Botox for Chronic Migraine: Effective Patterns and What You Need to Know

Let’s talk about Botox for migraines. Botox (Onabotulinum Toxin A) has been a game changer for the treatment of chronic migraine. I’ve frequently seen it give people their life back (as they often tell me), restored their ability to function normally in all aspects of life, and pulled them from the dark rut of chronic migraine that people get stuck in as described here. It can assist in stopping medication overuse headache (rebound headache), which often accompanies and drives chronic migraine. Once Botox is working, patients can often wean off daily pills being used for migraine prevention. 

Botox is a neurotoxin made by the Clostridium botulinum bacteria. When ingested, it is the same toxin that causes botulism, a severe form of food poisoning. Yes, this concept freaks many patients out. However, the amount used for chronic migraine is a much lower potency and dose, and when used correctly, can be an amazingly helpful medication.

Botox is produced by Allergan (now an AbbVie company), and was FDA approved for the treatment of chronic migraine in October 2010 following this study. Since that time, it has technically remained the only truly FDA-approved treatment specifically indicated for the treatment of chronic migraine prevention. With that said, the array of standard preventive migraine treatments as well as the CGRP monoclonal antibodies are also commonly used for all spectrum of migraine from episodic migraine (14 or less headache days per month) to chronic migraine (15 or more headache days per month).

Most insurances will generally require a failure of at least 2 categories of standard preventive medications before they will approve Botox coverage. With that said, 98% of commercial insurance plans cover Botox, and it’s actually fairly easy to get it approved through Medicare and Medicaid. In addition, Allergan provides a Botox Savings Program which will cover $1000 of any out of pocket costs per treatment and $4000 per year. So for most patients, Botox treatments can be covered 100% between this savings program and insurance coverage.

It is my hope that this blog can provide the education and guidance in optimizing Botox procedure precision and technique (based off the PREEMPT chronic migraine protocol with tweaks) for medical providers to give optimal results, as well as a great educational overview on Botox for patients so they have a better idea of how Botox works, the best pattern to get (which can be shared with their doctors), and what to expect in terms of how long it takes to work, suggested duration of use, side effects, and safety in pregnancy and breastfeeding.

How does Botox work for chronic migraine?

The primary and most important mechanism of how Botox works for chronic migraine is by disrupting the electrical communication signals of pain between nerves involved in migraine pathophysiology and ultimately stopping these signals from reaching the pain circuitry of the brain. Thus, it prevents the activation of pain and migraine networks in the brain, including disruption of CGRP activity, which has become a central focus in most of the new migraine medications on the market such as the gepants and CGRP monoclonal antibodies.

Botox does this by entering the nerve endings and cleaving a specific protein called SNAP25. The inactivation of this protein leads to the inhibition (stopping) of neurotransmitter and neuropeptide release from the nerve endings and the prevention of the electrical pain signals from firing off. It also causes temporary (3 months) paralysis of the muscle being innervated by those nerve endings. Thus, it also causes the muscles to chemically relax (by chemically paralyzing them). For example, this muscle relaxation is why Botox works for facial wrinkles. It causes the thin muscular layers to relax to where they can’t contract (and wrinkle the skin), and wrinkles go away. Interestingly, one of the early clues that led to Botox being studied for migraine treatment was that women who were getting Botox were also noticing that they would have much less migraine headaches. This eventually led to further trials looking at Botox treatment to prevent migraine.

How long does it take for Botox to work, how long should Botox be used for chronic migraine, and how effective is Botox?

Botox typically starts to kick in within 1-2 weeks, but many times patients say they feel it working within a day or so after they have been getting it for a while. Botox lasts about 3 months. Patients commonly notice some gradually increasing migraines 1-2 weeks or so before getting to the 3-month wear-off window. I have quite a few patients that can actually get a good 4 months out of a treatment, but that is not common. If patients consistently start to come in for their 3-month Botox appointment and migraines are not starting to increase significantly as it is wearing off, I will often try to extend the next treatment to 4 months. If they are still doing well at that time, I suggest that we try stopping it to see if the migraines have entered and sustained into a more infrequent episodic pattern. It can always be restarted if needed in the future. It should be avoided from repeating much earlier than 3 months because early dosing before the prior dose has worn off can lead to cumulative medication and subsequent side effects. This can also increase the risk of antibody formation against Botox which can make it less effective over time.

It is recommended to give the Botox a minimum of 2 rounds 3 months apart to get a good sense of how much benefit one can likely expect. The reason for this is that in the trials after the 2^nd round, there was continued upwards improvement. With that said, I typically expect (and usually see) good improvement with the 1^st round. Some doctors advocate for giving a full year (4 rounds separated by 3-month intervals) to see the full effect. However, I typically tell patients if they have gotten absolutely no benefit after the 2^nd round that we should move on to another treatment option. On average, Botox decreased chronic migraine days by 8-9 days per month, as opposed to placebo which was 6-7 days per month.

What are the Botox side effects?

A great thing about Botox is that it is so well tolerated with much lower side effect risks compared to many of the medications used for migraine prevention. I’ve done thousands of Botox treatments and have never seen someone have a bad reaction or an allergic response. In general, I tell patients there may be some tenderness in the injection sites temporarily. It is a very tiny needle injected just under the skin in a specific standardized dosing pattern and takes only a few minutes. Infrequently, patients can have a temporary flu-like muscle achiness for a day or so after the Botox. If the Botox spreads into some of the muscles in the forehead, I always mention that there is a risk of eye lid droopiness (ptosis), although I have not seen this occur. A more extensive list of potential side effect risks (which are extremely rare and I’ve not seen), can be read on the Botox for chronic migraine Allergan website. Caution is also advised if Botox is mixed with bupivacaine or other “caine” medications as this can be a fairly common allergy of some patients to these medications.

Can I get Botox with the Covid-19 vaccine?

The short answer is that we need to gather more data on this, so check back periodically for updates. However, this hasn’t been a reported issue thus far. There is no current evidence for an interaction between the Covid-19 vaccine and Botox injections, the same as any other vaccine. This has also been stated by the American Migraine Foundation. Patients receiving Botox were not excluded from the Covid-19 vaccine trials. There is no evidence at this time that Botox can not be used along with receiving Covid-19 vaccination, nor does it need to be delayed or timed any differently in relation to receiving Covid-19 vaccination. Most physicians feel that there should theoretically be no interaction or contraindication to receiving both because they are entirely different proteins with different mechanisms of action. The Covid-19 vaccine stimulates the immune system to form antibodies against the virus, should you encounter it.  However, Botox does not have any significant influence on the immune system (it does not cause immunosuppression, etc). Rarely, the immune system of some patients can form neutralizing antibodies against Botox, and this can weaken Botox’s effectiveness in decreasing migraine frequency and severity. However, this issue really has nothing to do with the mechanism and how the Covid-19 vaccine works. So, it is not felt that the Covid-19 vaccine will lessen the effectiveness of Botox, nor will Botox lessen the effectiveness of the Covid-19 vaccine. The topic of Covid-19 headache, Covid-19 vaccination, and the use of Botox or CGRP monoclonal antibodies (Aimovig, Ajovy, Emgality, Vyepti) is discussed further here.

Notably, there have been just a few isolated reports of dermal fillers used in dermatology causing some facial swelling in association with Covid-19 vaccination. These reports were with the Moderna Covid vaccine and resolved with steroids and/or antihistamines.

Is Botox safe in breastfeeding and pregnancy?

Historically, Botox has generally been avoided and saved as a last resort option in these scenarios, and often still is. The longstanding concern for using Botox during breastfeeding is based in theoretical concern that the Botox could seep into the breastmilk and effect the baby, although this really hasn’t been reported. It has been shown that Botox is not detectable in the blood after intramuscular use, so excretion into breast milk is considered unlikely. In fact, there was a reported case of a lactating woman who had foodborne botulism. However, when the breastmilk and infant were analyzed, neither showed any botulinum toxin at all, and the infant was safely breastfed. With this in mind, the doses of Botox used medically are much lower than those that cause botulism. Therefore, the amounts ingested by an infant, if any, are suspected to be small and not cause any adverse effects in breastfed infants. Regardless, for extra precaution, it is suggested to breastfeed before the Botox treatment, store some milk, and then 24 hours after the treatment before breastfeeding again (so plenty of milk should be saved ahead of time).

Similar to breastfeeding, there are no published studies on Botox use during pregnancy. So, it is still often avoided if possible and saved as a last resort option. However, since Botox is not detectable in the blood after intramuscular use it is not expected to affect fertility or pregnancy outcomes, and an Allergan safety database report has remained consistent with this conclusion. Botox is designated as a US Food and Drug Administration (FDA) pregnancy category C medicine, meaning that there are no well controlled studies in pregnant women, so it should only be used during pregnancy if the benefits outweigh the potential risks. The good thing is that the majority of women naturally get significant migraine improvement during pregnancy (especially 2^nd and 3^rd trimester) and it is not uncommon to hear migraines go away during pregnancy. So many times preventive therapy may not even be necessary.

What is the best way to do Botox for chronic migraine?

If you are going to get Botox, you need to make sure you are getting the optimal dose, pattern, and technique. A headache specialist will have the most refined technique and experience doing Botox injections, and should be sought out to ensure you are getting the best technique if one is available near you. If you cannot find a headache specialist near you, make sure whomever you get the Botox injections from does them very frequently with good reviews. Other doctors that may do Botox injections as alternatives if a headache specialist is not available include some neurologists, pain management doctors, and primary care doctors, as well as some physician assistants (PA) and nurse practitioners (NP). With knowledge of the precise pattern and technique as outlined below, and enough practice, anyone should be able to do Botox procedures proficiently in the office. It is an easy procedure and can provide dramatic improvement in chronic migraine pain and disability.

The pattern that should be used and modeled after is the PREEMPT protocol (Phase III REsearch Evaluating Migraine Prophylaxis Therapy), based off the trial that led to FDA approval for Botox in the prevention of chronic migraine. The pattern of injections described and illustrated below are of the PREEMPT protocol. However, sometimes I will tweak some of the injection sites depending on the patient’s pain pattern. For example, if their chronic migraine is 100% one sided, I may give additional on that side in the temporalis muscle and occipital regions, taken from the opposite side where they have no or minimal pain. If they have prominent occipital neuralgia, then I will give additional dosing over the correlating occipital nerves.

The PREEMPT protocol used 155-195 units of Botox. Botox vials come in 200 units (either two 100 unit vials or one 200 unit vial). For almost all patients, I use the full 200 units and spread the additional 5 between the trapezius muscles, or use it somewhere else where the pain is most common such as over an occipital nerve in the back of the head. I may use slightly less in patients that have no pain at all in many areas of the head or shoulders and have a very localized pain (such as just in one side of the forehead), are elderly, or young in late teens or early twenties and have not had it before.

Regardless, many of the spots the patient may receive it in, they may not have much pain. However, there should still be some degree of symmetry for muscle weakness balance and to still hit potential areas of chronic migraine input that aren’t recognized as overly painful areas by the patient. I also prefer to gently and briefly rub in the Botox spots right after injection. This helps to distract the brain from the immediate injection pain, flattens the area so it doesn’t leave the Botox as a small lump, and helps to slightly spread the area of coverage for the Botox to work. I like to hit as many of those sensory nerve fibers (the primary target of Botox for chronic migraine) and neuromuscular junctions as possible with each injection.

The depth of injection isn’t supposed to be deep. So if the needle is hitting the bone, it is too deep and will be less effective. The target of the injections is just below the skin and into the top of the muscle. This is where the sensory nerves travel (carrying migraine/headache/pain signals to the brain) and neuromuscular junctions lie (where the nerves that innervate and control the muscles enter the muscle). The sensory nerves traveling just above the muscular layer is really the main target of the Botox for chronic migraine.

So, I like to be strategic where the Botox goes. If your doctor or health care provider is just rapid firing it in (which is always more painful), hitting the bone, you have Botox running down your face, it is more painful than when you get it done with other providers, or you get eye-lid droopiness (ptosis), you should think about moving on to someone with a more refined technique. I see patients all the time that have been getting Botox with me and then they have to get a round sometimes with a different provider for some reason. They invariably say it doesn’t work as well, is significantly more painful, and afterwards they refuse to get Botox with anyone else besides me following that experience. There is validity in that. I’ve spoken to one of the main doctors/scientists involved with developing the original Botox pattern, technique, and dosing for chronic migraine and he agreed that technique and spreading the Botox around strategically and precisely will certainly lead to a better result as opposed to just quickly and less carefully “throwing the injections in”. In fact, they were originally thinking of adding more spots to further spread the Botox around to hit more nerve endings, but they settled on the current pattern to make it easier and less complex to do.

The Botox trials were done by mixing Botox in 0.9% normal saline (basically, sterile water). However, I will sometimes mix the Botox instead with a numbing medicine such as bupivacaine or ropivacaine. The Botox typically takes about 1-2 weeks to start kicking in. So the addition of a numbing medicine can provide some temporary relief as the Botox is slowly kicking in. Many times chronic migraine patients are significantly tender throughout their head to the point the hair can “hurt” and feel sore. This is called allodynia, or central sensitization, and is a common finding in chronic migraine. The additional numbing medicine can also provide some temporary relief throughout some of these sore areas. In most patients, they have tenderness over their occipital nerves in the back of the head (occipital neuralgia), and this can also provide some additional temporary relief over these nerves. Many chronic migraine patients also have tenderness throughout their shoulders, and many have associated fibromyalgia. This can also be helpful with some temporary relief through these muscles, and in a way is like getting trigger point injections at the same time.

So, let’s go over the treatment pattern that I have seen to be most useful. First, you will need to get the supplies together, of course. For doctors and health care providers who are here to learn how to do Botox or fine-tune their skills, a detailed video of what you need and how to draw up the Botox can be seen here. I won’t go through the detailed steps here in mixing and drawing the Botox up, but in short, you will need:

-Botox 200 units (100 unit vials x 2 are typically used, but single 200 unit vials available too)

-1 cc syringes x 4

-3 cc syringe x 1 (to draw up diluent and mix in Botox vial)

-30 gauge ½ inch needles x 4 (to place on end of 1 cc syringes prior to injections)

-18-22 gauge needle x 1 (to place on end of 3 cc syringe to draw up diluent and mix in Botox vial)

-0.9% normal saline vial x 1 (alternatively can consider 0.25% bupivacaine or similar)

-Alcohol pads

-Gauze pads

The Botox procedure: Face and frontal regions of head (frontalis and corrugator muscles)

For these injections, I prefer to have the patient lying supine on their back and I stand at the head of the exam table behind them. That way they don’t see the needle coming towards their face and all spots are easily accessed from the top and sides of the patient. These spots are pretty standard in all patients. The things to keep in mind are not doing the Botox too low in the forehead. This can cause ptosis, eyelid droop, and asymmetric eyebrow pointing (think Joker in Batman). I typically inject somewhere just below the hair line and in the very top edge portion of the frontalis muscles or just above it. The 1^stfrontalis muscle injection is identified as drawing an imaginary line from mid-pupil up to the top of the frontalis muscle and injecting there. The 2^nd is in a horizontal line about a half inch medial to the first injection on each side. The procerus is injected at approximately the middle of the brow right between the eyebrows. The corrugators are injected just lateral to each side of this central injection, about a half inch to each side. All injection sites are 5 units.

The Botox procedure: Side of head (temporalis muscles)

For these injections, I prefer to have the patient lying supine on their back and I stand at the head of the exam table behind them. That way they don’t see the needle coming towards their face and all spots are easily accessed from the sides of the patient. The way that I teach our headache fellows and other staff to do the temporalis muscles are to have the patient clench their jaw and feel for the temporalis muscle to contract. This is felt at the anterior point of the muscle just behind the hair line in the temple region. This is the 1^st injection. From here, imagine a triangle with this 1^st injection as the 1^stpoint in the triangle. Then draw an imaginary triangle from here extending further back on the side of the head with the next 2 injection points above and below (see illustration) this 1^st point. Then from here, imagine a square connected to the triangle. The next 2 injection points are horizontal and further back from the prior 2 injections points. All injection sites are 5 units.

The Botox procedure: Back of head (cervical paraspinal and occipitalis muscles)

For these injections, I prefer to have the patient sitting up on the exam table with their legs hanging over 1 side. I stand on the opposite side of the exam table behind them. The cervical paraspinal muscles are injected 1^st on each side. The 1^st cervical injection site is located by feeling the occipital protuberance (bump in the middle along the skull base), and going 2 fingerbreadths down and 1 over. This happens to be where the greater occipital nerve pierces through the musculature, and is also the first site of where occipital nerve blocks are done. The 2^nd cervical injection site is located just superior and lateral to the 1^st injection site.

Next come the 4 occipitalis muscle injections. These are done along the skull base and are evenly spaced out. The 1^st site is just lateral to the occipital protuberance. The 2^nd site is lateral to the 1^st over the occipital groove (this is a palpable groove). This is where the occipital nerve travels, and is also the 2^nd site where I normally do an occipital nerve block. The 3^rd site is lateral to the 2^nd site. The 4^th site is lateral to the 3^rd site and is located just posterior to the mastoid bone in another palpable groove. This also happens to be where the lesser occipital nerve travels, and is typically the 3^rdspot I usually do for an occipital nerve block.

If the patient has prominent occipital neuralgia on one or both sides, instead of the standard 5 units over the occipital groove region (where the occipital nerves travel), I will inject 10 units at once and take that extra dose away from the shoulder or temporalis muscle regions (depending on where they typically have the least amount of pain and may not need it as much). Otherwise, all injection sites are normally 5 units. Notice that the PREEMPT protocol does not include Botox injections further down through the neck. The reason is because this can often increase headaches and can cause head drop to the point where some patients may need to wear a soft collar for 3 months. Therefore, this area should be avoided.

The Botox procedure: Shoulders (trapezius muscles)

For these injections, I prefer to have the patient sitting up on the exam table with their legs hanging over 1 side. I stand on the opposite side of the exam table behind them. Patients with chronic migraine most often have a lot of neck and shoulder pain. 70% of patients that get a migraine will get pain and tightness in these regions. So, if they are stuck in a smoldering cycle of chronic migraine and high frequency headaches, it would make sense that they would have a lot pain and tightness in these areas. Many patients also have concurrent fibromyalgia, so these injections can also be helpful, similar to trigger point injections.

The 1^st 3 injections are along the top ridge of the trapezius muscle. If you feel the superior medial corner of the scapula, there is invariably a tender point and knot here. This is the 4^th injection site. The 5^th site is in the middle of the trapezius muscle bulk. This is the end of the PREEMPT protocol dosing. However, the last 5 units that is left over I typically split between sides by giving 2.5 units somewhere in the trapezius region on each side where there may be a tender or trigger point, or I’ll just give it all on one side if they have more spasm or pain on one side compared to the other.

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