Migraine Prophylaxis

General Notes

NHS Lanarkshire Guideline: Pharmacological Management of Migraine focuses on local pathways for the preventative treatment of migraine.

Choice of prophylactic treatment should be based on individual patient factors such as presence of co-morbidities, potential for drug interactions and possibility of pregnancy.

Effectiveness of prophylactic medication can be reduced by overusing analgesics or triptans for treatment of acute migraine.

Where there are concerns regarding medication overuse, the risk of medication-overuse headache and the potential reduction in efficacy of prophylactic treatments should be discussed with the patient.

Following dose optimisation, it is recommended that each trial of a prophylactic treatment is continued for 3 months before assessing efficacy.

Good response is a 50% reduction in severity and frequency of attacks.

Treatment failure is a lack of response to the highest tolerated dose used for 3 months.

Migraine prophylaxis should be reviewed every 6 to 12 months and consideration given to a trial reduction.

Following specialist advice, sodium valproate may be considered for migraine prophylaxis. Sodium valproate is not licensed for this indication, however such use is referenced in national guidelines.

Sodium valproate is associated with a significant risk of birth defects and developmental disorders in children exposed to valproate in utero.

For women of childbearing potential sodium valproate should only be considered as a prophylactic treatment when:

other treatment options have been exhausted
conditions of the Pregnancy Prevention Programme are met.

MHRA VALPROATE AND DEVELOPMENTAL DISORDERS ALERT

IMPORTANT NEW RESTRICTIONS: MHRA DRUG SAFETY UPDATES JANUARY 2024 AND SEPTEMBER 2024: Additional safety measures include changes to initiation of Valproate and ongoing prescription review for MALES and FEMALES.

Valproate must not be prescribed to women/girls of childbearing potential unless enrolled in pregnancy prevention programme (PPP).

Inform male patients (of any age) who may father children of the possible increased risk of neurodevelopmental disorders in children conceived around the time of valproate use and the recommendation to use effective contraception (condoms, plus contraception used by the female sexual partner) during valproate treatment and for at least 3 months after stopping valproate.

Source: MHRA Drug Safety Update Jan 2024: New safety and educational materials to support regulatory measures in men and women under 55 years of age, and Sep 2024: Valproate use in men: as a precaution, men and their partners should use effective contraception.

MHRA Resources: MHRA information page, Patient Guide, Patient card, Patient Information Leaflet, Healthcare Professional Guide, Annual Risk Acknowledgement Form for female patients, Risk Acknowledgement Form for male patients starting valproate, Advice for male patients on valproate to use contraception and Visual risk communication diagram to be used by a healthcare professional when counselling on the risks.

Pharmacological Prevention of Migraine - First Line

Preferred list (P)

PROPRANOLOL

Note potential interaction with rizatriptan: rizatriptan dose should be limited to 5mg in patients prescribed propranolol and administration should be separated by at least 2 hours.

AMITRIPTYLINE

CANDESARTAN

Note: use in migraine prophylaxis is off-label.

Pharmacological Prevention of Migraine - Calcitonin Gene Related Peptide (CGRP) Small Molecule Antagonists

Total list (T)

Calcitonin gene-related peptide (CGRP) small molecule antagonists, such as Rimegepant and Atogepant, are to be considered following prior failure of three or more preventative treatments. Within the NHSL Joint Adult Formulary they are listed as Total formulary options however referral to headache service may be considered with/prior to their initiation in primary care (see NHS Lanarkshire Guideline: Preventative Pharmacological Management of Migraine).
Also see NHS Lanarkshire guidance for actions for prescribers prior to prescribing Atogepant or Rimegepant as well as drug monitoring requirements.

RIMEGEPANT

Rimegepant is licensed for episodic migraine only (more than four migraines per month but less than 15 headache days per month - see SMC Restrictions).

ATOGEPANT

Atogepant is licensed for treatment of episodic and chronic migraine (at least 4 migraine days per month - see SMC Restrictions).

Pharmacological Prevention of Migraine - Botulinum Toxin A

Specialist use only (S²)

BOTULINUM TOXIN TYPE A powder for solution for injection vials (Botox^®)

SMC restriction: For use in adults with chronic migraine whose condition has failed to respond to ≥3 prior oral prophylactic treatments, where medication overuse has been appropriately managed. [SMC Advice February 2017].

Pharmacological Prevention of Migraine - Human Monoclonal Antibody

Specialist use only (S²)

ERENUMAB solution for injection pre-filled pen (Aimovig^®)

SMC restriction: For the prophylaxis of migraine in adults who have at least four migraine days per month and in whom at least three prior prophylactic treatments have failed [SMC Advice April 2019]

FREMANEZUMAB solution for injection pre-filled pen(Ajovy^®)

SMC restriction: For the treatment of patients with chronic and episodic migraine who have had prior failure on three or more migraine preventive treatments. [SMC Advice January 2020]

Pharmacological Prevention of Migraine - Topiramate

Specialist use only (S¹)

TOPIRAMATE

Not recommended to start topiramate in women of child bearing potential.
See MHRA warning below: prescribing of Topiramate should be avoided in patients of child bearing potential.
Restriction: For use in patients who have not responded to prophylactic treatment with at least one other agent [SMC advice].

IMPORTANT NEW RESTRICTIONS MHRA update (June 2024): introduction of new safety measures, including a Pregnancy Prevention Programme.

Topiramate should not be used in women of childbearing potential unless the conditions of the Pregnancy Prevention Programme are fulfilled. Clinicians are reminded of the need to use highly effective contraception throughout treatment and for at least four weeks after the last dose of topiramate.
Topiramate is an enzyme-inducer, meaning it may alter the effectiveness of different hormonal contraceptives. Guidance from Faculty of Family Planning and Sexual Health provides information on potential drug interactions with hormonal contraceptives and what this means for topiramate.

MHRA Resources: Patient Guide for Migraine and Epilepsy, Guide for Healthcare Professionals for Migraine and Epilepsy, Risk Awareness Form for Migraine and Epilepsy, Patient Card. For information on when these resources are to be utilised/provided please see Drug Safety Update June 2024.

Source: Drug Safety Update June 2024: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

NHSL Joint Adult Formulary Key

To indicate the category of a formulary medicine, updated sections adopt the following key:

Preferred list (P): First-line formulary choices.

Total list (T): Alternative choices when preferred list options not effective/not tolerated, or not indicated.

Specialist initiation (S¹): Specialist initiation, or on the advice of a Consultant or Specialist Practitioner in this therapeutic area. Continuation in primary care is acceptable.

Specialist use only (S²): Supply via hospital, Homecare Service or a hospital based prescription (HBP) for dispensing by community pharmacy. Not prescribed in primary care setting.