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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 assessment1although 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. Once daily dosing improves compliance for example.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 BASH and PRODIGY.
First-line prophylactic drugs
- 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 80mg od to 160mg bd. Good supporting evidence for efficacy, but not cardio-selective and requires two or three doses daily.
- Metoprolol 50-100mg bd. Cardioselective.
- Timolol has once daily dosing.
- Atenolol 25-100mg bd is cardioselective, hydrophilic and has no intrinsic sympathomimetic activity, but is unlicensed.
- Bisoprolol 5-10mg od may be ultimately the best but evidence is needed to establish efficacy.
- Amitriptyline
At a dose of 10-150mg 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
- Sodium valproate 300-1000mg bd. There is evidence for efficacy but it is unlicensed for this purpose. It is not safe in pregnancy but can be used with the hormone contraceptives.
- Topiramate 25mg od -50mg bd. This is still unlicensed but efficacy has been demonstrated.4
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 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.5,6
Combinations have also been suggested but the merits and efficacy of this approach are unproven.
| Table: Preventive treatments in migraine (adapted from Goadsby 7) On average most patients will have a 50% reduction in headache frequency with most preventive drugs, but they will have to choose between this benefit and side effects. It is useful to present the available drugs in this way listing selected side effects. | ||
|---|---|---|
| Agent | Dose | Selected side effects |
| Commonly used drugs | ||
| Pizotifen | 0.2- 2mg/ day | Weight gain drowsiness. |
| Beta blockers (propranolol) | 40- 120mg twice daily | Reduced energy, tiredness, postural symptoms. Contraindicated in asthma. |
| Tricyclics (amitriptyline) | 25mg- 75mg nocte | Drowsiness. Some patients very senstive and may only need 10mg (but 1- 1.5mg/ kg usually needed for response). |
| Valproate | 400-600mg twice daily | Drowsiness, weight gain, tremor, hair loss, foeatl abnormalities, haematological or liver abnormalities. |
| Topiramate | 25- 100mg twice daily | Paraesthesia, cognitive dysfunction, weight loss, renal stones, glaucoma. |
| Gabapentin | 900- 3600mg daily | Dizziness, sedation. |
| Methysergide | 1- 4 mg daily | Drowsiness, leg cramps, hair loss, retroperitoneal fibrosis (1 month drug holiday required every 6 months). |
| Flunarizine | 5- 10 mg daily | Drowsiness, weight gain, depression, parkinsonism. |
| Metabolic enhancers | ||
|
|
|
Non- pharmaceuticals
|
||
| Other preventives with controlled evidence for efficacy |
|
Cough. |
| Usual doses and common side effects are given, but refer to individual drug monographs for more detailed information. | ||
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.
Mefanamic acid 500mg qds 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. Propanolol and amitriptyline could be considered but drugs should be avoided.
Document References
- Tfelt-Hansen P; Prophylactic pharmacotherapy of migraine. Some practical guidelines.; Neurol Clin. 1997 Feb;15(1):153-65. [abstract]
- Loder E, Biondi D; General principles of migraine management: the changing role of prevention.; Headache. 2005 Apr;45 Suppl 1:S33-47. [abstract]
- Mulleners WM, Whitmarsh TE, Steiner TJ; Noncompliance may render migraine prophylaxis useless, but once-daily regimens are better.; Cephalalgia. 1998 Jan;18(1):52-6. [abstract]
- 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]
- Goldberg LD; The cost of migraine and its treatment.; Am J Manag Care. 2005 Jun;11(2 Suppl):S62-7. [abstract]
- Owens GM; Migraine in the managed care environment.; Am J Manag Care. 2005 Jun;11(2 Suppl):S68-71. [abstract]
- Goadsby PJ; Recent advances in the diagnosis and management of migraine.; BMJ. 2006 Jan 7;332(7532):25-9.
Internet and Further Reading
- BASH; British Association for the Study of Headache; BASH British Association for the Study of Headache
- Treatment guidelines for migraine, Migraine In Primary Care Advisors (2004)
DocID: 239
Document Version: 1
DocRef: bgp24970
Last Updated: 22 Aug 2007
Review Date: 21 Aug 2008
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