Options in Migraine Prophylaxis
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.
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.
Clinical trials have shown sodium valproate can reduce attack frequency by ≥50% in 45-50% of cases. The suggested dose is 1,250 to 2,000 mg per day. It was also shown to be generally well tolerated, with the most common side effects being mild to moderate nausea, weight gain, dyspepsia, dizziness and diarrhoea. It should be avoided in patients who have a history of hepatitis or abnormal liver function.
Update December 2015: The manufacturers of the drug Epilim, Sanofi wrote to Irish healthcare professionals earlier this year to advise them on new European-wide restrictions on the use of valproate in female children, adolescents, women of childbearing age or pregnant women. Click here for further information.
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.
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.
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
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.
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