This practice guideline provides updated evidence-based recommendations regarding the use of pharmacologic migraine prevention in adults. A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies published through June 6, 2024, and is available in a companion publication. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. Recommendations are provided on how to decide when it is appropriate to start a pharmacologic migraine preventive medication and how to decide which migraine preventive medication to start. Recommendations address decision making on appropriate choices of migraine preventive medications in specific situations and populations, including patients with fibromyalgia, obesity, or hypertension; considerations for older adults; treatment during pregnancy and lactation; sex-related factors in choosing medications; and treatment for patients with medication overuse. Recommendations on assessment of treatment efficacy, adverse effects, and discontinuing migraine preventive medications are provided.

BACKGROUND AND OBJECTIVES:This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS:A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS:A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION:This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

INTRODUCTION:The economic burden of migraine is substantial; determining the cost that migraine imposes on the Canadian healthcare system is needed. METHODS:Administrative data were used to identify adults living with migraine, including chronic migraine (CM) and episodic migraine (EM), and matched controls in Alberta, Canada. One- and two-part generalized linear models with gamma distribution were used to estimate direct healthcare costs (hospitalization, emergency department, ambulatory care, physician visit, prescription medication; reported in 2022 Canadian dollars) of migraine during a 1-year observation period (2017/2018). RESULTS:The fully adjusted total mean healthcare cost of migraine (n = 100,502) was 1.5 times (cost ratio: 1.53 [95% CI: 1.50, 1.55]) higher versus matched controls (n = 301,506), with a predicted annual incremental cost of $2,806 (95% CI: $2,664, $2,948) per person. The predicted annual incremental cost of CM and EM was $5,059 (95% CI: $4,836, $5,283) and $669 (95% CI: $512, $827) per person, respectively, compared with matched controls. All healthcare cost categories were greater for migraine (overall, CM and EM) compared with matched controls, with prescription medication the primary cost driver (incremental cost - overall: $1,381 [95% CI: $1,234, $1,529]; CM: $2,057 [95% CI: %1,891, $2,223]; EM: $414 [95% CI: $245, $583] per person per year). CONCLUSION:Persons living with migraine had greater direct healthcare costs than those without. With an estimated migraine prevalence of 8.3%-10.2%, this condition may account for an additional $1.05-1.29 billion in healthcare costs per year in Alberta. Strategies to prevent and effectively manage migraine and associated healthcare costs are needed.

OBJECTIVE:To explore the relationship between migraine attack onset in children and adolescents and Chinooks, which are dry and warm westerly winds that generally occur in the winter and bring about abrupt weather changes to the east of the Rocky Mountains in Southern Alberta, Canada. METHODS:This was a prospective longitudinal clinical cohort study with recruitment from November 2020 to May 2024. Participants were: 8-18 years old, had migraine as per International Classification of Headache Disorders 3rd edition criteria, had 1-15 headache days/month, lived in the geographical location where Chinook winds occur, and had exposure to at least one pre-Chinook or Chinook day during the study period. Chinook days were defined using Nkemdirim's criteria and Environment Canada data were used to categorize day type as either Chinook, pre-Chinook, or non-Chinook. Weather data were merged with data from daily headache diaries, completed for periods of 8-30 days. The primary outcome was attack onset, defined as a day with a new migraine attack of moderate or severe severity, as per the 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). Both univariate and adjusted models were used to determine if there was an association between migraine attack onset and day type (i.e., pre-Chinook, Chinook, or non-Chinook) at the aggregate study sample level. The adjusted models controlled for age and sex, and both models included a random intercept. Subsequently, individual n = 1 models were fitted to explore each individual participant's personal odds of migraine attack onset on both pre-Chinook and Chinook days versus non-Chinook days. Pre-Chinook/Chinook sensitivity values were calculated for each individual by dividing the model's regression coefficient by its standard error. Sensitivity values >1.96 suggest a significant association between pre-Chinook/Chinook days and attack onset. RESULTS:Sixty youth with 1253 days of complete data, of which 144 (12%) were attack onset days, participated in the study. There were 158 Chinook (13%), 124 pre-Chinook (10%), and 971 non-Chinook days (77%). There were 39 female participants (39 of 60; 65%), with a median age of 14 years (quartile [Q] 1 = 12, Q3 = 16), and a median headache frequency of 6.2 days/month (Q1 = 4, Q3 = 11). Neither the univariate nor the adjusted models found any significant association between day type and attack onset at an aggregate level (pre-Chinook adjusted odds ratio [OR], 0.98; 95% confidence interval [CI], 0.54-1.78, p = 0.947; Chinook adjusted OR, 1.15; 95% CI, 0.69-1.91, p = 0.596). No individual participants met the threshold for statistically significant pre-Chinook or Chinook sensitivity. CONCLUSION:We did not find a relationship between pre-Chinook and Chinook conditions and migraine attack onset. This may be due to the lack of an association between Chinooks and attack onset in youth with migraine, or due to a lack of statistical power in our study. Future studies with greater statistical power should aim to assess for a potential relationship between Chinooks and attack onset, as it could have important treatment implications.

The advent of the triptans revolutionized acute migraine treatment. The older migraine-specific drugs, the ergot alkaloids (ergotamine and dihydroergotamine), also relieve migraine attacks through agonism at the 5-HT1B and 5-HT1D receptors, but the triptans have much greater specificity for these receptors. Unlike the ergot alkaloids, the triptans do not activate many other receptor types, and therefore are much better tolerated. This reduction in side effects greatly enhanced their clinical utility as it allowed a far greater proportion of patients to take a full therapeutic dose. As a result, the clinical use of ergotamine is minimal today, although dihydroergotamine still has a significant clinical role. There is extensive evidence that the seven triptans available today, sumatriptan, zolmitriptan, rizatriptan, eletriptan, naratriptan, almotriptan, and frovatriptan, are effective in the acute treatment of migraine. Available formulations include oral tablets, orally dissolving tablets, subcutaneous injections, nasal sprays, and in some countries, rectal suppositories. For optimal benefit, therapy needs to be individualized for a given patient both regarding the triptan chosen and the formulation. This chapter discusses the ergot alkaloids and the triptans, including mechanism of action, evidence for efficacy, clinical use, and adverse effects.

ABSTRACT: Background: PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use. Methods: OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study. Results: A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified. Conclusions: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

CMAJ | February 6, 2023 | Volume 195 | Issue 5 E187 In this second in a series of 2 reviews focusing on the management of migraine, we discuss pharmacologic treatments that health care practitioners may prescribe to help reduce the frequency, severity, duration and disability of patients’ migraine attacks and optimize their use of medications for acute headache treatment. Our first article1 discussed diagnosis and acute treatment; herein, we focus on migraine prevention, an important part of management for which evidence is accumulating. The 2021 American Headache Society consensus guideline recommends that preventive pharmacologic therapy should be considered for patients with 4 or more migraine headache days per month or those with 2 or more migraine headache days per month that are associated with substantial disability despite use of acute medication.2 Preventive treatment should also be considered for patients with atypical aura (hemiplegic migraine, migraine with brain stem aura) and migraine with associated complications (e.g., persistent aura, migrainous infarction [stroke], migraine aura–triggered seizure, status migrainosus), even if the frequency of attacks is low.2 We draw on original research, reviews and clinical practice guidelines (Box 1).

Voir article connexe ici: [www.cmaj.ca/lookup/doi/10.1503/cmaj.221607-f][1]. [Pour lire un témoignage au sujet de la difficulté de trouver un traitement pour la migraine, voir www.cmaj.ca/lookup/doi/10.1503/cmaj.221813-f][2]; [voir la version anglaise de l’article ici: www.cmaj.ca/lookup/doi/10.

ABSTRACTBackground:The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA.Methods:Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days.Results:184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: −3.5 [6.3]; Tx4: −6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified.Conclusions:Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

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See related review article at www.cmaj.ca/lookup/doi/10.1503/cmaj.221607 (to be published February 6, 2023) and a first-person account of the difficulty of finding migraine treatment at [www.cmaj.ca/lookup/doi/10.1503/cmaj.221813][1] KEY POINTS Migraine affects about 12% of adults, with a

[Voir l’article connexe ici : www.cmaj.ca/lookup/doi/10.1503/cmaj.211969-f][1]. [Pour lire un témoignage au sujet de la difficulté de trouver un traitement pour la migraine, voir www.cmaj.ca/lookup/doi/10.1503/cmaj.221783][2]; [voir la version anglaise de l’article ici : www.cmaj.ca/lookup/doi

Objectives To assess real-world effectiveness, safety, and usage of erenumab in Canadian patients with episodic and chronic migraine with prior ineffective prophylactic treatments. Background In randomized controlled trials, erenumab demonstrated efficacy for migraine prevention in patients with <= 4 prior ineffective prophylactic migraine therapies. The "Migraine prevention with AimoviG: Informative Canadian real-world study" (MAGIC) assessed real-world effectiveness of erenumab in Canadian patients with migraine. Methods MAGIC was a prospective open-label, observational study conducted in Canadian patients with chronic migraine (CM) and episodic migraine (EM) with two to six categories of prior ineffective prophylactic therapies. Participants were administered 70 mg or 140 mg erenumab monthly based on physician's assessment. Migraine attacks were self-assessed using an electronic diary and patient-reported outcome questionnaires. The primary outcome was the proportion of subjects achieving >= 50% reduction in monthly migraine days (MMD) after the 3-month treatment period. Results Among the 95 participants who mostly experienced two (54.7%) or three (32.6%) prior categories of ineffective prophylactic therapies and who initiated erenumab, treatment was generally safe and well tolerated; 89/95 (93.7%) participants initiated treatment with 140 mg erenumab. At week 12, 32/95 (33.7%) participants including 17/64 (26.6%) CM and 15/32 (48.4%) EM achieved >= 50% reduction in MMD while 30/86 (34.9%) participants including 19/55 (34.5%) CM and 11/31 (35.5%) EM achieved >= 50% reduction in MMD at week 24. Through patient-reported outcome questionnaires, 62/95 (65.3%) and 45/86 (52.3%) participants reported improvement of their condition at weeks 12 and 24, respectively. Physicians observed improvement in the condition of 78/95 (82.1%) and 67/86 (77.9%) participants at weeks 12 and 24, respectively. Conclusion One-third of patients with EM and CM achieved >= 50% MMD reduction after 3 months of erenumab treatment. This study provides real-world evidence of erenumab effectiveness, safety, and usage for migraine prevention in adult Canadian patients with multiple prior ineffective prophylactic treatments.

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Background: Phase 3 PREEMPT established safety and efficacy of 155-195U onabotulinumtoxinA in adults with chronic migraine (CM). This analysis of the PREDICT study (NCT02502123) evaluates real-world effectiveness and safety of 155U, 156-195U and 195U-onabotulinumtoxinA in CM. Methods: Patients received onabotulinumtoxinA approximately every 12-weeks (≤7 treatment cycles [Tx]) per Canadian product monograph). Primary endpoint was mean change from baseline in Migraine-Specific Quality of Life (MSQ) at Tx4. Headache days, physician and patient satisfaction were evaluated. Analysis stratified safety population (≥1 onabotulinumtoxin A dose) into 3 groups (155U,156-195U,195U) by dose received on ≥3 of the first 4 Tx. Results: 184 patients received ≥1 onabotulinumtoxin A dose (155U, n=68; 156-195U, n=156; 195U, n=13 on ≥3 Tx). Headache days decreased over time compared to baseline (Tx4: -7.1[6.7] 155U; -6.5[6.7] 156-195U; -11.2[6.4] 195U). Physicians rated most patients as improved, and majority of patients were satisfied at final visit (80.8% 155U; 83.6% 156-195U; 90% 195U). Treatment-emergent adverse events (TEAEs) were reported in 18/68(26.5%) patients in 155U-group, 41/65(63.1%) in 156-195U-group and 10/13(76.9%) in 195U-group; treatment-related TEAEs were 9(13.2%), 10(15.4%) and 3(23.1%) respectively; serious TEAEs were 0, 3(4.6%) and 1(7.7%), none treatment-related. Conclusions: Long-term treatment with 155U, 156-195U, and 195U-onabotulinumtoxinA in PREDICT was safe and effective CM treatment. No new safety signals were identified.

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ABSTRACT: Background: Migraine, including episodic migraine (EM) and chronic migraine (CM), is a common neurological disorder that imparts a substantial health burden. Objective: Understand the characteristics and treatment of EM and CM from a population-based perspective. Methods: This retrospective population-based cross-sectional study utilized administrative data from Alberta. Among those with a migraine diagnostic code, CM and EM were identified by an algorithm and through exclusion, respectively; characteristics and migraine medication use were examined with descriptive statistics. Results: From 79,076 adults with a migraine diagnostic code, 12,700 met the criteria for CM and 54,686 were considered to have EM. The majority of migraineurs were female, the most common comorbidity was depression, and individuals with CM had more comorbidities than EM. A larger proportion of individuals with CM versus EM were dispensed acute (80.6%: CM; 63.4%: EM) and preventative (58.0%: CM; 28.9%: EM) migraine medications over 1 year. Among those with a dispensation, individuals with CM had more acute (13.6 ± 32.2 vs. 4.6 ± 10.9 [mean ± standard deviation], 95% confidence interval [CI] 7.7-8.3), and preventative (12.6 ± 43.5 vs. 5.0 ± 12.6, 95% CI 6.9-8.4) migraine medication dispensations than EM, over 1-year. Opioids were commonly used in both groups (proportion of individuals dispensed an opioid over 1-year: 53.1%: CM; 25.7%: EM). Conclusions: Individuals with EM and CM displayed characteristics and medication use patterns consistent with other reports. Application of this algorithm for CM may be a useful and efficient means of identifying subgroups of migraine using routinely collected health data in Canada.