PROPHYLAXIS FOR MIGRAINE
Guidance
Prophylaxis is indicated in patients with frequent migraine or if migraine
causes significant disability
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These medications should be initiated at low dose to minimise side effects
and the dose should be gradually titrated upwards depending on patient
response and tolerability. A 3-6 month trial is required to determine
efficacy.
As a general rule only one drug should be used at a time but combination
therapy can be useful in patients with difficult to control migraine. A useful
combination is nortriptyline and topiramate.
Choice may depend on co-morbid conditions and contra-indications
First choice for adults is usually ß blockers or tricyclic
Second choice for adults is an anti epileptic (caution in women using
COP). Risk of teratogenicity should be discussed with the patient
First choice for children (<16 years) is Pizotifen
Most prophylactic agents won’t work in the presence of medication
overuse. Overused medications should be withdrawn.
A patient leaflet with information about these drugs is available to
download from the NHSG intranet.
Adult Patient Prophylaxis Flow Chart
Migraine prophylaxis indicated and medication over use headache excluded
Propranolol or TCA (Nortriptyline or Amitriptyline)
No response to either after 3 month trial at maximum tolerated dose
Review
contraception
Good response, consider stopping
after 6-12 months
Consider antiepileptic
Topiramate
Gabapentin
Sodium valproate
No response to 3 anti epileptics after 3 month trial at maximum tolerated dose
Consider referral to headache clinic
Prophylactic drugs
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Beta-blockers
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Tricyclic anti– depressants
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First choice is propranolol starting at 10mg three times a day. The dose
should be increased every 2 weeks aiming for a target daily dose of
between 80 -240 mg. There is some evidence that splitting the dose in
to 3 divided doses is more effective than using slow release tablets. If
propranolol is not tolerated there is some evidence for atenolol 25-100
mg daily or metoprolol 100-200 mg daily. Propranolol is safe to use in
pregnancy up to a dose of 60 mg daily. Higher doses should be
discussed with an obstetrician.
Nortriptyline or amitriptyline 10-150 mg at night. The starting dose is
10mg at night which should be increased every 1-2 weeks aiming for a
dose that controls the headache whilst limiting side effects. Some
patients require doses approaching 100mg. There is empirical
evidence that Nortriptyline is better tolerated than amitriptyline.
Amitriptyline is safe to use in pregnancy up to a dose of 50mg. Higher
doses should be discussed with an obstetrician.
Anti - epileptics
These can all be initiated in primary care without specialist advice. Antiepileptics for
migraine are contra-indicated in pregnancy, They may interfere with contraception
and appropriate contraception should be discussed with women of child bearing age.
Topiramate 25mg to 100 mg daily in 2 divided doses. The starting dose is 25
mg daily and built up slowly every 1- 2 weeks. All side effects are dose
related. Please see the NHSG topiramate protocol below for more
information. Some patients get a fantastic response to topiramate virtually
being headache free. Others can’t tolerate side effects. Sometimes it takes 34 months to be effective so it is worth persevering even if there is no initial
headache response.
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Gabapentin 1200- 2400 mg daily in divided doses. Starting dose is 100 mg
three times a day. This can be increased by 100mg every 3-5 days depending
on tolerability.
Sodium valproate 200-600 mg twice a day. The starting dose is 200 mg
twice a day titrated up every 2-4 weeks aiming for a dose of 600 mg twice a
day.
Other agents with some evidence.
5HT2 antagonists pizotifen 500 mcg – 4.5mg daily (best taken at night
time)evidence is poor and often large doses above 3mg are needed in adults
which limits its use due to side effects of sedation and weight gain. Usual drug of
first choice in children
ARB Candesartan 2-16 mg daily.There is some evidence for its use in episodic
migraine. It is used as a first choice agent in some Northern European countries
due to its high tolerability. It should be reserved for patients failing or not
tolerating β blockers, tricyclics or anti epileptics or in patients in whom these
medications are contra-indicated.
SNRI Venlafaxine 75-150 mg daily has a SIGN grade B recommendation as an
effective alternative to tricyclic antidepressants for the prophylaxis of migraine.
Topiramate Protocol
Three large trials have shown that topiramate can reduce migraine frequency by 50%
in approximately half the patients using it. This is roughly similar to Beta-Blockers.
Topiramate has an early onset of action within the first 4 weeks and maintains the
reduction in migraine frequency over 6 months.
Dosage
The target dose is 100 mg a day in 2 divided doses. Some patients may experience
benefit at a total daily dose of 50mg/day. Many side effects are dose dependant so it is
best to initiate it at low dose titrating up slowly. Topiramate should be started with
one 25 mg tablet at night increasing by 25 mg/day at one – two week intervals i.e.
AM dose
PM dose
Week 1-2
25 mg
Week 3-4
25 mg
25 mg
Week 5-6
25 mg
50 mg
Week 7-8
50 mg
50 mg
Topiramate is available as 25 and 50 mg tablets or as sprinkle capsules. It can be
taken with or without food.
Contra Indications
Known hypersensitivity to topiramate or any of the tablet/capsule excipients
Not to be used in acute porphyrias.
Cautions
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Abrupt withdrawal of topiramate should be avoided, the dose should be
reduced gradually over at least 2 weeks to minimise the possibility of rebound
migraine headaches.
Patients should be advised to drink plenty of water to avoid dehydration and to
reduce the likelihood of developing kidney stones
Topiramate is teratogenic and therefore should not be used during pregnancy.
Women of childbearing potential should be advised to use adequate
contraception whilst taking topiramate. Topiramate should not be used during
breast feeding.
Topiramate may need to be titrated more slowly in patients with renal
impairment and should be used with caution in patients with hepatic
impairment.
Side Effects
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Common > 10%
o Paraesthesia in about 50%
o Anorexia, nausea
o Weight loss
o Fatigue
o URTI
o Diarrhoea
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Less common < 10%
o Cognitive effects such as memory, language and somnolence
o Depression and mood alteration
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Rare < 1 %
o Acute myopia secondary to angle closure glaucoma
o Choroidal effusions resulting in anterior displacement of the lens and
iris
Monitoring
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Response to therapy
o Topiramate should be administered for a minimum of 12 weeks
o If effective continue for 6 months and then withdraw to establish
continued need. (migraine prophylaxis should rarely be used
uninterrupted for more than 12 months)
o If not effective at adequate dosage or intolerable side-effects, treatment
should be withdrawn and alternative therapy considered. Cognitive
effects rarely settle so treatment should be withdrawn early if there are
significant problems.
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Treatment Safety
o Patients with new onset visual symptoms or signs should have their
intra ocular pressure measured urgently. If it is raised they should be
referred to the ophthalmology clinic immediately and the topiramate
stopped as rapidly as feasible
o Patients on long term topiramate should be weighed every 8 weeks and
discontinuation of treatment should be considered if weight loss is
greater than 10%.
o Patients should be monitored for signs of depression and advised to
seek medical help immediately if they have suicidal thoughts.