The effects of discontinuing topiramate after a treatment period of 6 months in 818 patients with migraine, enrolled from 88 clinics in 21 countries in Europe, the UK and Turkey, are reported from University Duisburg-Essen, Germany. Patients were mean age 39.8 years, 13% male and 87% female. Patients received topiramate in a 26-week open-label phase, after a 4-8 week lead-in period. Daily dose beginning at 25 mg was increased in steps of 25 mg every week to 100 mg. A further increase to 200 mg/day was made if required, but the dose remained stable for the last 4 weeks of treatment. Patients were randomly assigned to continue topiramate or switch to placebo for a 26-week double-blind phase. The number of days with migraine during the last 4 weeks of the double-blind phase was compared with the last 4 weeks of the open-label phase. The mean increase in number of migraine days was greater in the placebo group than in the topiramate group. Acute medication was used more frequently by the placebo than the topiramate group. Quality of life remained stable and patients were more satisfied with treatment efficacy while on topiramate compared to placebo. Tolerability was similar in both groups. Sustained benefit was obtained after discontinuing topiramate 6-month trial, but number of migraine days showed an increase. Patients should be treated for 6 months as a general rule, with the option to continue to 12 months in some patients. [1]

COMMENT. This study of migraine prophylactic treatment included greater numbers of patients and was of longer duration than most previous trials. The authors hypothesize that the long-term effect of topiramate might be to correct the neuronal dysfunction factor in migraine pathophysiology. Since frequent migraine might lower the threshold for future attacks and promote development of chronic migraine, long-term prophylactic therapy should be considered as an option in adolescents with recurrent severe attacks.

The pros and cons of preventive compared to abortive antimigraine treatment are discussed in an editorial [2]. What are the indications for preventive therapy? Is the improvement worth the potential adverse effects? Does tachyphylaxis develop with long-term treatment? How quickly should treatment be withdrawn? Does preventive therapy lessen or increase the incidence of chronic daily headache? The results of the above study indicate that rapid withdrawal of topiramate caused a rebound headache occurrence, and future trials should lengthen the period of withdrawal. The data support the conclusion that preventive topiramate therapy has a residual beneficial effect, resetting the migraine cycle and raising the threshold.