Abstract
Schoenen et al. (1) did a post hoc analysis of the Prolonged Migraine Prevention with Topiramate (PROMPT) study (2) to determine potential contributors to relapse. In the PROMPT study, all subjects had a six-month open-label topiramate phase. Subjects were then randomized to continue topiramate or switch to placebo in a six-month double-blind phase. Relapse was defined as a change in monthly migraine days after randomization compared with the month before randomization. The data were analyzed during the first month (“initial relapse”) and last month (“sustained relapse”) of the double-blind phase.
Surprisingly, variable-by-treatment interactions were significant in the initial relapse period, with a low Headache Impact Test (HIT-6) at doubleblind baseline and a decline in acute medication intake. Reporting of “anxiety” in the open-label phase was associated with relapse. For sustained relapse, no statistically significant interactions were observed. The authors concluded that relapse after topiramate discontinuation in migraine prophylaxis was unaffected by patient characteristics or baseline migraine frequency.
What does this mean? Why should less severely ill subjects with low HIT-6 scores and decreased acute medication initially do worse after discontinuing topiramate? These two predicting factors may represent patients who responded comparatively well and may be explained by regression to the mean.
The probability of sustained relapse after discontinuation of migraine prophylaxis with topiramate is not affected by patient characteristics or baseline migraine frequency.
The US Headache Consortium Guidelines (3) recommend re-evaluating therapy and consider tapering or discontinuing treatment after a period of stability. The PROMPT study suggests that after six months of stable treatment one can reevaluate treatment. If a patient is doing very well, one can consider slowly tapering the preventive drug. If the headaches worsen during the taper period, one can increase the dose. In my experience, the adjusted dose may be lower and be associated with fewer adverse events. At this time, we cannot predict who will relapse after discontinuation of migraine prevention.