been shown to work best for the condition under discussion, which would have been the logical choice if the intention was to educate clinicians on how to best help their patients. But some treatments mentioned have zero evidence of efficacy. For example, nortriptyline was mentioned as a frequently prescribed antidepressant with fewer side effects than amitriptyline. However, as a standalone treatment it has only been subjected to a single randomised placebo controlled trial, which found that it no more effective than placebo.3
On the other hand, strong peer-reviewed evidence support the use of acupuncture as an effective, efficacious and safe treatment for the prevention of migraine. According to the most recent Cochrane review, acupuncture is superior to no acupuncture (acute treatment only or routine care) and even to the diluted dose of acupuncture that masquerades as placebo.4 Of most clinical interest, though, was that acupuncture was more effective than prophylactic drugs (metoprolol, flunarizine and others), and with fewer adverse events. In terms of the proportion of patients whose headache frequency had at least halved after three months, this was 57% with acupuncture and 46% with drugs. In your own Internal Medicine journal, a recently published Chinese trial confirms the superiority of acupuncture over sham.
In summary, a review of treatments for migraine prophylaxis that fails to mention one of the best-studied, most effective and best tolerated treatments obviously does a great disservice to patients by misinforming clinicians about the best treatment options. This is why systematic reviews, and the clinical guidelines they inform, are considered the pinnacle of the evidence hierarchy. If there was a valid reason for this omission, we would be most interested to hear it because we couldn’t find one.
1 Schoenen, J., Vandersmissen, B., Jeangette, S., Herroelen, L., Vandenheede, M., Gerard, P., & Magis, D. (2013). Migraine prevention with a supraorbital transcutaneous stimulator: A randomized controlled trial. Neurology, 80(8), 697–704. doi.org/10.1212/WNL.0b013e3182825055
3 Domingues, R. B., Silva, A. L. P. D., Domingues, S. A., Aquino, C. C. H., & Kuster, G. W. (2009). A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine. Arquivos De Neuro-Psiquiatria, 67(4), 973–977.
4 Linde, K., Allais, G., Brinkhaus, B., Fei, Y., Mehring, M., Vertosick, E. A., et al. (2016). Acupuncture for the prevention of episodic migraine. (K. Linde, Ed.). Chichester, UK: John Wiley & Sons, Ltd. doi.org/10.1002/14651858.CD001218.pub3