Migraine Prevention Research Articles

Efficacy and safety of levetiracetam for migraine prophylaxis in children: a systematic review and meta-analysis.

Levetiracetam (LEV), an antiepileptic drug, has been effective in adult migraine prevention but lacks extensive research in children. This study evaluates LEV's efficacy and safety for pediatric migraine prophylaxis. We reviewed randomized controlled trials (RCTs) and non-RCTs in major databases through 8 January 2024, focusing on four efficacy endpoints and adverse drug reactions (ADRs). Data synthesis involved pooled relative risks or odds ratios for dichotomous outcomes and mean differences for continuous outcomes, using fixed- or random-effects models as appropriate. Eight studies with 190 participants showed that after taking LEV, the mean headache frequency decreased 5.19 per month (MD: -5.19, 95% CI: -7.11 to -3.27, p < 0.00001) and improved headache-free rates to 28% (95% CI: 0.17-0.41). More than 83% experienced a >50% reduction in monthly headache frequency. The migraine disability score decreased by 33.51 points (MD: -33.51, 95% CI: -38.46 to -28.55, p < 0.00001). ADR incidence did not significantly differ between LEV and control groups (RR: 1.06, 95% CI: 0.39 to 2.85, p = 0.91), with an overall ADR rate of 18% (95% CI: 0.13-0.24). The most common ADR was irritability (12%), leading to treatment discontinuation in 13% of cases (95% CI: 0.05-0.30). LEV has shown good efficacy in preventing pediatric migraines. However, its safety requires further confirmation through more extensive and well-designed RCTs. Identifier PROSPERO CRD42024497643.

Bidirectional two-sample Mendelian randomization analysis identifies causal associations between migraine and five psychiatric disorders.

The question of whether a correlation exists between migraine and five psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), anorexia nervosa (AN), bipolar disorder (BIP), and schizophrenia (SCZ), remains a matter of controversy. Hence, this research aims to investigate whether there is a possible association between migraine and five psychiatric disorders. We performed a bidirectional 2-sample Mendelian randomization (MR) analysis to assess the causality between migraine and five psychiatric disorders. Genetic associations of PTSD, MDD, AN, BIP, and SCZ were obtained from the Psychiatric Genomics Consortium (PGC) database and genetic associations of migraine with aura and migraine without aura were obtained from the FinnGen dataset. We used the inverse-variance weighted (IVW), weighted median, weighted mode, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and MR Egger regression methods to evaluate the association of genetically predicted exposure with the risk of outcome. MR demonstrated that MDD was associated with a high risk of migraine without aura (OR = 1.930578, 95% confidence interview (CI): 1.224510, 3.043550, p < 0.05), but BIP was related to a low risk of migraine without aura (OR = 0.758650, 95%CI: 0.639601, 0.899858, p < 0.05). According to the results of reverse MR, migraine with aura was associated with a high risk of BIP (OR = 1.019100, 95%CI: 1.002538, 1.035935, p < 0.05), and migraine without aura was associated with an increased risk of AN (OR = 1.055634, 95%CI: 1.023859, 1.088394, p < 0.05). Our results provide evidence of the potential causal association between migraine and some psychiatric disorders. It may contribute to the prevention of migraine and some psychiatric disorders.

Use of rimegepant as an alternative to triptans in migraine treatment

Introduction and aim of study: Migraine is a chronic neurological disorder that is considered one of the leading causes of disability worldwide. Increasing evidence indicates that the calcitonin gene-related peptide (CGRP), a neuropeptide released during trigeminal nerve activation, plays a major role in pathophysiology and serves as an important therapeutic target. Rimegepant is an antagonist for the receptor of this peptide and an alternative to the commonly used triptans. Materials and Methods: Two databases, Pubmed and Medline, were searched using the terms "rimegepant" and "migraine." Results: By reducing the severity and frequency of migraine attacks, rimegepant significantly improves patients' daily functioning and quality of life. A single 75 mg dose of rimegepant provided better efficacy than placebo in the acute treatment of migraine. Two hours after dosing, significantly more patients in the rimegepant group than in the placebo group reported pain relief (59.3% vs. 43.3%). Rimegepant was also effective in the long term when taken every other day for preventive treatment of migraine and/or as needed for acute migraine treatment. When used, rimegepant was well tolerated in both acute and preventive migraine treatment. The most common adverse events included nasopharyngitis, nausea, urinary tract infection, and upper respiratory tract infection. Conclusions: Rimegepant is an effective drug for treating migraine attacks, offering quick and long-lasting pain relief with a favorable safety profile, especially for patients with contraindications to triptans. Therefore, rimegepant represents a valuable alternative for patients who do not respond adequately to other available migraine therapies.

Health care resource utilization and direct costs incurred over 24 months after initiating galcanezumab or standard-of-care preventive migraine treatments in the United States.

Health care resource utilization (HCRU) and direct costs incurred over 12 months following initiation of galcanezumab (GMB) or standard-of-care (SOC) preventive migraine treatments have been evaluated. However, a gap in knowledge exists in understanding longer-term HCRU and direct costs. To compare all-cause and migraine-related HCRU and direct costs in patients with migraine initiating GMB or SOC preventive migraine treatments over a 24-month follow-up. This retrospective study used Optum deidentified Market Clarity Data. The study included adults diagnosed with migraine, with at least 1 claim for GMB or SOC preventive migraine therapy (September 2018 to March 2020), with continuous enrollment for 12 months before and 24 months after (follow-up) the index date (date of first GMB or SOC claim). Propensity score (PS) matching (1:1) was used to balance cohorts. All-cause and migraine-related HCRU and direct costs for GMB vs SOC cohorts were reported as mean (SD) per patient per year (PPPY) over a 24-month follow-up and compared using a Z-test. Costs were inflated to 2022 US$. After PS matching, 2,307 patient pairs (mean age: 44.4 years; female sex: 87.3%) were identified. Compared with the SOC cohort, the GMB cohort had lower mean (SD) PPPY all-cause office visits (17.9 [17.7] vs 19.1 [18.7]; P = 0.023) and migraine-related office visits (2.6 [3.3] vs 3.0 [4.7]; P = 0.002) at follow-up. No significant differences were observed between cohorts in other all-cause and migraine-related events assessed including outpatient visits, emergency department (ED) visits, inpatient stays, and other medical visits. The mean (SD) costs PPPY were lower in the GMB cohort compared with the SOC cohort for all-cause office visits ($4,321 [7,518] vs $5,033 [7,211]; P < 0.001) at follow-up. However, the GMB cohort had higher mean (SD) PPPY all-cause total costs ($24,704 [30,705] vs $21,902 [28,213]; P = 0.001) and pharmacy costs ($9,507 [12,659] vs $5,623 [12,605]; P < 0.001) compared with the SOC cohort. Mean (SD) costs PPPY were lower in the GMB cohort for migraine-related office visits ($806 [1,690] vs $1,353 [2,805]; P < 0.001) compared with the SOC cohort. However, the GMB cohort had higher mean (SD) PPPY migraine-related total costs ($8,248 [11,486] vs $5,047 [9,749]; P < 0.001) and migraine-related pharmacy costs ($5,394 [3,986] vs $1,761 [4,133]; P < 0.001) compared with the SOC cohort. There were no significant differences between cohorts in all-cause and migraine-related costs for outpatient visits, ED visits, inpatient stays, and other medical visits. Although total costs were greater for GMB vs SOC following initiation, changes in a few categories of all-cause and migraine-related HCRU and direct costs were lower for GMB over a 24-month follow-up. Additional analysis evaluating indirect health care costs may offer insights into further cost savings incurred with preventive migraine treatment.

Early Use of Erenumab Shows Efficacy in Management of Migraine Prevention

Early Use of Erenumab Shows Efficacy in Management of Migraine Prevention

Evaluating Modern Therapeutic Interventions for Migraine Management: A Systematic Review.

This systematic review evaluates the efficacy and safety of contemporary migraine treatments, synthesizing evidence from recent randomized controlled trials (RCTs). The focus is on both pharmacological interventions, such as calcitonin gene-related peptide (CGRP) monoclonal antibodies and non-specific oral migraine preventives, and non-pharmacological approaches like myofascial release. Through a detailed examination of the studies, this review identifies superior strategies for acute and preventive migraine management, assessing their impact on patient-reported outcomes and determining the prevalence of associated adverse events. Findings suggest that while CGRP monoclonal antibodies show promise as first-line treatments due to their efficacy and safety, myofascial release offers considerable benefits for pain and disability in tension-type and cervicogenic headaches. Challenges such as the variability in individual response and potential side effects emphasize the need for personalized treatment plans. This review underscores the importance of integrating new therapeutic discoveries into clinical practice to enhance the quality of care for migraine sufferers.

VPAC1 and VPAC2 receptors mediate tactile hindpaw hypersensitivity and carotid artery dilatation induced by PACAP38 in a migraine relevant mouse model

BackgroundPituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide pivotal in migraine pathophysiology and is considered a promising new migraine drug target. Although intravenous PACAP triggers migraine attacks and a recent phase II trial with a PACAP-inhibiting antibody showed efficacy in migraine prevention, targeting the PACAP receptor PAC1 alone has been unsuccessful. The present study investigated the role of three PACAP receptors (PAC1, VPAC1 and VPAC2) in inducing migraine-relevant hypersensitivity in mice.MethodsHindpaw hypersensitivity was induced by repeated PACAP38 injections. Tactile sensitivity responses were quantified using von Frey filaments in three knockout (KO) mouse strains, each lacking one of the PACAP-receptors (Ntotal = 160). Additionally, ex vivo wire myography was used to assess vasoactivity of the carotid artery, and gene expression of PACAP receptors was examined by qPCR.ResultsPACAP38 induced hypersensitivity in WT controls (p < 0.01) that was diminished in VPAC1 and VPAC2 KO mice (p < 0.05). In contrast, PAC1 KO mice showed similar responses to WT controls (p > 0.05). Myograph experiments supported these findings showing diminished vasoactivity in VPAC1 and VPAC2 KO mice. We found no upregulation of the non-modified PACAP receptors in KO mice.ConclusionsThis study assessed all three PACAP receptors in a migraine mouse model and suggests a significant role of VPAC receptors in migraine pathophysiology. The lack of hypersensitivity reduction in PAC1 KO mice suggests the involvement of other PACAP receptors or compensatory mechanisms. The results indicate that targeting only individual PACAP receptors may not be an effective migraine treatment.

Atogepant (Qulipta)

CADTH recommends that atogepant (Qulipta) be reimbursed by public drug plans for the prevention of migraine if certain conditions are met. For migraine prevention, Qulipta should only be covered in adult patients who have tried at least 2 other types of treatments for the prevention of migraine. Qulipta should only be reimbursed if it is prescribed by a prescriber with experience managing chronic migraine (CM) headaches and if the cost of Qulipta is not more than the least costly calcitonin gene–related peptide (CGRP) inhibitor currently funded for this population. Qulipta should not be reimbursed for use in combination with other CGRP inhibitors for the prevention of migraine in adult patients with CM.

Exploring Erenumab's Efficacy and Safety for Migraine Prevention in Real-World Settings: A Systematic Review.

Migraine causes debilitating headaches and significantly impacts quality of life. Effective migraine-specific treatments have been lacking until the advent of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) receptors, which have expanded therapy options for migraine treatment. This study explores the short- and long-term efficacy and safety of erenumab in migraine treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 criteria guided this systematic review. Five databases - PubMed, PubMed Central, Google Scholar, ScienceDirect, and Sage Journal - were searched for published, freely accessible, full-text articles in English from the past five years. Eligible patients included those with episodic or chronic migraines who received erenumab intervention. From an initial search yielding 680 relevant studies, 12 prospective observational cohort studies were selected after assessing the risk of bias through the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. All included studies demonstrated a significant reduction in monthly migraine days (MMDs) by the end of the treatment period, with mild adverse effects observed. No significant short-term or long-term safety concerns were identified.

Concomitant use of calcitonin gene-related peptide (CGRP) antagonists with azole antifungals in patients with hematological malignancies.

Small molecule calcitonin gene-related peptide (CGRP) antagonists such as rimegepant, ubrogepant, and atogepant have been approved for migraine treatment and/or prevention. These molecules are metabolized by cytochrome P-450 3A4 (CYP3A4) enzymes in vivo, hence they are contraindicated or recommended to be avoided in combination with strong/moderate CYP3A4 inhibitors, namely posaconazole (strong) and isavuconazonium (moderate). However, no literature has been published on the impact this interaction has on patient safety and tolerability. In this case series, we report five cases in which CGRP antagonists and azole antifungal therapy were given concurrently, to provide real-world outcomes of this interaction. Electronic medical records at our hospital system were reviewed between January 2021 and December 2023 to find patients who met the criteria of hematological malignancy, taking CGRP-antagonist and azole antifungal therapy. Records were then further investigated to find cases where CGRP antagonists and azole antifungals were used concomitantly. Concurrent use of CGRP antagonists and azole antifungal therapy was feasible for patients with migraines and hematological malignancies. None of the patients experienced any grade 3 or higher non-hematological toxicity from the proposed over-exposure to CGRP antagonist. The combination was well tolerated without any need for therapy discontinuation or dose modifications. It is recommended to follow the manufacturers' guidance on drug interactions, however, in the setting where there are no other options, concomitant use of CGRP antagonists with azole antifungals is possible with monitoring and observation for adverse effects.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol

ObjectiveThe aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis.MethodsWe report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared propranolol with placebo for migraine prophylaxis in adults. The outcomes of interest were informed by the Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in monthly migraine days, the reduction of monthly migraine days, and the number of adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB (risk of bias) 2.0 tool and the certainty of evidence by using the GRADE approach.ResultsOur search yielded twenty trials (n = 1291 patients) eligible for data synthesis and analysis. The analysis revealed a moderate certainty evidence that propranolol leads to a reduction in monthly migraine days versus placebo (-1.27; 95% CI: -2.25 to -0.3). We found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo with a relative risk of 1.65 (95% CI 1.41 to 1.93); absolute risk difference: 179 more per 1,000 (95% CI 113 to 256). We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30).ConclusionsThe present meta-analysis shows that propranolol has a prophylactic role in migraine, with an overall acceptable tolerability profile. Combining these results with its long-standing use and its global availability at a low cost confirms its role as a first line agent in the prophylaxis of migraine.

Tricaprilin (CER-0001) for the preventive treatment of migraine: A phase 2 randomised, double-blind, placebo-controlled pilot study

BackgroundIncreasing evidence indicates a metabolic etiology for migraines, with ketosis potentially rectifying metabolic and clinical features. We conducted a pilot study to evaluate CER-0001, a ketogenic agent, for migraine prevention without dietary changes. MethodsThis was a 2-part, double-blind, randomised, placebo-controlled study conducted in Australia. Adults with at least a 1-year history of migraine and ≥ 1 prior preventive treatment failure were randomised to either oral CER-0001 (up to 30 g twice a day) or placebo for 12 weeks. The primary endpoint was Month 3 change in Migraine Headache Days from baseline. ResultsPart 1 results are presented. 81 participants were randomised and dosed (n = 40 CER-0001, n = 41 placebo), and 61 participants had evaluable efficacy data. No statistically significant difference was observed in the primary endpoint (LSMean difference 0.92 days; p = 0.586). During Month 2, a mean improvement of −2.8 days was observed for CER-0001 (p = 0.056). Withdrawal rates were 45.0% and 53.7% (CER-0001; placebo). The proportion of participants reporting at least one treatment-emergent adverse event was similar between arms (90.0% CER-0001, 82.9% placebo), mostly gastrointestinal (85.0% CER-0001, 70.7% placebo). ConclusionResults suggest positive directional promise over 2–3 months for CER-0001. A new formulation will be used for larger, fully powered phase 2/3 studies. Trial registrationThis study is registered at ClinicalTrials.gov (NCT04437199).

Causality between multiple autoimmune disorders and migraine and its subtypes: a two-sample Mendelian randomization study.

Several studies have reported associations between various autoimmune diseases and migraine. Using Mendelian randomization (MR), this study aimed to evaluate the interplay between autoimmune diseases and migraine. Here, instrumental variables, exposure factors, and outcome factors for 10 common autoimmune diseases and migraine and its subtypes were screened. This screening utilized comprehensive statistics from Europe's largest genome-wide association study and performed reverse MR analysis on positive results. The causality between autoimmune diseases and migraine was comprehensively assessed using multiple analytical methods. Additionally, sensitivity analyses, such as the horizontal diversity heterogeneity and leave-one-out method, were performed. Random-effects inverse variance weighting analysis revealed a causal correlation between autoimmune hyperthyroidism and migraine (p = 0.0002), and this association was consistent across both migraine with aura (MA; p = 0.006) and migraine without aura (MO; p = 0.017). In addition, there was a positive causal association between systemic lupus erythematosus (SLE) and MA (p = 0.001) and between hypothyroidism and MO (p = 0.038). There is insufficient evidence to substantiate a causal link between outcomes and other autoimmune-related disorders, and reverse MR results did not reveal a causal relationship between migraines and these autoimmune disorders. The validity of the results was demonstrated by a sensitivity analysis; horizontal pleiotropy and heterogeneity were not observed. This study observed a positive genetic association between autoimmune hyperthyroidism and migraines. In addition, SLE positively affects MA, and hypothyroidism contributes to the incidence of MO. These results have great significance for future research and prevention of migraine.

The Modern Clinician as an "Argonaut" Guiding Through the "Symplegades" of Evidence for PFO Closure in Patients With Migraine.

Patent foramen ovale (PFO) has been associated with migraine, especially migraine with aura, and 30-50% of individuals with migraine with aura have a PFO, suggesting it could be more than just an "innocent bystander''. Observational data showed a reduction of the frequency and severity of migraine attacks, particularly those with aura, following transcatheter PFO closure for established indications. Three small randomized controlled trials have demonstrated significant benefits of PFO closure in most of their secondary endpoints, such as reductions in the mean number of monthly migraine attacks and migraine days. Since a significant proportion of patients experience important side effects from traditional migraine medications and newer highly effective migraine prevention strategies may need to be instituted. PFO closure could in this regard to be a valuable add-on in the armamentarium of migraine treatment, improving the quality of life by alleviating the need for medications. The effect of percutaneous PFO closure on migraine treatment is needed to be clarified. As the underlying pathophysiology remains poorly understood and largely hypothetical, future investigations, focusing on the causal relationship between PFO and migraine, will help to define the subgroup of patients most likely to benefit from PFO closure. More accurate patient recruitment may lead to greater postprocedural benefits and more significant symptom improvement. Additionally, randomized controlled trials need to be reported adequately with more realistic endpoints, sufficient duration of follow-up, and statistical power to detect differences between closure and placebo groups to ensure precise and reliable findings.

Patient preferences for preventive migraine treatments among Canadian adults: A discrete choice experiment.

To evaluate preferences for key attributes of injected or infused preventive migraine treatments and assess heterogeneity in preferences among Canadian participants with migraine. Current treatment options for migraine prevention differ in their attributes, including mode of administration, efficacy, and dosing frequency; preferences for such attributes can vary among patients. With the advent of new therapies, evidence demonstrating patient preferences for injected or infused preventive migraine treatments is necessary. Canadian adults self-reporting a diagnosis of migraine completed a cross-sectional, internet-based survey that included a discrete choice experiment. Participants were presented with attributes of preventive migraine treatments, including speed of onset, durability of efficacy, mode of administration, administration setting, and dosing frequency. Latent class analysis (LCA) was used to identify subgroups of patients who differed in their treatment preferences. In total, 200 participants completed the survey. Participants' treatment preferences were most sensitive to improvements in the durability of effectiveness from "wears off 2 weeks before next dose" to "does not wear off before the next dose" (absolute difference in weights = |-0.95 to 1.07| = 2.02) and improvements from "cranial injections" to "intravenous infusions" (|-1.04 to 0.58| = 1.62); participants equally preferred self-injection and intravenous infusion from a health-care provider (mean weight = 0.58 and 0.47, respectively) as a route of administration over cranial injections (mean weight = -1.04). Three subgroups were identified with LCA: group one (n = 103) prioritized fast-acting and durable therapies, group two (n = 54) expressed aversion to cranial injections, and group three (n = 43) favored treatments administered in a health-care provider setting. In this sample of Canadian adults with migraine, we showed that durability of effectiveness and mode of administration are key attributes influencing patient preferences for preventive migraine treatments; however, certain groups of patients may differ in their treatment priorities. Our results highlight the need for patient-provider discussions regarding treatment attributes and consideration of patients' preferences when selecting a preventive migraine treatment.

Neuromodulation treatments for migraine: a contemporary update.

Neuromodulation approaches have been a part of a revolution in migraine therapies with multiple devices approved or in development. These devices vary in the nerve(s) being targeted, implantable versus noninvasive form factors as well as their effectiveness for acute pain reduction or migraine prevention. This review will summarize these recent advancements and approaches that are being developed which build upon prior work and improved technology that may help enhance the effectiveness as well as the patient experience. Both noninvasive and implantable devices primarily targeting cranial nerves have shown the ability to help alleviate migraine symptoms. Multiple prospective and retrospective studies have demonstrated clinically meaningful reductions in headache intensity with noninvasive approaches, while prevention of migraine demonstrates more modest effects. Implantable neuromodulation technologies focusing on occipital and supraorbital stimulation have shown promise in migraine/headache prevention in chronic migraine patients, but there is a need for improvements in technology to address key needs for surgical approaches. Electrical neuromodulation approaches in the treatment of migraine is undergoing a transformation towards improved outcomes with better technologies that may suit various patient needs on a more individualized basis.

Biofeedback therapy using Cerebri for the prevention of migraine attacks in adults with episodic migraine (BioCer): a randomized, wait-list controlled trial – the study protocol

Introduction Biofeedback is a non-pharmacological treatment option valued for its minimal risk of adverse events and offers a safe alternative for individuals seeking preventive care for migraine. Despite level A evidence for migraine prevention, biofeedback treatment is still unavailable to most patients. We developed a novel medical device (Cerebri) for multimodal biofeedback treatment that omits the need for healthcare personnel involvement. Cerebri consists of a smartphone application (app) and two wireless sensors. Unique in its approach, the Cerebri app seamlessly integrates three biofeedback modalities – heart rate variability, temperature, and electromyography – making it a comprehensive, therapist-independent solution for non-pharmacological migraine management. Methods Biofeedback therapy using Cerebri for the prevention of migraine attacks in adults with episodic migraine (The BioCer study) was an open-label, randomized, waitlist-controlled, multicenter trial. This study investigated the safety and efficacy of daily home-based biofeedback sessions using the Cerebri device. A total of 286 participants will be randomized to either a 12-week intervention arm or waitlist control arm. The primary outcome was the change in the mean number of migraine days from baseline to the last 28-day period during the treatment phase in the treatment group compared with the control group. The primary outcome variable was prospectively collected through daily eDiary entries. Ethics and Dissemination Approval from the ethics committee and competent authorities was obtained prior to study initiation. Participation was voluntary and informed and written consent was obtained prior to inclusion. The results of this trial will be published in peer-reviewed international medical journals and communicated to patients and healthcare personnel through the relevant channels. Trial registration numbers EUDAMED: CIV-NO-22-08-040446 REK (Regional Committees for Medical and Health Research Ethics): 502734 Date of approval 2022-10-14 Trial registration: NCT05616741, 2022-11-15, https://clinicaltrials.gov/study/NCT05616741

Long-term effectiveness of eptinezumab in the treatment of patients with chronic migraine and medication-overuse headache.

This post hoc analysis of the PREVAIL study explored the effectiveness of eptinezumab for up to 2 years of open-label treatment in the subgroup of patients with chronic migraine who had a confirmed diagnosis of medication-overuse headache (MOH) at screening. MOH is a disabling and costly secondary headache disorder characterized by increased headache frequency and/or severity with increased acute headache medication use. Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduces headache frequency, severity, and associated disability and improves functioning and health-related quality of life as a preventive migraine therapy; short-term benefits in patients with concurrent MOH have also been reported. Participants received up to eight quarterly intravenous infusions of eptinezumab 300 mg in the phase 3, single-arm, open-label PREVAIL study. Safety and patient-reported outcome measures (Migraine Disability Assessment [MIDAS], 6-item Headache Impact Test [HIT-6], patient-identified most bothersome symptom [PI-MBS], Patient Global Impression of Change [PGIC], and 36-item Short-Form Health Survey [SF-36]) were conducted at predefined intervals. Patients were observed up to 20 weeks after their last infusion (Week 104). A total of 49/128 (38.3%) patients enrolled in PREVAIL had an MOH diagnosis at screening. In the MOH subgroup, long-term eptinezumab treatment was associated with reductions in headache frequency (43/49 [87.8%] patients reported ≥50% reduction in MIDAS-derived headache days at ≥1 visit), severity (2.2-point reduction [on a 10-point scale]), disability (mean MIDAS total score reduction of 51.9 points), and impact (mean HIT-6 total score reduction of 9.7 points) at Week 104. Most patients described a "much improved" or "very much improved" status by Week 48 (PI-MBS, 31/46 [67.4%]) and Week 104 (PGIC, 31/36 [86.1%]). Health-related quality of life improvements in the SF-36 were also observed. Eptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH.

A 3-year follow-up study of outcomes associated with patterns of traditional acute and preventive migraine treatment: An administrative claims-based cohort study in the United States.

To describe treatment patterns and direct healthcare costs over 3 years following initiation of standard of care acute and preventive migraine medications in patients with migraine in the United States. There are limited data on long-term (>1 year) migraine treatments patterns and associated outcomes. This was a retrospective, observational cohort study using US claims data from the IBM® MarketScan® Research Database (January 2010-December 2017). Adults were included if they had a prescription claim for acute migraine treatments (AMT) or preventive migraine treatments (PMT) in the index period (January 2011-December 2014). The AMT cohort was categorized as persistent, cycled, or added-on subgroups; the PMT cohort was categorized PMT-persistent, switched without gaps, or cycled with gaps. Migraine-specific annual direct costs (2017 US$) across AMT and PMT cohort subgroups were summarized at baseline through 3 years from index (follow-up). During the index period, 20,778 and 42,259 patients initiated an AMT and a PMT, respectively. At the 3-year follow-up, migraine-specific direct costs were lower in the persistent subgroup relative to the non-persistent subgroups in both AMT (mean [SD]: $789 [$1741] vs. $2847 [$8149] in the added-on subgroup and $862 [$5426] for the cycled subgroup) and PMT cohorts (mean [SD]: $1817 [$5892] in the persistent subgroup vs. $4257 [$11,392] in the switched without gaps subgroup and $3269 [$18,540] in the cycled with gaps subgroup). Acute medication overuse was lower in the persistent subgroup (1025/6504 [27.2%]) vs. non-persistent subgroups (11,236/58,863 [32.2%] in cycled with gaps subgroup and 1431/6504 [39.4%] in the switched without gaps subgroup). Most patients used multiple acute (19,717/20,778 [94.9%]) or preventive (38,494/42,259 [91.1%]) pharmacological therapies over 3 years following treatment initiation. Gaps in preventive therapy were common; an average gap ranged from 85 to 211 days (~3-7 months). Migraine-specific annual healthcare costs and acute migraine medication overuse remained lowest among patients with persistent AMT and PMT versus non-persistent treatment. Study findings are limited to the US population. Future studies should compare costs and associated outcomes between newer preventive migraine medications in patients with migraine.

Mediterranean ketogenic diet accounts for reduced pain frequency and intensity in patients with chronic migraine: A pilot study

BackgroundAn increasing amount of evidence suggests that migraine is a response to cerebral energy deficiencies or oxidative stress levels that exceed antioxidant capacity. Current pharmacological options are inadequate in treating patients with chronic migraine, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. The ketogenic diet, mimicking fasting that leads to an elevation of ketone bodies, is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. Moreover, Mediterranean elements like vegetables, nuts, herbs, spices, and olive oil that are sources of anti-inflammatory elements (omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics) may create a positive brain environment by reducing imbalance in the gut microbiome. MethodsOn the basis of these indications, a combined Mediterranean-ketogenic diet was administered to chronic migraine patients for 4 (T1) and 8 weeks (T2), and anthropometric estimations were collected at T1 and T2 while biochemical parameters at only T2. ResultsA significant reduction (p<0.01) in migraine frequency and intensity was detected as early as 4 weeks of dietary intervention, which was associated with a reduced fat mass (p<0.001) as well as Homa index (p<0.05) and insulin levels (p<0.01) after 8 weeks. ConclusionOverall, Mediterranean-ketogenic diet may be considered an effective non-pharmacological intervention for migraine, with positive outcomes on body composition.