Can botulinum toxin injections for headaches make your symptoms worse?

Ross Hauser, MD

When botulinum toxin injections for headaches make your symptoms worse

Article outline:

• Why were you or why are you being recommended for botulinum toxin injections then?
• Two-thirds of people will get a more than 50% reduction in headache from botulinum toxin injections some of the time. One-third of patients will not.
• Still, some uncertainties and concerns were issued regarding botulinum toxin A injections.
• Study: “For people with episodic migraine, we remain uncertain whether or not (Botulinum toxin) is effective.”
• Botulinum toxin A does not afford any additional benefit over acute medical withdrawal alone in study patients with migraine headaches.
• When botulinum toxin injections are said to work, are they long-lasting? How long do they last?
• The effect of three Botox® injections every month for upwards of 33 months on migraines
• “There is no headache in the world that is caused by botulism toxin deficiency.”

For some people, botulinum toxin injections (Botox^®) will help relieve a good portion of their headache symptoms, headache severity, and headache frequency.

For some people, botulinum toxin injections (Botox^®) will help relieve a good portion of their headache symptoms, headache severity, and headache frequency.  For some people, botulinum toxin injections will make their headache symptoms, headache severity, and headache frequency worse. In this article, I will discuss how botulinum toxin injections may affect you.

If you are reading this article you are likely someone who was recently recommended botulinum toxin injections for headaches and you would like to learn a little more, or, you are someone who had botulinum toxin injections and not only did the injections not help you, they made your situation worse and now you are looking for possible answers. You may also be someone who had botulinum toxin injections with great success and you are wondering why they are now “wearing off,” and your headaches have returned.

The people we see in our office are not the people who had great long-term success with botulinum toxin injections. We see the people for whom the headaches got worse and as the headaches got worse, so did other neurological problems such as vision difficulties, hearing difficulties, dizziness, and more.

Some people contact us after their first series of botulinum toxin injections. They had a treatment  “a few weeks back,” yet they still have terrible muscle spasms, their headaches are just as bad as they have been, and now they have developed new neck pain. They are here in our office to find out why.

Again, let me point out that many people have very successful botulinum toxin injections for their headaches. This article will be about some of the people we have seen, who did not.

Injections of botulinum toxin are typically recommended for certain types of headaches. Because muscle tension is a part of the pain of cervicogenic headaches, the paralysis of certain muscles reduces the pain, but again this is pain management it is not addressing a more curative long-term aspect.

In the video below I will explain some of the problems we see and give an introduction to our alternative options to botulinum toxin injections.

Summary transcript

• I get a lot of inquiries from people who feel like botulinum toxin injections made them worse and then in fact it actually did.
• When you get botulinum toxin injections it causes atrophy of muscles.
• If you have an injection of botulinum toxin into a muscle in your neck, that muscle, being injected and prone to atrophy, may be protecting you from cervical instability. It is relatively common for people to get botulinum toxin injections for headaches in the upper back of the neck and if the botulin toxin affects the obliquus capitis inferior muscle, that muscle is going to atrophy.
• That muscle helps stabilize the C2 so when that muscle is weakened the C2 rotates out of proper alignment.

At 1:10 of the video, Dr. Hauser describes how botulinum toxin injections can impact the obliquus capitis inferior muscle, the muscle that helps stabilize the C2.

What are we seeing in this still image from the video?

When you get botulinum toxin injections it can cause atrophy of muscles. If you have an injection of botulinum toxin into a muscle in your neck you may be limiting or preventing that muscle from protecting you from cervical instability. If the botulin toxin affects the obliquus capitis inferior muscle, the muscle that helps stabilize the C2, that vertebrae will rotate out of its natural position and can compress the vagus nerve it can cause a pinching of the C2 nerve root.

• If the botulin toxin affects the obliquus capitis inferior muscle, the muscle that helps stabilize the C2, that vertebrae will rotate out of its natural position and can compress the vagus nerve and it can cause a pinching of the C2 nerve root which turns into the occipital nerve and give you occipital neuralgia.
• These neck muscles are needed to protect the stability of the C1-C2-C0 area. Botulin toxin can create weakness in these muscles and cause worsening cervical instability.
• Worsening cervical instability is why many people have headaches and symptoms that worsen. The botulin toxin has atrophied the muscles.

What are we seeing in this image?

The possible impact of botulinum toxin injections at the location and relation between the suboccipital muscles to the C1 vertebra – the Atlas, and the C2 vertebra – the Axis and the path of the occipital nerve is illustrated. Upper cervical spine instability at C1-C2 can cause pressure on the base of the spine resulting in the contraction and spasm of the suboccipital muscle. This can cause headaches, migraines, and occipital neuralgia. 

Why were you or why are you being recommended for botulinum toxin injections then?

Botulinum toxin injections can help many people. These are typically the people we do not see in our office. We see the people as I mentioned earlier in this article who had botulinum toxin injections and continue to have headaches and worsening symptoms related to Cervical dystonia, also called spasmodic torticollis.

In an April 2020 study, researchers in Italy wrote in The Journal of Headache and Pain (1) to describe the benefits that some may achieve with botulinum toxin injections. They also suggest to their fellow doctors which patients may benefit the most or the least from Botulinum toxin injections. Here are the summary learning points:

Two-thirds of people will get a more than 50% reduction in headache from botulinum toxin injections some of the time. One-third of patients will not.

• Treatment with botulinum toxin A is safe and effective for chronic migraine. Several studies assessed possible predictors of response to treatment with botulinum toxin A, but there is little knowledge on the frequency and predictors of sustained response.
• 115 patients (84.3% female; the average age of 50 years had an average migraine duration of 30 years)  with chronic migraine were treated with botulinum toxin A and followed up for 15 months.
• Patients who achieved a more than 50% reduction in headache days during any three-month treatment cycle compared with the 3 months prior to initiation of botulinum toxin were considered “Anytime responders.” Patients who achieve a 50% reduction in headache during at least one of the three-month period as compared to pre-treatment.
• Patients who were “Sustained responders” are people who achieved a more than 50% reduction in headache days within the third treatment cycle and maintained response until the end of follow-up.
• Non-responders were defined as those patients who never achieved a more than 50% reduction in headache days during the follow-up.
• At the end of the follow-up, 66 patients (57.4%) were classified as anytime responders.
• Among the 51 patients who achieved a clinical response within the third month of treatment, 33 (64.7%) were sustained, responders.

Success is seen as fewer headache days within a 15-month period. For some people, any relief is seen as successful. But from most botulinum toxin injections, as successful as reported here, it is not curative.

Two late 2020 studies do however confirm success rates:

A December 2020 study in the journal Pain and Therapy noted outcomes at 24 weeks:(2)

“Treatment with on botulinum toxin A for 24 weeks was associated with clinically meaningful benefits beyond a reduction in headache days; including reductions in headache severity and headache-related impact, and improved quality of life. . .over 70% (of qualified participants) had clinically meaningful improvements on at least one outcome measure. (Reduction in headache days, severity, etc).”

In a separate December 2020 paper, the same research team added, that botulinum toxin A worked better than a placebo. (3)

A March 2022 study published in the journal Pain Research and Management (10) found the use of botulinum toxin type-A is a low-cost option for the treatment of various kinds of migraines, including chronic, episodic, unilateral, and vestibular types. Botulinum toxin type-A can reduce the frequency of migraine attacks per month and diminish the severity of pain.”

Still, some uncertainties and concerns issued on botulinum toxin A injections

There are also warnings issued on botulinum toxin A injections. That warning comes from the United States Library of Medicine (Medline Plus)(4)

• “Onabotulinumtoxin A injection is given as a number of tiny injections intended to affect only the specific area where injected. However, it is possible that the medication may spread from the area of injection and affect muscles in other areas of the body. If the muscles that control breathing and swallowing are affected, you may develop severe problems breathing or swallowing that may last for several months and may cause death. If you have difficulty swallowing, you may need to be fed through a feeding tube to avoid getting food or drink into your lungs.”

Study: “For people with episodic migraine, we remain uncertain whether or not (Botulinum toxin) is effective.”

Researchers at the Institute of Applied Health Research, University of Birmingham wrote (June 2018) in The Cochrane Database of Systematic Reviews: (5)

• “In chronic migraine, botulinum toxin type A (Onabotulinumtoxin A) may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non-serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low.”

Botulinum toxin A does not afford any additional benefit over acute medical withdrawal alone in study patients with migraine headaches.

A May 2019 randomized controlled trial outcome studying the impact of acute withdrawal, medication overuse, and botulinum toxin A in chronic migraine was published in the medical journal Brain (8) by researchers at the Department of Neurology, Leiden University Medical Centre in the Netherlands. Here are the summary points.

“Botulinum toxin A  is widely used as a treatment of chronic migraine. Efficacy in studies, however, was only modest and likely influenced by unblinding due to Botulinum toxin A-induced removal of forehead wrinkles. Moreover, most study participants were overusing acute headache medications and might have benefitted from withdrawal.”

What the researchers are saying is that studies may not be accurate because the Botulinum toxin A was given into the forehead and the “blinded” researchers started to recognize that some of the study’s patients had fewer forehead wrinkles and thus assumed it was those patients who were getting the botox injections and this could have skewed results. Another problem identified was that many of the headache patients in this study were overusing medications.

The goal then of this study was to see if in a double-blind, placebo-controlled, randomized clinical trial whether add-on therapy with Botulinum toxin A enhances the effectiveness of acute withdrawal of medications in patients suffering from headaches.

•  A total of 179 participants, male and female, aged 18-65, diagnosed with chronic migraine and overuse of acute headache medication were included.
• All participants were instructed to withdraw acutely from all medication for a 12-week period, in an outpatient setting.
• In addition, they were randomly assigned (1:1) to 31 injections with Botulinum toxin A or placebo (saline); to prevent unblinding, placebo-treated participants received low doses of Botulinum toxin A in the forehead, along with saline injections outside the forehead region.
  • Results: Botulinum toxin A did not reduce monthly headache days versus placebo.
  • Absolute changes in migraine days at 12 weeks for Botulinum toxin A versus placebo were -6.2 days versus -7.0 days.
  • Other secondary endpoints, including measures for disability and quality of life, did also not differ.
  • The withdrawal was well tolerated and blinding was successful. Thus, in patients with chronic migraine and medication overuse, Botulinum toxin A does not afford any additional benefit over acute withdrawal alone. Acute withdrawal should be tried first before initiating more expensive treatment with Botulinum toxin A.

When botulinum toxin injections are said to work, are they long-lasting? How long do they last?

An October 2021 study (6) examined 80 patients (70 females and 10 males) with chronic migraine were included. In this study, doctors from two of Turkey’s leading hospitals’ Departments of Neurology gave Onabotulinumtoxin A across 31 fixed-sites, and if the patient had pain, lesser dose injections were applied across 8 specific head/neck muscle areas. Headache days and analgesic intake were noted before the Onabotulinumtoxin A injection and during the interviews during the first, second, and third months after the Onabotulinumtoxin A injection.

• The average number of headache days per month before Onabotulinumtoxin A treatment was about 19 days.
• This number decreased to 10.5 days per month in the first month
• This number decreased to 9.3 days per month in the second month
• But this number increased to just about 12 days per month in the third month

Pain medication needed:

• The average pain medication analgesic intake before Onabotulinumtoxin A was 11.5 tablet units a month
• This number decreased to 6.5  tablet units a month in the first month
• This number decreased to 5.4  tablet units a month in the second month
• In the third month, it increased to 5.85 tablet units a month. The researchers called this “a significant increase in pain medication use from the second to the third month.”

“There was a significant reduction in analgesic intake and headache days in the first and second months after Onabotulinumtoxin A injection, and an increase was observed in the third month”

The researchers here concluded: “there was a significant reduction in analgesic intake and headache days in the first and second months after Onabotulinumtoxin A injection, and an increase was observed in the third month.”

Stanford Hospital and Clinics, Medstar Georgetown University, the Ain Shams University Faculty of Medicine in Cairo, the Mayo Clinic, and the University of California, San Diego compared the effectiveness of percutaneous interventional treatments for the prevention of migraine. This is from the study published in August 2021 in the journal Pain Medicine (7): “An expert panel was asked to develop recommendations for the multidisciplinary preventive treatment of migraine, including interventional strategies. The committee conducted a systematic review and (when evidence was sufficient) a meta-analytic review  (an examination of multiple studies that had been previously published). . . ” The goal was to help determine which adults with migraine should be offered prevention.

The committee agreed to assess the data from 16 previously published studies. This is what they found in comparing treatments:

• Onabotulinumtoxin A received a strong recommendation for chronic migraine prevention and a weak recommendation against use for episodic migraine prevention.
• Greater occipital nerve blocks received a weak recommendation for chronic migraine prevention.
• For greater occipital nerve block, steroids received a weak recommendation against use vs local anesthetic alone.
• Occipital nerve with supraorbital nerve blocks, sphenopalatine ganglion blocks, cervical spine percutaneous interventions, and implantable stimulation all received weak recommendations for chronic migraine prevention.
• The committee found insufficient evidence to assess trigger point injections in migraine prevention and highly discouraged use of intrathecal medication (“pain pumps”).

The effect of three Botox® injections every month for upwards of 33 months on migraines

A February 2022 study (9) led by the University College London and The National Hospital for Neurology and Neurosurgery, London reported on the effectiveness of botulinum toxin-A, Botox® (Allergan), in unmanageable chronic migraine patients non-responsive to previous pharmacological management and with largely no pain-free time, including those with new-onset daily persistent headache.

• Thirty-three patients, all with severe Headache Impact Test (HIT)-6 scores (a scoring system to determine the impact headaches had on the patient’s quality of life) at baseline, received 3-monthly injections of Botox®  over a maximum 33-month period.
  • Four patients had headaches at least 20 days a month;
  • the remaining patients had a daily headache with no pain-free time, including nine patients with new-onset persistent migraine.
• There was a significant reduction in HIT-6 scores following Botox® therapy.
• Twenty-one percent of the group exhibited a sustained reduction in HIT-6 scores.
  • The number of headache days and pain-free time did not change in five of the six responders, but disability improved.

“There is no headache in the world that is caused by botulism toxin deficiency.”
Treating botulism toxin deficiency is not a long-term resolution of the problem.

The above studies are cited as pain management studies because that is what the treatments do, manage pain. However, your neck does not become painful or unstable because you are deficient in botulinum toxin. You do not get headaches because of botulinum toxin deficiency. You get headaches and muscle spasms because the muscles are trying to hold your neck in proper ailment because you may have cervical capsular ligament damage and weakness. Botulinum toxin does not treat this problem.

In the illustration below we see a great variation at C1 – C2 in the flexion (head bent forward, chin in chest) and extension (head bent backward, chin in air) positions. This is a demonstration of cervical instability caused by cervical ligament damage or weakness. It is the ligaments that hold the vertebrae in place. When the ligaments fail, the muscles then try to take over the job of maintaining cervical stability. It is a difficult job for the muscles because that is not their intended job. That is why muscles become fatigued and tired and go into spasms.

As I discussed above:

• If the botulin toxin affects the obliquus capitis inferior muscle, the muscle that helps stabilize the C2, that vertebrae will rotate out of its natural position and can compress the vagus nerve and it can cause a pinching of the C2 nerve root which turns into the occipital nerve and give you occipital neuralgia.
• Botulin toxin can create weakness in these muscles and cause worsening cervical instability.
• Worsening cervical instability is why many people have headaches and symptoms that worsen. Over time the botulinum toxin injections have contributed to muscle atrophy and continued spasm.

What are we seeing in this image?

In the illustration, we see a great variation at C1 – C2 in the flexion (head bent forward, chin in chest) and extension (head bent backward, chin in air) positions. This is a demonstration of cervical instability caused by cervical ligament damage or weakness. It is the ligaments that hold the vertebrae in place. When the ligaments fail, the muscles then try to take over the job of maintaining cervical stability. It is a difficult job for the muscles because that is not their intended job. That is why muscles become fatigued and tired and go into spasms.

In this video, Ross Hauser, MD explains and demonstrates the use of Digital Motion X-ray (DMX) to help identify cervical neck and spine instability in the C1-C2 region in a patient with severe migraines.

The summary transcript of this video, with explanatory notes, is below the video.

Summary transcript:

I am going to demonstrate how we diagnose and plan treatments for a patient we suspect upper cervical spine instability as the cause of migraine headaches. In this video Digital Motion X-ray DMX is utilized to demonstrate the clues and signs of cervical spine instability, especially that surrounding the Dens or the C2 vertebrae.

• The patient in this video suffered a whiplash injury in 2011.
• The patient has migraine headaches every day, horrible pain behind the eyes, terrible neck pain, he has clicking, grinding, and crunching in his neck.

At the 1:00 mark of the video, the Digital Motion X-ray DMX of the patient’s cervical spine instability is demonstrated.

• As seen in the video, the DMX we see tilting of the C1 vertebrae is tilted through the full range of motion and this is one of the first signs that we see that a person has upper cervical instability.
• In the DMX open mouth view (At 1:18) the video we’re looking for several things the first thing is the symmetry of the C2 vertebrae this is where the Dens and the spinous process, the bony protrusion at the back of the vertebrae,  should be aligned with the Dens. In this particular patient, the C2 is shifted to the left. This misalignment, caused by cervical spine instability, is the reason that the person has migraine headaches primarily on their left side. That shift can be corrected with Prolotherapy. (Prolotherapy is a series of injections of simple dextrose. Below we will discuss the treatment further as well as provide medical research findings supporting its use in selected patients). This patient had 4 Prolotherapy treatments, his headaches are at a minimum. He will need a few more treatments to stabilize his cervical spine and further reduce and eliminate his migraines.

Prolotherapy injections for upper cervical c1-c2

This is the treatment we offer as an alternative to botulinum toxin injections. Prolotherapy does not address muscle spasms by causing a shut down of the spasms, it addresses cervical instability by addressing and repairing the damaged cervical ligaments.

Related articles:

If you are seeking information on botulinum toxin injections for a specific diagnosis. I invite you to continue your research on these pages dedicated to your diagnosis

• Vestibular migraine and spontaneous vertigo – Migraine Associated Vertigo
• Cervical dystonia and spasmodic torticollis treatment
• Cluster headache treatment – cervical ligament instability and the trigeminal and vagus nerves
• Cervicogenic headaches – Migraines, tension headaches, and cervical spine instability

Summary and contact us. Can we help you? How do I know if I’m a good candidate?

The main medicines used to abort severe headache and migraine pain, such as ergotamine, and sumatriptan, constrict the blood vessels. These medicines work, but only temporarily. The medicines act on the symptom of the dysfunction, but not the cause. The correlation is between cervical instability and sympathetic symptoms.¹³ Thus, the benefit is only temporary. Prolotherapy to the vertebrae in the neck is the treatment of choice to permanently eliminate cervicocranial syndrome. This occurs because Prolotherapy causes the vertebrae in the neck to move posteriorly (back) and no longer pinch the sympathetic nerves.

We hope you found this article informative and that it helped answer many of the questions you may have surrounding your headaches. Just like you, we want to make sure you are a good fit for our clinic prior to accepting your case. While our mission is to help as many people with chronic pain as we can, sadly, we cannot accept all cases. We have a multi-step process so our team can really get to know you and your case to ensure that it sounds like you are a good fit for the unique testing and treatments that we offer here.

Please visit the Hauser Neck Center Patient Candidate Form

References

1 Ornello R, Guerzoni S, Baraldi C, Evangelista L, Frattale I, Marini C, Tiseo C, Pistoia F, Sacco S. Sustained response to onabotulinumtoxin A in patients with chronic migraine: real-life data. The Journal of Headache and Pain. 2020 Dec;21:1-0. [Google Scholar]
2 Diener HC, Dodick DW, Lipton RB, Adams AM, DeGryse RE, Silberstein SD. Benefits beyond headache days with onabotulinumtoxinA treatment: a pooled PREEMPT analysis. Pain and Therapy. 2020 Dec;9(2):683-94. [Google Scholar]
3 Silberstein SD, Diener HC, Dodick DW, Adams AM, DeGryse RE, Lipton RB. The impact of onabotulinumtoxin A vs. placebo on efficacy outcomes in headache day responder and nonresponder patients with chronic migraine. Pain and Therapy. 2020 Dec;9(2):695-707. [Google Scholar]
4 Onabotulinumtoxin A Injection at MedLine Plus United States Library of Medicine.
5 Herd CP, Tomlinson CL, Rick C, Scotton WJ, Edwards J, Ives N, Clarke CE, Sinclair A. Botulinum toxins for the prevention of migraine in adults. Cochrane Database of Systematic Reviews. 2018(6). [Google Scholar]
6 Pak AT, Üstün İ, Sengul Y. Botulinum toxin type A wear-off phenomenon in chronic migraine patients: how long does the maximum efficiency last?. Arquivos de Neuro-Psiquiatria. 2021 Sep 20;79:886-90. [Google Scholar]
7 Barad M, Ailani J, Hakim SM, Kissoon NR, Schuster NM. Percutaneous Interventional Strategies for Migraine Prevention: A Systematic Review and Practice Guideline. Pain Medicine. 2021 Aug 11. [Google Scholar]
8 Pijpers JA, Kies DA, Louter MA, van Zwet EW, Ferrari MD, Terwindt GM. Acute withdrawal and botulinum toxin A in chronic migraine with medication overuse: a double-blind randomized controlled trial. Brain. 2019 May 1;142(5):1203-14. [Google Scholar]
9 Atraszkiewicz D, Ito R, Bahra A. The efficacy of botulinum toxin type-A for intractable chronic migraine patients with no pain-free time. British Journal of Pain. 2021 May 24:20494637211014544. [Google Scholar]
10 Shaterian N, Shaterian N, Ghanaatpisheh A, Abbasi F, Daniali S, Jahromi MJ, Sanie MS, Abdoli A. Botox (OnabotulinumtoxinA) for Treatment of Migraine Symptoms: A Systematic Review. Pain Research and Management. 2022 Mar 31;2022. [Google Scholar]

This article was updated April 24, 2022

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• Surgery
• NSAIDs
• Cortisone Shots
• R.I.C.E.