Number Of Migraine Days Research Articles

Role of memantine in the prophylactic treatment of episodic migraine: A systematic review.

The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine. Migraine is a prevalent chronic disease with significant costs to the health care system. Although various prophylactic treatment options are available, these medications have limitations based on efficacy, potential side effects, and patient preference. Memantine is an N-methyl-d-aspartate receptor antagonist used in dementia treatment that may have potential benefit for migraine prophylaxis. A systematic search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through December 2020 using the search terms: migraine disorders, migraine, headache disorders, or headache and memantine. Studies selected for the systematic review included prospective, interventional designs and evaluated memantine for prophylaxis of migraine. Animal studies, case reports, abstracts, review articles, protocols without results, and studies not written in English were excluded. Data were extracted using a standardized systematic process and included author, publication date, study design, sample size, patient characteristics, treatment regimen, clinical efficacy outcomes, and adverse drug effects. Four articles were identified for inclusion representing two prospective open-label studies and two randomized, double-blind trials, evaluating 183 patients on memantine overall. A reduction in number of migraine days and headache severity were shown in all four studies in the participants treated with memantine. The most common adverse effects included somnolence, sedation, and nausea, none of which were severe. The studies in this review establish that memantine has the potential for use as a treatment option for episodic migraine. Additional long-term studies using an active comparator would be useful to further elucidate its role.

Oral Cannabinoid Preparations for the Treatment of Chronic Migraine: A Retrospective Study.

To explore the effectiveness and safety of three oral cannabinoid preparations (FM2®, Istituto farmaceutico militare, Firenze, Italy; Bedrocan®, Bedrocan International, Vandaam, Netherlands; and Bediol®, Bedrocan International, Vandaam, Netherlands) in the treatment of chronic migraine. Retrospective, cohort study. Patients with chronic migraine who received FM2, Bedrocan, or Bediol daily for the off-label treatment of their headache, for up to 6 months. The number of migraine days per month, pain intensity, the number of acute medications taken per month, the number of days per month on which the patient took at least one acute medication, and adverse events were recorded at baseline and at 3 months and 6 months after the start of treatment with oral cannabinoid preparations. The number of migraine days did not change significantly after the third month or the sixth month when compared with baseline (P = 0.1182). The pain intensity (P = 0.0004), the acute medication consumption (P = 0.0006), and the number of days per month in which patients took at least one acute medication significantly decreased when compared with baseline (P = 0.0004). No significant differences were found between patients who were still taking a preventive treatment for chronic migraine and those who were not (all P > 0.05). Different oral cannabinoid preparations displayed similar levels of effectiveness (all P > 0.05). The adverse events were mostly mild and occurred in 43.75% of patients. Oral cannabinoid preparations may have a role in reducing pain intensity and acute medication intake in patients with chronic migraine, but the magnitude of the effect seems modest; further studies are needed.

Mig-RL: a Natural Preventive Treatment Against Migraine. Outcomes of a Randomized, Double-Blind Clinical Trial

BACKGROUND The efficacy and safety of Mig-RL (Commercial name HERBA MIG), a synergistic association of two plant extracts, Tanacetum parthenium (150mg, 0.5% parthenolide) and Salix Alba (150mg, 25% salicin) were investigated as a preventive treatment for episodic migraine. Mig-RL was compared with a placebo in a randomized, double-blind clinical trial. MATERIALS AND METHODS This trial included 129 patients having episodic migraine and diagnosed with migraines without aura for over a year and meeting the migraine criteria, as defined in the International Classification of Headache Disorder (ICHD-3 :1.1). P). Baseline data was collected for 28 days before the start of the three-months treatment period. Patients were randomized in a 1:1 ratio to receive either Mig-RL (a single dose of 300mg per day, per os) or placebo (identical capsules containing 300 mg starch, 1 per day, per os) for a period of 12 consecutive weeks. The primary endpoint was the mean change in the average number of migraine days per month, comparing the baseline 28-days pre-intervention period with the weeks 9 to 12 after the first dose of the trial regimen. Secondary endpoints were the percentage of patients with a reduction of at least 30% in the average number of migraine days per month and days of use of any acute headache medication per month. The HIT-6 and MIDAS scores were also evaluated vs. baseline between the two groups. RESULTS Out of 172 patients enrolled, 129 were randomly assigned to the Mig-RL arm (n=65) or the placebo arm (n=64). The mean (±SD) number of baseline migraine days per month was 8.4±1.9 and 8.7±1.9, respectively. The mean reduction in the average number of migraine days per month was 2.5±0.4 (p<0.001) with Mig-RL and 1.9±0.4 (p<0.001) with placebo. A difference of 0.6±0.4 (p=0.01) between the two groups. The percentage of patients with at least 30% reduction in average number of migraine days per month was 49% in Mig-RL and 32% in placebo (p<0.05 vs. placebo). Only a few isolated and minor side effects were reported and overall Mig-RL was well tolerated by patients. CONCLUSIONS Mig-RL, a synergistic combination of two plant extracts, seems to have a moderate effect in the prevention of migraines. Without side effects, the combination of Tanacetum parthenium and Salix alba could be an additional help for some patients. However, further investigations and an improvement in the quality of the plants are still necessary.

Long-Term Effects of Self-Administered Transcranial Direct Current Stimulation in Episodic Migraine Prevention: Results of a Randomized Controlled Trial

Migraine is a multifactorial neurovascular disorder, which affects about 12% of the general population. In episodic migraine, the visual cortex revealed abnormal processing, most likely due to decreased preactivation level. Transcranial direct current stimulation (tDCS) is able to modify cortical excitability and might result in an alleviation of migraine occurrence if used repetitively. To test the hypothesis that self-administered anodal tDCS over the visual cortex significantly decreases the number of monthly migraine days in episodic migraine. The study was single-blind, randomized, and sham-controlled. Inclusion criteria were age 18-80 years and an ICHD-3 diagnosis of episodic migraine. Exclusion criteria were pregnancy, presence of a neurodegenerative disorder, a contraindication against MRI examinations, and less than two migraine days during the 28-day baseline period. Patients in whom the baseline period suggested chronic migraine were excluded. After baseline, participants applied daily either verum (anodal-1mA to 20 min) or sham tDCS (anodal-1mA to 30 sec) at Oz (reference Cz electrode) for 28 days. Headache diaries were used to record the number of migraine days at baseline, during the stimulation period, and during four subsequent 28-day periods. Twenty-eight patients were included; two were excluded after the baseline period because less than two migraine days occurred; three were excluded because their headache diaries suggested the diagnosis of chronic migraine. Twenty-three datasets were taken for further analysis. Compared to sham tDCS (n=12), verum tDCS (n=11) resulted in a lower number of migraine days (p=0.010) across all follow-up periods. We found no significant change in total headache days (p=0.165), anxiety (p=0.884), or depression scores (p=0.535). No serious adverse events occurred; minor side effects were similar in both groups. This study provides Class II evidence that self-administered anodal tDCS over the visual cortex in episodic migraine results in a significantly lower number of monthly migraine days. However, it has neither an immediate nor a long-term effect.

Efficacy and safety of fremanezumab for episodic migraine prevention: Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial in Japanese and Korean patients.

ObjectiveTo evaluate the efficacy and safety of two dosing regimens of fremanezumab in Japanese and Korean patients with episodic migraine.BackgroundEpisodic migraine, which accounts for more than 90% of migraine cases, is inadequately addressed by widely available preventive therapies. Fremanezumab, a monoclonal antibody that selectively targets the trigeminal sensory neuropeptide calcitonin gene‐related peptide involved in migraine pathogenesis, has demonstrated efficacy in international Phase 3 trials of patients with both chronic and episodic migraine.MethodsThis Phase 3 randomized, placebo‐controlled trial randomly assigned patients with episodic migraine to receive subcutaneous fremanezumab monthly (225 mg at baseline, week 4, and week 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. The primary endpoint was the mean change from baseline in the monthly average number of migraine days during the 12‐week treatment period after the first dose.ResultsOf 357 patients enrolled (safety set, n = 356; full analysis set, n = 354), the least‐squares mean (±standard error) reductions in the average number of migraine days per month during 12 weeks were significantly greater with fremanezumab monthly (−4.0 ± 0.4, n = 121) and fremanezumab quarterly (−4.0 ± 0.4, n = 117) than with placebo (−1.0 ± 0.4, n = 116; p < 0.0001 for both comparisons). The proportion of patients reaching at least a 50% reduction in the monthly average number of migraine days during the 12‐week period after initial administration was also significantly improved with fremanezumab (fremanezumab monthly, 41.3%; fremanezumab quarterly, 45.3%; placebo, 11.2%; p < 0.0001 for both comparisons) as were other secondary endpoints (p < 0.001 for all comparisons between fremanezumab and placebo). Injection‐site reactions were more common in fremanezumab‐treated patients (fremanezumab monthly, 25.6%; fremanezumab quarterly, 29.7%; placebo, 21.4%).ConclusionFremanezumab prevents episodic migraine in Japanese and Korean patients to a similar extent than in previously reported populations with no new safety concerns.

PND62 China Adelphi Abstract

Although migraine is prevalent and has debilitating consequences, reports quantifying disease burden in China are sparse. Treatment patterns, current disease burden, and unmet needs were assessed among patients with episodic migraine (EM) in China using Adelphi Disease Specific Programme real-world data. Cross-sectional data was collected (January through June 2014) using Chinese language versions of Adelphi migraine surveys. Internists/neurologists (N=125) completed patient record forms for nine consecutively consulting patients with migraine. These patients were then invited to independently complete a patient self-completion questionnaire. Descriptive analyses of key parameters were performed: patient demographics, treatment patterns (current acute and preventive medication [AM/PM]), effectiveness, issues with existing treatment, symptom control, Migraine Disability Assessment (MIDAS) scores, and work productivity and activity impairment (WPAI). In total, 1113 patients with EM (monthly headache days <15) were identified. Mean (SD) age was 43.8(13.1) years; mean (SD) number of migraine days per month was 3.2(1.7). Physicians prescribed AM in 86.1% of patients (non-steroid anti-inflammatory drugs [NSAIDs]: 62.7%; triptans: 7.7%), PM in 38.5%, and both in 24.9% of patients. Physicians reported that 55.3% and 54.9% of patients experienced ≥ one issue with their current AM or PM, respectively, and that migraine-related symptoms (including nausea, sensitivity to light or sound) were fully controlled in < 50% of patients receiving NSAIDs (21.7%-38.4%) or triptans (32.4%-43.5%). Insufficient response to current AM (migraine headache fully resolved within 2 hours in ≤3/5 attacks) was reported by 42.5% patients. Patients reported mean (SD) MIDAS scores of 5.8(7.3), with mild-to-severe disability (II-IV) reported by 36.8% of patients. Overall work time impaired due to headaches was 58.0% (including work time missed and impairment while working). Our results suggest that despite existing treatment options for managing migraine, disease burden and unmet medical needs remain substantial in Chinese patients with EM.

Impact of a 12-week open-label placebo treatment on headache days in episodic and chronic migraine: a study protocol for a parallel-group, multicentre, randomised controlled trial

IntroductionMigraine is the most common neurological disorder and one of the major causes of years lived with disability. Its treatment (especially of chronic forms) is often challenging and accompanied with...

The Efficacy of Memantine for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies.

The efficacy of memantine for migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of memantine versus placebo on treatment in migraine patients. We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through February 2020 for randomized controlled trials assessing the effect of memantine versus placebo on treatment efficacy in migraine patients. This meta-analysis is performed using the random-effect model. Three randomized controlled trials are included in the meta-analysis. Overall, compared with control group in migraine patients, memantine treatment is associated with substantially reduced monthly attack frequency (mean difference [MD], -2.14; 95% confidence interval [CI], -2.83 to -1.46; P < 0.00001), number of migraine days (MD, -4.17; 95% CI, -6.40 to -1.93; P = 0.0003) and Migraine Disability Assessment (MD, -5.63; 95% CI, -6.46 to -4.79; P < 0.00001), but demonstrates no obvious influence on acute pain medications (MD, -1.23; 95% CI, -4.63 to 2.17; P = 0.48). Memantine treatment may benefit to the control of migraine.

Clinical features of migraine with onset prior to or during start of combined hormonal contraception: a prospective cohort study

Many studies have described the features of menstrually related migraines but there is a lack of knowledge regarding the features of migraine in combined hormonal contraceptive users (CHC). Hormone-withdrawal migraines in the pill-free period could differ from those in the natural cycle. Gynaecologic comorbidities, like dysmenorrhea and endometriosis, but also depression or a family history might modify the course of migraine. A better understanding of migraine features linked to special hormonal situations could improve treatment. For this prospective cohort study, we conducted telephone interviews with women using a CHC and reporting withdrawal migraine to collect information on migraine frequency, intensity, triggers, symptoms, pain medication, gynaecologic history and comorbidities (n = 48). A subset of women agreed to also document their migraines in prospective diaries. The mean number of migraine days per cycle was 4.2 (± 2.7). Around 50% of these migraines occurred during the hormone-free interval. Migraine frequency was significantly higher in women who suffered from migraine before CHC start (5.0 ± 3.1) (n = 22) in comparison to those with migraine onset after CHC start (3.5 ± 2.1) (n = 26). Menstrually related attacks were described as more painful (57.5%), especially in women with migraine onset before CHC use (72%) (p < 0.02). Comorbidities were rare, except dysmenorrhea. The majority of migraine attacks in CHC users occur during the hormone-free interval. Similar as in the natural cycle, hormone-withdrawal migraines in CHC users are very intense and the response to acute medication is less good, especially in those women, who developed migraine before CHC use.

Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial

BackgroundThe FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes.MethodsOverall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12 weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12 weeks of double-blind treatment, evaluated by country in these subgroup analyses.ResultsOf 14 countries contributing data, the Czech Republic (n = 188/838; 22%), the United States (n = 120/838; 14%), and Finland (n = 85/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12 weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, − 1.9 [− 3.25, − 0.47]; P = 0.009; monthly fremanezumab, − 3.0 [− 4.39, − 1.59]; P < 0.001), the United States (quarterly fremanezumab, − 3.7 [− 5.77, − 1.58]; P < 0.001; monthly fremanezumab, − 4.2 [− 6.23, − 2.13]; P < 0.001), and Finland (quarterly fremanezumab, − 3.0 [− 5.32, − 0.63]; P = 0.014; monthly fremanezumab, − 3.9 [− 6.27, − 1.44]; P = 0.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from – 5.6 to – 2.4 with quarterly fremanezumab and from − 5.3 to − 1.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups.ConclusionsMonthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes.Trial registrationClinicalTrials.gov Identifier: NCT03308968.

Transcutaneous auricular vagus nerve stimulation (taVNS) for migraine: an fMRI study

BackgroundDysfunction of the thalamocortical connectivity network is thought to underlie the pathophysiology of the migraine. This current study aimed to explore the thalamocortical connectivity changes during 4 weeks of continuous...

Treatment benefit among migraine patients taking fremanezumab: results from a post hoc responder analysis of two placebo-controlled trials

BackgroundMonoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, including the fully humanized monoclonal antibody (IgG2Δa) fremanezumab, have demonstrated safety and efficacy for migraine prevention. Clinical trials include responders and nonresponders; efficacy outcomes describe mean values across both groups and thus provide little insight into the clinical benefit in responders. Clinicians and their patients want to understand the extent of clinical improvement in patients who respond. This post hoc analysis of fremanezumab treatment attempts to answer this question: what is the benefit in subjects who responded to treatment during the two, phase 3 HALO clinical trials?MethodsWe included subjects with episodic migraine (EM) or chronic migraine (CM) who received fremanezumab quarterly (675 mg/placebo/placebo) or monthly (EM: 225 mg/225 mg/225 mg; CM: 675 mg/225 mg/225 mg) during the 12-week randomized, double-blind, placebo-controlled HALO EM and HALO CM clinical trials. EM and CM responders were defined as participants with a reduction of ≥ 2 or ≥ 4 monthly migraine days, respectively. Treatment benefits evaluated included reductions in monthly migraine days, acute headache medication use, and headache-related disability, and changes in health-related quality of life (HRQoL).ResultsOverall, 857 participants from the HALO trials were identified as responders (EM: 429 [73.8%]; CM: 428 [56.7%]). Reductions in the monthly average number of migraine days were greater among EM (quarterly: 5.4 days; monthly: 5.5 days) and CM (quarterly: 8.7 days; monthly: 9.1 days) responders compared with the overall population. The proportion of participants achieving ≥ 50% reduction in the average monthly number of migraine days was also greater in responders (EM: quarterly, 59.8%; monthly, 63.7%; CM: quarterly, 52.8%; monthly, 59.0%) than in the overall population. Greater reductions in the average number of days of acute headache medication use, greater reductions in headache-related disability scores, and larger improvements in HRQoL were observed among EM and CM responders compared with the overall populations.ConclusionsFremanezumab responders achieved clinically meaningful improvements in all outcomes. The magnitude of improvements with fremanezumab across efficacy outcomes was far greater in responders than in the overall trial population, providing insight into expected treatment benefits in participants who respond to fremanezumab in clinical practice.Trial registrationClinicalTrials.gov identifiers: NCT02629861 (HALO EM) and NCT02621931 (HALO CM).

Memantine for Episodic Migraine: A Systematic Review and Meta-analysis

Introduction. Migraine is a common, debilitating primary headache. Memantine is a non-competitive N-methyl D-aspartate (NMDA) antagonist that lowers neuronal excitability that could prevent migraine attacks. This study aimed to determine the efficacy and safety of memantine in patients with episodic migraine attacks using a systematic review and meta-analysis. Methods. We searched CENTRAL, MEDLINE, Scopus, Cochrane, LILACS, ClinicalTrials.gov, HERDIN and Google Scholar for relevant studies until July 31, 2020. Prespecified screening and eligibility criteria for inclusion were applied. Included studies underwent methodological quality assessment. Study design, patient characteristics, interventions given, and relevant outcomes were extracted and synthesized. Results. This review included five relevant articles – two randomized controlled trials (RCT) and three non randomized studies (one retrospective records review and survey, two prospective open-label single-arm trials). There were 109 patients included in the RCTs and 197 patients reported in the non-randomized studies. Pooled data from the two RCTs showed that memantine at 10 mg/day significantly decreased the monthly number of migraine days at 12 weeks compared to placebo with a mean difference of -1.58 [95% confidence interval (CI) -1.84, -1.32]. Non-randomized studies also showed a decrease in migraine days per month with memantine (5 to 20 mg/day) after 12 weeks [95% CI]: -9.1 [-11, -7.23], -7.2 [-8.85, -5.55], and -4.9 [-6.29, -3.51]. Adverse drug events (ADE) did not differ significantly between patients treated with memantine compared to placebo. Conclusion. Memantine may be effective and well-tolerated as prophylaxis for episodic migraine.

Open Label Prospective Experience of Supplementation with a Fixed Combination of Magnesium, Vitamin B2, Feverfew, Andrographis Paniculata and Coenzyme Q10 for Episodic Migraine Prophylaxis.

Background: To investigate the efficacy and safety of supplementation with a fixed combination of magnesium, vitamin B2, feverfew, andrographis paniculata and coenzyme Q10 in episodic migraine (EM) prevention. Methods: A pilot, single-arm, open-label study was conducted. After a one-month baseline period, the above-described supplementation was introduced in 113 EM Greek patients, who were prospectively followed-up for three months. The primary endpoint was the change in monthly migraine days between baseline period (BSL) and the third month of supplementation (T3). Secondary endpoints included changes in mean intensity of migraine and in days with use of acute migraine medications. Changes in scores of Migraine Disability Assessment questionnaire (MIDAS), Headache Impact Test-6 (HIT-6), Migraine Therapy Assessment questionnaire (MTAQ), Migraine-Specific Quality-of-life questionnaire (MSQ-QOL), Hospital Anxiety and Depression Scale (HADS) were also evaluated. Those with ≥50% reduction in monthly migraine days at T3, compared to BSL were considered supplementation-responders. Results: The mean number of migraine days was significantly decreased between BSL and T3 (9.4 ± 3.7 vs. 6.1 ± 3.5; p < 0.001). Likewise, days with peak headache intensity of >4/10 (5.7 ± 3.4 vs. 4.9 ± 3.1; p < 0.001) as well as days using acute headache medications per month (8.9 ± 3.6 vs. 5.7 ± 3.4; p < 0.001) were significantly reduced. At T3, 64 patients (56.6%) were classified as responders. The beneficial effect of supplementation was also associated with significant changes in HIT-6, MIDAS, MTAQ and MSQ-QOL scores. There were no safety concerns. Conclusions: The supplementation we have tested appears to be an effective and well-tolerated preventive approach against EM. A randomized, placebo-controlled study is needed to confirm our results.

Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial

Rimegepant is a calcitonin gene-related peptide receptor antagonist that has shown efficacy and safety in the acute treatment of migraine. We aimed to compare the efficacy of rimegepant with placebo for preventive treatment of migraine. We did a multicentre, phase 2/3, randomised, double-blind, placebo-controlled trial at 92 sites in the USA. Adults with at least a 1-year history of migraine were recruited. After a 4-week observation period, eligible participants were randomised using an interactive web response system to oral rimegepant 75 mg or matching placebo every other day for 12 weeks (double-blind treatment phase). The primary efficacy endpoint was change from the 4-week observation period in the mean number of migraine days per month in the last 4 weeks of the double-blind treatment phase (weeks 9-12). Participants who received at least one dose of their assigned study medication and who had 14 days or more of data in the observation period and 14 days or more of data for at least one 4-week interval during the double-blind treatment phase were analysed for efficacy. Those who received at least one dose of study medication were analysed for safety. This study is registered with ClinicalTrials.gov, NCT03732638. Between Nov 14, 2018, and Aug 30, 2019, 1591 participants were recruited and assessed for eligibility, of whom 747 were randomly allocated either rimegepant (n=373) or placebo (n=374). 695 participants were included in the analysis for efficacy, of whom 348 were assigned rimegepant and 347 were allocated placebo. Rimegepant was superior to placebo on the primary endpoint of change in the mean number of migraine days per month during weeks 9-12. The change from the observation period in mean number of migraine days per month during weeks 9-12 was -4·3 days (95% CI -4·8 to -3·9) with rimegepant and -3·5 days (-4·0 to -3·0) with placebo (least squares mean difference -0·8 days, 95% CI -1·46 to -0·20; p=0·0099). 741 participants received study medication and were included in the safety analysis. 133 (36%) of 370 patients who received rimegepant reported an adverse event, compared with 133 (36%) of 371 who received placebo. Seven (2%) participants who received rimegepant and four (1%) who received placebo discontinued the study due to an adverse event; no patients died. Taken every other day, rimegepant was effective for preventive treatment of migraine. Tolerability was similar to that of placebo, and no unexpected or serious safety issues were noted. Biohaven Pharmaceuticals.

Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials

Identifying the optimal fremanezumab treatment strategy is crucial in treating patients with migraines. The optimal strategy was investigated by assessing the cumulative 50% reduction rate (50%CRR), cumulative 75% reduction rate (75%CRR), reduction in the number of migraine days, treatment-related adverse events, and serious adverse events in patients treated with fremanezumab 225 mg monthly (225 mg), 675 mg monthly (675 mg), 900 mg monthly (900 mg), a single high dose of 675 mg (S675mg), 675 mg at baseline with 225 mg monthly (675/225 mg), and placebo. Biomedical databases were searched for randomized controlled trials on this topic, and data were individually extracted. Risk ratios and mean differences were used to present the pooled results. The surface under the cumulative ranking curve (SUCRA) was used to determine the effects of the medication strategies of fremanezumab. Five trials (n = 3404) were used to form a six-node network meta-analysis. All fremanezumab medication strategies displayed significantly higher cumulative 50% reduction rates than the placebo. The SUCRA revealed that treatment with 675 mg yielded the highest 50%CRR value (mean rank = 2.5). S675 mg was the only treatment with significantly higher 75%CRR reduction rate than placebo, whereas the SUCRA for 225 mg displayed the highest mean rank (2.2). Moreover, 225 mg (mean rank = 2.2) and S675 mg (mean rank = 2.2) presented lower probabilities of serious adverse events. Collectively, S675mg and 225 mg exhibited the optimal balance between efficacy and safety within three months. Long-term efficacy and safety remain unclear, and future studies should further evaluate the long-term outcomes.

Pharmacotherapy of migraine prevention based on the assessment of headache

Migraine as a recurrent, relapsing, and chronic disease is one of the most disabling disorders globally. Most patients are women in their reproductive age and their migraines are classified as episodic migraine. Although less than half of the episodic and most chronic migraineurs require preventive intervention, early discontinuation rates are high, owing to poor tolerability and insufficient awareness about migraine. This article aims to review the recent update of migraine prevention based on the practice guidelines for the prevention of episodic migraine published by the Korea Headache Society and the position statement of the American Headache Society in 2019. The goal of migraine prevention is to reduce migraine attack frequency by at least 50 %, the number of migraine days, and the attack severity to ultimately improve quality of life. The guidelines recommend considering the initiation of preventive medication when recurring migraines significantly interfere with daily life or when acute treatment is contraindicated or inappropriate. Preventive medications should be determined based on various qualified assessments. Pharmacologic treatments are recommended for migraine prophylaxis include antidepressant (amitriptyline), anti-epileptic drugs (topiramate, divalproex sodium), beta-blockers (propranolol, metoprolol), calcium channel blocker (flunarizine), and intramuscular injection of onabotulinumtoxin A. Furthermore subcutaneous or intravenous injection of calcitonin gene-related peptide monoclonal antibodies was recently approved as a new therapy for migraine prevention. Migraine is a chronic debilitating disorder. The initiation of evidence-based preventive management is necessary and management methods should be individually selected to improve quality of life.

Peripheral changes of endocannabinoid system components in episodic and chronic migraine patients: A pilot study.

Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine. The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components. Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake. The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field.clinicaltrials.gov NTC04324710.

Patterns of Perceived Stress Throughout the Migraine Cycle: A Longitudinal Cohort Study Using Daily Prospective Diary Data

To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study. Individuals with migraine aged ≥18years, who were registered to use the digital health platform N1-HeadacheTM , and completed 90days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant's chosen time with a single question, "How stressed have you felt today?" with response options graded on a 0-10 scale. Days were categorized into phases of the migraine cycle: Ppre =pre-migraine headache (the 2days prior to the first day with migraine headache), P0 =migraine headache days, Ppost =post-migraine headache (the 2days following the last migraine day with migraine headache), and Pi =interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90days in 120 calendar days or less) were eligible for inclusion in the analysis. Data from 351 participants and 2115 episodes were included in this analysis. Eighty-six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2-13, standard deviation=2.3) and the mean number of episodes was 6.0 (range 5-10, standard deviation=1.0) over the 90-day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the "let down" pattern, perceived stress in the interictal phase (Pi ) falls in the pre-headache phase (Ppre ) and then decreases more in the migraine phase (P0 ) relative to Pi . For cluster 2, the "flat" pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the "stress as a trigger/symptom" pattern, perceived stress in Ppre increases relative to Pi , and increases further in P0 relative to Pi . Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3.There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3. On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers and protective factors, and provide a framework for targeting individualized treatment plans.

Long-term safety, tolerability, and efficacy of fremanezumab in migraine: A randomized study.

ObjectiveTo assess the long-term safety, tolerability, and efficacy of fremanezumab, a fully humanized monoclonal antibody approved for the preventive treatment of migraine.MethodsA 52-week, multicenter, randomized, double-blind, parallel-group study evaluated fremanezumab monthly or quarterly in adults with chronic migraine (CM) or episodic migraine (EM). Safety and tolerability were assessed by adverse event (AE) monitoring (performed by the investigators), systematic local injection-site assessments (immediately and 1 hour after injection), laboratory/vitals assessments, and immunogenicity testing. Prespecified exploratory evaluations included change from baseline in the monthly number of migraine days, headache days of at least moderate severity, and days with any acute headache medication use. Change from baseline in headache-related disability (6-item Headache Impact Test scores) was also measured.ResultsOf 1,890 patients enrolled, 551 and 559 patients with CM received quarterly and monthly dosing; 394 and 386 patients with EM received quarterly or monthly, respectively. The most commonly reported AEs were injection-site reactions (induration 33%, pain 31%, and erythema 26%). Fremanezumab reduced monthly migraine days (CM quarterly −7.2 days, CM monthly −8.0 days, EM quarterly −5.2 days, EM monthly −5.1 days) and headache days of at least moderate severity (CM quarterly −6.4 days, CM monthly −6.8 days, EM quarterly −4.4, EM monthly −4.2 days) from baseline to 12 months. Reductions in any acute headache medication use and headache-related disability were also maintained over 12 months.ConclusionsFremanezumab quarterly and fremanezumab monthly were well tolerated and demonstrated sustained improvements in monthly migraine days, headache days, and headache-related disability for up to 12 months in patients with migraine.ClinicalTrials.govNCT02638103.Classification of evidenceThis study provides Class IV evidence that long-term fremanezumab treatment is safe, well tolerated, and effective at sustaining reductions in monthly migraine and headache days.