Anti-Epileptic Drugs (AEDs) are increasingly used for migraine prevention and there are a number of placebo-controlled trials proving their efficacy.[20
] A Cochrane Review of AEDs in migraine prophylaxis[24
] found that patients were more than twice as likely to have a 50% reduction in their headache frequency on AED treatment than with placebo.
Valproate, topiramate and gabapentin have all demonstrated some efficacy in migraine prevention.[20
] AEDs are particularly useful when migraine occurs in those with epilepsy, anxiety disorders or bipolar disease. Care must be taken when prescribing for women of childbearing age as many AEDs can be associated with foetal malformations and can interfere with the oral contraceptive.
Valproate is effective in reducing both migraine frequency and severity at a low dose (500-1000 mg/day).[24
] Placebo controlled studies have shown 40-50% of patients treated with valproate will have a 50% or more reduction in their headache frequency.[25
] In limited single blind or open trials,[23
] valproate has been shown to be as effective as propranolol and flunarizine.
Valproate is especially useful for those patients with co-existing depression or bipolar disease. The most common side effects of valproate are nausea and vomiting (often transient), tremor, weight gain and hair loss. These often make the drug less appealing for women. On rare occasions, the drug can be associated with severe idiosyncratic side effects such as hepatitis or pancreatitis. Although hepatic dysfunction is not a problem in healthy patients, liver function tests should be monitored every 3 months. Valproate is potentially teratogenic so all women should be informed of the risks and discussions regarding contraception should be had before starting the drug. The drug is contraindicated in pregnancy, a history of hepatic dysfunction and with caution in those with blood disorders or bleeding disorders. Most patients will have a therapeutic effect within the range 500 – 1000 mg a day.
Topiramate has been shown to be effective in migraine prevention in three large placebo-controlled trials.[26
] Topiramate 100 mg/day[23
] has been shown superior to placebo in reducing average monthly migraine days and rescue medication use.[26
The common adverse effect of paraesthesia of the extremities and lips is transient and often disappears with a gradual titration. If bothersome, the sensation can be reduced by eating bananas or drinking orange juice. Other adverse effects include word-finding difficulties, cognitive impairments and mood disturbance. Topiramate is associated with a two to fourfold increase of renal calculi and infrequent cases of acute closed angle glaucoma have been reported. One adverse effect that many female patients find desirable is weight loss. Clinical trials showed an average weight loss of 3-4% of body weight[23
] but it can be more dramatic and lead to discontinuation of the drug. Topiramate may be a useful drug in patients with migraine and obesity, migraine and idiopathic intracranial hypertension and potentially migraine and diabetes. Topiramate is a hepatic enzyme inducer and can interfere with the efficacy of the oral contraceptive pill, the progesterone only pill and the contraceptive implant. The drug has no effect on the progesterone only injection or intra-uterine devices. All women of childbearing age being considered for treatment with topiramate must be given appropriate contraceptive advice. Topiramate should be given at a dose of 50-100 mg/day. Above this dose there does not seem to be a significant increase in efficacy but the rate of adverse effects does increase.[26
Gabapentin has been shown to be effective in a small number of single blind trials and has had variable performance in placebo-controlled studies[23
] (responder rates of 36% - 46%[20
]). However, in clinical practice, gabapentin appears to be less effective than both valproate and topiramate. The most common adverse effects seen are dizziness and drowsiness and high withdrawal rates due to adverse effects have been seen in some studies.[20
] Given its positive effect on neuropathic pain, gabapentin may be advantageous in those patients with co-existing neuropathy, chronic pain or trigeminal neuralgia. Therapeutic effect is seen with doses of 600-3200 mg/day.
Other AEDs are used in migraine prevention although little evidence exists for their use. Lamotrigine blocks sodium channels thought to be involved in the process of cortical spreading depression. It has not been found to be effective for migraine prevention[28
] but some studies suggest it is beneficial in the treatment of troublesome migrainous auras.[23