Headache prophylaxis (2)

Identifying newer prophylactics

Newer prophylactics being explored for their potential role in migraine management include monoclonal antibodies, botulinum toxin, nonsteroidal anti-inflammatory drugs (NSAIDs), serotonin antagonists, trigger point therapy and nerve blocks.

Monoclonal antibodies

Research on the biochemistry of migraines has focused on a protein in the brain, calcitonin gene-related peptide (CGRP). When CGRP is given to people who are susceptible to migraines, an attack is triggered, and CGRP is elevated during an attack in patients with migraines. It has also been shown that blocking this peptide from exerting its effect will prevent migraine.

These findings have led to the development of monoclonal antibodies against CGRP which affect the peptide or block its action. Four monoclonal antibodies have been approved for use:

• Atogepant: 10 mg, 30 mg, and 60 mg tablets available to be administered for prophylaxis once a day
• Eptinezumab-jjmr: 100 mg / 1 mL single-dose vial to be injected into a 100 mL bag of 0.9% sodium chloride and infused over 30 minutes every 3 months
• Rimegepant: – 75 mg orally disintegrating tablet every other day for prophylaxis – can use up to 18 tablets per month
• Galcanezumab: loading dose of 300 mg injected subcutaneously at the onset of cluster headaches followed by a 100 mg injection once a month for the next 3 months to a maximum of 300 mg

Use of any of these antibodies significantly reduces the amount of headache days, the severity and duration of headache. These agents are generally safe and do not have widespread immune effects.

Botulinum toxin

Onabotulinum toxin type A (otherwise known as Botox) is approved by the FDA for chronic migraine in which there are > 15 days of headache a month. Injections of a small amount of toxin are placed in the frontalis, temporalis, nasalis, and corrugator muscles as well as into the posterior strap muscles.

The dose is typically 155 mouse units every 12 weeks. Potential side effects are facial muscle weakness and asymmetry, generalized weakness, swallowing dysfunction, and local pain.

NSAIDs

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen and ketoprofen have also been used for prophylaxis. In some headache centers, NSAIDs are used along with riboflavin and magnesium.

Serotonin antagonists

Methysergide and methylergometrine are anti-serotonin drugs, or serotonin antagonists, from the ergot family. They cannot be used long term due to the potential development of pulmonary fibrosis.

Although cyproheptadine is an antihistamine, it has actions as a serotonin antagonist. Cyproheptadine is often used in children, but in adults it tends to be too sedating.

Trigger point therapy

When the physical exam indicates a musculoskeletal contribution to the headaches, trigger point injections or dry needling might be considered.

Nerve blocks

Occipital nerve blocks with steroids and lidocaine, or a longer acting agent, might prove helpful in some cases.

Other novel prophylactic treatments for headaches

Other treatments have been tried with varying success:

• Acupuncture
• Behavioral training for relaxation • Biofeedback • Cervical facet blocks • Cognitive behavioral therapy (CBT)
• Physical therapy
• Craniosacral manipulation
• Neurostimulation using noninvasive transcranial magnetic stimulation
• Trigeminal nerve stimulation using the CEFALY device (used for both prevention and acute treatment)

References

• The International Classification of Headache Disorders 3rd edition
• Rizzoli PB. Acute and preventive treatment of migraine. Continuum (Minneap Minn). 2012 Aug;18(4):764-82
• Mauskop A. Nonmedication, alternative, and complementary treatments for migraine. Continuum (Minneap Minn). 2012 Aug;18(4):796-806.
• Parikh SK, Silberstein SD. Calcitonin gene-related peptide monoclonal antibodies. Practical Neurology. 2018; 17: 20–22.
• Tepper SJ, Tepper DE. Neuromodulation and headache. Practical Neurology. 2018; 17: 42–45. 
• Natekar A, Malya S, Yuan H, Nahas S. Migraine Preventative Therapies in Development. Practical Neurology. 2018; 17: 54–57.
• Blumenfeld AM. Botox for chronic migraine: Tips and tricks. Practical Neurology. 2018; 17: 27–36
• Escher CM, Paracka L, Dressler D, Kollewe K. Botulinum toxin in the management of chronic migraine: clinical evidence and experience. Ther Adv Neurol Disord. 2017 Feb;10(2):127-135.
• Halker Singh RB, Starling AJ, VanderPluym J. Migraine acute therapies. Practical Neurology. 2019; 17: 63–67
• Krel R, Mathew PG. Procedural treatments for headache disorders. Practical Neurology. 2019; 17: 76–79.
• Motwani M, Kuruvilla D. 2019. Behavioral and integrative therapies for headache. Practical Neurology. 2019; 17: 85–89

Neurology Library: Headache – Treatment

• Coni R. Headache treatment. LITFL
• Coni R. Headache treatment: Prophylactic medication. LITFL
• Coni R. Headache treatment: Prophylactic medication (2). LITFL
• Coni R. Headache treatment: Abortive medication. LITFL
• Coni R. Headache treatment: Rescue medication. LITFL
• Coni R. Headache: Diagnostic challenge. LITFL