A headache diary for a minimum of eight weeks from the patient can help with decisions about on-going treatment.

Offer combination therapy with:

• Oral sumatriptan and an NSAID (see section 4.7.4 Antimigraine drugs and section 10.1.1 Non-steroidal anti-inflammatory drugs (NSAIDs))

Or

• Oral sumatriptan and paracetamol (see section 4.7.4 Antimigraine drugs and section 4.7.1 Non-opioid analgesics and compound analgesic preparations)

For patients who prefer to take only one drug consider monotherapy with:

• Oral sumatriptan (see section 4.7.4 Antimigraine drugs) or,
• An NSAID (see section 10.1.1 Non-steroidal anti-inflammatory drugs (NSAIDs)) or,
• Aspirin (900mg dose) (not for children under 16 years of age) (see section 2.9 Antiplatelet drugs) or,
• Paracetamol (see section 4.7.1 Non-opioid analgesics and compound analgesic preparations)

Consider adding an anti-emetic even in the absence of nausea and vomiting to promote gastric emptying and peristalsis:

• Metoclopramide (see section 4.6 Drugs used in nausea and vertigo)
• Prochlorperazine (see section 4.6 Drugs used in nausea and vertigo)
• Domperidone (see section 4.6 Drugs used in nausea and vertigo)

Notes:

5HT1 agonists (triptans)

1. When prescribing a triptan, start with the one that has the lowest acquisition cost; if this is consistently ineffective, try one or more alternative triptans
2. Should be taken as soon as possible after the onset of headache
3. Triptans are associated with return of symptoms within 48 hours in 20-50% of patients who have initially responded
4. Triptans are contraindicated in patients with the following conditions: ischaemic heart disease, previous myocardial infarction, coronary vasospasm, symptoms or signs consistent with ischaemic heart disease, peripheral vascular disease, cerebrovascular accident, transient ischaemic attack, moderate and severe hypertension, and mild uncontrolled hypertension
5. To treat an attack of migraine, only one dose of a triptan should be taken, not repeated if the first dose is ineffective
6. If the headache recurs, a repeated oral dose may be necessary but taken at least two hours after the first dose. Subcutaneous sumatriptan can be repeated after one hour for a recurring headache
7. Patients who overuse triptans may develop daily migraine-like headaches or an increase in migraine frequency. See "Medication Overuse Headache" below for guidance

Ergots or opioids

1. Do not offer ergot or opioids for the acute treatment of migraine. Opiates and opiate derivatives increase nausea and are addictive. Codeine and dihydrocodeine are associated with medication overuse headache.

Medication Overuse Headache

1. Be alert to the possibility of medication overuse headache in people whose headache developed or worsened while they were taking the following drugs for 3 months or more:
   1. Triptans, opioids, ergots or combination analgesic medications on 10 days per month or,
   2. Paracetamol, aspirin or an NSAID, either alone or in any combination, on 15 days or more per month
2. If medication overuse headache is suspected, all overused acute headache treatment should be stopped for at least 1 month. Ideally wait for 1 to 2 months following withdrawal of overused medication, and then assess the need for further management of the underlying headache disorder, and whether prophylaxis is required. Seek advice from a neurology department or Pain clinic.

Anti-emetic

1. Please refer to the MHRA Drug Safety Updates for domperidone and for metoclopramide which can be found in section 4.6 Drugs used in nausea and vertigo.

Always consider the possibility of medication overuse in patients with chronic headache.

If medication overuse headache is suspected, all overused acute headache treatment should be stopped for at least 1 month. ideally wait for 1 to 2 months following withdrawal of overused medication, and then assess the need for further management of the underlying headache disorder, and whether prophylaxis is required. Seek advice form a neurology or Pain clinic.

Prophylaxis is used to reduce the number of acute attacks when acute therapy is inadequate. Acute treatment will still be required as preventative therapy does not eliminate attacks completely.

In general, consider prophylaxis where the:

• Patient suffers three moderate to severe headache days a month when acute medications are not reliably effective
• The patient has greater than eight headache days a month even when acute medications are optimally effective because of the risk of medication overuse headache

Prophylactic drugs that are apparently not effective should not be discontinued too soon, since efficacy may be slow to develop, particularly when dose titration is necessary. In the absence of unacceptable side-effects, 8-10 weeks is a reasonable trial following dose titration.

Review the need for continuing migraine prophylaxis six months after the start of prophylactic treatment. Withdrawal should be considered to establish continued need. Withdrawal is best achieved by tapering the dose over 2-3 months. Migraine is cyclical and treatment is required for periods of exacerbation. Uninterrupted prophylaxis over very long periods is rarely appropriate.

Treatment pathway

NICE CG150: Provides recommendations on 1st line and 2nd line options for young people (aged 12 years and over) and adults.

NICE is reviewing its guidance in light of the MHRA Drug Safety Update (June 2024) introducing new safety measures for topiramate.

First line options

Offer propranolol or topiramate after a full discussion of the benefits and risks of each option. Include in the discussion:

• the potential benefit in reducing migraine recurrence and severity
• the risk of foetal malformations with topiramate (see topiramate, note 1 below)
• the risk of reduced effectiveness of hormonal contraceptives with topiramate
• the importance of effective contraception for women and girls of childbearing potential who are taking topiramate (see topiramate, note 1 below)

In addition, discuss the new safety measures for topiramate, including the Pregnancy Prevention Programme (MHRA Drug Safety Update, June 2024)

Propranolol

1. Licensed for migraine prophylaxis in adults, off-label for young people aged 12 to 17 years.
2. 80mg-240mg daily in divided doses
3. Contraindications include heart disease, asthma, chronic obstructive pulmonary disease, and peripheral vascular disease
4. See section 2.4 Beta-adrenoreceptor blocking drugs

OR

Topiramate

1. New safety measures have been introduced for girls and women of child-bearing potential including a Pregnancy Prevention Programme (MHRA Drug Safety Update, June 2024):
   1. Refer to the safety update for further information
   2. The safety update includes advice for health professionals to provide to patients
2. Licensed for migraine prophylaxis in adults, off-label for young people aged 12 to 17 years.
3. Starting dose is 25mg at night for one week followed by weekly increases of 25mg/day. If the patient is unable to tolerate the titration, longer intervals between dose adjustments can be used. Usual dose 50mg-100mg/day in two divided doses.
4. Topiramate is associated with decreased appetite. Patients should be monitored for weight loss.
5. Adequate hydration is advised to reduce the risk for renal stone formation.
   For CSM warning on secondary angle closure glaucoma (see section 4.8.1 Control of the epilepsies).
6. See section 4.8.1 Control of the epilepsies

Second line option

Amitriptyline

1. Licensed for migraine prophylaxis in adults, off-label for young people aged 12 to 17 years.
2. To minimise side effects, treatment should be started at a low dose (10mg at night) and increased to 40mg-50mg at night. Local specialist advice is that tolerability is reduced at higher doses and a maximum dose of 100mg at night is recommended
3. See section 4.3.1 Tricyclics and related anti-depressants

Further options

Treatment with atogepant and rimegepant may be started in primary care on the advice of a specialist. Review effectiveness at 12 weeks of treatment (see below).

Although currently classified as amber, initiation of atogepant or rimegepant by GPs who are confident to do this without specialist input is accepted (see below for patient groups requiring specialist input).

It is anticipated that initiation of atogepant and rimegepant in primary care without specialist input will increase as GPs become more familiar with these medicines.

• Episodic migraine (at least four and fewer than 15 headache days per month): atogepant or rimegepant
• Chronic migraine (15 or more headache days per month, with at least 8 of those having features of migraine): atogepant

Patient groups requiring specialist input:

• Patients with vascular disease
• Elderly patients
• Patients planning a pregnancy and patients who are pregnant
• Complex chronic migraine with multimorbidity

Treatment review:

• Review effectiveness at 12 weeks of treatment. Stop atogepant or rimegepant after 12 weeks if the frequency of migraines does not reduce by: 
  • at least 50% in episodic migraine
  • at least 30% in chronic migraine
• Where these criteria are not met, refer the patient to a specialist for consideration of other options.
• If treatment is effective, review the need for continuing treatment at 12 months.

Atogepant

1. Oral option
2. Licensed for episodic or chronic migraine
3. 60mg once daily; dose reduction to 10mg once daily with concurrent use of certain medicines (see Interactions) or CrCl < 30mL/minute.
4. Interactions: Atogepant is metabolised by CYP3A4 and eliminated via the OATP pathway. Reduce daily dose of atogepant to 10mg once daily with concomitant administration of strong CYP3A4 or OATP inhibitors. Refer to the BNF or atogepant SmPC for advice on drug interactions.
5. Acute treatment of migraine:
   1. Treatment options (triptans, NSAID, paracetamol, aspirin).
   2. Co-administration of an anti-emetic (metoclopramide, prochlorperazine, domperidone)
6. Cardiovascular disease: see the drug entry here for patients excluded from phase 3 trials
7. Tolerability: most commonly reported adverse drug reactions in clinical trials were nausea (7%), constipation (7%), and fatigue/somnolence (5%). The adverse reaction that most commonly led to discontinuation was nausea (0.6%) (atogepant SmPC).
8. Avoid in pregnancy and in breastfeeding. Refer to the SmPC and discuss with the patient.
9. Annual cost: the annual cost per patient for prophylaxis of migraine is £2,368.
10. For further information, see drug entry (section 4.7.4 Antimigraine drugs) and atogepant SmPC.

OR

Rimegepant

1. Oral lyophilisate.
2. Licensed for episodic migraine.
3. 75mg once daily on alternate days for prophylaxis of migraine.
   
4. Maximum daily dose is one 75mg lyophilisate. Rimegepant is licensed for both acute treatment and prophylaxis of migraine. Patients should not take an additional 75mg lyophilisate for acute treatment of migraine on the same day as receiving rimegepant for prophylaxis of migraine.
5. Interactions: Rimegepant is metabolised by CYP3A4. Concomitant administration with strong CYP3A4 inhibitors, or moderate or strong CYP3A4 inducers is not recommended. Rimegepant is also associated with additional drug interactions. Refer to the BNF or rimegepant SmPC for advice on drug interactions.
6. Acute treatment of migraine:
   1. Rimegepant is licensed for acute treatment (see note above on maximum daily dose). Use of rimegepant for acute treatment in addition to prophylaxis is not recommended with concomitant use of certain medicines (refer to BNF or SmPC for advice on drug interactions)
   2. Other treatment options (triptans, NSAID, paracetamol, aspirin)
   3. Co-administration of an anti-emetic (metoclopramide, prochlorperazine, domperidone)
7. Cardiovascular disease: see the drug entry here for patients excluded from phase 3 trials
8. Tolerability: most common adverse reaction in clinical trials was nausea for acute treatment (1.2%) and for migraine prophylaxis (1.4%) (rimegepant SmPC)
9. Pregnancy and breastfeeding: There are limited data from the use of rimegepant in pregnant women and in breastfeeding. Refer to the SmPC and discuss with the patient
10. Annual cost: the annual cost per patient for prophylaxis of migraine is £2,354.
11. For further information, see drug entry (section 4.7.4 Antimigraine drugs) and rimegepant SmPC.

Additional options are included under section 4.7.4 Antimigraine drugs and section 4.9.3 for botulinum toxin

Other drugs

1. The use of sodium valproate, pizotifen and gabapentin for migraine prophylaxis has been superseded
2. NICE CG150 recommends that for people who are already having treatment with another form of prophylaxis and whose migraine is well controlled, continue the current treatment as required
3. Patients currently receiving sodium valproate: refer to the Drug Safety Update below for new safety measures in addition to the existing Pregnancy Prevention Programme.
   1. Sodium valproate is not licensed for the prophylaxis of migraine.
   2. Refer female patients under 55 years currently receiving valproate to specialists for discussion of alternative treatment options.
   3. As a precaution, male patients under 55 years currently receiving valproate who are planning a family within the next year should speak to a healthcare professional about their treatment options. Additional recommendations are expected later in 2024 in relation to review of men under 55 years of age on valproate.
   4. MHRA Drug Safety Update (January 2024): 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

Migraine during pregnancy is quite unusual, with 60% -70% of women experiencing an improvement in symptoms. In general, drug treatment should be limited during pregnancy. If treatment is essential, it should be prescribed at the lowest effective dose for the shortest possible time and a discussion of the risks and benefits documented.

Seek specialist advice if prophylactic treatment for migraine is needed during pregnancy.