Migraine Prophylaxis in Adults

See Also - Migraine Management

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.

Before considering drug treatment the overall migraine management should be reviewed with the patient. Prophylaxis should be considered when appropriately used acute management gives inadequate control of symptoms. There are no definitive guidelines on when to use prophylaxis but the following points are worth considering at review:

• Is the diagnosis correct?
• Is the acute treatment being used correctly?
• Have predisposing factors been identified and treated?
• Have trigger factors been identified and treated?
• To what extent is control of symptoms inadequate?

Review of a migraine diary will help the assessment,¹ although ultimately patient judgement on adequacy of control and patient preference for available treatments will be important factors. Prophylactic drugs should be considered when:

• Acute medication is being used on more than one day per week. Using medication more than two days every week carries a high risk of medicine over-use headache (MOH).
• Acute medication is ineffective or contraindicated.
• Significant disability is produced. Time off work or school is a guide.
• Migraine is of an uncommon type such as hemiplegic migraine, migraine with prolonged aura or migrainous infarction.

There has been recent speculation that timely use of prophylactic medication may prevent transformation of migraine to a chronic and more disabling form of migraine.²

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
• Contraindications
• Concordance issues (e.g. once daily dosing improves compliance)³

Most drugs are started at low dose and titrated upwards to avoid adverse effects. Unfortunately this can delay the onset of effect and adversely effect compliance. In general they should be tried for at least 4 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 the British Association for the Study of Headache (BASH) and Clinical Knowledge Summaries (CKS).^4,5,6

First-line prophylactic drugs

1. Beta-blockers. In theory the ideal beta-blocker for use in migraine should be hydrophilic and cardio-selective 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 contraindications.
   • Propranolol LA 80 mg o.d. to 160 mg b.d. Good supporting evidence for efficacy, but not cardio-selective and requires two or three doses daily.
   • Metoprolol 50-100 mg b.d. Cardioselective.
   • Timolol has once daily dosing.
   • Atenolol 25-100 mg b.d. is cardioselective, hydrophilic and has no intrinsic sympathomimetic activity, but is unlicensed.
   • Bisoprolol 5-10 mg o.d. may be ultimately the best but evidence is needed to establish efficacy.
   They may be especially useful when the migraineur also has hypertension or anxiety, but contraindications such as asthma, depression, and peripheral vascular disease often limit use.
2. Amitriptyline

At a dose of 10-150 mg daily 1-2 hours before bedtime, especially when:

• Chronic pain coexists
• Insomnia coexists
• Depression coexists

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. Sodium valproate 300-1000 mg b.d. 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.
2. Topiramate 25 mg o.d.-50 mg b.d. This is still unlicensed but efficacy has been demonstrated.⁷

Third-line prophylactic drugs

A variety of other drugs have been suggested but limited evidence for efficacy and potentially serious side effects leads CKS to suggest these for use by specialists only. Examples are gabapentin, clonidine, methysergide, selective serotonin reuptake inhibitors, 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.
• More recently botulinum toxin injected into pericranial locations at three monthly intervals has been suggested for prophylaxis. Evidence of efficacy has not been established.^8,9

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

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 2 days of onset of menstruation and at no other time over three months.
• Mefenamic acid 500 mg q.d.s. as first line if menorrhagia and/or dysmenorrhoea co-exists taken at the onset of menstruation and continued prophylactically until the last day of bleeding.
• Oestrogen supplements alone, if still menstruating and the patient has an intact uterus, can be given. Transdermal oestrogen 100 microgrammes is recommended starting 3 days before onset of menses and continued for 7 days. If this dose is effective but poorly tolerated, 50 microgrammes can be tried. Alternatively oestradiol gel can be used and may be better as levels of oestrogen are more stable.

Migraine in pregnancy and lactation

Often migraine improves during pregnancy and prophylaxis is not required. Propranolol and amitriptyline could be considered but drugs should be avoided if possible.