Neurological disease

Migraine

Migraine is a complex condition, but it is characterised as a moderate to severe, pulsating headache that is typically unilateral, and is often accompanied by nausea and disturbed vision (aura). Migraines can last from two hours to several days. Associated symptoms can include nausea and vomiting, as well as sensitivities to light, sound or smell.

Medical intervention is indicated when the migraines become frequent and/or are severe.

Treatments for acute migraine

Simple analgesics including aspirin, paracetamol and NSAIDs may provide symptomatic relief. Concomitant anti-emetic treatment (e.g. metoclopramide or domperidone, or phenothiazine and antihistamine antiemetics) may be beneficial.

If analgesics are ineffective, acute attacks can be treated with 5HT1-receptor agonists (triptans). The triptans available to treat acute migraine include almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. 5HT1-receptor agonists can be co-administered with a NSAID such as naproxen in patients with prolonged and recurrent attacks.

Historically ergot alkaloids such as ergotamine were used to treat migraine, but since efficacy is limited (by difficulties in absorption and adverse side-effects) their use is best avoided.

Migraine prophylaxis

For patients experiencing frequent attacks, identifying and reducing potential provoking factors (such as stress, lack of sleep, or chemical triggers including alcohol and nitrates) can be beneficial.

Preventative treatments should be considered for patients who:

  • experience >2 attacks per month
  • experience increasing attack frequency
  • experience significant resistance to prescribed treatments
  • are intolerant to suitable anti-migraine treatments
  • suffer from rare migraine subtypes or are at risk of migrainous infarction.

In these patients groups beta-blockers (propranolol, atenolol, metoprolol, nadolol, and timolol) can be effective. Tricyclic antidepressants, topiramate, valproic acid, and gabapentin show some efficacy, but use of these drugs as migraine prophylactics is unlicensed. Botulinum toxin type A is licensed for the prophylaxis of headaches in adults with chronic migraine.

Novel mechanistic approach to migraine prophylaxis

A recent advance in migraine prophylaxis saw the FDA approval (in May 2018) of the first-in-class biologic drug erenumab (Aimovig).  Erenumab acts as a functional calcitonin receptor-like receptor (CGRPR) antagonist, by selectively blocking binding of endogenous calcitonin-related polypeptide (CGRP) to its receptor complex and arresting downstream signalling. CGRP is a neuropeptide that is involved in migraine pathophysiology (Hansen et al., 2010), and the receptor-ligand pathway has been validated as a novel mechanistic target for drug discovery as a migraine prevention strategy by erenumab's clinical approval (Edvinsson et al., 2018; Edvinsson, 2018). As a result of the long serum half-life of monoclonal antibodies, erenumab need only be administered once-monthly. See Dodick et al. (2018) for detailed results from the Phase 3 ARISE clinical trial.