Migraine preventive therapy is often recommended for a period of 6-12 months only, but no data are available to indicate how migraine frequency is affected by the discontinuation of effective preventive therapy.OBJECTIVE
To compare the effects of discontinuation of topiramate therapy after 6 months with continuation of therapy.DESIGN AND INTERVENTION
The Prolonged Migraine Prevention with Topiramate (PROMPT) study was conducted at 88 neurology clinics in 21 countries in Europe and the Middle East. From December 2003 to February 2005, the trial enrolled adults (18-80 years old) who fulfilled the International Headache Society criteria for migraine with or without aura. Further inclusion criteria were a history of migraine for at least 1 year before enrollment, and a mean of ≥4 migraine days per month during the 3 months before the trial began. Patients who used prophylactic medication for migraine in the month before the trial began and those who were overusing acute medication were excluded. After a 4-8-week baseline phase, 818 patients received open-label topiramate (target dose 100 mg/day) for 26 weeks. Of these, 514 patients were included in the subsequent 26-week double-blind phase and were randomly allocated to continue with topiramate treatment (n =255) or to receive a placebo equivalent (n =259). Throughout the study, patients kept diaries to record migraine type, severity, frequency and duration. Health-related quality of life was assessed with the Migraine Disability Assessment (MIDAS) questionnaire.OUTCOME MEASURE
The primary outcome parameter was the change in the number of migraine days from the end of the open-label phase to the end of the double-blind phase.RESULTS
During the open-label topiramate phase, the mean number of headache days was reduced from 8.93 ± 4.29 at baseline to 5.83 ± 4.89 at week 26 (P <0.0001).During the double-blind phase, headache frequency increased in both the treatment and the placebo groups, but it did not return to the baseline value. The increase in the mean number of headache days during the double-blind phase was greater in the placebo group than in the topiramate group (+ 1.19 days [95% CI 0.71-1.66 days] vs + 0.10 days [95% CI -0.36 to 0.56 days]; P =0.0011).In addition, patients in the placebo group reported a greater increase in the mean number of days on acute medication than did those who continued on topiramate (+ 1.13 days vs + 0.18 days; P =0.0007). Topiramate therapy during the open-label phase resulted in considerable improvements in health-related quality of life (mean change in the MIDAS score -21.18 points [95% CI -25.20 to -17.17 points;P <0.0001]). In the placebo group, the mean MIDAS score increased by six points after treatment discontinuation, whereas there was no change in the topiramate group after initiation of the double-blind phase. At study end, patients in the topiramate group were more satisfied with the efficacy of their treatment than were patients in the placebo group; the groups did not differ with regard to satisfaction with the tolerability of treatment.CONCLUSION
Discontinuation of topiramate after 6 months is associated with sustained benefits, although the number of migraine days can increase.