Managing Migraine

Preventative treatments for migraine

Principles of treatment

There are two fundamentally different, though not mutually exclusive ways of treating migraine with medications. The first is to take medications when migraines occur; these are acute treatments such as non-steroidal anti-inflammatories or triptans. The second approach is to take medications regularly to try to reduce the number of migraines that occur; these are preventative or prophylactic treatments. Not all patients with migraine need to take medications; many milder migraines will settle simply with rest or sleep, and many patients find that lifestyle adjustments such as regularising meals and sleep significantly reduce the frequency of their attacks.

The decision to take preventative treatment is an individual one for the patient. There are no firm rules about when these medications should be tried. Generally speaking, however, preventative treatment should be considered when migraine frequency or severity increases to a point where it is interfering significantly with work, school, or social life. In most cases this point is arrived at when patients are experiencing about one attack each week. However if the attacks are long or the response to acute treatment is poor, then preventative treatment might be introduced at a lower frequency of attacks than that. The condition of patients with rarer forms of migraine, such as basilar-type or hemiplegic migraine, may warrant preventative treatment even if the attacks are very infrequent.

There are numerous medications that have been shown to be effective in the preventative treatment of migraine. It should be noted that not all of these are licensed for the treatment of migraine in the United Kingdom. Details of some of the more commonly used preventative treatments are outlined below. The choice of treatment can be influenced to varying degrees by the particular pattern of migraine, patient co-morbidity, tolerability, teratogenecity, potential side effects, ease of use, and patient choice. Guidelines on the choice of preventative medication have been produced by the British Association for the Study of Headache, and the American Academy of Neurology, amongst others.

Preventative treatments should be commenced at a low dose, to minimise the possibility of developing side effects. The dose should be steadily and regularly increased until, ideally, the medication works, or else until intolerable side effects kick in, or until a maximum dose is reached, whichever comes first. It can thus be concluded whether that medication is going to work or not for that individual patient. If it doesn’t another preventative treatment can then be tried.

Assuming the preventative treatment works well, that medication can then be continued for a few months, after which begins a process of weaning the dose down. It is unusual for migraine frequency suddenly to bounce back again during weaning down. Migraine frequency does rise and fall in people’s lives, however, and it is acknowledged that patients may need to take preventative treatment on several occasions during their lifetime.

First line preventative treatments

Beta-blockers

Beta-blockers such as propranolol, metoprolol and nadolol have been used as preventative treatments for migraine since the 1970s. They are effective treatments, especially for patients with frequent migraines interspersed by periods of headache freedom. Many patients tolerate beta-blockers well and take them for many years, but they can cause tiredness, dizziness, cold extremities, decreased libido, and nightmares. They may also exacerbate asthma, a fact that often limits their use in young people. Propranolol is the most commonly used medication in the preventative treatment of migraine; it should be started at 20-30 mg daily (in divided doses) and increased steadily to as high as 240 mg daily. Some patients may respond well to this medication: the once daily prolonged release formulation may be a reason, though this has never been systematically tested in migraine.

Tricyclics

Tricyclic antidepressants were developed in the 1960s, but first entered use in migraine over the next two decades. Medications such as amitriptiline, nortriptiline or dosulepin are now as commonly used for headaches and neuropathic pain as for depression; the doses used in migraine are generally much lower than those regarded as effective for depression. The commonest side effects are drowsiness, dry eyes, and dry mouth; tricyclics are usually taken in the evening, about twelve hours before the patient wishes to get up. Amitriptiline may be started at 10-25 mg daily, and steadily increased to 70-100 mg daily. Some patients with chronic daily headache may only respond to doses as high as 150-200 mg daily.

Pizotifen

Pizotifen (Sanomigran) was first developed in London in the late 1960s as a specific anti-migraine drug. It is a serotonin antagonist which is often used as the first preventative treatment in children. It is a highly effective preventative treatment, but its use is often limited by drowsiness or weight gain. In general practice it is usually started at 0.5 mg daily, and increased as high as 1.5-2 mg daily; in specialist headache clinics patients can sometimes be titrated up as high as 4.5 mg daily.

Second-line (specialist) preventative treatments

Anticonvulsants

Several drugs originally developed to treat epilepsy have been found to be useful in the preventative treatment of migraine. Not all anticonvulsants have this dual role, however. High quality evidence exists for sodium valproate (Epilim) and topiramate (Topamax); other anticonvulsants which are probably helpful include gabapentin (Neurontin) and pregabalin (Lyrica); in certain circumstances lamotrigine (Lamictal), levetiracetam (Keppra) or zonisamide (Zonegran) may be tried, but the use of these medications is not supported by decent trial evidence, and is generally restricted to tertiary headache clinics.

Methysergide

The use of methysergide (a serotonin antagonist) in migraine dates back 50 years. It was the first widely available effective preventative treatment for migraine; its introduction was in no small part responsible for changing migraine from a psychological to a neurological disorder. Methysergide remains a highly effective preventative treatment, though its use is restricted by the potential it has to cause pulmonary, pericardial or retroperitoneal fibrosis. Modern practise therefore limits its use to only 5-6 months at a stretch, and the dose to no more than (and usually rather less than) 9 mg daily. Patients taking methysergide should have regular tests of their heart, lung and kidney function.

Flunarizine

Flunarizine is a calcium channel blocking agent which is one of the most commonly prescribed preventative treatments for migraine on the Continent. It has never been widely marketed in this country, but is available on a named-patient basis. It may be particularly useful in patients with severe aura symptoms, including hemiplegic migraine. Flunarizine takes several weeks to kick in, and its maximum effect may take up to 3-4 months to be seen. Tiredness, dizziness and constipation are the commonest side effects; very rarely patients on flunarizine may develop muscular stiffness and slowness reminiscent of Parkinson’s disease; this is reversible fortunately but it can take time to wear off.

Miscellaneous other preventative treatments

Various other medications have been used in the preventative treatment of migraine. In most cases their use is supported by few, if any decent clinical trials. Antihypertensives in some classes other than beta-blockers can be helpful; lisinopril and candesartan fall in this category. Some authorities still use older drugs such as clonidine or cyproheptadine, though the use of these medications has largely fallen out favour. High dose riboflavin (vitamin B2), magnesium, and co-enzyme Q10 have all been tested in small trials. Finally, Phase III clinical trials of onabotulinum toxin A (Botox) presented at the International Headache Congress at Philadelphia in September 2009 suggest that this medication may be effective in patients with chronic migraine.

Written by

Dr Mark W Weatherall
Princess Margaret Migraine Clinic
Charing Cross Hospital