See also separate articles Migraine and Migraine Management.

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. 50% of patients will have fewer migraines with preventative medication.¹

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.²

Prodigy suggests that:³

• 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.

There has been speculation that timely use of prophylactic medication may prevent transformation of migraine to a chronic and more disabling form of migraine.⁴

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.
• Contra-indications.
• Concordance issues, e.g. once-daily dosing improves compliance.⁵

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 Prodigy guidance.^2,3

First-line prophylactic drugs

1. Beta-blockers. 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.
   They may be especially useful when the migraine sufferer also has hypertension or anxiety, but contra-indications such as asthma, depression and peripheral vascular disease often limit use.
   
   
2. Amitriptyline. A dose of 10-150 mg daily 1-2 hours before bedtime, especially when:
   • Chronic pain co-exists
   • Insomnia co-exists
   • Depression co-exists
   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

1. Topiramate 25 mg od-50 mg bd. This is licensed and efficacy has been demonstrated.⁶
2. Sodium valproate 300-1000 mg bd. There is evidence for efficacy but it is unlicensed for this purpose. It is not safe in pregnancy but can be used with hormonal contraceptives.

Third-line prophylactic drugs

A variety of other drugs have been suggested but limited evidence for efficacy and potentially serious side-effects leads Prodigy to suggest these are for use by specialists only. Examples are gabapentin, clonidine, methysergide, selective serotonin reuptake inhibitors (SSRIs), verapamil, angiotensin-II receptor antagonists and a variety of antiepileptics.

• 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.
• Feverfew, a herbal remedy, has long been reputed to prevent migraine attacks but with little evidence to support its use.
• Botulinum toxin injected into pericranial locations at three-monthly intervals has been suggested for prophylaxis. Evidence of efficacy has not been established.⁵

Combinations have also been suggested but the merits and efficacy of this approach are unproven.

Prophylaxis for hormone-related migraine

Menstrual migraine

• 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.²

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.

Document references

1. Goadsby PJ; Recent advances in the diagnosis and management of migraine; BMJ. 2006 Jan 7;332(7532):25-9.
2. Guidelines for All Healthcare Professionals in the Diagnosis and Management of Migraine, Tension-Type, Cluster and Medication-Overuse Headache, British Association for the Study of Headache - BASH (2010)
3. Migraine, Prodigy (October 2010)
4. Loder E, Biondi D; General principles of migraine management: the changing role of prevention.; Headache. 2005 Apr;45 Suppl 1:S33-47. [abstract]
5. Cady R, Schreiber C; Botulinum toxin type A as migraine preventive treatment in patients previously Headache. 2008 Jun;48(6):900-13. Epub 2007 Nov 28. [abstract]
6. Diamond M, Dahlof C, Papadopoulos G, et al; Topiramate improves health-related quality of life when used to prevent migraine.; Headache. 2005 Sep;45(8):1023-30. [abstract]

Internet and further reading

• Treatment guidelines for migraine, Migraine In Primary Care Advisors (2004)