www.MigraineTreatmentReport.com
https://www.prnewswire.com/news-releases/theranica-reports-positive-study-results-of-nerivio-for-chronic-migraine-patients-301094164.html
Theranica Reports Positive Study Results of Nerivio® for Chronic Migraine Patients
New Peer-Reviewed Article Publishes Results of Clinical Study Testing Efficacy of Remote Electrical Neuromodulation in Acute Treatment of Migraine in Chronic Migraine Patients
https://journals.lww.com/clinicalneuropharm/Abstract/2020/07000/The_Efficacy_and_Safety_of_DFN_15_for_the.3.aspx
https://www.ncbi.nlm.nih.gov/pubmed/32658036?dopt=Abstract
The Efficacy and Safety of DFN-15 for the Treatment of Migraine: A Meta-Analysis of Randomized Controlled Studies.
Clin Neuropharmacol. 2020 Jul/Aug;43(4):107-111
Authors: Deng Y, Chen Y, Peng Z, Yang H
Abstract
OBJECTIVES: The efficacy of DFN-15 for pain control of migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of DFN-15 versus placebo on pain control in migraine patients.
PATIENTS AND METHODS: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through November 2019 for randomized controlled trials assessing the effect of DFN-15 versus placebo on pain control in migraine patients. This meta-analysis is performed using the random-effects model.
RESULTS: Three randomized controlled trials are included in the meta-analysis. Overall, compared with the control group in migraine patients, lasmiditan treatment shows a positive impact on pain freedom at 2 hours (risk ratio [RR], 1.96; 95% confidence interval, 1.61-2.40; P < 0.00001), headache response at 2 hours (RR, 1.40; 95% CI, 1.25-1.57; P < 0.00001), and pain freedom at 24 hours (RR, 1.87; 95% CI, 1.33-2.62; P = 0.0003), but has no obvious influence or no substantial impact on no or mild disability level (RR, 1.21; 95% CI, 0.97-1.52; P = 0.09) or nausea (RR, 2.42; 95% CI, 0.53-11.01; P = 0.25). In addition, lasmiditan seems to result in the increase in dizziness (RR, 7.33; 95% CI, 1.83-29.30; P = 0.005) and paresthesia (RR, 5.17; 95% CI, 2.08-12.86; P = 0.0004). CONCLUSIONS: DFN-15 treatment may be effective and safe for pain control in migraine patients. PMID: 32658036 [PubMed - as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04464707
https://clinicaltrials.gov/ct2/show/NCT04464707?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Interventions : Drug: Fremanezumab; Drug: Placebo
Sponsor : Teva Branded Pharmaceutical Products R&D, Inc.
Not yet recruiting
A Study to Test if Fremanezumab is Effective in Preventing Chronic Migraine in Patients 6 to 17 Years of Age
NCT04464707
Thu, 09 Jul 2020 12:00:00 EDT
Last Update Posted: 07/09/20 08:37AM
https://www.cureus.com/articles/33683-therapeutic-implications-of-altered-energy-metabolism-in-migraine-a-state-of-the-art-review
https://www.ncbi.nlm.nih.gov/pubmed/32670707?dopt=Abstract
Related Articles
Therapeutic Implications of Altered Energy Metabolism in Migraine: A State-of-the-Art Review.
Cureus. 2020 Jun 12;12(6):e8571
Authors: Hassan SA, Farooque U, Choudhry AS, Pillai B, Sheikh FN
Abstract
Currently, the management strategies aimed at the resolution of migraine are pharmacological. Most of these therapies are known to alter the serotonin balance of the brain. Furthermore, therapies blocking the calcitonin gene-related peptide (CGRP) have also proven to be quite effective in their treatments. However, apart from being expensive, these therapies do not influence premonitory and aura symptoms. This suggests an incomplete approach and an inadequate understanding of the migraine pathophysiology. Recent metabolic studies have indicated that migraine should be considered as an adaptive response to the mismatch between the cerebral energy reserves and expenditure. Therefore, understanding the underlying metabolism helps derive possible novel therapeutic modalities for migraines. In this review, we highlight the underlying metabolic abnormalities found in migraine patients. This will form the basis of our evidence-based discussion on metabolic therapeutic options for migraines.
PMID: 32670707 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT04384367?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Interventions : Drug: Rizatriptan 10 mg + Naproxen 550mg; Drug: Maxalt 10Mg Tablet; Drug: Flanax 550mg; Drug: Placebo oral tablet
Sponsor : Eurofarma Laboratorios S.A.
Not yet recruiting
Efficacy and Safety of Rizatriptan-Naproxen (10/550 mg) in the Acute Treatment of Migraine
NCT04384367
Tue, 12 May 2020 12:00:00 EDT
Last Update Posted: 05/12/20 06:48AM
Celecoxib Oral Solution Approved for Acute Migraine Treatment
Celecoxib Oral Solution Approved for Acute Migraine Treatment
https://www.ncbi.nlm.nih.gov/pubmed/32384032?dopt=Abstract
http://www.eurekaselect.com/181777/article
Current Status at Drug Delivery Approaches and Assay of Anti-Migraine Drugs.
Curr Drug Deliv. 2020 May 07;:
Authors: Esim O, Savaser A, Karadurmus L, Bakirhan NK, Ozkan SA, Ozkan Y
Abstract
Migraine is a chronic, painful, neurological disorder that affects approximately 15% of the population worldwide. It is a form of neurovascular headache: a disorder in which neural events result in the dilation of blood vessels that, in turn, results in pain and further nerve activation. The pathogenesis of migraine was not completely understood but it is thought that both central and peripheral stimulations can play a role in migraine. Experimental pharmacological evidence suggests that some drugs can have actions at migraine treatment and oral drug delivery is the first choice for these drugs. However, the oral absorption of many drugs is delayed during migraine attacks. Therefore, there may be an advantage to other drug delivery routes such as parenteral and intranasal. Moreover, nanoparticles can be used for improved drug delivery of anti-migraine agents as they can protect the encapsulated drug from biological and/or chemical degradation, and extracellular transport by P-gp efflux proteins. Various analytical studies have been performed to sensitive and selective assays of antimigraine drugs from commercial and real samples. The single or combination with other drugs of anti-migraines can be easily detected by several analytical methods such as ultraviolet spectrometry, visible spectrometry, high performance liquid chromatography, liquid chromatography- mass spectrometry, high performance thin layer chromatography. This review focuses on the status of anti-migraine drug delivery technologies and possible routes for drug delivery. Moreover, it will present their analytical assays with different methods.
PMID: 32384032 [PubMed – as supplied by publisher]
https://www.businesswire.com/news/home/20200506005819/en/Dr.-Reddys-Laboratories-Received-Approval-NDA-ELYXYB%E2%84%A2
Dr. Reddy’s Laboratories Received Approval for Their NDA, ELYXYB™ (celecoxib oral solution) 25 mg/mL, in the U.S.
https://journals.lww.com/aenjournal/FullText/2020/04000/Ketamine_for_Migraine_in_the_Emergency_Department.4.aspx
https://www.ncbi.nlm.nih.gov/pubmed/32358422?dopt=Abstract
Related Articles
Ketamine for Migraine in the Emergency Department.
Adv Emerg Nurs J. 2020 Apr/Jun;42(2):96-102
Authors: Bilhimer MH, Groth ME, Holmes AK
Abstract
Ketamine is utilized often in the emergency department (ED) for rapid sequence intubation, procedural sedation, and acute pain management. The treatment of migraine headache in the ED varies widely and is dependent on several factors including migraine cause, previous successful abortive methods, and provider preference. Several medications are currently employed to treat acute migraine including nonsteroidal anti-inflammatory drugs, triptans, antihistamines, prochlorperazine, and corticosteroids, among others. Interest in ketamine as an abortive agent to treat migraine has increased as evidenced by recent studies evaluating its use in the ED. This review examines the data regarding the use of ketamine to treat migraine headache. The concept of treating migraine headache with ketamine has been studied for more than 20 years. Early studies conducted primarily in the outpatient setting evaluated ketamine through multiple routes of administration and differing migraine causes with varying results. These early data seem to suggest that ketamine provides relief from headache severity but provides little information regarding the optimal dose and route of administration. Recent active comparator and placebo-controlled trials in the ED utilizing subdissociative doses of ketamine (0.2-0.3 mg/kg intravenously) show conflicting results. To confound the decision regarding its use further, ED providers encounter differing recommendations regarding its place in therapy. Current data suggest that ketamine may provide pain relief to patients with migraine headache. Although there may be a role for ketamine in certain cases after more robust evidence becomes available, currently it is premature to incorporate ketamine into routine use. Several questions remain to be answered including its overall efficacy, place in therapy, dosage, and risk of undesirable side effects.
PMID: 32358422 [PubMed – as supplied by publisher]
https://www.ajmc.com/newsroom/novel-therapy-may-help-reduce-acute-migraine-medication-use
Novel Therapy May Help Reduce Acute Migraine Medication Use
remote electrical neuromodulation (REN)
https://clinicaltrials.gov/ct2/show/NCT04360044?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Conditions : Migraine; Cannabis; THC; CBD
Interventions : Drug: THC ~4%; Drug: CBD ~6%; Drug: THC ~4% and CBD ~6%; Drug: Sham Cannabis
Sponsors : University of California, San Diego; Migraine Research Foundation
Not yet recruiting
Cannabis for Acute Migraine: a Randomized, Double-blind, Placebo-controlled, Crossover Trial
NCT04360044
Fri, 24 Apr 2020 12:00:00 EDT
Last Update Posted: 04/24/20 07:26AM
https://pubmed.ncbi.nlm.nih.gov/32336482/?dopt=Abstract
https://www.brainanddevelopment.com/article/S0387-7604(20)30121-2/pdf
https://www.brainanddevelopment.com/article/S0387-7604(20)30121-2/pdf
https://www.ncbi.nlm.nih.gov/pubmed/32336482?dopt=Abstract
Related Articles
Effectiveness of low-dose riboflavin as a prophylactic agent in pediatric migraine.
Brain Dev. 2020 Apr 23;:
Authors: Yamanaka G, Suzuki S, Takeshita M, Go S, Morishita N, Takamatsu T, Daida A, Morichi S, Ishida Y, Oana S, Nara S, Shimura M, Nishimata S, Kawashima H
Abstract
BACKGROUND: Riboflavin may prevent migraine episodes; however, there is limited evidence of its effectiveness in pediatric populations. This study investigated the effectiveness of riboflavin and clinical predictors of response in children with migraines.
METHODS: We retrospectively reviewed data from 68 Japanese children with migraines, of whom 52 also exhibited another type of headache. Patients received 10 or 40 mg/day of riboflavin. We evaluated the average migraine frequency per month as a baseline and after 3 months of riboflavin therapy to determine the effectiveness and clinical predictors of response.
RESULTS: The frequency of migraine episodes was significantly lower at 3 months than at baseline (median, [interquartile range], 5.2 (3-7) vs. 4.0 (2-5); p < 0.01). Twenty-five patients (36.7%) showed 50% or greater reduction in episode frequency (responders), while 18 (26.5%) showed a 25%-50% reduction. We compared responders (n = 25) and non-responders (n = 43) and found no significant differences in sex, familial history, riboflavin dose, migraine type (i.e., presence or absence of aura), age at headache onset, or age at consultation. However, non-responders were more likely to have co-morbid non-migraine headaches (odds ratio, 4.11; 95% confidence interval [CI], 1.27-13.33; p = 0.02); this variable was also significant in a multivariate analysis (adjusted odds ratio, 3.8; 95% CI, 1.16-12.6; p = 0.03). Of the co-morbid headache types, only tension headaches were significant (odds ratio, 0.176; 95% CI, 0.04-0.73; p = 0.013). No adverse effects of riboflavin were identified. CONCLUSIONS: Low-dose riboflavin is safe and modestly effective for migraines in children. It may be especially beneficial for children without other co-morbid headache types. PMID: 32336482 [PubMed - as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT04355117?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Intervention : Drug: Each subject will subcutaneously self-administer TEV 48125 at 225 mg/1.5 mL (150 mg/mL) once monthly for a total of 2 doses.
Sponsor : Otsuka Pharmaceutical Co., Ltd.
Recruiting
A Safety Evaluation Trial of TEV-48125 Self-administered in Migraine Patients
NCT04355117
Tue, 21 Apr 2020 12:00:00 EDT
Last Update Posted: 04/21/20 06:59AM
https://www.healio.com/primary-care/pain-management/news/online/%7Be367b2f4-7ddc-48fa-93f3-0ccaa5f4738d%7D/axs-07-effective-against-migraine-pain-in-phase-3-intercept-trial
AXS-07 effective against migraine pain in phase 3 INTERCEPT trial
https://finance.yahoo.com/news/catalent-partners-biohaven-fast-dissolve-130000630.html
https://www.biospace.com/article/lundbeck-s-vyepti-is-greenlit-for-the-preventative-treatment-of-migraine/
Lundbeck’s Vyepti Wins Approval for Preventative Treatment of Migraines
https://abcnews.go.com/Health/migraine-medication-green-light/story?id=69000737
New migraine medication given the green light: Reyvow is a new prescription medication that was recently approved by the DEA
https://www.biospace.com/article/releases/lilly-s-reyvow-lasmiditan-c-v-the-first-and-only-medicine-in-a-new-class-of-acute-treatment-for-migraine-ditan-now-available-for-prescription/
Lilly’s REYVOW™ (lasmiditan) C-V, the First and Only Medicine in a New Class of Acute Treatment for Migraine (ditan), Now Available for Prescription
https://n.neurology.org/content/early/2020/01/13/WNL.0000000000008944
Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy
Kathleen Mullin, David Kudrow, Robert Croop, Meghan Lovegren, Charles M. Conway, Vladimir Coric, Richard B. Lipton
First published January 13, 2020, DOI: https://doi.org/10.1212/WNL.0000000000008944
https://www.forbes.com/sites/danadovey/2019/12/24/new-migraine-treatment-relieves-pain-in-as-little-as-4-hours/#294d3eab5b4c
New Migraine Treatment Relieves Pain In As Little As 2 Hours
https://www.upi.com/Health_News/2019/12/23/FDA-approves-new-drug-to-treat-migraines/8191577137389/
FDA approves new drug to treat migraines
https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-019-1066-0
Mechanisms of migraine as a chronic evolutive condition
https://www.health.harvard.edu/blog/lasmiditan-new-first-in-class-drug-treatment-approved-for-migraine-2019121218416
Lasmiditan: New first-in-class drug treatment approved for migraine
https://www.reuters.com/article/us-biohaven-pharma-study/biohaven-pharma-says-treatment-for-acute-migraine-succeeds-in-study-idUSKBN1YL1GM
Biohaven Pharma says treatment for acute migraine succeeds in study
https://pittsburgh.cbslocal.com/2019/12/12/new-migraine-devices-treatment/
New Devices And Advancements Being Used To Fight Migraines
https://www.sciencedirect.com/science/article/abs/pii/S0306452219308024?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/31785356?dopt=Abstract
The influence of metoclopramide on trigeminovascular nociception: possible anti-migraine mechanism of action.
Neuroscience. 2019 Nov 27;:
Authors: Dolgorukova A, Osipchuk AV, Murzina AA, Sokolov AY
Abstract
Metoclopramide widely used as an abortive migraine therapy due to the advantage of having not only antiemetic, but also analgesic properties. Despite the proven clinical efficacy of metoclopramide in acute migraine, the mechanism of its anti-cephalalgic action has not been entirely elucidated. Taking into account the key role of the trigeminovascular system activation in migraine pathophysiology, we aimed to investigate metoclopramide effects on the excitability of central trigeminovascular neurons and neurogenic dural vasodilation using valid electrophysiological and neurovascular models of trigeminovascular nociception. Extracellular recordings of the activity of second-order dura-sensitive neurons were made in the trigeminocervical complex (TCC) of 16 anaesthetised rats. Cumulative metoclopramide infusion (three steps in 30 min intervals, 5 mg/kg i.v. per step, n=8) significantly and dose-dependently suppressed both ongoing firing of the TCC neurons and their responses to dural electrical stimulation, maximally to 30%[0%-49%] (median[Q1-Q3]) and 4%[0%- 30%] of the initial level, respectively (both p=0.001, compared to saline (n=8)). By contrast, the neurogenic dural vasodilation studied in a separate group of 12 rats was not significantly affected by cumulative infusion of metoclopramide (5 mg/kg i.v. per step, n=6) compared to both baseline values and the vehicle group (n=6) (all p>0.05). These results provide evidence that metoclopramide is unable to affect the peripheral response to trigeminovascular activation, but it does suppress the central response, which is highly predictive of anti-migraine action. Thus, here we show the neurophysiological mechanism underlying the therapeutic efficacy of metoclopramide in migraine.
PMID: 31785356 [PubMed – as supplied by publisher]
https://www.cnn.com/2019/11/19/health/ubrogepant-migraine-drug-trial/index.html
https://pittsburgh.cbslocal.com/2019/11/19/new-drug-to-fight-migraines-shows-promise/
New drug to fight migraine shows promise
https://clinicaltrials.gov/ct2/show/NCT04161807?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Chronic Migraine
Intervention : Device: Nerivio
Sponsor : Theranica
Recruiting
Efficacy and Safety of Nerivio™, a Remote Electrical Neuromodulation Device, for Acute Treatment of Migraine in People With Chronic Migraine: an Open Label, Single Arm, Multicenter Study
NCT04161807
Wed, 13 Nov 2019 12:00:00 EST
Last Update Posted: 11/13/19 12:03PM
https://www.ncbi.nlm.nih.gov/pubmed/31710104?dopt=Abstract
Rapid Onset of Effect of Galcanezumab for the Prevention of Episodic Migraine: Analysis of the EVOLVE Studies.
Headache. 2019 Nov 11;:
Authors: Detke HC, Millen BA, Zhang Q, Samaan K, Ailani J, Dodick DW, Aurora SK
Abstract
OBJECTIVE: To evaluate onset of effect of galcanezumab in patients with episodic migraine.
BACKGROUND: Galcanezumab is a monoclonal antibody that binds to calcitonin gene-related peptide and is indicated for preventive treatment of migraine.
DESIGN/METHODS: Data on the primary outcome measure were analyzed from 2 previously published double-blind, Phase 3 studies (EVOLVE-1 [N = 858] and EVOLVE-2 [N = 915]) wherein adult patients with episodic migraine were randomized to receive monthly subcutaneous injections of galcanezumab 120 mg (with 240-mg loading dose) or 240 mg or placebo for up to 6 months. Monthly onset of effect was defined as the earliest month at which galcanezumab achieved and subsequently maintained statistical superiority to placebo on the mean change from baseline in the number of monthly migraine headache days (MHDs). If onset occurred in Month 1, weekly onset was evaluated and defined as the earliest week at which galcanezumab statistically separated from placebo and maintained statistical separation for remaining weeks in that month. Day of onset of effect was also analyzed, as were monthly and weekly onset, for occurrence of ≥50% reduction from baseline in number of MHDs.
RESULTS: For both studies, change from baseline in monthly MHDs showed a statistically significant separation of galcanezumab from placebo at Month 1 and each subsequent month (each P < .001). Analysis of the first month for both studies indicated onset of effect in the first week, with galcanezumab-treated patients having significantly higher odds of having fewer MHDs in the first week (odds ratio [95% confidence interval] for EVOLVE-1, 2.71 [2.00, 3.66], and for EVOLVE-2, 2.88 [2.16, 3.86]; both P < .001) and each subsequent week compared with placebo-treated patients (P ≤ .004). Daily analysis showed onset of effect at Day 1 (first day after injection day). Galcanezumab also demonstrated superiority to placebo on occurrence of ≥50% reduction in MHDs starting at Week 1 (percentage of patients with 50% response in galcanezumab group vs placebo group for EVOLVE-1, 54.3% vs 32.4% [P < .001], and for EVOLVE-2, 59.4% vs 38.0% [P < .001]). CONCLUSION: Rapid onset of preventive effect on the first day after injection of galcanezumab was confirmed in both studies of episodic migraine. PMID: 31710104 [PubMed - as supplied by publisher]
https://journals.sagepub.com/doi/abs/10.1177/0333102419888485?journalCode=cepa
https://www.ncbi.nlm.nih.gov/pubmed/31707814?dopt=Abstract
Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial.
Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents.
Cephalalgia. 2019 Nov 10;:333102419888485
Authors: Amanat M, Togha M, Agah E, Ramezani M, Tavasoli AR, Azizi Malamiri R, Fashandaky F, Heidari M, Salehi M, Eshaghi H, Ashrafi MR
Abstract
BACKGROUND: Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents.
METHODS: We carried out a randomized double-blind placebo-controlled trial in the Children’s Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents.
RESULTS: A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation.
CONCLUSION: Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.
PMID: 31707814 [PubMed – as supplied by publisher]
https://www.prnewswire.com/news-releases/american-headache-society-publishes-article-demonstrating-the-promise-of-remote-electrical-neuromodulation-ren-as-first-line-treatment-for-acute-migraine-relief-300954693.html
American Headache Society Publishes Article Demonstrating the Promise of Remote Electrical Neuromodulation (REN) as First-Line Treatment for Acute Migraine Relief
Studies Conducted Using FDA De Novo-Cleared Prescription Migraine Wearable Device, the Nerivio™
https://clinicaltrials.gov/ct2/show/NCT04153409?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Acute Migraine
Interventions : Drug: LAT8881; Drug: Placebo
Sponsor : Lateral Pharma Pty Ltd
Recruiting
A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine
NCT04153409
Wed, 06 Nov 2019 12:00:00 EST
Last Update Posted: 11/06/19 08:27AM
https://link.springer.com/article/10.1007%2Fs12011-019-01931-z
https://www.ncbi.nlm.nih.gov/pubmed/31691193?dopt=Abstract
Related Articles
The Role of Magnesium in Pathophysiology and Migraine Treatment.
Biol Trace Elem Res. 2019 Nov 05;:
Authors: Dolati S, Rikhtegar R, Mehdizadeh A, Yousefi M
Abstract
Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium (Mg) is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Mg is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Mg in serum and cerebrospinal fluid (CSF). Deficits in magnesium have significant role in the pathogenesis of migraine. Mg has been extensively used in migraine prophylaxis and treatment. This review summarizes the role of Mg in migraine pathogenesis and the potential utilizations of Mg in the prevention and treatment of migraine with the emphasis on transdermal magnesium delivery.
PMID: 31691193 [PubMed – as supplied by publisher]
https://headachejournal.onlinelibrary.wiley.com/doi/abs/10.1111/head.13669
Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine
Alan M. Rapoport MD Tamar Lin PhD Stewart J. Tepper MD
First published: 05 November 2019 https://doi.org/10.1111/head.13669
https://www.ncbi.nlm.nih.gov/pubmed/31538885?dopt=Abstract
http://www.eurekaselect.com/175025/article
Integrating Pathophysiology in Migraine: Role of the Gut Microbiome and Melatonin.
Curr Pharm Des. 2019 Sep 20;:
Authors: Anderson G
Abstract
The pathoetiology and pathophysiology of migraine are widely accepted as unknown. The current article overviews the wide array of data associated with the biological underpinnings of migraine and provides a framwork that integrates previously disparate bodies of data. The importance of alterations in stress- and pro-inflammatory cytokine- induced gut dysbiosis, especially butyrate production, is highlighted. This is linked to a decrease in the availability of melatonin, and a relative increase in the N-acetylserotonin/melatonin ratio, which has consequences for the increased glutamatergic excitatory transmission in migraine. It is proposed that suboptimal mitochondria functioning and metabolic regulation drive alterations in astrocytes and satellite glial cells that underpin the vasoregulatory and nociceptive changes in migraine. This provides a framework not only for classical migraine associated factors, such as calcitonin-gene related peptide and serotonin, but also for a developmental pathoetiology of migraine. A number of future research and treatment implications arise, including the clinical utilization of sodium butyrate and melatonin in the management of migraine.
PMID: 31538885 [PubMed – as supplied by publisher]
Interim Trial Results Show Lasmiditan Is Well Tolerated in Migraine Treatment
Interim Trial Results Show Lasmiditan Is Well Tolerated in Migraine Treatment
https://clinicaltrials.gov/ct2/show/NCT04089761?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Acute Migraine
Intervention : Device: Nerivio
Sponsor : Theranica
Not yet recruiting
Safety and Efficacy of Nerivio™ for the Acute Treatment of Migraine in Adolescents
NCT04089761
Fri, 13 Sep 2019 12:00:00 EDT
Last Update Posted: 09/13/19 06:52AM
https://headachejournal.onlinelibrary.wiley.com/doi/abs/10.1111/head.13635
https://www.ncbi.nlm.nih.gov/pubmed/31508812?dopt=Abstract
Trigeminal-Targeted Treatments in Migraine: Is 60% the Magic Number?
Headache. 2019 Sep 11;:
Authors: Barbanti P, Egeo G, Mitsikostas DD
Abstract
Trigeminal-targeted treatments (TTTs), the most specific and selective therapeutic migraine approach to date, are effective in approximately 60% of patients regardless of treatment type or mechanism, at least if used alone. Sixty percent is also the proportion of migraineurs who develop migraine-like episodes following experimental intravenous administration of trigeminal neuropeptides and roughly 60% is the percentage of patients with a unilateral migraine tracing the area of cutaneous distribution of the trigeminal ophthalmic branch. Hence, mechanisms other than the trigeminovascular activation are probably involved in the 40% of migraineurs who do not respond to TTTs. A closer cooperation between clinical and basic neuroscientists is needed to explore migraine models because only a careful appraisal of migraine endophenotypes may help to unravel their underlying multifaceted pathophysiological machinery.
PMID: 31508812 [PubMed – as supplied by publisher]
https://journals.lww.com/md-journal/fulltext/2019/09130/Efficacy_of_metoclopramide_for_the_treatment_of.19.aspx
https://www.ncbi.nlm.nih.gov/pubmed/31517828?dopt=Abstract
Efficacy of metoclopramide for the treatment of acute migraine.
Medicine (Baltimore). 2019 Sep;98(37):e17065
Authors: Jiang C, Wang T, Qiu ZG, Chen B, Fang BJ
Abstract
BACKGROUND: In this study, we will assess the efficacy and safety of metoclopramide for the treatment of acute migraine (AM).
METHODS: We will comprehensively search Cochrane Library, PUMBED, EMBASE, Google Scholar, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the inception to July 1, 2019 to identify any eligible studies. Only randomized controlled trials will be considered for inclusion. The study selection, data collection, and management will be completed by two authors independently. The risk of bias will be assessed using Cochrane risk of bias tool. RevMan 5.3 software will be used for statistical analysis.
RESULTS: The primary outcome includes pain intensity, as measured by visual analogue scale or others. The secondary outcomes are success rate, requirement of rescue medicine, quality of life, relapse, and adverse events.
CONCLUSIONS: This study will summarize the latest evidence for the clinical efficacy and safety of metoclopramide for the treatment of AM.
PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019142795.
PMID: 31517828 [PubMed – in process]
https://www.biospace.com/article/releases/teva-to-present-new-analyses-of-fremanezumab-efficacy-and-safety-in-adult-patients-with-difficult-to-treat-migraine-at-19th-congress-of-the-international-headache-society/
Teva to Present New Analyses of Fremanezumab Efficacy and Safety in Adult Patients with Difficult-to-Treat Migraine at 19th Congress of the International Headache Society
The New Era Of Disease Modifying Migraine Drugs (DMMDs)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613428/
https://www.ncbi.nlm.nih.gov/pubmed/31359939?dopt=Abstract
Memantine Ameliorates Migraine Headache.
Ann Indian Acad Neurol. 2019 Jul-Sep;22(3):286-290
Authors: Shanmugam S, Karunaikadal K, Varadarajan S, Krishnan M
Abstract
Background and Objective: A significant number of migraine patients do not find effective and safe treatment to reduce the frequency and severity of their migraine attacks. Hence, a need for newer therapeutic agent exists. In this study, we examined the efficacy and safety of memantine for the treatment of migraine.
Materials and Methods: It was a randomized, placebo-controlled, double-blind study including adult patients with 3-12 migraine headache for the last 6 months conducted in India. Patients received memantine (10 mg/day, once a day) or placebo for the period of 24 weeks after a washout period. Migraine frequency per month, the 50% responder rate, rescue medication use, and adverse events were recorded every 4 weeks.
Results: Among 81 patients screened, 60 were enrolled for the study. Thirty patients received memantine and other 30 received placebo. Data were analyzed for 28 patients in memantine group and 29 patients in placebo group. At the baseline, all the parameters were similar in both groups. By 24 weeks, migraine frequency/4 weeks was memantine group versus placebo; 2.57 (±0.38) versus 5.07 (±0.69), P = 0.003 and rescue medication use was 0.75 (±0.23) versus 3.72 (±0.63) P = 0.0001. The 50% responder rate was 85.7% versus 51.7% (P = 0.005). Only a few mild adverse events were recorded in both the groups. No severe adverse events and death were recorded during the study.
Conclusion: Memantine (10 mg oral, once daily) is effective, well tolerated, and safe for patients with migraine.
PMID: 31359939 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT04068051?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Intervention : Drug: AXS-07
Sponsor : Axsome Therapeutics, Inc.
Recruiting
Open-Label Long-Term Safety Study of AXS-07 for the Acute Treatment of Migraine
NCT04068051
Mon, 26 Aug 2019 12:00:00 EDT
Last Update Posted: 08/28/19 11:26AM
https://clinicaltrials.gov/ct2/show/NCT03874351?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine Disorders
Intervention : Device: non-invasive transcranial direct current stimulation (tDCS)
Sponsors : MJHS Institute for Innovation in Palliative Care; New York Headache Center
Not yet recruiting
A Study of Home-Delivered Neurostimulation for Migraine
NCT03874351
Thu, 14 Mar 2019 12:00:00 EDT
Last Update Posted: 11/18/19 11:23AM
https://www.ncbi.nlm.nih.gov/pubmed/31378003?dopt=Abstract
https://link.springer.com/article/10.1007%2Fs10067-019-04771-3
Gut Microbiota Dysbiosis Enhances Migraine-Like Pain Via TNFα Upregulation.
Mol Neurobiol. 2019 Aug 04;:
Authors: Tang Y, Liu S, Shu H, Yanagisawa L, Tao F
Abstract
Migraine is one of the most disabling neurological diseases worldwide; however, the mechanisms underlying migraine headache are still not fully understood and current therapies for such pain are inadequate. It has been suggested that inflammation and neuroimmune modulation in the gastrointestinal tract could play an important role in the pathogenesis of migraine headache, but how gut microbiomes contribute to migraine headache is unclear. In the present study, we investigated the effect of gut microbiota dysbiosis on migraine-like pain using broad-spectrum antibiotics and germ-free (GF) mice. We observed that antibiotics treatment-prolonged nitroglycerin (NTG)-induced acute migraine-like pain in wild-type (WT) mice and the pain prolongation was completely blocked by genetic deletion of tumor necrosis factor-alpha (TNFα) or intra-spinal trigeminal nucleus caudalis (Sp5C) injection of TNFα receptor antagonist. The antibiotics treatment extended NTG-induced TNFα upregulation in the Sp5C. Probiotics administration significantly inhibited the antibiotics-produced migraine-like pain prolongation. Furthermore, NTG-induced migraine-like pain in GF mice was markedly enhanced compared to that in WT mice and gut colonization with fecal microbiota from WT mice robustly reversed microbiota deprivation-caused pain enhancement. Together, our results suggest that gut microbiota dysbiosis contributes to chronicity of migraine-like pain by upregulating TNFα level in the trigeminal nociceptive system.
PMID: 31378003 [PubMed – as supplied by publisher]
https://www.frontiersin.org/articles/10.3389/fphar.2019.00795/full
https://www.ncbi.nlm.nih.gov/pubmed/31354502?dopt=Abstract
Network Meta-Analysis of Calcitonin Gene-Related Peptide Receptor Antagonists for the Acute Treatment of Migraine.
Front Pharmacol. 2019;10:795
Authors: Xu F, Sun W
Abstract
Background: Research has indicated that calcitonin gene-related peptide (CGRP) receptor antagonists can be effective in the acute treatment of migraine. Six major drugs are included within this category: telcagepant, olcegepant, BI 44370, rimegepant (BMS-927711), MK3207, and ubrogepant. However, no previous studies have performed network meta-analyses to directly compare the effects of these drugs. In the present study, we assessed the therapeutic qualities of these six different drugs to inform further clinical research. Methods: We searched PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register for Controlled Trials for relevant randomized controlled trials (RCTs) published through to October 2018. Two reviewers performed a network meta-analysis of efficacy and toxicity on the basis of odds ratios (ORs). Results: Ten randomized controlled trials involving 8,174 patients were included in our analysis. Olcegepant (OR: 4.09; CI: 1.81, 9.25), ubrogepant (OR: 2.11; CI: 1.10, 4.05), and BI 44370 (OR: 3.36; CI: 2.24, 5.04) were more effective in ensuring pain relief 2 h after treatment than was placebo treatment. BI 44370 was associated with an increased risk of adverse events when compared with placebo treatment (OR: 1.57; CI: 1.32, 1.88). Surface under the cumulative ranking curve analysis revealed that olcegepant was most effective and ubrogepant was associated with the lowest risk of adverse events among the six treatment options. Conclusion: Olcegepant was more effective, and ubrogepant had lower toxicity than the remaining treatments. CGRP antagonists are promising for the acute treatment of migraine, especially among patients who are unable to take triptans.
PMID: 31354502 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT03972124?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Chronic Migraine
Interventions : Drug: CBD 50 mg BID; Drug: CBD 100 mg BID; Drug: Placebo
Sponsor : University of Calgary
Not yet recruiting
Cannabis for the Prophylactic Treatment of Migraine
NCT03972124
Mon, 03 Jun 2019 12:00:00 EDT
Last Update Posted: 06/03/19 07:42AM
https://www.sciencedirect.com/science/article/pii/S0378874118324656?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30853645?dopt=Abstract
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Efficacy of Anise (Pimpinella anisum L.) oil for migraine headache: A pilot randomized placebo-controlled clinical trial.
J Ethnopharmacol. 2019 May 23;236:155-160
Authors: Mosavat SH, Jaberi AR, Sobhani Z, Mosaffa-Jahromi M, Iraji A, Moayedfard A
Abstract
Seyed Hamdollah Mosavat has made substantial contributions in conception, designing, acquisition of data and preformed clinical trial., Amin Moayedfard and Abbas Rahimi Jaberi had contribution in designing and preformed clinical trial. Zahra Sobhani and Maryam Mosaffa-Jahromi designed and prepared drugs of study. Aida Iraji has made drug biochemical assay. Seyed Hamdollah Mosavat had contribution in designing and revised the manuscript critically for important intellectual content and had contribution in designing and analyzing of data. Seyed Hamdollah Mosavat, Amin Moayedfard and Abbas Rahimi Jaberi had contribution in conception and designing and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.
PMID: 30853645 [PubMed – indexed for MEDLINE]
HEALTH NOTES: Jab offers hope to migraine patients
https://www.dailymail.co.uk/health/article-7044479/HEALTH-NOTES-Jab-offers-hope-migraine-patients.html
https://www.ncbi.nlm.nih.gov/pubmed/31102144?dopt=Abstract
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Long-Term Safety and Tolerability of OnabotulinumtoxinA Treatment in Patients with Chronic Migraine: Results of the COMPEL Study.
Drug Saf. 2019 May 17;:
Authors: Winner PK, Blumenfeld AM, Eross EJ, Orejudos AC, Mirjah DL, Adams AM, Brin MF
Abstract
INTRODUCTION: OnabotulinumtoxinA is approved in the USA for the prevention of headache in adults with chronic migraine, a debilitating neurologic disease characterized by headaches occurring on ≥ 15 days per month for > 3 months and including migraine features on ≥ 8 days per month.
OBJECTIVE: The COMPEL Study (NCT01516892), a 108-week, multi-center, open-label study, evaluated the long-term efficacy and safety of onabotulinumtoxinA in adults with chronic migraine. The objective of this subanalysis was to examine the safety and tolerability of onabotulinumtoxinA after each of nine treatment cycles.
METHODS: OnabotulinumtoxinA 155 U was administered every 12 weeks. Safety and tolerability, overall and by treatment cycle, were assessed. Treatment-emergent adverse events reported between successive treatments were attributed to the preceding treatment. The safety population received one or more doses of onabotulinumtoxinA. The primary efficacy outcome was the reduction in headache days at week 108 compared with baseline.
RESULTS: Of 716 patients enrolled, 373 patients (52.1%) completed the study and 343 (47.9%) withdrew; 481 patients (67.2%) received 60 weeks of treatment and 402 (56.1%) received 108 weeks of treatment. In total, 436 (60.9%) patients reported treatment-emergent adverse events; most were mild/moderate in severity. Thirty-two patients (4.5%) discontinued the study after experiencing treatment-emergent adverse events. The incidence of treatment-emergent adverse events typically decreased with repeated onabotulinumtoxinA treatment: first cycle, 24.2%; fourth cycle, 18.4%; ninth cycle, 12.2%. Neck pain (2.7%), eyelid ptosis (1.8%), musculoskeletal stiffness (1.4%), injection-site pain (1.3%), and headache (1.3%) were the most common treatment-emergent adverse events after the first cycle. Seventy-five patients (10.5%) reported serious treatment-emergent adverse events, 13 (1.8%) withdrew. Treatment-related adverse events were reported by 131 patients (18.3%), one was considered serious. OnabotulinumtoxinA significantly reduced headache day frequency by 10.7 (6.4) days per 28-day period (p < 0.0001) at week 108. CONCLUSIONS: OnabotulinumtoxinA treatment was well tolerated over 108 weeks; no new safety signals were identified. The overall incidence of treatment-emergent adverse events and the most common individual events decreased with repeated onabotulinumtoxinA administration. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; NCT01516892. PMID: 31102144 [PubMed - as supplied by publisher]
https://www.clinicalpainadvisor.com/home/topics/migraine-headache/bidirectional-association-between-migraine-and-fibromyalgia/
https://www.kwtx.com/content/news/New-treatment-offers-promise-of-relief-for-migraine-sufferers-509340081.html
https://www.prnewswire.com/news-releases/lilly-to-present-new-data-at-aan-2019-on-emgality-galcanezumab-gnlm-and-lasmiditan-reinforcing-breadth-of-headache-disorders-portfolio-300842385.html
https://www.tandfonline.com/doi/abs/10.1080/14737175.2019.1614742?journalCode=iern20
https://www.ncbi.nlm.nih.gov/pubmed/31043094?dopt=Abstract
Related Articles
Fremanezumab as a preventive treatment for episodic and chronic migraine.
Expert Rev Neurother. 2019 May 01;:
Authors: Bigal ME, Walter S, Rapoport AM
Abstract
INTRODUCTION: The importance of calcitonin gene-related peptide (CGRP) in migraine pathogenesis is well established. Fremanezumab is a humanized IgG2a monoclonal antibody that binds to CGRP. Areas covered: In this paper we review the development of fremanezumab, from early development into approval. The authors focus on the efficacy and safety of fremanezumab in both migraine stages. The authors highlight studies conducted in special populations and focus on unique aspects of its development, as well as on clinical pearls supported by the data. Expert opinion: Fremanezumab was shown to be effective in episodic and chronic migraine, with a monthly and quarterly dose of administration, as monotherapy and add-on therapy. As with other monoclonal antibodies, anti-CGRP onset of action was remarkably quick, and the effect seems to be maintained over time. No overt safety concerns emerged from the clinical studies, although long term surveillance is necessary.
PMID: 31043094 [PubMed – as supplied by publisher]
https://onlinelibrary.wiley.com/doi/abs/10.1111/head.13546
https://www.ncbi.nlm.nih.gov/pubmed/31038740?dopt=Abstract
Zonisamide for Cluster Headache Prophylaxis: A Case Series.
Headache. 2019 Apr 30;:
Authors: Limmer AL, Holland LC, Loftus BD
Abstract
OBJECTIVE: There is very little literature surrounding the prophylactic use of zonisamide in cluster headaches. The study aims to evaluate the effectiveness of zonisamide for prophylaxis of cluster headache in patients with chronic or episodic cluster headache.
BACKGROUND: Both chronic and episodic cluster headaches are debilitating disorders which are often refractory to multiple prophylactic medication regimens. There is a scarcity of research in this area, and current prophylactic options for patients are fairly limited, which is troublesome for affected patients. Zonisamide is an established antiepileptic with a multifactorial mechanism of action which has shown to be useful in other headache disorders such as migraine.
METHODS: Twenty cluster headache patients, both episodic (n = 12; ICHD 3.1.1) and chronic (n = 8; ICHD 3.1.2), who had been or currently were treated with zonisamide, were retrospectively evaluated. Effectiveness of the medication was assessed and identified as headache remission or a reduction in severity or frequency of cluster headache of greater than 50%. Responder status, side effects, and dosage were recorded.
RESULTS: Fourteen (70%) patients responded to zonisamide treatment, while 6 (30%) did not. Recorded effective plasma zonisamide levels ranged from 10.2 to 31.9 μg/mL. Of the 6 non-responders, 2 stopped the medication due to ineffectiveness, while 4 discontinued the medication secondary to intolerable side effects ranging from gastrointestinal upset to malaise. No more serious adverse events occurred. Eight patients total experienced weight loss/anorexia which many perceived as a positive effect; they lost an average of 10.5% of their body weight in the first 6 months of therapy.
CONCLUSIONS: Zonisamide appears to be an effective prophylactic treatment for patients with chronic and episodic cluster headache disorders. Further research in this area is clearly warranted.
PMID: 31038740 [PubMed – as supplied by publisher]
https://www.ncbi.nlm.nih.gov/pubmed/31035923?dopt=Abstract
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The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules.
J Headache Pain. 2019 Apr 29;20(1):43
Authors: Körtési T, Tuka B, Nyári A, Vécsei L, Tajti J
Abstract
BACKGROUND: Migraine is a neurovascular primary headache disorder, which causes significant socioeconomic problems worldwide. The pathomechanism of disease is enigmatic, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Migraine research of recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide 1-38 (PACAP1-38) as potential pathogenic factors and possible therapeutic offensives. The goal of present study was to investigate the simultaneous expression of CGRP and precursor of PACAP1-38 (preproPACAP) in the central region of the TS in a time-dependent manner following TS activation in rats.
METHODS: The right whisker pad of rats was injected with 50 μl Complete Freund’s Adjuvant (CFA) or saline. A mechanical allodynia test was performed with von Frey filaments before and after treatment. Transcardial perfusion of the animals was initiated 24, 48, 72 and 120 h after injection, followed by the dissection of the nucleus trigeminus caudalis (TNC). After preparation, the samples were stored at - 80 °C until further use. The relative optical density of CGRP and preproPACAP was analyzed by Western blot. One-way ANOVA and Kruskal-Wallis followed by Tukey post hoc test were used to evaluate the data. Regression analysis was applied to explore the correlation between neuropeptides expression and hyperalgesia.
RESULTS: Orofacial CFA injection resulted in significant CGRP and preproPACAP release in the TNC 24, 48, 72 and 120 h after the treatment. The level of neuropeptides reached its maximum at 72 h after CFA injection, corresponding to the peak of facial allodynia. Negative, linear correlation was detected between the expression level of neuropeptides and value of mechanonociceptive threshold.
CONCLUSION: This is the first study which suggests that the expression of CGRP and preproPACAP simultaneously increases in the central region of activated TS and it influences the formation of mechanical hyperalgesia. Our results contribute to a better understanding of migraine pathogenesis and thereby to the development of more effective therapeutic approaches.
PMID: 31035923 [PubMed – in process]
https://www.ajmc.com/newsroom/study-calls-for-more-effective-prophylactic-treatments-for-migraine
https://clinicaltrials.gov/ct2/show/NCT03927144?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Episodic Migraine
Interventions : Drug: Erenumab; Drug: Oral Prophylactic
Sponsors : Amgen; Novartis
Not yet recruiting
Study of Sustained Benefit of Erenumab in Adult Episodic Migraine Patients
NCT03927144
Thu, 25 Apr 2019 12:00:00 EDT
Last Update Posted: 04/25/19 07:33AM
https://www.reuters.com/article/us-teva-pharm-ind-cluster-headache/teva-stops-testing-its-migraine-drug-as-cluster-headache-treatment-idUSKCN1RZ1EH
https://www.ncbi.nlm.nih.gov/pubmed/31014235?dopt=Abstract
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Female versus male migraine: an event-related potential study of visual neurocognitive processing.
J Headache Pain. 2019 Apr 23;20(1):38
Authors: Guo Y, Xu S, Nie S, Han M, Zhang Y, Chen J, Hou X, Hong Y, Liu X
Abstract
BACKGROUND: Several studies have suggested cognitive deficits in migraineurs, and sex differences have also been observed in migraine, such as a higher prevalence in females. Nevertheless, little is known about gender-related differences in cognitive processing. In this study, we aimed to investigate the effect of gender on neurocognitive processing in migraineurs.
METHODS: Altogether, 46 migraine patients without aura (23 females; mean age 32.848 years) during the interictal period and 46 age-matched healthy controls (23 females; mean age 32.652 years) were recruited. The emotional characteristics of participants were evaluated, and attentive processing was analyzed via event-related potential examinations using a three-stimulus visual oddball paradigm.
RESULTS: We found that migraineurs suffered from emotional and visual cognitive processing abnormalities compared with healthy controls, including higher levels of anxiety and reduced P3 amplitude. These parameters were modulated by gender in migraine patients, but not in healthy participants. Our findings indicated that female patients seemed to be more anxious and have more severe impairment in attentive processing of visual stimuli than their male counterparts. The gender-related differences in migraineurs were further validated using event-related potential difference waveforms.
CONCLUSIONS: These results suggested that migraine might have an additional influence on females and lead to more dysfunction in their interictal neurocognitive processing. Our findings provide evidence that a gender effect exists in migraineurs, which should be considered when designing experiments and exploring treatment approaches. The gender-related differences and underlying mechanisms deserve further investigation for patients with migraine.
PMID: 31014235 [PubMed – in process]
https://www.ncbi.nlm.nih.gov/pubmed/30992607?dopt=Abstract
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Effect of adjunctive intermittent theta-burst repetitive transcranial magnetic stimulation as a prophylactic treatment in migraine patients: A double-blind sham-controlled study.
Indian J Psychiatry. 2019 Mar-Apr;61(2):139-145
Authors: Sahu AK, Sinha VK, Goyal N
Abstract
Background: The left dorsolateral prefrontal cortex (DLPFC) seems to exert a bilateral control of chronic pain states such as migraine. Repetitive transcranial magnetic stimulation (rTMS) is known to modulate brain excitability, neurotransmitters, and endogenous opioids involved in pathophysiology of migraine.
Aim: This study was designed to assess the efficacy of adjunctive intermittent theta-burst stimulation (iTBS) to the left DLPFC, as a prophylactic treatment in migraine.
Materials and Methods: The study was a double-blind, sham-controlled experiment. Patients with migraine were allotted to active (n = 20) or sham (n = 21) rTMS, respectively. Each patient received ten sessions of iTBS over the left DLPFC. Patients were rated at baseline and at 2, 4, 6, and 12 weeks after receiving the treatment. Scores were obtained from the headache diary and by applying the Migraine Disability Assessment Scale (MIDAS).
Results: There was a significant decrease in frequency, duration, and severity of migraine in the active group than the sham group over the study period. The effect was more pronounced during the initial 2 weeks. The MIDAS score reduced significantly in the active group than the sham group at 12 weeks. There were no significant adverse effects observed during the entire period of study.
Conclusion: Compared to sham stimulation, adjunctive active iTBS over the left DLPFC was safe and effective in reducing the frequency, duration, and severity of migraine headache and in reducing disability associated with the illness.
PMID: 30992607 [PubMed]
https://clinicaltrials.gov/ct2/show/NCT03919045?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Chronic Migraine
Interventions : Drug: Saline injection; Procedure: Placebo
Sponsor : Göteborg University
Not yet recruiting
Saline Injections for Prophylactic Treatment of Chronic Migraine
NCT03919045
Thu, 18 Apr 2019 12:00:00 EDT
Last Update Posted: 04/18/19 08:20AM
https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-019-0974-3
https://www.ncbi.nlm.nih.gov/pubmed/30995909?dopt=Abstract
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Therapeutic novelties in migraine: new drugs, new hope?
J Headache Pain. 2019 Apr 17;20(1):37
Authors: Do TP, Guo S, Ashina M
Abstract
BACKGROUND: In the past decade, migraine research has identified novel drug targets. In this review, we discuss recent data on emerging anti-migraine therapies.
MAIN BODY: The development of ditans, gepants and anti-calcitonin gene-related peptide monoclonal antibodies for the treatment of migraine is one of the greatest advances in the migraine field. Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders. The monoclonal antibodies are migraine specific prophylactic drugs with high responder rates and favorable adverse event profiles. Furthermore, they offer convenient treatment regimens of 4- or 12-week intervals.
CONCLUSION: Collectively, novel migraine therapies represent a major progress in migraine treatment and will undoubtedly transform headache medicine.
PMID: 30995909 [PubMed – in process]
https://www.ncbi.nlm.nih.gov/pubmed/30989485?dopt=Abstract
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Pathophysiological Mechanisms in Migraine and the Identification of New Therapeutic Targets.
CNS Drugs. 2019 Apr 15;:
Authors: Haanes KA, Edvinsson L
Abstract
Migraine is a strongly disabling disease characterized by a unilateral throbbing headache lasting for up to 72 h for each individual attack. There have been many theories on the pathophysiology of migraine throughout the years. Currently, the neurovascular theory dominates, suggesting clear involvement of the trigeminovascular system. The most recent data show that a migraine attack most likely originates in the hypothalamus and activates the trigeminal nucleus caudalis (TNC). Although the mechanisms are unknown, activation of the TNC leads to peripheral release of calcitonin gene-related protein (CGRP), most likely from C-fibers. During the past year monoclonal antibodies against CGRP or the CGRP receptor have emerged as the most promising targets for migraine therapy, and at the same time established the strong involvement of CGRP in the pathophysiology of migraine. The viewpoint presented here focuses further on the activation of the CGRP receptor on the sensory Aδ-fiber, leading to the sensation of pain. The CGRP receptor activates adenylate cyclase, which leads to an increase in cyclic adenosine monophosphate (cAMP). We hypothesize that cAMP activates the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, triggering an action potential sensed as pain. The mechanisms behind migraine pain on a molecular level, particularly their importance to cAMP, provide clues to potential new anti-migraine targets. In this article we focus on the development of targets related to the CGRP system, and further include novel targets such as the pituitary adenylate cyclase-activating peptide (PACAP) system, the serotonin 5-HT1F receptor, purinergic receptors, HCN channels, adenosine triphosphate-sensitive potassium channels (KATP), and the glutaminergic system.
PMID: 30989485 [PubMed – as supplied by publisher]
https://www.dovepress.com/once-monthly-galcanezumab-for-the-prevention-of-migraine-in-adults-an–peer-reviewed-article-TCRM
https://www.ncbi.nlm.nih.gov/pubmed/31043785?dopt=Abstract
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Once-monthly galcanezumab for the prevention of migraine in adults: an evidence-based descriptive review and potential place in therapy.
Ther Clin Risk Manag. 2019;15:557-569
Authors: Lupi C, Guerzoni S, Negro A, Benemei S
Abstract
In the last 15 years relevant efforts have been made to demonstrate that calcitonin gene-related peptide (CGRP) antagonism is a valuable and druggable mechanism for treatment or prevention of migraine. Galcanezumab is one of the antibodies developed and studied to prevent migraine by targeting CGRP. The scope of this review is to report data currently available on galcanezumab. According to available data, galcanezumab is safe and efficacious in preventing migraine in episodic migraine patients, also reducing disability and functional impairment due to the disorder. In September 2018, galcanezumab was approved in the USA for the prevention of migraine in adults. The placement of galcanezumab into the current therapeutic scenario will be a revolution for migraine patients, and probably in a less near future also for patients affected by other primary headaches.
PMID: 31043785 [PubMed]
https://www.mdpi.com/2072-6643/11/4/811
https://www.ncbi.nlm.nih.gov/pubmed/30974836?dopt=Abstract
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Potential Protective Mechanisms of Ketone Bodies in Migraine Prevention.
Nutrients. 2019 Apr 10;11(4):
Authors: Gross EC, Klement RJ, Schoenen J, D’Agostino DP, Fischer D
Abstract
An increasing amount of evidence suggests that migraines are a response to a cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity. The ketogenic diet (KD), a diet mimicking fasting that leads to the elevation of ketone bodies (KBs), is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. KBs are an alternative fuel source for the brain, and are thus likely able to circumvent some of the abnormalities in glucose metabolism and transport found in migraines. Recent research has shown that KBs-D-β-hydroxybutyrate in particular-are more than metabolites. As signalling molecules, they have the potential to positively influence other pathways commonly believed to be part of migraine pathophysiology, namely: mitochondrial functioning, oxidative stress, cerebral excitability, inflammation and the gut microbiome. This review will describe the mechanisms by which the presence of KBs, D-BHB in particular, could influence those migraine pathophysiological mechanisms. To this end, common abnormalities in migraines are summarised with a particular focus on clinical data, including phenotypic, biochemical, genetic and therapeutic studies. Experimental animal data will be discussed to elaborate on the potential therapeutic mechanisms of elevated KBs in migraine pathophysiology, with a particular focus on the actions of D-BHB. In complex diseases such as migraines, a therapy that can target multiple possible pathogenic pathways seems advantageous. Further research is needed to establish whether the absence/restriction of dietary carbohydrates, the presence of KBs, or both, are of primary importance for the migraine protective effects of the KD.
PMID: 30974836 [PubMed – in process]
https://www.mdpi.com/1424-8247/12/2/54
https://www.ncbi.nlm.nih.gov/pubmed/30970581?dopt=Abstract
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TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities.
Pharmaceuticals (Basel). 2019 Apr 09;12(2):
Authors: Benemei S, Dussor G
Abstract
Migraine is the second-most disabling disease worldwide, and the second most common neurological disorder. Attacks can last many hours or days, and consist of multiple symptoms including headache, nausea, vomiting, hypersensitivity to stimuli such as light and sound, and in some cases, an aura is present. Mechanisms contributing to migraine are still poorly understood. However, transient receptor potential (TRP) channels have been repeatedly linked to the disorder, including TRPV1, TRPV4, TRPM8, and TRPA1, based on their activation by pathological stimuli related to attacks, or their modulation by drugs/natural products known to be efficacious for migraine. This review will provide a brief overview of migraine, including current therapeutics and the link to calcitonin gene-related peptide (CGRP), a neuropeptide strongly implicated in migraine pathophysiology. Discussion will then focus on recent developments in preclinical and clinical studies that implicate TRP channels in migraine pathophysiology or in the efficacy of therapeutics. Given the use of onabotulinum toxin A (BoNTA) to treat chronic migraine, and its poorly understood mechanism, this review will also cover possible contributions of TRP channels to BoNTA efficacy. Discussion will conclude with remaining questions that require future work to more fully evaluate TRP channels as novel therapeutic targets for migraine.
PMID: 30970581 [PubMed]
https://www.frontiersin.org/articles/10.3389/fphar.2019.00363/full
https://www.ncbi.nlm.nih.gov/pubmed/31024319?dopt=Abstract
Related Articles
New Trends in Migraine Pharmacology: Targeting Calcitonin Gene-Related Peptide (CGRP) With Monoclonal Antibodies.
Front Pharmacol. 2019;10:363
Authors: Scuteri D, Adornetto A, Rombolà L, Naturale MD, Morrone LA, Bagetta G, Tonin P, Corasaniti MT
Abstract
Migraine is a common neurologic disorder characterized by attacks consisting of unilateral, throbbing headache accompanied by photophobia, phonophobia, and nausea which remarkably reduces the patients’ quality of life. Not migraine-specific non-steroidal anti-inflammatory drugs (NSAIDs) are effective in patients affected by mild episodic migraine whilst in moderate or severe episodic migraine and in chronic migraineurs triptans and preventative therapies are needed. Since these treatments are endowed with serious side effects and have limited effectiveness new pharmacological approaches have been investigated. The demonstrated pivotal role of calcitonin gene-related peptide (CGRP) has fostered the development of CGRP antagonists, unfortunately endowed with liver toxicity, and monoclonal antibodies (mAbs) toward circulating CGRP released during migraine attack or targeting its receptor. Currently, four mAbs, eptinezumab, fremanezumab, galcanezumab for CGRP and erenumab for CGRP canonical receptor, have been studied in clinical trials for episodic and chronic migraine. Apart from the proven effectiveness, these antibodies have resulted well tolerated and could improve the compliance of the patients due to their long half-lives allowing less frequent administrations. This study aims at investigating the still poorly clear pathogenesis of migraine and the potential role of anti-CGRP mAbs in the scenario of prophylaxis of migraine.
PMID: 31024319 [PubMed]
https://www.scotsman.com/news/life-changing-drug-for-chronic-migraine-approved-in-scotland-1-4904022
https://clinicaltrials.gov/ct2/show/NCT03902496?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Interventions : Other: HIT-6 Questionnaire; Device: Avulux Spectacles; Device: Sham Spectacles
Sponsor : Avulux, Inc.
Recruiting
Optical Treatment of Migraines Using the Avulux™ Optical Filter in the Form of Spectacle Lenses.
NCT03902496
Thu, 04 Apr 2019 12:00:00 EDT
Last Update Posted: 04/04/19 07:50AM
https://www.ncbi.nlm.nih.gov/pubmed/30950844?dopt=Abstract
How much do calcitonin gene-related peptide monoclonal antibodies improve the quality of life in migraine? A patient’s perspective.
Curr Opin Neurol. 2019 Apr 03;:
Authors: Torres-Ferrus M, Alpuente A, Pozo-Rosich P
Abstract
PURPOSE OF REVIEW: Migraine is a prevalent and extremely disabling brain disorder, with an impact on the individual, family, workplace and society. This review focuses on describing Calcitonin Gene Related Peptide Monoclonal Antibodies (CGRP-mABs) efficacy on improving the quality of life (QoL) and decreasing the disability and impact of migraine measured with patient related outcomes (PROs), on patients who participated in clinical trials with erenumab, fremanezumab, galcanezumab and eptinezumab. The goal is to better reflect the effect of these preventive migraine treatments in the daily life of our patients.
RECENT FINDINGS: CGRP-mABs have been approved by the Food and Drug Administration’s (FDA) and European Medicines Agency (EMA) as the first migraine specific treatment for the prevention of migraine. In clinical trials, CGRP-mABs have proven to achieve their primary endpoint which is to reduce the number of headache days, and also have shown to have an impact on disability, QoL and workplace productivity.
SUMMARY: CGRP-mABs have an impact on the disability, QoL, workplace productivity and global impression of improvement of migraine, which will translate into changes in the real world of migraine patients who are treated with CGRP-mABs.
PMID: 30950844 [PubMed – as supplied by publisher]
https://clinicaltrials.gov/ct2/show/NCT03900611?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Intervention : Device: peripheral electrical stimulation
Sponsor : Taipei Veterans General Hospital, Taiwan
Not yet recruiting
Peripheral Electrical Stimulation for Migraine Prevention
NCT03900611
Wed, 03 Apr 2019 12:00:00 EDT
Last Update Posted: 04/03/19 07:39AM
https://clinicaltrials.gov/ct2/show/NCT03901482?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Conditions : Migraine; Migraine With Aura; Migraine Without Aura
Interventions : Drug: Dihydroergotamine; Drug: Placebos
Sponsor : Satsuma Pharmaceuticals, Inc.
Not yet recruiting
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate STS101 in the Acute Treatment of Migraine
NCT03901482
Wed, 03 Apr 2019 12:00:00 EDT
Last Update Posted: 04/03/19 07:39AM
https://www.mdmag.com/medical-news/fda-issues-crl-rizaport-acute-migraine-treatment
https://www.tandfonline.com/doi/abs/10.1080/17460441.2019.1598373?journalCode=iedc20
https://www.ncbi.nlm.nih.gov/pubmed/30924698?dopt=Abstract
The discovery and development of inhaled therapeutics for migraine.
Expert Opin Drug Discov. 2019 Mar 29;:1-9
Authors: Vandenbussche N, Goadsby PJ
Abstract
INTRODUCTION: Migraine is a disabling primary headache disorder that requires effective treatments. Inhalation is currently being explored for the delivery of drugs for migraine. Pulmonary-route delivery of drugs shows potential advantages for its use as a treatment, particularly compared the oral route. Areas covered: The authors highlight the current state of the literature and review multiple therapies for migraine-utilizing inhalation as the route of administration. The following therapeutics are discussed: inhaled ergotamine, inhaled dihydroergotamine mesylate (MAP0004), inhaled prochlorperazine, and inhaled loxapine. Coverage is also given to normobaric oxygen, hyperbaric oxygen, and nitrous oxide therapies. Expert opinion: Inhalation of MAP0004 showed promising results in terms of efficacy for acute migraine treatment in phase 3 studies, together with a more favorable tolerability profile compared to parenteral dosing and a better pharmacokinetic profile versus oral or intranasal delivery. In phase 2 trials, inhaled prochlorperazine shows good pharmacokinetics and efficacy, in contrast to inhaled loxapine that did not provide encouraging results in terms of efficacy. The authors see the potential for the use of dihydroergotamine mesylate in clinical practice pending regulatory approval.
PMID: 30924698 [PubMed – as supplied by publisher]
https://www.news-medical.net/news/20190329/New-migraine-associated-mechanism-discovered.aspx
https://clinicaltrials.gov/ct2/show/NCT03896256?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine Headache With Intractable Migraine
Intervention : Drug: ketamine infusion
Sponsor : Thomas Jefferson University
Enrolling by invitation
Ketamine for Refractory Chronic Migraine: a Pilot Study
NCT03896256
Fri, 29 Mar 2019 12:00:00 EDT
Last Update Posted: 03/29/19 09:48AM
https://clinicaltrials.gov/ct2/show/NCT03896009?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine
Interventions : Drug: AXS-07 (MoSEIC meloxicam and rizatriptan); Drug: Meloxicam; Drug: Rizatriptan; Drug: Placebo
Sponsor : Axsome Therapeutics, Inc.
Recruiting
Maximizing Outcomes in Treating Acute Migraine
NCT03896009
Fri, 29 Mar 2019 12:00:00 EDT
Last Update Posted: 03/29/19 09:48AM
https://journals.sagepub.com/doi/10.1177/0333102419840780
https://www.ncbi.nlm.nih.gov/pubmed/30917684?dopt=Abstract
A new era for migraine: Pharmacokinetic and pharmacodynamic insights into monoclonal antibodies with a focus on galcanezumab, an anti-CGRP antibody.
Cephalalgia. 2019 Mar 27;:333102419840780
Authors: Kielbasa W, Helton DL
Abstract
PURPOSE: To review pharmacokinetic and pharmacodynamic characteristics of antibodies that bind to soluble ligands within the framework of calcitonin gene-related peptide antibodies.
OVERVIEW: Calcitonin gene-related peptide has been implicated in the pathophysiology of migraine. Galcanezumab is an antibody that binds to the ligand calcitonin gene-related peptide. Other antibodies that target calcitonin gene-related peptide include eptinezumab and fremanezumab. To understand how antibodies can affect the extent and duration of free ligand concentrations, it is important to consider the dose and pharmacokinetics of an antibody, and the kinetics of the ligand and antibody-ligand complex. Insights regarding the pharmacokinetic/pharmacodynamic properties of galcanezumab as a probe antibody drug and calcitonin gene-related peptide as its binding ligand regarding its clinical outcomes are provided.
DISCUSSION: Antibodies are administered parenterally because oral absorption is limited by gastrointestinal degradation and inefficient diffusion through the epithelium. The systemic absorption of antibodies following intramuscular or subcutaneous administration most likely occurs via convective transport through lymphatic vessels into blood. The majority of antibody elimination occurs via intracellular catabolism into peptides and amino acids following endocytosis. Binding of ligand to an antibody reduces the free ligand that is available to interact with the receptor and efficacy is driven by the magnitude and duration of the reduction in free ligand concentration. A galcanezumab pharmacokinetic/pharmacodynamic model shows that galcanezumab decreases free calcitonin gene-related peptide concentrations in a dose- and time-dependent manner and continues to suppress free calcitonin gene-related peptide with repeated dosing. The model provides evidence for a mechanistic linkage to galcanezumab therapeutic effects for the preventive treatment of migraine.
PMID: 30917684 [PubMed – as supplied by publisher]
https://www.nature.com/articles/d41586-019-00895-3
http://omjournal.org/articleDetails.aspx?coType=1&aId=2432
https://www.ncbi.nlm.nih.gov/pubmed/30918603?dopt=Abstract
Wet Cupping Reduces Pain and Improves Health-related Quality of Life Among Patients with Migraine: A Prospective Observational Study.
Oman Med J. 2019 Mar;34(2):105-109
Authors: Kaki A, Sawsan R, Samiha M, Al Jaouni S, Elalah MA, Ibrahim N
Abstract
Objectives: To determine the benefits of wet cupping on pain and health-related quality of life (HRQOL) in adult patients with migraine headaches.
Methods: We conducted a prospective observational study of wet cupping in 128 patients referred to the cupping clinic at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2013 and December 2015. Bloodletting was performed at the base of the head and between the shoulders monthly four times. We assessed migraine headache pain using the visual analog scale (VAS) and the quality of life of patients before and after each cupping session using the World Health Organization Quality of Life assessment instrument.
Results: The mean age of the patients was 40.5±11.3 years with a preponderance of females (n = 114, 89.1%). VAS was averaged at 7 before the procedure and reduced to 3 after wet cupping, both during rest and activity (p ≤ 0.005). Ninety-five patients agreed to complete the quality of life questionnaire. There was a significant improvement in the quality of life after wet cupping treatment in most of the displayed items (p < 0.050). None of the patients reported post-procedure complications. Conclusions: Wet cupping might be considered a complementary treatment for migraine headache pain relief and improvement to a patient's quality of life. PMID: 30918603 [PubMed]
https://www.sciencedirect.com/science/article/abs/pii/S1052514919300061?via%3Dihub
https://www.ncbi.nlm.nih.gov/pubmed/30926116?dopt=Abstract
Related Articles
The Connection Between Patent Foramen Ovale and Migraine.
Neuroimaging Clin N Am. 2019 May;29(2):261-270
Authors: Kumar P, Kijima Y, West BH, Tobis JM
Abstract
“Observational studies have identified a relationship between patent foramen ovale (PFO) and migraine headache. In people who have migraine with aura, 40% to 60% have a PFO, compared with 20% to 30% in the general adult population. It is hypothesized that migraine, especially migraine with aura, may be triggered by hypoxemia or vasoactive chemicals (eg, serotonin), which are ordinarily metabolized during passage through the lungs. Although PFO closure is currently not a FDA-approved therapy for migraines, randomized trials suggest that this intervention may benefit a subgroup of migraineurs.”
PMID: 30926116 [PubMed – in process]
https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-019-0984-1
https://www.ncbi.nlm.nih.gov/pubmed/30909864?dopt=Abstract
Related Articles
Histamine and migraine revisited: mechanisms and possible drug targets.
J Headache Pain. 2019 Mar 25;20(1):30
Authors: Worm J, Falkenberg K, Olesen J
Abstract
OBJECTIVE: To review the existing literature on histamine and migraine with a focus on the molecule, its receptors, its use in inducing migraine, and antihistamines in the treatment of migraine.
BACKGROUND: Histamine has been known to cause a vascular type headache for almost a hundred years. Research has focused on antihistamines as a possible treatment and histamine as a migraine provoking agent but there has been little interest in this field for the last 25 years. In recent years two additional histamine (H3 and H4) receptors have been discovered and a series of non-sedating antihistamines have been developed. It is therefore timely to review the field again.
METHODS: For this review the PubMed/MEDLINE database was searched for eligible studies. We searched carefully for all articles on histamine, antihistamines and histamine receptors in relation to migraine and the nervous system. The following search terms were used: histamine, migraine disorders, migraine, headache, antihistamines, histamine antagonists, clinical trials, induced headache, histamine H3 receptor, histamine H4 receptor and pharmacology. Four hundred thirty-six titles were read, 135 abstracts were read, 112 articles were read in full and 53 articles were used in this review. Review process resulted in 12 articles added to a total of 65.
FINDINGS: Early studies of H1 and H2 antihistamines lack scientific strength and show conflicting results. Most of the antihistaminic drugs used in these trials bind also to other receptors which makes it difficult to conclude on the antihistaminic effect. Histamine is an efficient inducer of migraine attacks in migraine patients by an H1 mechanism most likely extracerebrally. These findings merit further investigation of antihistamines in clinical drug trials. The H3 and H4 receptors are found in primarily in CNS and immune tissues, respectively. H3 is likely to be involved in antinociception and has been linked with cognitive, neurodegenerative and sleep disorders. The only marketed H3 agent, pitolisant, is a brain penetrant H3 antagonist/inverse agonist which increases central histamine and causes headache. The experimental H3 agonist Nα-methylhistamine has shown promising results as a migraine preventative in studies of uncertain quality. With the current limited knowledge of the H4 receptor it is questionable whether or not the receptor is involved in migraine.
CONCLUSION: There is insufficient support for first generation antihistamines (both H1 and H2) as preventive migraine medications and sedation and weight gain are unacceptable side effects. Non-sedating H1 antihistamines need to be appropriately tested. Central H3 receptors seem to have a role in migraine that merit further investigation. The histaminergic system may be a goal for novel migraine drugs.
PMID: 30909864 [PubMed – in process]
https://journals.sagepub.com/doi/10.1177/1744806919842483
https://www.ncbi.nlm.nih.gov/pubmed/30900511?dopt=Abstract
Atypical functional connectivity between the anterior cingulate cortex and other brain regions in a Rat Model of Recurrent Headache.
Mol Pain. 2019 Mar 22;:1744806919842483
Authors: Jia Z, Chen X, Tang W, Zhao D, Yu S
Abstract
We explored the atypical functional connectivity (FC) between the anterior cingulate cortex (ACC) and other brain areas in rats subjected to repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Rats were subdivided according to the frequency of the IS infusions. FC analysis seeded on the ACC was performed on rats 21 days after IS infusion. Glyceryl trinitrate was injected following baseline scanning in the low-frequency IS (LF-IS) group and magnetic resonance imaging (MRI) data were acquired 1 hour after the injection. The rats exhibited nociceptive behavior after high-frequency IS (HF-IS) infusion. The ACC showed increased FC with the cerebellum in the IS groups. The medulla showed increased FC with the ACC in the ictal period in the LF-IS rats. Several areas showed increased FC with the ACC in the HF-IS group, including the pontine tegmentum, midbrain, thalamus, corpus callosum, hippocampus, and retrosplenial, visual, sensory, and motor cortices. This study indicated that the medulla participates in the early stage of a migraine attack and may be associated with the initiation of migraine. Sensitization of the trigeminal nociceptive pathway might contribute to the cutaneous allodynia seen in chronic migraine. Brain areas important for memory function may be related to the chronification of migraine. Electrophysiological studies should examine those migraine-related areas and provide new targets for migraine treatment and prevention.
PMID: 30900511 [PubMed – as supplied by publisher]
https://www.jem-journal.com/article/S0736-4679(18)31196-X/fulltext
https://www.ncbi.nlm.nih.gov/pubmed/30910061?dopt=Abstract
Related Articles
The THINK (Treatment of Headache with Intranasal Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine with Intravenous Metoclopramide.
J Emerg Med. 2019 Mar;56(3):248-257.e1
Authors: Benish T, Villalobos D, Love S, Casmaer M, Hunter CJ, Summers SM, April MD
Abstract
BACKGROUND: Headache is a common chief complaint in the emergency department (ED) setting.
OBJECTIVES: To compare analgesia with metoclopramide and diphenhydramine vs. intranasal ketamine among ED patients with primary headache.
METHODS: We enrolled a convenience sample of adults with a primary headache in a randomized, single-blind, placebo-controlled trial. We randomized patients to either a control arm (intravenous metoclopramide and diphenhydramine) or intranasal ketamine. The primary outcome was change in pain 0-100 mm visual analog scale (VAS) score measured at study start and 30 min post completion of initial medication administration. Secondary outcomes included side effects, hospital admission, and return to care within 48-72 h.
RESULTS: All 53 enrolled subjects completed the study, 26 of whom were allocated to the control arm and 27 to intranasal ketamine. The mean change in pain VAS score at 30 min post intervention was 22.2 mm in the control arm vs. 29.0 in the intranasal ketamine arm (effect size difference 6.8 mm, 95% confidence interval -5.8-19.4). The incidence of reported side effects was 65.4% in the control arm vs. 66.7% in the ketamine arm. Three patients (11.5%) allocated to the control arm required admission for headache pain control vs. 1 patient (3.7%) in the intranasal ketamine arm. Three (11.5%) additional patients in the control arm returned to the ED within 48-72 h for headache pain vs. none in the ketamine arm.
CONCLUSIONS: In this small randomized study, intranasal ketamine was not superior to standard therapy among ED patients with primary headache syndromes.
PMID: 30910061 [PubMed – in process]
https://clinicaltrials.gov/ct2/show/NCT03886012?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Conditions : Dizziness; Nausea; Headache; Confusion
Interventions : Device: Otoband; Device: Otoband sham
Sponsor : Otolith Labs
Not yet recruiting
Efficacy of a Transcranial Vibrating System for Mitigation of Migraine Associated Vertigo
NCT03886012
Fri, 22 Mar 2019 12:00:00 EDT
Last Update Posted: 03/22/19 09:27AM
https://clinicaltrials.gov/ct2/show/NCT03887325?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Headache, Migraine
Interventions : Drug: Maxipost; Drug: Saline
Sponsor : Danish Headache Center
Recruiting
The Effects of Maxipost (BMS 204352) on Cerebral Hemodynamic and Headache in Healthy Volunteers and Migraine Patients
NCT03887325
Fri, 22 Mar 2019 12:00:00 EDT
Last Update Posted: 03/22/19 09:26AM
https://www.ajmc.com/newsroom/botox-effective-in-realworld-settings-to-prevent-migraine-study-says
https://clinicaltrials.gov/ct2/show/NCT03885154?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Condition : Migraine in Children
Interventions : Drug: Valproic Acid (VPA); Drug: Dihydroergotamine (DHE)
Sponsor : Kimberly S Jones
Recruiting
Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine
NCT03885154
Thu, 21 Mar 2019 12:00:00 EDT
Last Update Posted: 03/21/19 09:51AM
https://www.ncbi.nlm.nih.gov/pubmed/30893102?dopt=Abstract
Emerging treatments for cluster headache: hopes and disappointments.
Curr Opin Neurol. 2019 Mar 19;:
Authors: Magis D
Abstract
PURPOSE OF REVIEW: Cluster headache stands among the worst debilitating pain conditions. Available treatments for cluster headache have often disabling side effects, are not tolerated, or are ineffective. The management of drug-refractory chronic forms is challenging. New treatments are warranted and reported here.
RECENT FINDINGS: In cluster headache acute treatment, delivery systems like Demand Valve Oxygen or nonrebreather-type masks could enhance the effectiveness of inhaled oxygen therapy. Noninvasive vagus nerve stimulation relieves cluster headache pain at short-term in episodic patients. Sphenopalatine ganglion stimulation combines acute and preventive properties in subsets of patients and is of interest in selected refractory chronic forms. In cluster headache prevention, ‘hypothalamic’ deep brain stimulation is being refined using slightly different stereotactic coordinates or lower risk methods like endoventricular stimulation. Anti-CGRP monoclonal antibodies provide interesting results in episodic cluster headache, have a good safety profile, but do not appear effective in chronic cluster headache.
SUMMARY: These novel approaches provide additional alternatives to conventional cluster headache management, but results obtained in chronic forms are often disappointing. Research on cluster headache is often hampered by the lack of awareness in the medical world and by the relatively low prevalence of cluster headache compared with migraine. However, common features shared by these two primary headaches could help developing disease-specific therapies.
PMID: 30893102 [PubMed – as supplied by publisher]
https://www.tallahassee.com/story/life/wellness/2019/03/18/researchers-discover-link-between-sodium-migraines/3196545002/
https://link.springer.com/article/10.1007%2Fs11940-019-0559-0
https://www.ncbi.nlm.nih.gov/pubmed/30880363?dopt=Abstract
Related Articles
Other Preventive Anti-Migraine Treatments: ACE Inhibitors, ARBs, Calcium Channel Blockers, Serotonin Antagonists, and NMDA Receptor Antagonists.
Curr Treat Options Neurol. 2019 Mar 18;21(4):17
Authors: Rau JC, Dodick DW
Abstract
PURPOSE OF REVIEW: Migraine causes more years of life lived with disability than almost any other condition in the world and can significantly impact the lives of individuals with migraine, their families, and society. The use of medication for the prevention of migraine is an integral component to reducing disability caused by migraine. There are many different drug classes that have been investigated and shown efficacy in migraine prophylaxis. This article examines several of the classes of medications that are used for migraine preventive treatment, specifically, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, serotonin antagonists, alpha-adrenergic agonists, and N-methyl-D-aspartic acid receptor antagonists.
RECENT FINDINGS: There have been randomized control trials investigating medications in these drug classes since the most recent guidelines for migraine prevention in adults were published by the American Academy of Neurology, American Headache Society, and the Canadian Headache Society. In these investigations, enalapril, candesartan, and memantine all demonstrated efficacy for migraine prevention. The evidence for these and the aforementioned drug classes are reviewed. When oral medications are being selected for migraine prevention, comorbid and coexistent medical conditions, concomitant medications, patient preference, and pregnancy and breast-feeding plans should be considered. Within the drug classes discussed, memantine and candesartan have a moderate level of evidence for efficacy.
PMID: 30880363 [PubMed]
https://link.springer.com/article/10.1007%2Fs11940-019-0558-1
https://www.ncbi.nlm.nih.gov/pubmed/30880369?dopt=Abstract
Related Articles
Current Status of Antiepileptic Drugs as Preventive Migraine Therapy.
Curr Treat Options Neurol. 2019 Mar 18;21(4):16
Authors: Parikh SK, Silberstein SD
Abstract
BACKGROUND: Antiepileptic drugs (AEDs) are an important class of agents used in the treatment of migraine, a neurological disorder that imparts significant socioeconomic burden. It is important for neurologists to understand the rationale for AEDs in migraine-preventive treatment, as well as each agent’s efficacy and tolerability profile, in order to best determine clinical care.
PURPOSE OF THIS REVIEW: This article specifically provides the following: (1) a review of the mechanism of action, efficacy, and tolerability of topiramate and divalproex sodium/sodium valproate, the most widely used AEDs for migraine prevention, (2) a discussion on emerging evidence regarding the efficacy of zonisamide and levetiracetam, and (3) comments on gabapentin, pregabalin, carbamazepine, oxcarbazepine, and lamotrigine, AEDs which have insufficient evidence for use in migraine prevention.
RECENT FINDINGS: The potential role for new extended-release formulations of topiramate in migraine prevention is discussed. There is substantial evidence supporting the use of AEDs in migraine prevention. Specific agents should be chosen based on their efficacy and tolerability profiles. Further studies are needed to determine the efficacy of the newer AEDs, zonisamide and levetiracetam, in migraine prevention and to clarify the role of gabapentinoids in headache management.
PMID: 30880369 [PubMed]
https://www.calcalistech.com/ctech/articles/0,7340,L-3758541,00.html
https://clinicaltrials.gov/ct2/show/NCT03877718?type=Intr&cond=Migraine&sfpd_d=14&sel_rss=new14
Conditions : Migraine; Pain; Nausea; Vomiting; Aura
Interventions : Drug: Arm 1: CL-H1T; Drug: Arm 2: CL-H1T; Drug: Arm 3: Sumatriptan Succinate 100 mg capsule; Drug: Arm 4: Promethazine HCl 18.75 mg; Drug: Arm 5: Promethazine HCl 37.5 mg; Other: Placebo
Sponsor : Charleston Laboratories, Inc
Recruiting
A Study to Assess the Efficacy and Safety of Oral CL-H1T in the Treatment of Acute Migraine Pain
NCT03877718
Mon, 18 Mar 2019 12:00:00 EDT
Last Update Posted: 03/18/19 10:46AM
https://clinicaltrials.gov/ct2/show/NCT03488563?type=Intr&cond=Migraine&lupd_s=03%2F01%2F2019&lupd_d=14
Condition : Migraine
Interventions : Biological: B244; Biological: Vehicle
Sponsors : AOBiome LLC; Veristat, Inc.
Active, not recruiting
Study to Determine Safety and Efficacy of B244 in Subjects With Episodic Migraine
NCT03488563
Thu, 05 Apr 2018 12:00:00 EDT
Last Update Posted: 03/15/19 11:30AM
https://clinicaltrials.gov/ct2/show/NCT03401346?type=Intr&cond=Migraine&lupd_s=03%2F01%2F2019&lupd_d=14
Condition : Migraine Headache
Interventions : Combination Product: INP104; Drug: Dihydroergotamine Mesylate (DHE); Combination Product: Migranal Nasal Spray
Sponsor : Impel NeuroPharma Inc.
Completed
Bioavailability of DHE Administered by I123 POD Device, IV Injection, and Migranal Nasal Spray in Healthy Adults
NCT03401346
Wed, 17 Jan 2018 12:00:00 EST
Last Update Posted: 03/15/19 11:30AM
