Migraine for Clinicians

Migraine is the most common disabling headache disorder, ranked as 7th highest among specific causes of disability globally and is responsible for 2.9% of all years of life lost to disability.

The global lifetime prevalence is 10% in men and 22% in women.

Peak prevalence increases to the age of 40 years and declines thereafter in both women and men, though can present de novo later in life.

Chronic migraine is a highly disabling primary headache disorder that affects 2% of the population, with reduced quality of life, increased risk of anxiety, depression and chronic pain  and greater use of healthcare resource.

Around two-thirds of patient with chronic migraine have medication overuse.

Migraine is characterised by recurrent episodes of moderate to severe headaches, unilateral or bilateral and frequently throbbing. There may be associated nausea/vomiting, and light, noise and/or motion sensitivity. (IHS classification).

Attacks can last 4-72 hours with freedom from symptoms in between, and vary in frequency from one per year to a few times per month.

The median frequency is one to two attacks per month.

Headache on 15 or more days per month for 3 consecutive months, of which at least 8 days have features of migraine, is termed chronic migraine (IHS classification).

The most sensitive and specific features of migraine are:

• Nausea
• Disability (limitation of activity
• Photophobia

Prior to the onset of headache, patients can frequently experience premonitory symptoms, the most common of which are feeling tired (72%), difficulty concentrating (51%), and a stiff neck (50%).

After the headache has ended patients often experience postdrome symptoms of a similar nature.  In most attacks (93%), there was return to normal within 24 hours.

Aura affects around a third of migraine sufferers.

A typical aura comprises of fully reversible visual and/or sensory/ and/or speech symptoms, evolving over minutes with a total duration of up to 60 minutes (IHS classification).

Aura may occur without headache particularly in older patients.

Aura usually precedes, but may occur during, or after the headache.

Aura is not unique to migraine.  It may occur in other forms of primary headaches.

General Principles

Validate the impact the condition has on the individual and family.

Manage expectations:   Patients may have low or unrealistic expectations of what is achievable.  Explain that most headache disorders cannot be cured but can be effectively managed in most cases.

Reassurance:  Patients often worry about an underlying serious disorder. Explaining the nature of the condition to the patient can be of therapeutic value.

Empower the patient to help promote self-management.

Brain Scans and Primary Headache

Outside of an emergency setting, current data indicates that the risk of finding serious secondary pathology in patients with isolated headache and a normal neurological examination is similar to that in people who do not have headache 

Normal imaging can reduce subsequent health care utilisation in the short term (less than one year) presumably because of reassurance.  The effect however does not appear to be sustained in patients with anxiety and depression.

Moreover, there is a significant potential for uncovering incidental findings in 6-15% patients, which may not necessarily require further management but can themselves increase anxiety, and even potentially affect insurance coverage/premiums for that individual.

An information sheet can be useful to give to the patient to act as an ‘aide memoire’ when discussing these issues- available from this site.

When considering medication:-

Potential issues of medication overuse, both with respect to the impact on headache and side effects should be discussed.

Prescribing decisions should be made with reference to the patient’s current clinical situation and their future plans (e.g. pregnancy or contraception).

A daily headache diary for at least three months may be helpful able to establish the patterns of headache- a template diary is available from this site

Ensure that the patient does not take painkillers too often. Taking painkillers on more than 2 days per week can cause a medication overuse headache

In medication overuse – the headache improves in about 70% of people once pain killers are reduced and adequate preventative treatment established

If there is difficulty restricting use of pain killers to less than 2 days per week, consider referral to clinical psychologist/pain team to develop pain management skills to be able to manage the pain better.

If the patient is experiencing migraine on more than 4 headache days a month which need treating with some sort of pain killer, a prescribed preventative medication might be appropriate.

When prescribing acute treatments there are two broad strategies:

1. Stepped approach: start with simple analgesics and if ineffective step-up e.g. to a triptan
2. Stratified approach: target treatment based on attack severity

The stratified approach is associated with better health related outcomes and lower indirect costs (e.g. GP and hospital visits).

Adding an anti-emetic to an acute treatment improves efficacy unrelated to nausea and/or vomiting and can improve gastric motility and hence drug absorption.

The end point of an effective treatment is a significant response at two hours, because the natural history for most attacks is to spontaneously improve in 4 hours.

If a treatment is not effective at 2 hours, then it is unlikely to work in that attack at that dose and considering an alternative acute treatment or combination treatment would be reasonable.

Lack of response to one triptan does not predict response to other triptans.

Triptans are most effective when taken early in the headache phase of the attack.

Triptans are less likely to be effective at treating the headache if taken during the preceding aura.

After 2 treatment failures with a particular triptan a trial with an alternative triptan is recommended.  This rationale is based on the finding that in patients who experienced treatment failure in two attacks, 70% failed to respond in the third attack. Around 30% patients do not respond to any triptan.a

Acute treatments can be associated with the development of medication overuse headache.

Opioids are not recommended for the treatment of acute headache because of the significant risk of medication overuse and the most protracted withdrawal.

For patients attending the emergency department parenteral NSAIDs or subcutaneous sumatriptan should be considered, and evidence also supports the use of antiemetics. Opioids have not been shown to be significantly effective and should not be used.

Recommended acute treatments are included in the tables below.

Choosing a triptan

Sumatriptan 6 mg subcutaneous remains the most rapid and effective treatment for pain relief but has a higher risk of adverse events than other formulations.

Combination of a triptan and an NSAID with a long half-life, such as naproxen, is better than monotherapy.

In comparison to sumatriptan 100 mg:

• Lower adverse events: naratriptan 2.5 mg, almotriptan 12.5 mg and frovatriptan 2.5 mg
• Better 2-hour pain response: eletriptan 80 mg and rizatriptan 10 mg, almotriptan 12.5 mg
• Lower recurrence rate: frovatriptan 2.5 mg, and eletriptan 40 mg

Contraindications to triptans include ischaemic heart disease, cerebrovascular disease, previous myocardial infarction, and uncontrolled or severe hypertension. The cardiovascular risk of triptans is very low in the absence of these contra-indications.

The NNTs for therapies to achieve the outcome of pain freedom at two hours from a baseline of moderate to severe pain can be accessed by the SIGN guideline.

Recommended acute treatments – simple analgesics and antiemetics

DRUG	DOSE	MAXIMUM DAILY DOSE	INFORMATION
Simple analgesics
ASPIRIN	600-1000 mg (UK doses are 300-900 mg)	4000 mg (for oral dosing)
DICLOFENAC	25 mg	150 mg
IBUPROFEN	400-600 mg	2400 mg
KETOPROFEN	75-150 mg	150 mg
NAPROXEN	250 mg	1000 mg
PARACETAMOL	1000 mg	4000 mg
TOLFENAMIC ACID	200 mg	400 mg
Antiemetics
DOMPERIDONE	10 mg	30 mg	Safety alert: MHRA-Domperidone
PROCHLORPERAZINE	10 mg	30 mg
METOCLOPRAMIDE	10 mg	30 mg	Safety alert: MHRA – Metoclopramide

Recommended acute treatments – triptans

DRUG	FORMULATION	STRENGTH	SINGLE DOSE	MAX/24 HOURS
ALMOTRIPTAN	TABLET	12.5 mg	12.5 mg	25 mg
ELETRIPTAN	TABLET	40 mg	40 mg	80 mg
FROVATRIPTAN	TABLET	2.5 mg	2.5 mg	5 mg
NARATRIPTAN	TABLET	2.5 mg	2.5 mg	5 mg
RIZATRIPTAN	TABLET ORODISPERS LYPOPHILLISATE	5 mg/10 mg 10 mg 10 mg	10 mg 10 mg 10 mg	20 mg 20 mg 20 mg
SUMATRIPTAN	TABLET SPRAY SUBCUT INJ	50 mg/100 mg 100 mg/ml or 200 mg/ml 6 mg	50-100 mg 10 – 20 mg 6 mg	300 mg 12 mg
ZOLMITRIPTAN	TABLET ORODISPERS SPRAY	2.5 mg/5 mg 2.5 mg/ 5 mg 50 mg/ml	5 mg 5 mg 5 mg	10 mg 10 mg 10 mg

General Principles

Prescribing decisions should be made with reference to the patient’s current clinical situation and their future plans (e.g. pregnancy or contraception).

Preventive treatment should be offered as an option to patients with 4 or more migraine days a month as this frequency is associated with significant disability. Such an approach will also mitigate the risk of escalation of acute treatment and consequent development of medication overuse headache.

Acute treatment on more than 2 days per week is associated with medication overuse, which renders preventive treatment less effective.

As there are relatively few head to head comparative studies, the choice of preventive depends primarily upon the side-effect profile of the drug and co-existing morbidities.

Preventive medications must be titrated slowly to an effective or maximum tolerable dose and continued for at least 6-8 weeks to adequately assess effect.

A headache diary may help evaluate response to treatment.

Consider gradual withdrawal after 6-12 months of effective preventive.

Monitor quality of life through validated tools such as HIT-6. The HIT-6 score can be downloaded or can be found in the information sheet section of these guidelines (Patient reported outcome measure HIT-6).

Treatment options

In selecting a preventative treatment, a reasonable strategy would be to consider which options might be most suitable for the individual patient, given their previous treatment, medical and other co-morbidities, personal preferences, and side effect profiles of the various treatments.

Table 5 shows the dose and titration regimen for recommended preventive treatments in both episodic and chronic migraine.

Table 6 shows dose and treatment regimen for recommended preventive treatments in chronic migraine only.

All preventive treatments with randomised placebo-controlled trial data are listed as an appendix.

Onabotulinumtoxin A

The efficacy and safety of Onabotulinumtoxin A for prophylaxis of Chronic Migraine has been shown through in the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical programme.

Patient selection: Treatment is licensed for adult patients with chronic migraine. Treatment is not effective in episodic migraine (< 15 days a month).

BASH considers it good practice to address medication overuse prior to commencing Botox treatment. Patients are advised to restrict their acute headache medication to no more than two days a week on a regular basis.

As 60% of patients failed two oral preventive treatments in the PREEMPT trial, BASH recommends considering use of 2-3 oral preventive treatments prior to Botox therapy.

Treatment response should be monitored using quality of life measures, for example HIT-6.

Recommended preventive treatments in episodic and chronic migraine

DRUG	START DOSE	TITRATION	TRIAL STUDIED DAILY DOSES
Amitriptyline	10-25 mg OD	10 -25 mg	25-150 mg
Candesartan	2 mg OD	2 mg	8-16 mg total/day
Propranolol	10 mg BD	10-20 mg BD	120-240 mg total/day
Topiramate	25 mg daily	25 mg od	25-200 mg total/day
CGRP monoclonal antibodies
Erenumab	70-140 mg monthly	Max dose as per licensed indication
Fremanezumab	225 mg monthly 675 mg three-monthly	Max dose as per licensed indication
Galcanezumab	120-240 mg monthly	Max dose as per licensed indication

Recommended preventive treatments for chronic migraine only

Onabotulinumtoxin A

155-195 IU intramuscularly, as per PREEMPT protocol

Every 12 weeks

Menstrual Migraine

A proportion of women suffer from migraine attacks in association with the menstrual cycle, termed menstrual related migraine (MRM). MRM occurs between days -2 and +3 of the first day of menstruation (which is +1) in at least 2 out of 3 menstrual cycles.

Women with MRM will also have attacks at other times.

Less than 10% of women report migraine exclusively with menstruation and at no other time (‘pure’ menstrual migraine)

Acute Treatment

The acute treatment of menstrual related attacks is no different to non-menstrual attacks. 

Head-to-head studies do not show clear superiority of one triptan over any other.

Recommended triptans for short term prevention of menstrual related migraine or pure menstrual migraine

DRUG	FORMULATION	STRENGTH
FROVATRIPTAN	TABLET	2.5 mg twice daily on the days migraine is expected (generally from two days before until three days after bleeding starts).
ZOLMITRIPTAN	TABLET	2.5 mg twice or three times a day on the days migraine is expected (generally from two days before until three days after bleeding starts).

All treatments for short term prevention of menstrual related migraine or pure menstrual migraine

DRUG	FORMULATION	STRENGTH
FROVATRIPTAN	TABLET	2.5 mg twice daily on the days migraine is expected (generally from two days before until three days after bleeding starts)
NARATRIPTAN	TABLET	2.5 mg twice daily on the days migraine is expected (generally from two days before until three days after bleeding starts)
ZOLMITRIPTAN	TABLET	2.5 mg twice or three times a day on the days migraine is expected (generally from two days before until three days after bleeding starts)

Targeted oestrogen supplementation

Menstrually targeted oestrogen supplementation (assuming no contraindications) has been found in some studies to offer benefit in menstrual related migraine.

However, a rebound increase in migraine attack frequency has been found when the effect of this strategy has been considered over the whole menstrual cycle.

The risk of stroke in migraine with aura, when taking oestrogen-containing contraceptives

Females suffering migraine with aura have an inherent increased risk of stroke. 

Use of the oestrogen contraceptive pill is also associated with increased risk of stroke in all individuals.  The incidence of stroke in females with migraine with aura, who are also taking the oestrogen-containing contraceptive pill is additionally increased. 

Consequently, contraceptive methods other than oestrogen containing contraception are advised for women with migraine with aura. There is no established additional risk in migraine without aura.

Treatment in pregnancy & breast feeding

• In the majority of women, migraines improve during pregnancy
• Caution is advised and checking with British National formulary data and pregnancy register is recommended especially when prescribing in pregnancy, breast feeding, and considering contraception. The resource Best Use of Medicine in Pregnancy (BUMPS) may also be of help to patients (http://www.medicinesinpregnancy.org/)
• Paracetamol is not generally considered to be associated with a significantly elevated risk throughout pregnancy and lactation
• The Sumatriptan & Naratriptan Pregnancy Registry found no evidence of teratogenicity associated with major birth defects for sumatriptan