Migraine Prophylaxis in Adults

Last updated by Peer reviewed by Dr Laurence Knott, MBBS
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This article is for Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Migraine Treatment (including Triptans) article more useful, or one of our other health articles.

Read COVID-19 guidance from NICE

Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.

See also the separate Migraine and Migraine Management articles.

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.

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 preventative treatment is to reduce the frequency, severity, and duration of migraine attacks, and avoid medication-induced headache[1] .

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] .

The National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) suggests prophylaxis where[1] :

  • Migraine attacks are having a significant impact on quality of life and daily function - eg, they occur frequently (more than once a week on average) or are prolonged and severe despite optimal acute treatment.
  • Acute treatments are either contra-indicated or ineffective.
  • There is risk of medication-induced headache due to frequent use of acute drugs.

Uncommon types of migraine, such as hemiplegic migraine, or migraine with prolonged aura, should be seen by a specialist for appropriate management.

Consider non-pharmacological therapies as an adjunct or alternative to pharmacological therapy - for example:

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.

Acupuncture (up to 10 sessions over 5-8 weeks) if both topiramate and propranolol are unsuitable or ineffective. The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches[4] .

Riboflavin 400 mg once a day - may be effective in reducing migraine frequency and intensity for some people (avoid if planning a pregnancy or pregnant).

The choice of treatment depends on factors such as patient preference, drug interactions, and other comorbidities. Treatment should be started at a low dose and gradually increased to the maximum effective and tolerated dose.

Preventative treatment should be tried for at least three months at the maximum tolerated dose, before deciding whether or not it is effective. A good response to treatment is defined as a 50% reduction in the severity and frequency of migraine attacks. A review of ongoing prophylaxis should be considered after 6-12 months; treatment can be gradually withdrawn in many patients. Patients should be referred to a neurology or specialist headache clinic if trials with three or more drugs have been unsuccessful.

Propranolol (80-160 mg daily, in divided doses). Propranolol hydrochloride is recommended as first-line preventative treatment in patients with episodic or chronic migraine. If propranolol is unsuitable, other beta-blockers that can be considered are metoprolol tartrate, atenolol (unlicensed indication), nadolol, and timolol maleate. Bisoprolol fumarate (unlicensed indication) may also be considered, especially in patients already taking it for cardiac reasons under the advice of their cardiologist.

Topiramate (50-100 mg daily, in divided doses (contra-indicated in pregnancy). Topiramate can be given if a beta-blocker is unsuitable. In women of childbearing potential, advice should be given on the associated risks during pregnancy, the need to use highly effective contraception and to seek further information if pregnant or planning a pregnancy.

Amitriptyline (25-75 mg at night). Amitriptyline hydrochloride is effective for migraine prophylaxis and should be considered for patients with episodic or chronic migraine. A less sedative tricyclic antidepressant can be used if amitriptyline hydrochloride is not tolerated.

Candesartan cilexetil [unlicensed indication) can be considered in patients with episodic or chronic migraine, although there is limited evidence to support its use.

Sodium valproate (unlicensed indication) can also be considered in patients with episodic or chronic migraine. The Medicines and Healthcare products Regulatory Agency (MHRA)/Commission on Human Medicines (CHM) have released important safety information on the use of antiepileptic drugs and the risk of suicidal thoughts and behaviour. In addition, the MHRA has advised that sodium valproate must not be used in women of childbearing potential unless the conditions of the Pregnancy Prevention Programme are met and alternative treatments are ineffective or not tolerated. It must not be used during pregnancy for migraine prophylaxis.

Editor's note

Dr Krishna Vakharia, 29th January 2024

The Medicines and Healthcare products Regulatory Agency (MHRA ) has issued an update to the use of sodium valproate due to the known risks associated with pregnancy and birth defects; and the emerging increased risks of neurodevelopmental disorders seen in children whose fathers took valproate in the 3 months before conception.[6]

New guidance states that:

  • Valproate should not be started in any new patients - both male and female- younger than 55 years of age.
  • Two specialists independently can consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply if sodium valproate is to be considered.
  • At their next annual specialist review, women of childbearing potential and girls receiving valproate should be reviewed using the revised valproate Annual Risk Acknowledgement Form. A second specialist signature will be needed if the patient is to continue on valproate, however subsequent annual reviews will only require one specialist.
  • General practice and pharmacy teams should continue to prescribe and dispense valproate and if required offer patients a referral to a specialist to discuss their treatment options. Valproate should be dispensed in the manufacturer’s original full pack.
  • Report suspected adverse drug reactions associated with valproate on a Yellow Card.

Patients should be told to not stop taking valproate without advice from a specialist. This is because their condition may worsen without treatment.


Flunarizine (unlicensed) can also be considered in patients with episodic or chronic migraine (specialist use only). Pizotifen is used but evidence to recommend its use is limited.

Gabapentin should not be used for migraine prophylaxis. A Cochrane review found that there was evidence that gabapentin was not effective for the prophylaxis of episodic migraine in adults[7] .

Galcanezumab
NICE has issued guidance on the use of the humanised monoclonal antibody galcanezumab[8] that binds to the calcitonin gene-related peptide (CGRP) ligand, blocking its binding to the receptor. For migraine that has not responded to at least three preventative treatments, clinical trial evidence shows that galcanezumab works better than best supportive care in both episodic and chronic migraine.

NICE therefore recommends galcenezumab as an option for migraine prophylaxis for patients with at least four migraine days a month and for whom at least three preventative drug treatments have failed. It should only be considered if the company provides it according to the commercial arrangement agreed with the NHS.

Erenumab
Erenumab is another human monoclonal antibody that binds to the CGRP receptor, inhibiting the function of CGRP, and thereby preventing migraine attacks.

Erenumab is recommended by NICE as an option for preventing migraine in adults, only if[9] :

  • They have four or more migraine days a month.
  • At least three preventative drug treatments have failed.
  • The 140 mg dose of erenumab is used.

NICE recommends stopping erenumab after 12 weeks of treatment if:

  • In episodic migraine (fewer 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 eight of those having features of migraine) the frequency does not reduce by at least 30%.

Editor's note

Dr Sarah Jarvis, 7th February 2022

Fremanezumab for preventing migraine
NICE has issued new guidance on the use of fremanezumab - another human monoclonal antibody that binds to the CGRP receptor - for prevention of migraine. It recommends that fremanezumab is considered as an option for patients fulfilling the same criteria as for erenumab, and that the same criteria for discontinuation should be used[10] .

Editor's Note

Dr Krishna Vakharia, 4th May 2023

Eptinezumab for preventing migraine[11]

NICE has recommended eptinezumab be recommended as an option for preventing migraine in adults. It is given as an infusion unlike erenumab, fremanezumab and galcanezumab, which are injections.

To be considered as an option, they must fulfil the same criteria as those for the other monoclonal antibody options and they also have the same criteria for discontinuation.

Editor's Note

Dr Krishna Vakharia, 28th July 2023

Rimegepant for preventing migraine[12]

NICE has recommended the use of the oral medication rimegepant as an option for preventing episodic migraine in adults who have at least 4 and fewer than 15 migraine attacks per month. It is only indicated for those that have tried at least 3 preventative treatments and they have not worked.

It has been advised that rimegepant should be stopped after 12 weeks of treatment if the frequency of migraine attacks has not reduced by at least 50%.

Clinical trial evidence shows that rimegepant reduces monthly migraine days more than placebo. It has been suggested that it is similar to or less effective than the injectable options - erenumab, fremanezumab or galcanezumab.

Botulinum toxin type A

Botulinum toxin type A (specialist use only) is recommended for prophylaxis of chronic migraine where medication overuse has been addressed and where three or more oral prophylactic treatments have failed.

Botulinum toxin type A is recommended by NICE as an option for the prophylaxis of headaches in adults with chronic migraine[13] :

  • 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[13] :

  • 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.

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.
  • 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.

For women with predictable menstrual-related migraine that does not respond adequately to lifestyle measures and standard acute treatment and where there are no contra-indications, consider treatment (off-label) with:

  • Frovatriptan (unlicensed indication) can be given instead of, or in addition to, standard prophylactic treatment in women with perimenstrual migraine. It is given from two days before until three days after menstruation starts.
  • Both zolmitriptan (unlicensed indication) and naratriptan (unlicensed indication) are suitable alternatives to frovatriptan.

In order for treatment to be effective, the patient's menstrual cycle must be regular.

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.

Arrange follow-up to monitor effectiveness, titrate dose and assess for adverse effects.
Review regularly during titration (for example every 2-3 weeks). Advise the person:

  • To keep a headache diary.
  • To seek review sooner if adverse effects/new features develop.
  • That improvement may take 4-8 weeks from initiation of treatment to become apparent.

Consider the need for referral to neurology if prophylactic treatment in primary care fails, is not appropriate or any red flags or atypical clinical features develop.

Treatment is considered to have failed if there is a lack of response to the highest tolerated dose after three months of treatment.

After 6-12 months of successful therapy:

  • Review the need for continuing migraine prophylaxis.
  • Consider gradual drug withdrawal.

Consider admission or urgent referral if:

  • A serious cause of headache is suspected.
  • There is severe, uncontrolled status migrainosus (migraine lasting for more than 72 hours).

Seek advice/refer to neurology (with urgency depending on the clinical situation) if:

  • A complication of migraine has developed.
  • Atypical symptoms (such as motor weakness or poor balance) are present.
  • The diagnosis is uncertain.
  • Optimal treatment in primary care does not adequately control the symptoms (consider medication overuse headache).
The Medicines and Healthcare products Regulatory Agency (MHRA ) have issued an update to the use of sodium valproate due to the known risks associated with pregnancy and birth defects; and the emerging increased risks of neurodevelopmental disorders seen in children whose fathers took valproate in the 3 months before conception
New guidance states that:
Valproate should not be started in any new patients - both male or female- younger than 55 years of age.
Two specialists independently can consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply if sodium valproate is to be considered.
At their next annual specialist review, women of childbearing potential and girls receiving valproate should be reviewed using the revised valproate Annual Risk Acknowledgement Form. A second specialist signature will be needed if the patient is to continue on valproate, however subsequent annual reviews will only require one specialist.
General practice and pharmacy teams should continue to prescribe and dispense valproate and if required offer patients a referral to a specialist to discuss their treatment options. Valproate should be dispensed in the manufacturer’s original full pack.
Report suspected adverse drug reactions associated with valproate on a Yellow Card.
Patients should be told to not stop taking valproate without advice from a specialist. This is because their condition may worsen without treatment.

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Further reading and references

  1. Migraine; NICE CKS, October 2020 (UK access only)

  2. Diagnosis and Management of Migraine, Tension-Type, Cluster and Medication-Overuse Headache; British Association for the Study of Headache (BASH) Guidelines, (2010 - reviewed 2014)

  3. Carod-Artal FJ; Tackling chronic migraine: current perspectives. J Pain Res. 2014 Apr 87:185-94. doi: 10.2147/JPR.S61819. eCollection 2014.

  4. Linde K, Allais G, Brinkhaus B, et al; Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev. 2016 Jun 28(6):CD001218. doi: 10.1002/14651858.CD001218.pub3.

  5. British National Formulary (BNF); NICE Evidence Services (UK access only)

  6. Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell▼): new safety and educational materials to support regulatory measures in men and women under 55 years of age; Medicines & Healthcare products Regulatory Agency, GOV.UK (January 2024)

  7. 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.

  8. Galcanezumab for preventing migraine; NICE Technology Appraisal Guidance, November 2020

  9. Erenumab for preventing migraine; NICE Technology Appraisal Guidance, March 2021

  10. Fremanezumab for preventing migraine; NICE Technology appraisal guidance, February 2022

  11. Fremanezumab for preventing migraine; NICE Technology appraisal guidance, February 2022

  12. Eptinezumab for preventing migraine; NICE Technology appraisal guidance, March 2023

  13. Rimegepant for preventing migraine; NICE Technology appraisal guidance, July 2023

  14. Botulinum toxin type A for the prevention of headaches in adults with chronic migraine; NICE Technology Appraisal Guidance, June 2012

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