Migraine remains a condition with no cure and without a fully understood pathophysiology, although a significant percentage of patients appear to have a genetic predisposition to it. The condition is quite complex and has a variety of symptoms, with the main one being a painful headache, usually accompanied by sensitivity to light, blurred vision, vomiting etc..

The symptoms can vary from patient to patient as does attack severity and duration, often lasting from some hours to 2-3 days. On the other hand, patients can go into remission with no attacks for months or even years. The impact to the personal, professional and social life of individuals is great, especially to those with frequent attacks (>4/month).

 

Dealing with migraine

Migraine treatments fall into three main categories:

  • Lifestyle & alternative medicine
  • Symptoms relief treatments
  • Preventive treatments

 

The lifestyle approach

Lifestyle approaches include relaxation/meditation techniques (stress is a well known factor that triggers attacks), a stable sleeping/eating routine, staying hydrated and regular physical exercise. 

A headache diary is always useful, as it can help patients monitor attacks and identify possible triggers. Alternative treatments such as acupuncture, biofeedback, cognitive behavioural therapy, herbs, vitamins and minerals, can be beneficial to some patients. For example, high doses of vitamin B2 or coenzyme Q10 supplements might decrease the frequency of attacks.

 

Acute medications

When an attack occurs, it is important that any symptom-relief medication is taken as soon as possible. On first sign of the upcoming attack, or on first symptom, patients can resort to one of the following:

  • Painkillers (OTC or prescription) like aspirin and ibuprofen. However when taken for a long period, serious side effects can occur. Combinations with caffeine and/or acetaminophen are effective usually only in mild cases
  • Triptans are prescription medicines (Imitrex, Tosymra, Maxalt), taken as pills, nasal spray or shot, that block pain pathways, but could be unsafe for those with risk of stroke or heart attack
  • Dihydroergotamines can be taken as shot or as a nasal spray (D.H.E. 45, Migranal) and are most effective for migraines that usually go on for more than 24 hours. However, as a side effect, migraine-related nausea and vomiting could get intensified. Coronary artery disease, high blood pressure and kidney/liver disease are cases where these medications should not be taken
  • Opioid medications (with or without codeine) can be highly addictive and are only used when no other treatment is effective
  • Anti-nausea drugs, like chlorpromazine, metoclopramide (Reglan) or prochlorperazine (Compro) can be helpful but must be accompanied by pain relief medication
  • Lasmiditan is a new medication (REYVOW); a serotonin 1F receptor agonist), first of its kind, which has shown a significant improvement in pain reduction in clinical trials, as well as improvements in nausea and sensitivity to light/sound. The drug stimulates the serotonin 1F receptor, which is believed to play a role in migraine creation. As a side effect, it can act as a sedative and cause dizziness, restricting some activities for up to 8 hours. It should be avoided if alcohol is consumed or if CNS-depressant drugs are taken
  • Ubrogepant (UBRELVY) is a calcitonin gene-related peptide (CGRP)-targeting drug that is taken orally and is the first of its kind. Clinical trials showed that it is effective in pain relief, nausea and sensory sensitivity, within two hours of administration. Side effects can include dry mouth and excessive sleepiness. Strong CYP3A4 inhibitor drugs and ubrogepant should not be mixed
  • Rimegepant (NURTEC ODT) is another CGRP inhibitor pill that was approved in 2020 in the US and is also designed to stop migraine attacks as they happen

 

Prevention is possible

Preventive medications can be very helpful for those with frequent and long-lasting attacks. Though not a cure, these drugs can reduce greatly the number and severity of attacks. Such medications are:

  • Blood pressure-lowering medications like β-blockers (Inderal, Innopran XL, Lopressor, etc) and calcium channel blockers (Tarka, Verelan)
  • Amitriptyline, an antidepressant, can prevent migraines but due to side effects (sleepiness, weight gain, etc), other medications might be prescribed instead
  • Anti-seizure drugs might help for less frequent migraines, but have side effects such as dizziness, weight changes, nausea etc.
  • BOTOX injections every 3 months can prevent migraines in some patients
  • Medical devices are a new approach and there are, already, three of them available, which offer non-invasive non-medication migraine treatment. Cefaly is a nerve stimulator, which stimulates a nerve that impedes migraine pathways. SpringTMS is a magnetic stimulator that disrupts migraine signals. Both can be used for prevention or during an attack. GammaCore stimulates the vagus nerve and can be used during an attack.
  • One of the most recent additions in the fight against migraine, are monoclonal antibodies that disrupt CGRP activity by targeting either the ligand or the CGRP receptor itself and thereby disrupting migraine-causing signals. These anti-CGRP mAbs (as well as the oral CGRP inhibitors) do not have the downside of traditional medications, such as blood vessel constriction, thus making them safe for those that had a stroke, heart attack or vascular disease. Three anti-CGRP mAbs, AIMOVIG, EMGALITY and AJOVY, are delivered once a month (with AJOVY also being delivered every three months) as subcutaneous injections. A fourth  mAb (VYEPTI) was also approved in 2020 and it is the first one administered through IV infusion once every three months..

 

Among all the new classes of drugs and devices used to fight migraine, CGRP inhibitors have opened up a window of hope for a cure in the future, as their development has uncovered new pathways and mechanisms in migraine, which have moved the migraine research field forward. An effective treatment or even a cure for migraine could now be closer than ever.

 

Sources:

https://www.migrainetrust.org/about-migraine/

https://www.mayoclinic.org/diseases-conditions/migraine-headache/diagnosis-treatment/drc-20360207

https://news.psu.edu/story/610953/2020/03/04/medical-minute-new-treatments-migraines-show-promise

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413335/

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CNS headache migraine