Migraine prophylaxis may be underused. This may be because of patient resistance in the face of unwanted side-effects, but may also be because GPs are less experienced in the use of prophylactic drugs. It may be appropriate to offer referral when control of migraine is unsatisfactory and expertise in migraine prophylaxis is needed. However, it is often appropriate to manage prophylaxis in general practice. When successful, it is very beneficial to patients' quality of life.
Aim of migraine management and prophylaxis
Migraine cannot be cured and the aim, shared with the patient, is to minimise the impact of the illness on the patient's life and lifestyle. The aim of prophylaxis is to reduce the number of migraine attacks.
Indications for prophylaxis
British Association for the Study of Headache (BASH) guidelines state that prophylaxis should be used when symptoms are inadequately controlled with acute prescriptions, or the frequency of attacks is leading to overuse of acute medicines.
The National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) suggests:
- Frequent attacks are two or more attacks per month that produce disability lasting for three days or more.
- Medication overuse is a risk when medication is used on more than two days per week on a regular basis. Overuse needs to be addressed before further treatment can begin.
- Prophylaxis should be used when standard analgesia and triptans are either contra-indicated or ineffective.
Uncommon types of migraine, such as hemiplegic migraine, or migraine with prolonged aura, should be seen by a specialist for appropriate management.
Choice of drug for migraine prophylaxis
A large number of drugs have been suggested but selection can be made according to:
- Efficacy and strength of evidence.
- The effect on other conditions the patient might have.
- Concordance issues - eg, once-daily dosing improves compliance.
Most drugs are started at a low dose and titrated upwards to avoid adverse effects. Unfortunately, this can delay the onset of effect and adversely affect compliance. In general they should be tried for at least four weeks and, if effective, continued for 4-6 months before tapering off over 2-3 weeks to establish continued need. The following guide to first-, second- and third-line drugs is adapted from BASH and NICE CKS guidance.[1, 2]
First-line prophylactic drugs
In theory, the ideal beta-blocker for use in migraine should be hydrophilic and cardioselective so as to produce fewer side-effects, and have no sympathomimetic activity, so as to be more effective. Their use is limited by interactions and contra-indications:
- Atenolol 25-100 mg bd is cardioselective, hydrophilic and has no intrinsic sympathomimetic activity, but is unlicensed. BASH suggests it is to be preferred over the others, currently.
- Metoprolol 50-100 mg bd is cardioselective.
- Propranolol LA 80 mg od to 160 mg bd. Good supporting evidence for efficacy, but not cardioselective and often requires two doses daily.
- Bisoprolol 5-10 mg od may be ultimately the best but evidence is needed to establish efficacy.
- Timolol and nadolol are listed in the British National Formulary (BNF) as possible alternative beta-blockers for migraine.
Beta-blockers may be especially useful when the person with migraine also has hypertension or anxiety, but contra-indications such as asthma, depression and peripheral vascular disease often limit use.
A dose of 10-150 mg daily 1-2 hours before bedtime, especially when:
- Chronic pain co-exists
- Insomnia co-exists
- Depression co-exists
NB: use of other tricyclics and antidepressants generally is not supported by evidence. Amitriptyline should be used with caution in heart disease and epilepsy.
Second-line prophylactic drugs
Topiramate and sodium valproate can be used for preventing migraines.[4, 5]A Cochrane review found that there was evidence that gabapentin was not effective for the prophylaxis of episodic migraine in adults.
Third-line prophylactic drugs
Pizotifen 1.5 mg daily has been used for a long time but evidence of efficacy is limited and certainly there is no justification for higher doses. Pizotifen may cause weight gain.
Botulinum toxin type A
Botulinum toxin type A may be a useful treatment option for patients with poor compliance, adherence, or adverse effects with oral prophylactic treatments.
Botulinum toxin type A is recommended by NICE as an option for the prophylaxis of headaches in adults with chronic migraine:
- That has not responded to at least three prior pharmacological prophylaxis therapies, and
- Whose condition is appropriately managed for medication overuse.
Treatment with botulinum toxin type A that is initially recommended should be stopped in people whose condition:
- Is not adequately responding to treatment (defined as less than a 30% reduction in headache days per month after two treatment cycles), or
- Has changed to episodic migraine (defined as fewer than 15 headache days per month) for three consecutive months.
There is evidence that butterbur is effective for migraine prevention. The evidence for feverfew is variable but indicates that feverfew is effective for some patients. There is insufficient evidence regarding the use of hyperbaric oxygen for migraine prevention.
The evidence for the benefit of acupuncture treatment is inconsistent but acupuncture may be effective for migraine prophylaxis.A Cochrane review on acupuncture for migraine prophylaxis showed acupuncture to be at least as effective as prophylactic drug treatment.
Biofeedback, relaxation technique, and cognitive behavioural therapies have shown efficacy in the prevention of episodic migraine but data regarding efficacy in chronic migraine are limited. Cognitive behavioural therapy can be helpful as part of a combined treatment programme, and should be integrated with pharmacological interventions.
Accurate diagnosis to treat this successfully is essential. This should be confirmed with diary evidence to show migraine without aura occurring regularly within up to two days of onset of menstruation and at no other time over three months.
- Mefenamic acid 500 mg qds as first-line if menorrhagia and/or dysmenorrhoea co-exist, taken at the onset of menstruation and continued prophylactically until the last day of bleeding.
- Oestrogen supplements alone can be given, if the patient is still menstruating and has an intact uterus. Transdermal oestrogen 100 micrograms is recommended starting three days before onset of menses and continued for seven days. If this dose is effective but poorly tolerated, 50 micrograms can be tried.
- Progestogen-only methods (that inhibit the ovarian cycle) may also be used if contraception is also required. Cerazette®, Nexplanon® or depot medroxyprogesterone acetate are all suggested.
Migraine in pregnancy and lactation
Often migraine improves during pregnancy and prophylaxis is not required. Propranolol and amitriptyline have the best evidence for safety and efficacy but drugs should be avoided if possible.
Further reading and references
Diagnosis and Management of Migraine, Tension-Type, Cluster and Medication-Overuse Headache; British Association for the Study of Headache (BASH) Guidelines, (2010 - reviewed 2014)
Migraine; NICE CKS, August 2013 (UK access only)
Linde M, Mulleners WM, Chronicle EP, et al; Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev. 2013 Jun 246:CD010610. doi: 10.1002/14651858.CD010610.
Linde M, Mulleners WM, Chronicle EP, et al; Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev. 2013 Jun 246:CD010611. doi: 10.1002/14651858.CD010611.
Linde M, Mulleners WM, Chronicle EP, et al; Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev. 2013 Jun 246:CD010609. doi: 10.1002/14651858.CD010609.
Cady R, Schreiber C; Botulinum toxin type A as migraine preventive treatment in patients previously Headache. 2008 Jun48(6):900-13. Epub 2007 Nov 28.
Botulinum toxin type A for the prevention of headaches in adults with chronic migraine; NICE Technology Appraisal Guidance, June 2012
Holland S, Silberstein SD, Freitag F, et al; Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012 Apr 2478(17):1346-53. doi: 10.1212/WNL.0b013e3182535d0c.
Li Y, Zheng H, Witt CM, et al; Acupuncture for migraine prophylaxis: a randomized controlled trial. CMAJ. 2012 Mar 6184(4):401-10. doi: 10.1503/cmaj.110551. Epub 2012 Jan 9.
Carod-Artal FJ; Tackling chronic migraine: current perspectives. J Pain Res. 2014 Apr 87:185-94. doi: 10.2147/JPR.S61819. eCollection 2014.
Linde K, Allais G, Brinkhaus B, et al; Acupuncture for migraine prophylaxis. Cochrane Database Syst Rev. 2009 Jan 21(1):CD001218.