Using BOTOX® for Migraine Treatment

David Fuller

Last Updated On: March 27, 2024

Understanding Migraines

Compared to other headache types, migraine is unilateral, throbbing, and often associated with sensitivity to sound and light, visual disturbances, nausea, and vomiting. It is recurrent, with each attack lasting from hours to days. The neuropeptides CGRP, serotonin, and PACAP¹ have a significant role in the disease mechanism. 

Migraines can be broadly divided into two types:

• With aura – usually preceded by sensory disturbances.
• Without aura – no focal or neurological symptoms are seen.

On the surface, a migraine headache is often the result of environmental and genetic factors acting together. The triggers can range from stress, medications, and sleep disturbances to food items, strong sensory inputs, and even the effects of the sun. Further studies are underway to understand its pathophysiology better.

A chronic migraine² is a medical condition characterized by experiencing migraine headaches for at least 15 days per month, lasting for more than 4 hours each time, over a period of 3 months. 

In contrast, an episodic migraine is a type of migraine that is less frequent, with less than 15 headache days per month.

BOTOX®: What Is It? 

BOTOX®, or more specifically, onabotulinumtoxinA (OBTA), is a neurotoxin derived from the bacterium Clostridium botulinum. It achieves its best clinical effect intramuscularly and is preferred by clinicians for its myorelaxant properties. 

The FDA approved BOTOX® use to relieve migraines after a successful clinical study on 1384 patients in 2010. It is available in 7 serotypes, but only A and B serotypes are recommended for therapeutic use.  

Mechanism of Action:

Evidence suggests⁴ that BOTOX® exerts its clinical activity through not one but several mechanisms:  

• Blocking neuromuscular activity by inhibiting the release of neuropeptides and neurotransmitters from cholinergic nerve fibers. 
• At the cellular level, the injected BOTOX® cuts SNAP-25, inhibits neuropeptide release, and blocks receptor insertion. 
• Extracranially, BOTOX® affects pain by inhibiting C-fiber responses, potentially relieving the painful activity or reducing CGRP. It interrupts the activation of C-fiber nociceptors, preventing sensitization and A-delta fiber activation. This interruption reduces afferent flow to the trigeminocervical complex. 

These mechanisms showcase BOTOX®’s potential in managing the severity and frequency of migraines.

Suitable Candidates for BOTOX® Treatment

Patients needing BOTOX® for headaches should fulfill the following criteria:

• Adult patients aged 18 years and above.

• Affected with chronic migraine characterized by
  • 15 or more headache days per month.
  • Headache episodes lasting four or more hours every day.

• Have no history of allergy to BOTOX® ingredients or products, including Dysport® (abobotulinumtoxinA), Myobloc® (rimabotulinumtoxinB), or Xeomin® (incobotulinumtoxinA).

• Have no active skin infection at the injection site. 
• Free of neuromuscular conditions such as Lambert-Eaton syndrome, Lou Gehrig’s disease (ALS), or myasthenia gravis.

• Are not pregnant or planning a child at present.

A detailed medical profile, including details of present health condition, family history, and ongoing medications, can aid the clinician in conducting an accurate patient assessment and case selection. It is also helpful to record details regarding the use of BOTOX® products in the past four months. 

How Is BOTOX® Administered for Migraines?

According to the FDA, treating migraines with BOTOX® involves following an indication-specific regimen. The maximum cumulative dose that can be administered should be at most 360 units in 3 months. 

Onabotulinumtoxin-A vials are typically vacuum-dried when supplied; therefore, they must be rehydrated with 0.9% Normal Saline injection (USP) before use. 

The essential aspects of BOTOX® for chronic migraine treatment² are listed as follows:

Aspect	Information
Recommended Dilution	200 Units/4 mL or 100 Units/2 mL
Final Concentration	5 Units/0.1 mL
Recommended Dose	155 Units I/M
Injection Needle	30-gauge, 0.5-inch for most sites1-inch needle for thick neck muscles
Injection Sites	31 sites across 7 head/neck muscle areas
Avoid	Periosteum, eyelid region, visible blood vessels
FDA Approved Dosage	155 Units in 31 sites (PREEMPT trials)
Total Dose Range	25 to 360 Units over multiple injection sites
Target	Superficial to the peripheral sensory nerves such as: Occipital nerveTrigeminal nerveC3 – C5 Cervical sensory rami
Peak Clinical Effect	7-10 days
Duration of Therapeutic Effect	3-4 months (neuromuscular blockade).Pain reduction can last longer.

BOTOX® for Migraines – Injection Sites of Therapeutic Relevance

In 2010, the PREEMPT⁵ study group created an injection plan for BOTOX® in migraines, blending fixed and follow-the-pain sites² based on studies in patients with different types of headaches.

Muscle	Dosing (Units)	Sites	Bilateral Distribution
Procerus	5	1	No
Frontalis	20	4	Yes
Corrugator	10	2	Yes
Occipitalis	30	6	Yes
Temporalis	40	8	Yes
Trapezius	30	6	Yes
Cervical Paraspinal Group	20	4	Yes

After injection, patients should know that optimal effects may require multiple treatments. Also, headache relief may not always align with restored muscle function.

To ensure successful treatment, clinicians should advise patients to record their headache episodes, focusing on the location, intensity, and medications used. The Migraine Disability Assessment (MIDAS) scale can also aid in assessing treatment changes and adjusting therapy.

Possible Side Effects of BOTOX® for Migraines

The possibility of adverse events with BOTOX® is usually injection-related and, therefore, temporary and easy to manage. However, some complications may demand prompt medical attention. 

Here are some adverse events² associated with using BOTOX® for migraine treatments:

• Allergic reactions include redness, rashes, wheezing, difficulty breathing, or dizziness. 
• Risk of toxin spread beyond the injection site, leading to generalized muscle weakness, loss of strength, double or blurred vision, drooping eyelids, hoarseness or voice changes, difficulty speaking, urinary incontinence, dyspnea, and swallowing.
• Post-injection pain, bruising, swelling, and tenderness.
• Neck pain;
• Headache;
• Ptosis of the eyelid(s);
• Musculoskeletal stiffness or weakness;
• Bronchitis;
• Upper respiratory tract infection;
• Myalgia
• Musculoskeletal pain;
• Facial paresis;
• Muscle spasms;
• Hypertension;
• Other adverse reactions (with minimal occurrences)
  • Vertigo;
  • Dry eye;
  • Eyelid edema;
  • Dysphagia;
  • Eye infection;
  • Jaw pain.

Therefore, the clinician must be adept at carefully selecting cases and analyzing potential complications beforehand. This will improve the overall control over the procedure and enhance patient trust in their clinician. 

You can refer to this document for detailed information on BOTOX®-related side effects. 

BOTOX® for Chronic Migraines vs. Episodic Migraines 

Although BOTOX® is a valuable preventive⁶ treatment aid for chronic migraines, its efficacy in managing its ‘episodic’ counterpart is yet under study. Typically, the BOTOX® regimen is continued until the frequency of headaches comes down to isolated incidents. However, a recent study has shown that injections of onabotulinumtoxinA could be a game-changer for those suffering from high-frequency episodic migraine (HFEM). 

*Please note that BOTOX® isn’t approved for managing episodic migraines yet. 

Conclusion 

Over time, migraine-affected people have significantly benefited from a holistic treatment approach that blends healthy lifestyle modifications along with preventive and interceptive measures. 

The efficacy of BOTOX® in managing migraine is comparable to topiramate and sodium valproate, with the additional benefit of better tolerance and improved effectiveness. The catch is that medications may need to be continued with BOTOX® injections.

Nonetheless, the current evidence shows that in the hands of an expert clinician, BOTOX® is a promising treatment option that is both safe and effective, with minimal adverse effects.

References

1. Parastoo Amiri, Somayeh Kazeminasab, Seyed Aria Nejadghaderi et al. Migraine: A Review on Its History, Global Epidemiology, Risk Factors, and Comorbidities. Front Neurol. 2021. doi: 10.3389/fneur.2021.800605

2. Alberto Jaime Kalach-Mussali, Daniel Mondlak Algazi. Botulinum Toxin for the Treatment of Chronic Migraines. Botulinum Toxin Edited by Nikolay Serdev. 2018  DOI: 10.5772/intechopen.78777 – 

3. Claus M Escher, Lejla Paracka, Dirk Dressler, et al. Botulinum toxin in the management of chronic migraine: clinical evidence and experience. The Adv Neurol Disord 2017. 2016. doi: 10.1177/1756285616677005 

4. Warner J. Becker. Botulinum Toxin in the Treatment of Headache. Toxins (Basel). 2020. doi: 10.3390/toxins12120803. 

5. Michel Lanteri-Minet, Anne Ducros, Clement Francois et al. Effectiveness of onabotulinumtoxinA (BOTOX®) for the preventive treatment of chronic migraine: A meta-analysis on 10 years of real-world data. Cephalalgia. 2022. doi: 10.1177/03331024221123058. 

6. Clare P Herd, Claire L Tomlinson, Caroline Rick, et al. Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine. BMJ Open 2019;9:e027953. doi:10.1136/ bmjopen-2018-027953 

7. Marco A. Pescador Ruschel, Orlando De Jesus. Migraine Headache. StatPearls Publishing; 2023 Jan. https://www.ncbi.nlm.nih.gov/books/NBK560787/  Accessed November 8, 2023.

Where is BOTOX® injected for migraines?

According to the PREEMPT protocol, specific doses of  BOTOX® are injected in 31 different sites to achieve optimal therapeutic effect. These include specific spots in the scalp, forehead, temple, face, and neck region. 

Does BOTOX® reduce the frequency of chronic migraines? 

Yes, studies have shown that BOTOX® can effectively reduce the frequency of chronic migraines and bring them down to minimal or isolated episodes. Some studies have shown promising results by indicating a significant reduction in migraine days per month.

Does BOTOX® for migraines change the patient’s face?

While BOTOX® certainly has cosmetic uses, the doses used for migraine treatment are lower. Additionally, the therapy aims to achieve functional improvements to relieve pain rather than changing one’s facial appearance.