Botox for migraine

All You Need To Know About Botox for Migraine

Botox for migraine was first found to help prevent attacks while being studied as a treatment for wrinkles (Binder 2000). Botulinum toxin is a protein produced by a species of bacteria known as Clostridium, which prevents the release of molecules from nerve cells. By preventing nerve signaling, botulinum toxin has been used as a cosmetic treatment for wrinkles and for various medical conditions, including migraine, lazy eye, muscle spasms, excessive sweating, and bladder problems.

Botox is just one of the brands of botulinum toxin. You may have heard of other forms of botulinum toxin, such as Dysport, Xeomin, Myobloc, Jeuveau, and Daxxify. Botox was the first form of botulinum toxin approved by the Food and Drug Administration (FDA) in 1989. Botox was approved by the FDA to treat migraine in 2010. It is the only form of botulinum toxin that is currently approved by the FDA for migraine prevention.

Botox as a Treatment for Migraine

To prevent migraine, 155 units of Botox are administered in 31 injections all around the head including the forehead, upper neck, and shoulders. Your physician may modify this protocol to better target specific areas where you feel the most pain. While 31 injections may seem daunting, the needle is much smaller than the one used for IVs or vaccines.

The entire process takes about 5-10 minutes. The effects of Botox typically last about 3 months, so injections are usually scheduled every 12 weeks. Based on your response to Botox, the frequency of the appointments can sometimes be adjusted to be a little earlier or later to help you remain as headache-free as possible. If you’re already taking other medications to prevent migraines these are typically continued until your headaches are under good control with Botox, then your doctor may gradually taper
these medications. Sometimes adding Botox and continuing your other migraine medications can be more effective than either treatment individually.

Not every person with migraine is a candidate for Botox. Botox is currently the only FDA-approved for patients with chronic migraine. To be diagnosed with chronic migraine, you must have 15 or more headache days per month for at least 3 months, of which at least 8 of those headaches must be migraine headaches (Headache Classification Committee of the International Headache Society 2013). Most health insurance also requires that you have tried other preventative medications first that either didn’t work or
caused side effects, or have a medical reason why you cannot safely take these medications.

How Does Botox Work

Botox works by irreversibly preventing the release of proteins from the end of nerve cells (Ramachandran 2014). This prevents nerve cells from triggering muscles to contract, which can help relieve tension in the muscles of the head, neck, and shoulders. Botox also stops nerves from releasing proteins involved in relaying pain signals, including CGRP and substance P. There is also evidence that nerve cells may move
Botox from the nerve endings into the main body of the nerve in the brainstem, which can alter the way the brain perceives pain.

Botox typically takes 1-2 weeks to take effect, but a reduction in headache frequency can be seen as early as 4 weeks after the first set of injections. It takes new nerve endings about 3 months to regrow, which is why Botox needs to be repeated at that interval.

Not everyone with chronic migraine will respond to Botox in a similar way. Two studies found that migraine attacks that were described as imploding, crushing, vicelike, or eye-popping were more likely to have a better response to Botox than patients with migraine attacks described as exploding or pressure building up inside their head (Jakubowski 2006, Kim 2010). Other factors that have been associated with a better response to Botox includes scalp tenderness and a one-sided headache (Mathew 2008). The response rate is also much higher in patients who have had migraine attacks for less than 30 years (Eross 2005). However, as of the present time, there aren’t any reliable biomarkers that predict which patients will have a favorable response to treatment.

The Efficacy of Botox for Migraine Management

Many studies have evaluated the effectiveness of Botox in preventing chronic migraine (Herd 2019, Lanteri-Minet 2022). Randomized controlled trials of Botox compared to placebo showed that Botox reduces headache days by about 7 to 10 days per month, whereas placebo reduces headaches by 5 to 6 days per month. Averaged over these trials, Botox is estimated to result in 2 fewer headache days per month relative to placebo. This decrease in headache frequency is maintained for at least 2 years, with
an average reduction of 12 headache days per month after 9 treatments (Diener 2010).

After two rounds of injections, about half of patients have at least a 50% reduction in the number of headache days per month, and 26% of patients have at least a 75% reduction in headache days (Blumenfeld 2018). There was also found to be a significant improvement in migraine-associated disability and quality of life in patients treated with Botox (Aydinlar 2017, Lipton 2011).

Botox has been shown to have about the same rates of effectiveness as amitriptyline and topiramate in preventing migraines (Escher 2017). Studies have also shown that Botox is effective in reducing headache days in patients with chronic migraine who also have rebound headaches from overusing as-needed anti-migraine medications (Silberstein 2013, Ahmed 2015).

Most patients that have a good response to Botox will experience improvement in their headaches after the first set of injections (Silberstein 2015). However, about 25% of patients who do not notice a significant improvement after the initial injections have a good response after the second or third set of injections, so most physicians recommend doing three rounds of injections before concluding that Botox is ineffective for a given patient.

Potential Side Effects and Considerations

Any time an injection is given, there is a potential risk of infection or bleeding. The needles and the Botox medication are sterile and the skin is cleaned with an alcohol swab prior to the injections, which reduces the risk of developing an injection. Your physician will review your medication list to see if you’re taking any blood thinners, including aspirin, that could increase your risk of bleeding during the procedure. Being on a blood thinner doesn’t mean you can’t have Botox though. If there is any bleeding, your physician will hold pressure over the area until the bleeding stops. Your headaches may flare initially for the first week while Botox takes effect due to nerve irritation from the repeated injections.

Side effects from Botox are usually mild and short-lasting. The most common side effects are neck pain (4.3%), injection site pain (2.1%), eyelid droop (1.9%), and muscular weakness (1.6%) (Aurora 2014). Less than 4% of patients end up stopping Botox because of side effects (Bendtsen 2018).

There have been a few very rare cases of generalized weakness occurring distant from the sites of the injections, including eyelid droop, double vision, difficulty speaking, swallowing, and breathing. This is thought to be more likely to occur with higher doses of Botox is used for other conditions (over 600 units per treatment), which is far beyond the 155 units used to treat migraines (Crowner 2010). One article reviewed 72 cases of weakness following treatment with Botox or other botulinum toxin products, however, none of these cases occurred in patients treated for migraines (Locke 2021).

You should not receive Botox if you have a skin infection at any of the injection sites or if you are hypersensitive to any botulinum toxin product. If you have a neuromuscular disorder such as myasthenia gravis, you should discuss with your neurologist if receiving Botox is safe as Botox may worsen weakness in this condition.

In some patients, Botox may eventually lose efficacy. This may be due to the intrinsic worsening of the underlying migraine disorder, the initial placebo effect, or the development of antibodies against Botox (Escher 2017). The body may develop antibodies that bind to the Botox molecule and prevent it from functioning, which may render the Botox ineffective in patients who initially responded well to treatment. This is a rare event, occurring in about 0.5% of all people treated with Botox, although this seems to be more common when Botox is used to treat non-migraine conditions (Jankovic 2023).

There aren’t enough studies to say definitively if Botox is safe during pregnancy and breastfeeding, although the risks to the infant are thought to be low (Organization of Teratology Information Specialists 2023). Botox is not absorbed from the injection site into the bloodstream and Botox is unable to cross the placenta, so theoretically it should be safe to continue using during breastfeeding and pregnancy. There are reports of some patients using Botox during pregnancy that suggested no harm occurred to the
fetus. However, there haven’t been any clinical trials conducted on the effects of Botox use in pregnant or lactating patients to conclude whether Botox use is safe for the infant. The potential risks and benefits of continuing Botox during pregnancy or while breastfeeding should be discussed with your doctor (Trivedi 2017).

Does Botox Change Your Face?

The most well-known use for Botox is for cosmetic purposes to smooth wrinkles in the face. The standard protocol for migraine involves injection of Botox at several sites across the forehead, which are similar in location to areas injected for aesthetics. This may result in the smoothing of horizontal forehead lines and the creases between the eyebrows. Overall, most patients like this cosmetic effect. You may also have less
ability to raise or furrow your eyebrows than usual, however, your forehead shouldn’t appear “frozen” with the doses used for Botox. Regardless of whether you like or dislike these effects, they will also fade over 3-4 months.

There is a small reported risk of developing a slight facial asymmetry with Botox. Most frequently, reports state asymmetric eyebrows, which resolve over 3 months as the Botox effect wears off. For migraine, Botox is not injected in areas of the face that should cause eyebrow or eyelid droop. However, if the Botox shifts to other areas of the face, that may potentially cause this. Because of this reason, most doctors will advise you to avoid washing your face or lying flat for 4 hours after the injections and avoid strenuous exercise and rubbing or massaging the injected areas for the next 24 hours, to ensure that Botox remains in the targeted areas.

Expert Opinions

Botox is an excellent treatment option for certain patients with chronic migraine. Botox works for migraine by a unique mechanism, so even if you haven’t had success with other pills or injections, there is still hope that Botox can be effective in reducing your headache burden. One of the other major upsides of Botox is that there is minimal absorption of Botox into the bloodstream. That means that there aren’t major side effects, so it may be a good choice if you find that you tend to be sensitive to a lot of
medications. Botox is also a good treatment option if you have other medical conditions that prevent the safe use of other preventative drugs.

Botox is currently only FDA-approved for chronic migraine, meaning you have headaches at least 15 days of the month, of which at least 8 are migraine. So not everyone suffering from migraine is a candidate for Botox. Health insurance companies will usually only pay for Botox if you’ve already tried other oral preventative medications that haven’t worked or caused side effects, or have reasons why it would be unsafe for you to take these medications.

References

Ahmed, Fayyaz, et al. "Does analgesic overuse matter? Response to OnabotulinumtoxinA in patients with chronic migraine with or without medication overuse." Springerplus 4 (2015): 1-8.

Aurora, S. K., et al. "OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program." Acta Neurologica Scandinavica 129.1 (2014): 61-70.

Aydinlar, Elif Ilgaz, et al. "OnabotulinumtoxinA effectiveness on chronic migraine, negative emotional states, and sleep quality: a single-center prospective cohort study." The journal of headache and pain 18 (2017): 1-10.

Bendtsen, Lars, et al. "Guideline on the use of onabotulinumtoxinA in chronic migraine: a consensus statement from the European Headache Federation." The Journal of Headache and Pain 19 (2018): 1-10.

Binder, William J., et al. "Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study." Otolaryngology–Head and Neck Surgery 123.6 (2000): 669-676.

Blumenfeld, Andrew M., et al. "Long-term study of the efficacy and safety of OnabotulinumtoxinA for the
prevention of chronic migraine: COMPEL study." The journal of headache and pain 19 (2018): 1-12.

Crowner, Beth E., et al. "Systemic weakness after therapeutic injections of botulinum toxin a: a case series and review of the literature." Clinical neuropharmacology 33.5 (2010): 243-247.

Diener, H. C., et al. "OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind,
randomized, placebo-controlled phase of the PREEMPT 2 trial." Cephalalgia 30.7 (2010): 804-814.

Eross, Eric J., et al. "Duration of migraine is a predictor for response to botulinum toxin type A." Headache: The Journal of Head and Face Pain 45.4 (2005): 308-314.

Escher, Claus M., et al. "Botulinum toxin in the management of chronic migraine: clinical evidence and
experience." Therapeutic advances in neurological disorders 10.2 (2017): 127-135.

Headache Classification Committee of the International Headache Society (IHS). "The international
classification of headache disorders, (beta version)." Cephalalgia 33.9 (2013): 629-808.

Herd, Clare P., et al. "Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine." BMJ open 9.7 (2019): e027953.

Jakubowski, Moshe, et al. "Exploding vs. imploding headache in migraine prophylaxis with botulinum toxin A." Pain 125.3 (2006): 286-295.

Jankovic, Joseph, et al. "Neutralizing antibody formation with OnabotulinumtoxinA (BOTOX®) treatment from global registration studies across multiple indications: a meta-analysis." Toxins 15.5 (2023): 342.

Kim, Christine C., et al. "Predicting migraine responsiveness to botulinum toxin type A injections." Archives of dermatology 146.2 (2010): 159-163.

Lanteri-Minet, Michel, et al. "Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data." Cephalalgia 42.14 (2022): 1543-1564.

Lipton, R. B., et al. "OnabotulinumtoxinA improves the quality of life and reduces the impact of chronic migraine." Neurology 77.15 (2011): 1465-1472.

Locke, Jennifer A., et al. "Systemic muscular weakness after botulinum toxin A administration: a review of the literature." Drugs & Therapy Perspectives 37.7 (2021): 315-327.

Mathew, Ninan T., Jayasree Kailasam, and Lori Meadors. "Predictors of response to botulinum toxin type A
(BoNTA) in chronic daily headache." Headache: The Journal of Head and Face Pain 48.2 (2008): 194-200.

Organization of Teratology Information Specialists. “Mother to Baby Fact Sheets: OnabotulinumtoxinA (Botox)”. Brentwood, TN. Dec 2023. https://www.ncbi.nlm.nih.gov/books/NBK582605/

Ramachandran, Roshni, and Tony L. Yaksh. "Therapeutic use of botulinum toxin in migraine: mechanisms of action." British Journal of Pharmacology 171.18 (2014): 4177-4192.
Silberstein, Stephen D., et al. "OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week
pooled subgroup analysis of patients who had acute headache medication overuse at baseline." Journal of the Neurological Sciences 331.1-2 (2013): 48-56.

Silberstein, Stephen D., et al. "Per cent of patients with chronic migraine who responded per
onabotulinumtoxinA treatment cycle: PREEMPT." Journal of Neurology, Neurosurgery & Psychiatry 86.9
(2015): 996-1001.

Trivedi, M. K., G. Kroumpouzos, and J. E. Murase. "A review of the safety of cosmetic procedures during
pregnancy and lactation." International journal of women's dermatology 3.1 (2017): 6-10.

Meghan Piccinin

Meghan Piccinin, M.D.

Meghan Piccinin is currently an attending neurologist at Allegheny Health Network in Pittsburgh formerly a Headache Medicine Fellow at Cleveland Clinic. 

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