Common anti-epileptic medication shows promise in reducing migraine aura

A new study by researchers at Lund University in Sweden found that 85 percent of patients with aura-dominant migraine experienced a reduction in monthly aura days by at least half following treatment with the anti-epileptic drug lamotrigine. The findings need to be confirmed in a controlled study, but could eventually be significant for a patient group that currently lacks a specific treatment for the aura itself.

Around 1.5 million people in Sweden suffer from migraine. Migraine affects both individuals' daily lives and society as a whole. The disease limits the ability to work and participate in social activities, and leads to significant costs through sick leave, reduced productivity and increased healthcare needs. Women are three times as likely to be affected as often as men, a difference that is largely due to hormonal factors.

Up to a third of people with migraine experience aura – a temporary neurological symptom that can cause visual disturbances, loss of vision, sensory disturbances, balance problems, and speech and language difficulties, among other symptoms. For some patients, aura is the most debilitating symptom of the disease, but there is currently no established treatment that specifically targets it. 

"Around 50,000 people in Sweden suffer from aura-dominant migraine. Aura is thought to be linked to cortical spreading depolarisation (CSD), a slowly progressing wave of altered nerve cell activity in the cerebral cortex," says Gürdal Sahin, a researcher at Lund University and a specialist in neurology at the Skåneuro private clinic. 

Migraine with aura is also associated with a slightly increased risk of ischaemic stroke, particularly when combined with other vascular risk factors. It is therefore important to reduce modifiable risk factors. 

"There are now several effective treatments for migraine, including new medicines that block the neurotransmitter CGRP, which plays a key role in migraine attacks. Botulinum toxin is also used as a preventative treatment for chronic migraine. However, as there is no established treatment that specifically targets the aura itself, migraines with and without aura are often treated in a similar way, even though the aura appears to be partly based on mechanisms other than the headache itself," Gürdal Sahin continues. 

The medicine lamotrigine is approved for the treatment of epilepsy and bipolar disorder, but not for migraine. However, as both epilepsy and migraine aura involve temporary changes in nerve cell activity, the researchers wanted to investigate whether the drug could also prevent aura. Lamotrigine affects the electrical activity of nerve cells by acting on sodium and potassium channels, and also reduces the release of, amongst other things, the neurotransmitter glutamate. In this way, the medicine can reduce the excessive excitability of the nerve cells. In theory, these mechanisms could help to prevent the emergence and spread of CSD.

In our study, we examined 81 patients with frequent or particularly troublesome migraine aura and treated them with lamotrigine. Among the patients included the number of days with aura fell on average from 6.9 to 1.4 days per month, representing a reduction of around 80 per cent."

Sena Uzun, doctoral student, Lund University 

While previous studies involving lamotrigine have shown mixed results, the results of this study were particularly promising for patients with aura-dominant migraine. In this group, 85 per cent of patients experienced at least a 50 per cent reduction in the number of days with aura. Another interesting observation was that a slower dose escalation was associated with fewer side effects, which may be relevant when the treatment is evaluated in future clinical trials. 

"As the study is retrospective and lacks a control group, the results need to be confirmed. We are now proceeding with a national, randomised, double-blind, placebo-controlled trial of lamotrigine. If the results can be confirmed, the drug could become a relatively inexpensive and well-established treatment option for a group of patients who currently have no treatment for the aura itself," concludes Sena Uzun.

The four stages of a migraine attack

Migraine attacks are usually divided into four phases, although not all sufferers experience all of them during every attack.

• Prodrome (lasting from a few hours to several days): irritability, low mood, fatigue, sensitivity to light and sound, difficulty concentrating, nausea, difficulty speaking and reading, and difficulty sleeping.
• Aura (usually lasting 5-60 minutes per individual aura symptom): visual disturbances or loss of vision, tingling, numbness, impaired balance, speech disturbances.
• Headache phase (4-72 hours): headache, often accompanied by nausea or vomiting, increased sensitivity to light, sound and smell, and occasionally dizziness and other autonomic symptoms.
• Postdrome (up to 24-48 hours): tiredness, low mood, difficulty concentrating and a feeling of mental sluggishness.