Randomized Controlled Trials: Persistence
Since persistence can be calculated as the inverse of discontinuation,
persistence can be inferred from discontinuation
rates reported in RCTs. Nineteen RCTs provided sufficient data
on discontinuation, as part of trial design, among propranolol,
amitriptyline, and topiramate. The populations of migraine
patients were generally similar, as evidenced by the similar age
and gender distributions and comparable recruitment criteria
(inclusion/exclusion) across the RCTs reviewed. Differences
were assumed to be negligible; therefore, results were pooled
and weighted by sample size to calculate a weighted average
discontinuation rate for each medication of interest (Table
3). Although some studies evaluated medications other than
those included in this review, only patients on propranolol,
amitriptyline, topiramate, and placebo were pooled. Time
horizons varied across studies, ranging from 8 weeks to 26
weeks. This difference was adjusted for by stratifying into 2
separate groups: 8-12 weeks and 16-26 weeks. The weighted
average discontinuation rate of each medication and placebo
were compared for each time horizon group and presented in
Figure 2 as the proportion of patients who stayed persistent
(calculated as 1–discontinuation at the end of the study time
horizon). The primary reasons for discontinuation across the
different medications were also compared and summarized
in Table 4 as well as Figure 3. The pooled data show that persistence
declines rapidly over time, with nearly half of RCT
participants discontinuing from clinical trials of amitriptyline
and topiramate by 12-26 weeks (45% and 43%, respectively).
Adverse events were the most common reason for discontinuation
cited, especially among patients treated with topiramate
(24%) and amitriptyline (17%). Individual study data from each
RCT are available in Table 2.