METHODS: This is a systematic review protocol describing essential reporting items based on the PRISMA for systematic review protocols (PRISMA-P) (Registration number: CRD42020220636). We aim to review the effectiveness, tolerability, and safety of hf-rTMS at DLPFC in randomised controlled trials (RCTs) as migraine prophylactic treatment. We will search Scopus, Cumulative Index to Nursing and Allied Health Literature Plus, PubMed, Cochrane Central Register of Controlled Trials and Biomed Central for relevant articles from randomised controlled clinical trials that used hf-rTMS applied at DLPFC for the treatment of migraine. The risk of bias will be assessed using the version 2 "Risk of bias" tool from Cochrane Handbook for Systematic Reviews of Interventions Version 6.1. We will investigate the evidence on efficacy, tolerability and safety and we will compare the outcomes between the hf-rTMS intervention and sham groups.

METHODS: A cross-sectional online survey was conducted among employees in two multinational banks in Malaysia between April and July 2019. Screening for migraine was conducted using the self-administered ID-Migraine™ questionnaire. Migraine-related disability (MIDAS) and headache frequency were recorded. Impact of migraine on work productivity and activities were evaluated using the Work Productivity and Activity Impairment (WPAI) questionnaire.

RESULTS: Of the 1268 employees who submitted complete responses, 47.2% (n = 598) were screened positive for migraine. Strikingly, the mean percent productivity loss at work (presenteeism) was almost 20-fold higher than the mean percent work time missed due to migraine (absenteeism) (39.1% versus 1.9%). The mean percent productivity loss in regular activity (activity impairment) and overall work productivity loss (work impairment) was 38.4% and 39.9%, respectively. It was also found that the costs related to presenteeism (MYR 5392.6) (US$1296) was 3.5-fold higher than absenteeism (MYR1,548.3) (US$370). Highest monetary loss related to presenteeism was reported in migraineurs with frequency of headache of above 3 days (MYR 25,691.2) (US$6176), whereas highest monetary loss related to absenteeism was reported in migraineurs with MIDAS grade IV (MYR 12,369.1) (US$2973). Only 30% of migraineurs of MIDAS grade IV reported taking prescribed medication. Notably, a vast majority (96%) of migraineurs who had three or lower episodes of migraine per month did not seek treatment.

METHODS: One hundred thirteen patients who met International Headache Society criteria for migraine and who did not experience satisfactory response to nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of headache and pain-free response rates, absence of associated symptoms, and functional response. Global ratings of treatment effectiveness and preference were obtained at 24 hours.

RESULTS: The pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%; the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours postdose, relief of baseline associated symptoms was achieved by 41% of patients with nausea compared to 82% of patients at 4 hours; for patients with phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional response was achieved by 70% of patients by 2 hours postdose. The high level of acute response was maintained over 24 hours, with only 24% of patients experiencing a headache recurrence and only 10% using rescue medication. At 24 hours postdose, 74% of patients rated eletriptan as preferable to any previous treatment for migraine. The most frequent reasons cited for this treatment preference were faster headache improvement (83%) and functional response (78%). Overall, eletriptan was well tolerated; most adverse events were transient and mild to moderate in severity. No serious adverse events were reported.