"BOTOX for Migraines?"

A recent encounter with one of my headache patients got me thinking. I am treating this young woman for chronic migraine with BOTOX injections. She told me that one of her other physicians had been surprised to hear about this use for onabotulinumtoxin A. According to my patient, the gastroenterologist’s words were, “BOTOX for migraines? I’ve never heard of that.” 

I wondered whether this physician’s statement indicated there might be colleagues in other medical specialties unaware of this approved treatment. Or, perhaps many are aware of the treatment but don’t know the specifics. I decided a short review of this topic was worthwhile.

[[{"type":"media","view_mode":"media_crop","fid":"46163","attributes":{"alt":"","class":"media-image media-image-left","id":"media_crop_9643214150530","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5344","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 303px; width: 300px; float: left;","title":"©Lightspring/Shutterstock.com ","typeof":"foaf:Image"}}]]Chronic migraines are what were formerly known as “transformed” migraines. These are near daily headaches, sometimes with migraine features but otherwise with frequent features of tension headaches. This may sound trivial but the treatment for tension headaches, typically with analgesics, would only make this syndrome worse. We learned that treating these with migraine preventive medications proved mostly effective. The current International Classification of Headache Disorders defines chronic migraine as a recurrent headache that has been ongoing for the past 3 months, occurs on at least 15 days per month, lasts at least 4 hours per day, and has 8 or more days per month when the headache has features of a migraine or responds to a typical migraine medication.

In the mid- to late-1990’s dermatologists were the first to report headache relief to migraineurs who were receiving BOTOX injections to reduce facial (forehead) wrinkles. Initially there was significant controversy about whether BOTOX really did help migraine patients. The use of BOTOX for treatment of tension headaches was studied and found to be no more effective than placebo. With migraines, it was more complex. In 2009 the data showed that BOTOX injected in particular areas of the head and neck in patients who met the International Classification of Headache Disorders criteria for chronic migraine provided sufficient benefit to recommend the treatment modality. In 2010, the FDA approved BOTOX for chronic migraine and recommended the protocol of injections and treatment frequency that had been successful in the studies.

How does BOTOX work in migraines? The current theory is that BOTOX disrupts the trigeminal nerve terminal end. This leads to down-regulation of the trigeminal nerve cells and suppression of neurotransmitter release in two critical areas: central neuronal glutamate release and peripheral nerve inflammatory-inducing compounds such as CGRP in the cerebral blood vessels.

A BOTOX “treatment” consists of 31 injections to the head and neck areas, if adherence to the FDA approved protocol is followed. Except for injection into the procerus, which is in the midline, all others are paired sets of injections on the left and right sides. Muscles included are the frontalis and temporalis areas as well as the occipitalis, upper cervical paraspinals, and trapezii. The amount injected at each of the 31 injection sites is small-5 units of BOTOX in a volume of 0.1 mL normal saline or sterile water. A total of 155 units is are typically used.

A BOTOX “treatment” consists of 31 injections to the head and neck areas, if adherence to the FDA-approved protocol is followed.

Adverse effects that may be noted include focal pain from the injections, unwanted muscle weakness such as eyelid ptosis, blurred vision, dry mouth, swallowing difficulties, and some patients report diffuse fatigue. Most of these “direct” side effects improve or resolve in the first 7 to 10 days after injections.

Although one cannot predict exactly who will respond, I find that those patients who are going to respond will note some improvement in headaches following the first set of injections. Repeat injection sets can be performed on the same patient no sooner than every 3 months, as long as a benefit is seen. Most insurers require that you document at least a 50% improvement in the chronic migraine frequency and/or severity for continued coverage. I usually recommend that my migraine patients have a second set of injections before deciding that this treatment modality is of no benefit to them.

[[{"type":"media","view_mode":"media_crop","fid":"46165","attributes":{"alt":"","class":"media-image media-image-left","id":"media_crop_8089112498757","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5346","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 128px; width: 200px; float: left;","title":"©Luiscar/Shutterstock.com ","typeof":"foaf:Image"}}]]I usually keep my patients on migraine preventative medications until we have seen sufficient relief of migraine to warrant a taper to a lower dose or even an attempt at medication discontinuation. Patients are free to use their typical migraine abortive medications for breakthrough migraines. There are some patients that find that they still require their other anti-migraine medications for full migraine control.

In my experience, this, like all other treatments we use in medicine, doesn’t benefit every patient. I find that it helps a majority of appropriate patients, that is, those patients with a diagnosis of chronic migraine who have failed not just abortive but also preventative migraine treatments. Is there sufficient benefit, however, to outweigh the cost and pain of this treatment? In the case of most of my patients, the answer is yes.

Bibliography

Aurora SK, Dodick DW, Turkel CC, et al. OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30:793-803.

Blumenfeld A. Botulinum toxin treatment of migraine. MEDMERITS web site.

Blumenfeld A, Silberstein SD, Dodick DW, et al. Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program. Headache. 2010;50:1406-1418.

Negro A, Curto M, Lionetto L, et al. OnabotulinumtoxinA 155U in medication overuse headache. Springerplus eCollection. 2015;4:826.

United States Food and Drug Administration. FDA approves Botox to treat chronic migraine. Available at:http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm229782.htm. News Release October 2010.

Welch KM, Goadsby PJ. Chronic daily headache: nosology and pathophysiology. Curr Opin Neurol. 2002;15:287-295.