We have previously shown that quarterly preventive onabotulinumtoxin A (BTA) injections administered to diurnally active patients for chronic migraines (CM) associate with increased discomfort when performed in the morning. The purpose of this study was to further examine if the effectiveness of preventive BTA injections depends on the procedure's circadian timing. A total of 90 diurnally active patients with a medical history of CM and undergoing BTA injection therapy were enrolled in the study. One hundred and fifty-five units of BTA were administered according to the standardized PREEMPT protocol, either during the course of morning (AM) or afternoon (PM) clinic hours. Patients were asked to keep headache diaries, which were reviewed at the time of their follow-up BTA injections 3 months later. The number of headache days experienced during the first, second, and third month following BTA injection, and the number of headache days during the last 7 days prior to follow-up was collected, as was the self-rating of the effectiveness of BTA treatment. Fifty-five (61%) patients were injected during the AM clinic and 35 (39%) during the PM clinic. There was no difference in gender, race, and age variables between the AM and PM patients. The average total number of headache days during 3 months following injection was significantly higher for the AM-treated compared to the PM-treated patients (22.37 ± 18.85 vs. 10.54 ± 7.5, p =.0007). AM patients also reported a higher number of headache days during each of the 3 months following BTA injection. In contrast, PM patients reported higher effectiveness of preventive BTA treatment. The average number of headache days during the week prior to the follow up, as well as the presence of headache on the day of the follow-up was not significantly different between the AM and PM groups. Scheduling diurnally active CM patients with stable circadian sleep/wake routine for afternoon BTA injections appear to improve the effectiveness of BTA therapy as well as patients' satisfaction with the treatment.
Keywords: Onabotulinumtoxin A;chronic migraine; chronotherapy; circadian rhythm; effectiveness; prevention.