Intolerance to topiramate in migraine

In my practice, patients with migraine frequently cannot tolerate even low doses of topiramate. In contrast, patients with epilepsy can usually take quite high doses of this medication.

This difference between migraine and epilepsy is reflected in experimental trials in these conditions. For example, in two studies of treatment with topiramate (1,2), 44% of migraine patients withdrew from 125 mg per day, whereas only 17% of patients with epilepsy withdrew from a much higher dose of 1000 mg.

However, it should also be noted that, in the same studies, patients with migraine withdrew at a higher rate of 10% from placebo, in comparison to only 2% in patients with epilepsy.

The intolerance to topiramate may be specific, or a reflection of a more general problem with medication.

A specific intolerance in migraine could be due to 1) altered metabolism of topiramate resulting in higher levels, or 2) abnormal neuronal systems that have an increased vulnerability to its actions.

A more general problem might be explained by 1) enhancement of side effects due to heightened sensitivity to stimulation, or 2) difficulty participating in any treatment, even placebo, because of associated anxiety.

Intolerance to topiramate, specific or otherwise, limits its use in migraine and deserves further investigation.

The first step would be a systematic review of the clinical trials of all drugs used to treat both migraine and other conditions, comparing withdrawal rates from placebo as well as active treatment.