Clinical

Guidelines

Migraine Treatment

Migraine Clinical Guidelines and Treatment

In the absence of a cure for migraine, the aims of migraine management at primary care level are:

  • The successful treatment of the migraineur’s acute attack
  • The prevention and limitation of future attacks
  • To encourage migraine sufferers to continue with their care
  • The identification and referral of the minority of patients who need specialist services

Stratified Care

The Stratified Care approach is the approach of choice when treating headache disorders, whereby the doctor decides what treatment is necessary based on the evidence for that treatment and the individual patient’s needs. Recent best practice guidelines on the management of migraine such as the Migraine in Primary Care Advisors (MIPCA) guidelines from the UK, the US Headache Consortium, and the Primary Care Network guidelines are based on the Stratified Care model.

‘Stratified Care’ has now largely superceded the ‘stepped care’ approach which began with analgesics (perhaps with an anti-emetic) for all patients regardless of headache impact, severity or frequency, and if those are not effective, the patient is “stepped up” to the next level of treatment, reserving the more powerful triptans as third-line options.

Primary Care Advisors
Primary Care Network

Stratified Care Approach

Under a stratified approach:

  • Each patient should have an individual treatment plan, based on factors such as headache frequency, duration and severity, non-headache symptoms, the impact it has on the patient’s life and the patient’s own history and preference.
  • Migraine specific treatments should be provided from the start if necessary. Rescue medication is recommended in case the initial therapy fails.

The MIDAS and Headache Impact Test (HIT) tests can be useful for helping the doctor implement a stratified treatment plan.

MIDAS

Treatment

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Prophylactic
Treatments
Prophylaxis
Options
Triptan
Therapy

Prophylactic Treatments

for Migraine

The role of prevention is to achieve a reduction in the frequency, severity and duration of attacks.  Effective prophylaxis can achieve up to a 50% reduction in the frequency in approximately 50% of migraineurs. Prophylaxis cannot be expected to eliminate migraine completely.

It is thought that while about 50% of all people with migraine are candidates for prophylaxis, only about 10% are actually on a preventative medication.

Indications for Prophylaxis

Prophylaxis is indicated in patients who:

  • Experience two or more attacks per month and do not respond satisfactorily to acute therapy
  • Suffer from concomitant co-morbidities
  • Suffer from a medical illness precluding first line acute therapy
  • Suffer attacks that significantly interfere with the patients daily routine
  • Demonstrate regular patterns to their attacks
  • Experience long duration attacks
  • Have Basilar or Hemiplegic migraine
  • Are at risk of Medication induced headache from over use of acute treatments.

Mode of Action of Prophylactic Agents

The preventative therapies are thought to mediate their benefit by antagonism of central serotonergic receptors, by regulation of calcium ion channels, and by enhancement of central antinociceptive mechanisms.  This results in raising the threshold for both cortical spreading depression and trigeminovascular activation.

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General Principles

of Migraine Prophylaxis

There are no sound criteria for preferring one prophylactic drug over another. However, the following should be taken into account (1) Comorbidities  (2) Drug interactions (3) Possible side effects (4) Lifestyle issues e.g. a preventative that lead to weight gain may not be the best option in young women with a tendency to gain weight.

A once daily dose can help improve patient compliance.

Start low and go slow. To minimise possible side effects, patients should be started on the lowest dose of a prophylactic medicine and increased gradually if required.

Allow an adequate time for the drug to show benefit. An appropriate trial length for most preventive medications is 8 to 12 weeks. Patients should be maintained on preventatives for at least 6 -9 months before reduction and gradual withdrawal is considered.

As with acute treatments, many patients will not respond well to certain medications and responses cannot be predicted.

Patients should keep a Migraine Diary to record of the frequency, severity, and duration of attacks and of medications consumed for each attack. This is the most reliable way to know if the preventive medication is having the desired effect.

Remember that while on a course of prophlyactic treatment, patients still need to have access to an effective acute treatment to deal with breakthrough attacks.

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Options in

Migraine Prophylaxis

β-Blockers

The β-Blockers have been used for prophylaxis for more than 25 years and continue to be a strong option unless contraindicated in patients with asthma or peripheral vascular disease.

Propranolol 80mg – 160mg is the preferred dose and can be titrated up to 320mg. Propranolol has been shown to lead to a ≥50% reduction in attack frequency in 35-60% of patients, though it has no impact on the severity or duration of attacks that actually occur. It may take 12 weeks at an adequate dose to begin to work.

Propranolol is lipophilic, crosses the blood brain barrier and has actions at adrenergic, nonadrenergic and 5-HT2 receptors.

Other β -Blockers known to confer benefit are Atenolol and metoprolol. β-Blockers are contraindicated in patients with depression, asthma, type 1 diabetes, heart block, and hypotension. They are all generally well tolerated. Side effects can include fatigue, arterial hypotension, impotence, decreased endurance and depression.

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Anti-Convulsants

Topiramate

In 2004, Topiramate was licensed in Ireland for migraine prophylaxis in adults unresponsive to or intolerant of other treatments.

The recommended total daily dose of topiramate for prophylaxis of migraine is 100 mg a day administered in 2 divided doses. The drug should be slowly titrated to this dosage over 4 weeks, starting as low as 25 mg a day in week 1.

In two multi-centre, randomised, double-blind, placebo-controlled trials, patients taking 100mg a day experienced a decrease in mean monthly migraine frequency from 5.4 to 3.3 days. 54% of patients taking 100mg exhibited a 50% of more reduction in monthly migraine frequency. Patients should be maintained on the medication for 2-3 months before evaluating its therapeutic effect.

Although generally well tolerated, the most common adverse events are parastesia and difficulty in concentration. Other side effects include weight loss, taste perversion, anorexia and fatigue.

Gabapentin

Gabapentin may also be useful in clinical practice, especially in treating transformed migraine. Gabapentin can cause weight gain, drowsiness, ataxia, and impaired cognition. The suggested dose is 900mg to 2,400 mg per day.

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5-HT2 Antagonists

Pizotifen

Pizotifen is a 5-HT2 antagonist and anti-histamine that was developed specifically as a migraine-preventive agent. It has been shown to reduce attack frequency by ≥50% in 35-50% of patients. The dose is 0.5mg – 3mg and is best taken as a single dose in the evening.  It is frequently used in children and adolescents. Pizotifen. Pizotifen has few contraindications (ie, pyloric stenosis, use of a monoamine oxidase inhibitor) or adverse effects (increased appetite with associated weight gain and drowsiness)

Update November 2015: After exhaustive investigation, MAI can confirm that Novartis has discontinued the manufacture of Sanomigran (Pizotifen) in Ireland and the UK. If you are currently taking Sanomigran as a preventative medication, please consult your GP to discuss a suitable alternative.

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Tricyclic Anti-Depressants

Low dose tricyclic anti-depressants such as Amitriptyline have shown continued efficacy in migraine prophylaxis for several decades and are most beneficial in those who suffer from concurrent tension type or chronic daily headache and in those for whom migraine and depression are co-morbid.

Antidepressant therapy also may prove helpful in patients refractory to other standard forms of treatment. The effective dose range is 20mg to 75mg per day. Side effects include dry mouth, drowsiness, arterial hypotension and urinary retention. Contraindications for their use are glaucoma, prostatism, and heart disease. They should also not be used with drugs that inhibit monoamine oxidase or with medications that slow the brain’s processes, Epinephrine should not be used with amitriptyline, since the combination can cause severe high blood pressure

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Calcium Antagonists

Flunarizine

Flunarizine has a long half-life and is a good alternative if β-blockers are contraindicated.  The dose is 5-10mg daily at bedtime and is frequently prescribed for patients with prolonged aura or for patients who frequently awaken with migraine.  Side effects can be severe and include sedation and Parkinsonian symptoms after long-term use due to anti-dopaminergic actions.  Other side effects include weight gain, edema, constipation, and depression.

Verapamil

The suggested dose range of Verapamil is 180 to 320 mg per day. The rationale for using these agents stems from their effect on intracranial vasoconstriction. In addition to this marked selectivity, verapamil has also demonstrated antiplatelet effect.

Verapamil may reduce the elimination and increase the blood levels of carbamazepine, simvastatin, atorvastatin and lovastatin. This can lead to toxicity from these drugs.

Drugs with limited and / or unproven efficacy

  • Clonidine
  • SSRIs
  • NSAIDs
  • Cyproheptadine
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