Treatment Of Acute Migraine Attacks Research Articles

Dipyrone for the acute treatment of migraine attacks in children and adults

Dipyrone for the acute treatment of migraine attacks in children and adults

Breastfeeding-Related Adverse Drug Reactions of Triptans: A Descriptive Analysis Using Four Pharmacovigilance Databases.

Objective: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Methods: Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). Results: A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. Discussion and Conclusion: The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.

Exploration of Lasmiditan 200 mg Versus 100 mg for the Treatment of Migraine: A Meta-analysis Based on Aggregate Data.

Lasmiditan holds important potential in treating migraine, but its ideal dose remains elusive. This meta-analysis is conducted based on aggregate data and aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for acute treatment of migraine attack. PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were systematically searched, and we included the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model or fixed-effect model based on the heterogeneity. The primary outcome was pain free at 2 hours. Secondary outcomes included pain relief at 2 hours, pain free at 24 hours, most bothersome symptom free at 2 hours, and adverse events. Seven randomized controlled trials and 6515 patients were included in this meta-analysis. Compared with lasmiditan 100 mg for migraine patients, lasmiditan 200 mg was able to significantly improve pain free at 2 hours (odd ratio [OR], 1.28; 95% confidence interval [CI], 1.14-1.44; P < 0.0001) and pain free at 24 hours (OR, 1.35; 95% CI, 1.14-1.60; P = 0.0005), but showed no effect on pain relief at 2 hours (OR, 1.00; 95% CI, 0.90-1.12; P = 0.98) or most bothersome symptom free at 2 hours (OR, 0.93; 95% CI, 0.83-1.03; P = 0.17). Lasmiditan 200 mg was associated with the increase in adverse events compared with lasmiditan 100 mg (OR, 1.28; 95% CI, 1.15-1.43; P < 0.0001). Lasmiditan 200 mg is more effective to improve pain free at 2 hours and 24 hours than lasmiditan 100 mg for the acute treatment of migraine patients.

Zavegepant for Acute Treatment of Migraine: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks. A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs. Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72). Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.

Nasal spray (Zavegepant) for migraines: a mini-review.

Neurological disorders, especially migraines, pose a significant global burden. This has driven the recent innovative research being conducted in the field of anti-migraine therapies, including the discovery of Zavegepant for the treatment of acute migraine attacks. Zavegepant is a novel, first-in-class, intranasally administered calcitonin gene-related peptide (CGRP) receptor antagonist that has recently been approved for use in acute migraine attacks. Recent randomized controlled trials comparing Zavegepant with a placebo have demonstrated favorable results with respect to primary endpoints, as well as a desirable safety profile. The current first-line therapy consists of oral triptans, which are associated with lower efficacy, weaker safety profile, and an unsatisfactory preference rate among patients. Moreover, the intranasal method of administration is a characteristic advantage of Zavegepant, as patients suffering from acute migraine attacks cannot easily ingest oral medication, due to severe nausea and vomiting. In this mini-review, the efficacy and safety of Zavegepant will be compared with those of alternative treatments available for migraines, including oral triptans, intranasal triptans, and other CGRP antagonists currently available in the market. With currently available research, Zavegepant holds superiority over other forms of treatment and can be included in the current treatment guidelines for migraine attacks. However, further research is necessary to effectively assess Zavegepant's long-term efficacy, safety, tolerability, and drug-drug interactions.

Interim Analysis of Long-Term Safety and Tolerability Data of STS101 From the Phase 3 Open-Label ASCEND Study (P13-12.004)

<h3>Objective:</h3> To assess long-term safety and tolerability of STS101 in the acute treatment of migraine attacks. <h3>Background:</h3> The ASCEND study assesses the safety and tolerability of STS101 5.2 mg (dihydroergotamine nasal powder) in the acute treatment of migraine attacks with/without aura over 12 months. STS101 is a novel investigational product for rapid and easy nasal delivery. <h3>Design/Methods:</h3> ASCEND (NCT04406649) was a multi-center, multiple-dose, open-label 12-month study in 344 adults (18–65 years) with migraine. Participants may use up to 2 doses of STS101 within 24 hours to treat a migraine attack with up to 12 doses/month for 12 months. This interim safety analysis included those participants who exclusively used the STS101, incorporating the second-generation nasal delivery device planned for commercialization. Safety evaluations included treatment-emergent adverse event (TEAE) assessments, physical exams, vital signs, nasal exams, electrocardiograms, and lab tests. <h3>Results:</h3> This population included 344 adults who treated 5,571 migraine attacks with a total of 6,918 doses of STS101; the population mean±SD age was 40.4±10.9 years, 85.8% female, and 87.5% Caucasian. A total of 157 (45.6%) subjects reported TEAEs for 763 (13.7%) attacks, and 14 (4.1%) discontinued the study due to TEAEs. Most frequently reported (≥3% of subjects) related TEAEs were nasal discomfort (38 [11.0%] subjects; 338 [6.1%] attacks), dysgeusia (26 [7.6%]; 154 [2.8%]), and nasal congestion (14 [4.4%]; 198 [3.6%]); of these events, 82.7%, 16.0%, and 1.2% were mild, moderate, and severe, respectively. One serious TEAE (NSTEMI) was reported in a subject who should have been excluded from the study due to prior myocardial infarction and other conditions disqualifying for study participation. Physical exams, vital signs, nasal exams, electrocardiograms, and lab tests did not show any clinically relevant findings. <h3>Conclusions:</h3> The results of the ASCEND study show that STS101 was well tolerated when used long-term for the acute treatment of migraine attacks. <b>Disclosure:</b> Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alphasights. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aruene. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atheneum. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Becker Pharmaceutical Consulting. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biodelivery Scences International. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cleaview Healhcare Partners. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CoolTech. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CRG. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Decision Resources. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Defined Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DRG. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ExpertConnect. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FCB Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fenix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Advances. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Science Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HMP Communications. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for InteractiveForums. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Keyquest. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Krog and Partners. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for M3 Global Research. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Magnolia Innovation. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MJH Holdings. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurolief. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for P Value Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pain Insights Inc. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Palion Medical. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pulmatrix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Putnam Associates. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SAI MedPartners. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Satsuma. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Slingshot Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spherix Global Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Strategy Inc. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for System Medical Comm. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taylor and Francis. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tremeau. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Trinity Partners. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UnityHA. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for XOC. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zosano. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Click Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miravo. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurofront Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rehaler. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Synapse Medical Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ClickTherapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CoolTech. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Miravo Healthcare. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pulmatrix. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. The institution of Dr. Tepper has received research support from Abbvie. The institution of Dr. Tepper has received research support from Amgen. The institution of Dr. Tepper has received research support from Eli Lilly. The institution of Dr. Tepper has received research support from Lundbeck. The institution of Dr. Tepper has received research support from Neurolief. The institution of Dr. Tepper has received research support from Novartis. The institution of Dr. Tepper has received research support from Satsuma. The institution of Dr. Tepper has received research support from Zosano. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Writer with American Headache Society. An immediate family member of Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Writer with American Headache Society. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with AAN. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Diamond Headache Clinic. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Forefront Collaborative. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Medical Learning Institute Peerview. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Medical Education Speakers Network. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Miller Medical Communications. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with North American Center for CME. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Physicians’ Education Resource. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with WebMD/Medscape. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with American Headache Society. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Annenberg Center for Health Sciences. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Catamount Medical Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Haymarket Medical Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Migraine Association of Ireland. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with National Association for Continuing Education. Dr. Tepper has received personal compensation in the range of $0-$499 for serving as a CME speaker with The Ohio State University. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with PlatformQ Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Primed. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Vindico Medical Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with HMP Global. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CMe speaker with Medical Learning Institute Peerview. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Detlef Albrecht has received personal compensation for serving as an employee of Satsuma. Detlef Albrecht has stock in Satsuma.

Efficacy of Celecoxib Oral Solution in Adults With and Without Baseline Nausea: Post Hoc Analysis of Results From Two Randomized, Double-Blind Placebo-Controlled Trials in the Acute Treatment of Migraine (P14-12.009)

<h3>Objective:</h3> To compare the efficacy of celecoxib oral solution 120 mg with placebo in the acute treatment of migraine attacks with and without baseline nausea. <h3>Background:</h3> Celecoxib oral solution (Elyxyb) is a liquid formulation of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drug indicated for the acute treatment of migraine in adults. NSAIDs are thought to exacerbate nausea. <h3>Design/Methods:</h3> Post-hoc analysis of pooled data from 2 randomized, double-blind, placebo-controlled trials; adults treated 1 moderate-severe migraine attack with celecoxib oral solution 120 mg/4.8 mL or placebo. Efficacy endpoints were pain freedom, freedom from most bothersome symptom (MBS), and pain relief at 2 hours postdose. The population was stratified by the presence or absence of nausea at baseline. Regression models compared efficacy in the subgroups (with vs. without baseline nausea) using a treatment-by-nausea interaction. A regression model evaluated treatment-emergent nausea at 2 hours postdose in subjects without baseline nausea. <h3>Results:</h3> Among 214 participants, baseline nausea was similar in the celecoxib oral solution and placebo treatment groups (20.2% vs 19.6%). At 2 hours postdose, celecoxib oral solution 120 mg was superior to placebo for pain freedom in subjects with baseline nausea (22% vs 15%, <i>p</i>&lt;0.001) and without baseline nausea (37% vs 25%, <i>p</i>&lt;0.001); MBS freedom in subjects with baseline nausea (53% vs 40%, <i>p</i>&lt;0.001) and without baseline nausea (59% vs 44%, <i>p</i>&lt;0.001); and pain relief in subjects with baseline nausea (63% vs 51%, <i>p</i>&lt;0.001) and without baseline nausea (74%% vs 60%, <i>p</i>&lt;0.001). Among subjects without baseline nausea, treatment-emergent nausea at 2 hours postdose was more common with placebo than celecoxib oral solution, but the difference was not statistically significant (32.3% vs 23.7%, <i>p</i>=0.065). <h3>Conclusions:</h3> Celecoxib oral solution 120 mg was more effective than placebo for pain freedom, MBS freedom, and pain relief at 2 hours postdose in subjects with or without baseline nausea. Celecoxib oral solution did not cause treatment-emergent nausea. <b>Disclosure:</b> Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aeon. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alphasights. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aruene. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atheneum. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Becker Pharmaceutical Consulting. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biodelivery Scences International. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cleaview Healhcare Partners. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CoolTech. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CRG. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Decision Resources. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Defined Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for DRG. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Eli Lilly. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ExpertConnect. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FCB Health. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fenix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GLG. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint Global. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Advances. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health Science Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for HMP Communications. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Impel. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for InteractiveForums. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Keyquest. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Krog and Partners. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for M3 Global Research. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Magnolia Innovation. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MJH Holdings. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurolief. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for P Value Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pain Insights Inc. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Palion Medical. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pulmatrix. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Putnam Associates. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SAI MedPartners. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Satsuma. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Slingshot Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spherix Global Insights. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Strategy Inc. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for System Medical Comm. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Taylor and Francis. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Theranica. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tremeau. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Trinity Partners. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UnityHA. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for XOC. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zosano. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Click Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Miravo. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurofront Therapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rehaler. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Synapse Medical Communications. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pfizer. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Aeon. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ClickTherapeutics. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CoolTech. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Tepper has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Miravo Healthcare. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pulmatrix. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Satsuma. The institution of Dr. Tepper has received research support from Abbvie. The institution of Dr. Tepper has received research support from Amgen. The institution of Dr. Tepper has received research support from Eli Lilly. The institution of Dr. Tepper has received research support from Lundbeck. The institution of Dr. Tepper has received research support from Neurolief. The institution of Dr. Tepper has received research support from Novartis. The institution of Dr. Tepper has received research support from Satsuma. The institution of Dr. Tepper has received research support from Zosano. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Writer with American Headache Society. An immediate family member of Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a Writer with American Headache Society. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with AAN. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Diamond Headache Clinic. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Forefront Collaborative. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Medical Learning Institute Peerview. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Medical Education Speakers Network. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with Miller Medical Communications. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with North American Center for CME. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME Speaker with Physicians’ Education Resource. Dr. Tepper has received personal compensation in the range of $5,000-$9,999 for serving as a CME Speaker with WebMD/Medscape. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with American Headache Society. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Annenberg Center for Health Sciences. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Catamount Medical Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Haymarket Medical Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Migraine Association of Ireland. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with National Association for Continuing Education. Dr. Tepper has received personal compensation in the range of $0-$499 for serving as a CME speaker with The Ohio State University. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with PlatformQ Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Primed. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with Vindico Medical Education. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CME speaker with HMP Global. Dr. Tepper has received personal compensation in the range of $500-$4,999 for serving as a CMe speaker with Medical Learning Institute Peerview. The institution of Dr. Serrano has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for OPEN Health Group. The institution of Dr. Serrano has received research support from NIH/FDA. Dr. Ko has received personal compensation for serving as an employee of Collegium Pharmaceutical. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care. Mr. Kunkel has received personal compensation for serving as an employee of Collegium Pharmaceutical . Mr. Kunkel has stock in Collegium .

The Safety of Celecoxib as an Acute Treatment for Migraine: A Narrative Review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first-line choice for the acute treatment of migraine attacks for decades; however, the safety of a particular NSAID is related to its treatment dose, duration, and mechanism of action. Although adverse event (AE) risks differ substantially among individual migraine treatments, increased or prolonged exposure to any NSAID elevates risks and severity of AEs. For this narrative review, we conducted a literature search of PubMed until July 2022, focusing on the history, mechanism of action, and treatment guidelines informing the safety and efficacy of celecoxib oral solution for the acute treatment of migraine attacks. Here we discuss the mechanisms of action of nonselective NSAIDs vs. cyclooxygenase-2 (COX-2) inhibitors, and how these mechanisms underlie the AEs associated with these treatments. We review the clinical trials that influenced the regulatory history of NSAIDs, specifically COX-2 inhibitors, the role of traditional and new formulations of NSAIDs including celecoxib oral solution, and special considerations in the acute treatment of migraine attacks. Low-dose formulations of NSAIDs, such as celecoxib oral solution, provide acute migraine analgesia with similar or fewer associated cardiovascular and gastrointestinal events than previous formulations.

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature.

We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines. Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving n = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan. Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself.PROSPERO trial registration: CRD42022308224.

Adherence to the IHS Guidelines for Controlled Trials of Acute Treatment of Migraine Attacks with Parenteral NSAIDs (P1-1.Virtual)

Adherence to the IHS Guidelines for Controlled Trials of Acute Treatment of Migraine Attacks with Parenteral NSAIDs (P1-1.Virtual)

Functionality, satisfaction, and global impression of change with ubrogepant for the acute treatment of migraine in triptan insufficient responders: a post hoc analysis of the ACHIEVE I and ACHIEVE II randomized trials

BackgroundTriptans are the first-line option for the acute treatment of migraine attacks; however, triptans are contraindicated in people with certain underlying cardiovascular risk factors and are associated with inadequate efficacy or poor tolerability in some individuals. Ubrogepant is an oral calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine.MethodsThis post hoc analysis of the phase 3 ACHIEVE trials examined the impact of ubrogepant on the Functional Disability Scale (FDS), satisfaction with medication, and Patient Global Impression of Change (PGIC) in participants who were self-reported triptan insufficient responders (TIRs), defined as those who are unable to take triptans due to contraindications, tolerability issues, or insufficient efficacy. Responder definitions for the FDS, satisfaction measures, and PGIC were based on qualitative interpretation of the respective response options for the pooled ubrogepant 50 mg and placebo groups.ResultsIn the pooled analysis population (n = 1799), 451 (25%) participants were TIRs, with most (80%) reporting insufficient efficacy with triptan use. A significantly higher proportion of TIRs treated with ubrogepant vs placebo reported being able to function normally from 2 to 8 h post dose (P < 0.05). Notably, significance was demonstrated at the time of the primary outcome assessments (2 h post dose), where rates of normal function were 38% for ubrogepant vs 29% for placebo (P = 0.048). A greater proportion of TIRs in the ubrogepant arm vs the placebo arm were satisfied with treatment at 2 (33% vs 21%, P = 0.006) and 24 h (58% vs 28%, P < 0.001) and indicated that their migraine improved at 2 h vs placebo (30% vs 18%, P = 0.006). Results were generally similar in the insufficient efficacy subpopulation of TIRs as in the overall TIRs group. Ubrogepant was safe and well tolerated in TIRs, with no new safety signals identified.ConclusionsIn people with migraine who are TIRs, individuals treated with ubrogepant had favorable 2-h outcomes, as measured by the FDS, satisfaction with medication, and PGIC, compared with placebo.Trial registrationClinicalTrials.gov: NCT02828020 (ACHIEVE I), registered July 11, 2016; NCT02867709 (ACHIEVE II), registered August 16, 2016.

Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM)

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2–8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904.

Efficacy of ketorolac in the treatment of acute migraine attack: A systematic review and meta-analysis.

This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache. We searched databases Cochrane Central Register of Controlled Trials (CENTRAL), Medline, and Google Scholar up to January 2021 and identified randomized controlled trials comparing ketorolac to any other medications in treating patients presenting with migraine headache. Thirteen trials were included in our review, comprising 944 participants. We derived seven comparisons: ketorolac versus phenothiazines, metoclopramide, sumatriptan, dexamethasone, sodium valproate, caffeine, and diclofenac. There were no significant differences in the reduction of pain intensity at 1h under the comparisons between ketorolac and phenothiazines (standard mean difference [SMD]= 0.09, p= 0.74) or metoclopramide (SMD= 0.02, p= 0.95). We also found no difference in the outcome recurrence of headache (ketorolac vs. phenothiazines (risk ratio [RR]=0.98, p= 0.97)], ability to return to work or usual activity (ketorolac vs. metoclopramide [RR= 0.64, p= 0.13]), need for rescue medication (ketorolac vs. phenothiazines [RR= 1.72, p= 0.27], ketorolac vs. metoclopramide [RR 2.20, p= 0.18]), and frequency of adverse effects (ketorolac vs. metoclopramide [RR= 1.07, p= 0.82]). Limited trials suggested that ketorolac offered better pain relief at 1h compared to sumatriptan and dexamethasone; had lesser frequency of adverse effects than phenothiazines; and was superior to sodium valproate in terms of reduction of pain intensity at 1h, need for rescue medication, and sustained headache freedom within 24h. Ketorolac may have similar efficacy to phenothiazines and metoclopramide in treating acute migraine headache. Ketorolac may also offer better pain control than sumatriptan, dexamethasone, and sodium valproate. However, given the lack of evidence due to inadequate number of trials available, future studies are warranted.

Intravenous ibuprofen versus sodium valproate in acute migraine attacks in the emergency department: A randomized clinical trial

ObjectiveSodium valproate and ibuprofen are drugs with known efficacy in the treatment of headache associated with acute migraine attacks. In this study, our aim was to compare the efficacy of these two drugs in the treatment of acute migraine attacks when administered as a single intravenous (IV) dose in the emergency department. Materials and methodThis study was designed as a prospective, randomized controlled, double-blinded study and included patients aged 18 to 65 years who presented to the emergency department with acute headache and met the criteria of ‘migraine without aura’ according to the International Classification of Headache Disorders. The patients were randomized into two groups and given a single dose of 800 mg sodium valproate or 800 mg ibuprofen in 150 mL of normal saline by IV infusion over five minutes. Changes in pain levels were assessed using the Numerical Rating Scale (NRS) for pain over a two-hour period. ResultsNinety-nine patients (49 patients in the sodium valproate group and 50 in the ibuprofen group) completed the trial, and their data were included in the statistical analysis. The mean decrease in the post-treatment delta NRS values was statistically significantly higher in the sodium valproate group than in the ibuprofen group. The mean differences were 1.69 [confidence interval (CI): 1.02–2.37, p<0.001], the mean difference between N0 and N2 was 3.61 (CI: 2.96-4.26, p < 0.001), the mean difference between N0 and N3 was 4.11 (CI: 3.54-4.67, p < 0.001), and the mean difference between N0 and N4 was 3.92 (CI: 3.67-4.46, p < 0.001). The number of patients who achieved the primary endpoint of pain relief was significantly higher in the sodium valproate group than in the ibuprofen group (p < 0.001). According to the Kaplan-Meier analysis showing the rates of reaching the targeted endpoint, there was a significant difference in the efficacy of the two-treatment group (χ2 = 79.98, CI: 80.35-99.65; p = 0.000).

CGRP-targeted drugs for migraine: still many uncertainties

The discovery by Goadsby and colleagues 1 Goadsby PJ Edvinsson L Ekman R Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurol. 1988; 23: 193-196 Google Scholar that calcitonin-gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine was the most important advance in migraine research in the past 35 years. The mechanism of CGRP in the generation of migraine attacks led to the development of oral gepants for the treatment of acute migraine attacks and the prevention of migraine; monoclonal antibodies against CGRP or the CGRP receptor were developed for migraine prophylaxis. These new compounds have shown efficacy in large placebo-controlled trials. 2 VanderPluym JH Halker Singh RB Urtecho M et al. Acute treatments for episodic migraine in adults: a systematic review and meta-analysis. JAMA. 2021; 325: 2357-2369 Google Scholar , 3 Ray JC Kapoor M Stark RJ et al. Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects. J Neurol Neurosurg Psychiatry. 2021; 92: 1325-1334 Google Scholar Particularly noteworthy is the good tolerability of these new drugs. Tolerability is important in migraine prophylaxis; the main disadvantage of traditional migraine prophylactic drugs was the high prevalence of adverse reactions, which resulted in poor compliance. Oral medication for acute therapy or prophylaxis also has the disadvantage that it is not uncommon for patients to forget to take the tablets. This problem is avoided by subcutaneous or intravenous administration of monoclonal antibodies against CGRP or its receptor. Calcitonin gene-related peptide-targeting drugs for migraine: how pharmacology might inform treatment decisionsMigraine is the second most disabling disorder across all age groups worldwide. Since 2018, two classes of drugs that inhibit the actions of calcitonin gene-related peptide (CGRP), which is implicated in migraine pathophysiology, have become available: gepants (CGRP receptor antagonists) and monoclonal antibodies directed against CGRP or its receptor. Despite phase 3 clinical trials and some real world evidence, knowledge of the pharmacology and related clinical effects of these drugs is low, and trial data are not necessarily generalisable to all populations. Full-Text PDF

Monthly migraine days, tablet utilization, and quality of life associated with Rimegepant \u2013 post hoc results from an open label safety study (BHV3000\u2013201)

BackgroundThe objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks.MethodsEligible subjects were adults with ≥1 year history of migraine and ≥ 6 MMD at baseline, who used rimegepant 75 mg up to once daily PRN (at their discretion) for up to 52-weeks in an open-label safety study (BHV3000–201; NCT03266588). Mean MMD were calculated at each 4-week period, along with mean monthly tablets taken. Migraine-specific quality of life (MSQv2) data were mapped to EQ-5D utilities and used to characterize HRQoL over time. A published network meta-analysis was used to characterize pain hours as well as time periods spent migraine free.ResultsOne thousand forty four subjects were included in this post-hoc analysis. Overall mean MMD were 10.9 at baseline and decreased to 8.9 by week 52. Tablet use remained stable over the follow-up period. A total of 0.08 incremental QALYs were associated with rimegepant use.ConclusionFor subjects with 6 or more MMD, acute treatment of migraine attacks with rimegepant 75 mg on a PRN basis over one-year of follow-up was found to be associated with reduced MMD frequency without an increase in monthly tablet utilization, and improved HRQoL. There was no evidence of medication-related increases in MMDs when rimegepant 75 mg was used as needed for the acute treatment of migraine over 52-weeks.Trial registrationClinicalTrials.gov identifier NCT03266588.

Rimegepant 75 mg for acute treatment of migraine is associated with significant reduction in monthly migraine days: Results from a long-term, open-label study

Background:Rimegepant, a small molecule oral calcitonin gene-related peptide (CGRP) receptor antagonist, is approved for the acute and preventive treatment of migraine. We hypothesized that intermittent CGRP receptor blockade with rimegepant 75 mg acute treatment as needed (PRN) might result in reductions in monthly migraine days (MMD) over time, and was evaluated as the study objective.Methods:This was a post-hoc analysis of adults with ≥6 MMD at baseline who self-administered rimegepant 75 mg orally PRN for acute treatment of migraine up to 52-weeks in an open-label safety study (BHV3000-201; NCT03266588). Outcome measures (defined as median time to) and response rates (defined as proportion of patients reporting) were captured for ≥30% and ≥50% reduction of baseline MMD.Results:1044 participants with ≥6 MMD at baseline were analyzed. Median time to ≥30% reduction in MMD was 12 weeks (IQR; 4–40 weeks); median time to ≥50% reduction was 32 weeks (IQR; 12-NR weeks). Reduction in MMD was observed over time regardless of baseline migraine frequency, however higher baseline MMD were associated with a longer time to achieving ≥30% or ≥50% MMD reduction.Conclusion:In participants presenting with ≥6 MMD, PRN acute treatment of migraine attacks over 52-weeks with oral rimegepant 75 mg was observed to confer reductions in migraine frequency.Trial registration:NCT03266588

Parenteral NSAIDs for acute treatment of migraine: Adherence to the IHS guidelines for controlled trials

Background: Parenteral non-steroidal anti-inflammatory drugs (NSAIDs) are important alternatives to oral NSAIDs, especially in patients with severe migraine who have emesis or gastroparesis. With increasing research on using parenteral NSAIDs for acute migraine, it is critical to examine the quality of these studies. Our goal was to assess the adherence of these trials to the International Headache Society (IHS) controlled trial guidelines for acute treatment of migraine. Methods: We queried PubMed for clinical trials investigating parenteral NSAIDs for acute treatment of migraine in adult patients. We developed a 14-point scoring system based on the essential components of the IHS guidelines. To date, four versions of the IHS’s Guidelines for controlled trials of acute treatment of migraine attacks have been published. Each trial was evaluated with the appropriate edition of the guidelines. Results: We identified 216 studies and assessed 27 eligible clinical trials. The mean score was 6.7 ± 2.1 (2–11). Most trials followed the IHS migraine diagnosis criteria (85.2%), but only six (22.2%) selected patients based on the recommended headache frequency. Most trials were randomized (88.8%), but fewer were double-blinded (74.1%) or placebo-controlled (11.1%). Almost every trial clearly explained the pain scale (96.3%), and three-quarters (77.8%) assessed headache-associated symptoms. However, no trial utilized the recommended primary endpoint: pain-freedom at 2-hours. Conclusions: Most clinical trials on parenteral NSAIDs for acute migraine did not fully adhere to the IHS recommendations. Future studies should pay special attention to the IHS guideline to improve the quality of clinical trials for the acute treatment of migraine.

Efficacy of Greater Occipital Nerve and Supraorbital Nerve Blockade in The Treatment of Acute Migraine Attack

Objective: Migraine is the most common neurological disorder among primary headaches that can cause loss of quality of life. Medical agents are generally used for the treatment and prophylaxis of acute migraine attack. However, the effectiveness of pericranial nerve blocks in the treatment and prophylaxis of acute attacks has been experienced for many years. In this study, we investigated the effectiveness of bilateral greater occipital nerve (GON) and supraorbital nerve (SON) blockade in terminating acute migraine attacks that did not improve with medical treatment.&#x0D; Material and Method: In this retrospective study, 191 patients with acute migraine attacks resistant to medical treatment were evaluated. First GON block was applied to all patients, SON block was applied to patients whose visual analog scale (VAS) did not fall below ‘5’ at the fifth minute after GON block. The zero, fifth and 30th mi-nute VAS results were evaluated.&#x0D; Results: 76.96 % of the patients were women. Subraorbital nerve blockade (22.51%) was applied in addition to those with a VAS value above 5 at the 5th minute after bilateral greater occipital nerve blockade. Pericranial nerve blockade including bilateral GON and SON blockade improved the VAS level in 97.4% of our cases (mean VAS; fifth min: 1.3769±1.9746, 30th min: 0.3979±1.3013).&#x0D; Conclusion: The results of our study show that pericranial nerve blockages are beneficial in the treatment of acute migraine attacks

Geographic variation in the use of triptans and opioids for the acute treatment of migraine attacks.

To assess the geographic variations in triptan and opioid prescribing patterns for patients with migraine. Numerous guidelines recommend triptans as the standard of care for migraine attacks, yet opioids are still widely used for migraine treatment. Variation in the use of opioids and triptans for the treatment of migraine by geographic location is not well known. Using a US claims database, we conducted a retrospective cohort study of adults diagnosed with migraine between 2016 and 2018. We used a 12-month follow-up period to assess triptan and opioid utilization, stratified by the nine Census Bureau-designated divisions. To examine the geographic factors that affect triptan and opioid use among patients, we conducted two sets of multivariable analyses. First, we analyzed the odds of a patient being a triptan or opioid user in the follow-up period, defined as ≥1 triptan or opioid claim. We then analyzed the medication use rate among triptan or opioid users. Overall, we had a final study population of 113,921 patients. In the follow-up period, 52.9% (60,247/113,921) [range: 48.0%-56.3%] of patients were triptan users and 41.0% (46,708/113,921) [range: 28.9%-48.4%] of patients were opioid users with significant differences across census divisions (p<0.001). Triptan users had a mean (SD) of 4.8 (4.7) triptan claims annually with no significant differences across divisions (p=0.188). Opioid users had a mean (SD) of 5.4 (6.8) opioid claims annually with significant differences across divisions (p<0.001). The observed variation in opioid use stemmed from the proportion of patients using opioids in each region and not from the number of opioid prescriptions per user. There was a significant geographic variation in the use of opioids and to a lesser degree the use of triptans. The widespread use of opioids and the large variation in use other than triptans as the standard of care suggest that improvements could be made in the acute treatment of migraine attacks.