Prevention of migraine

Identifying and avoiding trigger factors can reduce the frequency of migraine attacks by up to 50%.

Migraine recurring four or more times per month should be treated prophylactically (1). This is because prophylactic agents only have limited success and risk chronic side effects. Also, 5HT1 agonists can more effectively deal with many attacks than previous acute treatments.

NICE suggests that (2):

• Migraine with or without aura
  • topiramate or propranolol are the suggested first-line prophylactic agents
    
    • for the prophylaxis of migraine, offer topiramate or propranolol after a full discussion of the benefits and risks of each option. Include in the discussion:
      • the potential benefit in reducing migraine recurrence and severity
      • the risk of fetal malformations with topiramate
      • the risk of reduced effectiveness of hormonal contraceptives with topiramate
      • the importance of effective contraception for women and girls of childbearing potential who are taking topiramate (for example, by using medroxyprogesterone acetate depot injection, an intrauterine method or combined hormonal contraception with a barrier method)
    • Follow the MHRA safety advice on antiepileptic drugs in pregnancy
    • In November 2015, this was an off-label use of topiramate in children and young people
    • People with depression and migraine could be at an increased risk of using propranolol for self-harm. Use caution when prescribing propranolol, in line with the Healthcare Safety Investigation Branch's report on the under-recognised risk of harm from propranolol
• amitriptyline is also an option for the prophylactic treatment of migraine according to the person's preference, comorbidities and risk of adverse events
  
  
• do not offer gabapentin for the prophylactic treatment of migraine
  
  
• if both topiramate and propranolol are unsuitable or ineffective, consider a course of up to 10 sessions of acupuncture over 5-8 weeks according to the person's preference, comorbidities and risk of adverse events
  
  
• for people who are already having treatment with another form of prophylaxis, and whose migraine is well controlled, continue the current treatment as required
  
  
• review the need for continuing migraine prophylaxis 6 months after the start of prophylactic treatment
  
  
• advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people.

Notes:

• BASH guidance (3) suggests - note * denotes unlicensed indication
  • first-line prophylactic drugs
    • beta-adrenergic blockers without partial agonism are first-line if not contraindicated by asthma, heart failure, peripheral vascular disease or depression. Cardioselectivity and hydrophilicity both improve the side-effect profile; on this basis, atenolol* 25-100mg bd is to be preferred over metoprolol 50-100mg bd and this over propranolol LA 80mg od-160mg bd
      • on the same basis plus the knowledge that once-daily dosing is associated with significantly better compliance, bisoprolol* 5 10mg od may be the beta-blocker of choice but better evidence of its efficacy is needed. Commonly reported adverse events include cold extremities, reduced exercise tolerance and dizziness
    • amitriptyline* 10-150mg daily, at or 1-2 hours before bedtime, is first-line when migraine coexists with:
      • troublesome tension-type headache
      • another chronic pain condition
      • disturbed sleep
      • depression
      • except in the last case it is wise to explain the choice of this drug to patients who do not consider themselves depressed or they may reject it. Commonly reported adverse events include dry mouth, sedation, dizziness and nausea. These are most apparent in the first couple of weeks and usually settle with continued use
    • desipramine*, nortriptyline* and protriptyline* are less sedative alternatives with no formal evidence of efficacy
      
  • second-line prophylactic drugs
    • topiramate 25mg od-50mg bd and sodium valproate* 300-1000mg bd are second-line options
    • Follow the MHRA safety advice on antiepileptic drugs in pregnancy
      
  • third-line prophylactic drugs
    • third-line options mentioned include gabapentin, methysergide and combination of beta-blocker and amitriptyline
      
  • other drugs used in prophylaxis but with limited or uncertain efficacy Pizotifen and clonidine have been widely used for many years but with little clinical trials evidence of efficacy
    • should now be superseded
    • verapamil* MR 120-240mg bd has limited clinical-trials evidence of efficacy. Headache is sometimes a side effect
      
      
• Migraine prophylaxis with botulinum toxin (4)
  • Botulinum toxin type A is recommended as an option for the prophylaxis of headaches in adults with chronic migraine (defined as headaches on at least 15 days per month of which at least 8 days are with migraine):
    • that has not responded to at least three prior pharmacological prophylaxis therapies and whose condition is appropriately managed for medication overuse
      
      
• Migraine prophylaxis with fremanezumab (5)
  • fremanezumab is recommended as an option for preventing migraine in adults, only if:
    • the migraine is chronic, that is, 15 or more headache days a month for more than 3 months with at least 8 of those having features of migraine
    • at least 3 preventive drug treatments have failed
      
      
• Migraine prophylaxis with galcanezumab (6)
  • galcanezumab is recommended as an option for preventing migraine in adults, only if:
    • they have 4 or more migraine days a month
    • at least 3 preventive drug treatments have failed and
    • the company provides it according to the commercial arrangement
  • stop galcanezumab after 12 weeks of treatment if:
  • in episodic migraine (less than 15 headache days a month) the frequency does not reduce by at least 50%
  • in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine) the frequency does not reduce by at least 30%.
    
    
• Migraine prophylaxis with erenumab (7)
  • erenumab is recommended as an option for preventing migraine in adults, only if:
    • they have 4 or more migraine days a month
    • at least 3 preventive drug treatments have failed
    • the 140mg dose of erenumab is used
    • and the company provides it according to the commercial arrangement
  • stop erenumab after 12 weeks of treatment if:
    • in episodic migraine (less than 15 headache days a month) the frequency does not reduce by at least 50%
    • in chronic migraine (15 headache days a month or more with at least 8 of those having features of migraine) the frequency does not reduce by at least 30%.

For comprehensive details of prophylaxis of migraine see BNF.

Reference:

1. Drug and Therapeutics Bulletin (1998); 36(6):41-4.
2. NICE (May 2021). Headaches in the over 12s
3. British Association of the Study of Headache (BASH) guidelines, 2010.
4. NICE (June 2012). Botulinum toxin type A for the prevention of headaches in adults with chronic migraine.
5. NICE (June 2020). Fremanezumab for preventing migraine
6. NICE (November 2020). Galcanezumab for preventing migraine.
7. NICE (March 2021).Erenumab for preventing migraine