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1.
A new hypothesis linking oxytocin to menstrual migraine.
Bharadwaj, VN, Porreca, F, Cowan, RP, Kori, S, Silberstein, SD, Yeomans, DC
Headache. 2021;(7):1051-1059
Abstract
OBJECTIVE To highlight the emerging understanding of oxytocin (OT) and oxytocin receptors (OTRs) in modulating menstrual-related migraine (MRM). BACKGROUND MRM is highly debilitating and less responsive to therapy, and attacks are of longer duration than nonmenstrually related migraine. A clear understanding of the mechanisms underlying MRM is lacking. METHODS We present a narrative literature review on the developing understanding of the role of OT and the OTR in MRM. Literature on MRM on PubMed/MEDLINE database including clinical trials and basic science publications was reviewed using specific keywords. RESULTS OT is a cyclically released hypothalamic hormone/neurotransmitter that binds to the OTR resulting in inhibition of trigeminal neuronal excitability that can promote migraine pain including that of MRM. Estrogen regulates OT release as well as expression of the OTR. Coincident with menstruation, levels of both estrogen and OT decrease. Additionally, other serum biochemical factors, including magnesium and cholesterol, which positively modulate the affinity of OT for OTRs, both decrease during menstruation. Thus, during menstruation, multiple menstrually associated factors may lead to decreased circulating OT levels, decreased OT affinity for OTR, and decreased expression of the trigeminal OTR. Consistent with the view of migraine as a threshold disorder, these events may collectively result in decreased inhibition promoting lower thresholds for activation of meningeal trigeminal nociceptors and increasing the likelihood of an MRM attack. CONCLUSION Trigeminal OTR may thus be a novel target for the development of MRM therapeutics.
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Cinnarizine as an alternative recommendation for migraine prophylaxis: a narrative review.
Togha, M, Martami, F, Abdollahi, M, Mozafari, M, Cheraghali, H, Rafiee, P, Shafaei, M
Expert review of neurotherapeutics. 2020;(9):943-951
Abstract
INTRODUCTION Despite the available prophylactic and acute drugs for migraine management, this disabling disorder remains undertreated especially among pediatrics. In this review, the authors aim at assessing the preventive role cinnarizine plays in treating migraine based on previously published studies. AREAS COVERED Randomized clinical trials, randomized controlled trials, non-randomized open-label trials, and retrospective studies concerning cinnarizine in migraine prevention in children and adults were reviewed. Especial attention was given to the response rate, migraine characteristics, and tolerability. EXPERT OPINION The majority of reviewed trials demonstrated that cinnarizine is comparable to the conventional drugs used in migraine prophylaxis. However, most of the reviewed studies were limited by a non-controlled open-label design. Due to poor planning and possibility of high placebo responses, particularly in children and adolescents, the interpretation of open-label studies' results should be done cautiously. The evidence shows that cinnarizine's effectiveness was more promising in pediatric migraineurs and adults with migraine-associated vertigo such as vestibular migraine. Therefore, while the efficacy of cinnarizine cannot be dismissed, before reaching a definite conclusion on its effectiveness, it is necessary to do further high-quality RCTs among both children and adults.
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Intravenous Migraine Treatment in Children and Adolescents.
Werner, K, Qaiser, S, Kabbouche, M, Murphy, B, Maconochie, I, Hershey, AD
Current pain and headache reports. 2020;(8):45
Abstract
PURPOSE OF REVIEW Pediatric migraine is a common, chronic, and disabling neurological disorder in children and adolescents. Outpatient management is not always effective, and intravenous migraine management may be necessary for headache treatment in the pediatric emergency department. Most current treatment is based on retrospective evidence and there is a lack of well-designed randomized double-blinded controlled pediatric studies. Intravenous drug treatment agents including intravenous fluids, prochlorperazine, diphenhydramine, metoclopramide, dexamethasone, magnesium, valproate and propofol, and dihydroergotamine are reviewed in this paper. RECENT FINDINGS Nineteen studies were reviewed including one prospective randomized double-blind; one single-blinded randomized; one prospective; and one open-label, randomized clinical trial. Most studies were retrospective and the quality of the studies was limited. No definite conclusions can be drawn from the studies, but appropriate prospective trials between major pediatric headache institutions will move pediatric intravenous migraine management forward.
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Clinical use of omega-3 fatty acids in migraine: A narrative review.
Cardia, L, Calapai, F, Mondello, C, Quattrone, D, Elisa Sorbara, E, Mannucci, C, Calapai, G, Mondello, E
Medicine. 2020;(42):e22253
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Abstract
BACKGROUND Omega-3 fatty acids (FAs) can produce several beneficial effects and are commonly used for the treatment of migraine symptoms. Although current therapeutic measures for migraine included pharmacological therapies, dietary supplements, and herbal ingredients, dietary patterns, acupuncture, relaxation techniques, biofeedback, and psychotherapy, omega-3 FAs therapeutic role seems to be obtained through the inhibition or reduction of the release of inflammatory cytokines. The present review aims to provide updated information about the effects of omega-3 FAs in migraine treatment, investigating their clinical effects alone or in combination with other substances. METHODS Bibliographic research was conducted by examining scientific literature from January 2000 until January 31, 2020. Ten clinical studies were included in the review. Quality assessment of randomized controlled trials was performed by using the JADAD scale. RESULTS Clinical studies methodology is not always of good quality and results show moderate evidence concerning the therapeutic role of omega-3 FAs in migraine. CONCLUSION Further clinical trials are necessary to implement the knowledge concerning the use of omega-3 fatty acids in the treatment of migraine.
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Lifestyle Advice for Pediatric Migraine: Blaming the Patient, or Evidence Based?
Gelfand, AA, Irwin, SL
Seminars in neurology. 2020;(3):277-285
Abstract
Children and teenagers with migraine are often advised to live a life of perfect balance-to sleep regularly and well, to eat breakfast each day, to drink plenty of water, and to exercise religiously. The logic is that doing so will decrease their migraine frequency. The corollary that follows is that failing to follow such advice will result in the patient continuing to experience migraine at its current frequency. This opens the door to potentially blaming the patients for their migraine and contributing to migraine stigma. This article reviews the current state of the evidence for each of these behavioral interventions for migraine prevention, and provides the clinician with practical advice for counseling patients.
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Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate.
Maier, JA, Pickering, G, Giacomoni, E, Cazzaniga, A, Pellegrino, P
Nutrients. 2020;(9)
Abstract
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.
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Managing migraine in pregnancy and breastfeeding.
Parikh, SK, Delbono, MV, Silberstein, SD
Progress in brain research. 2020;:275-309
Abstract
The disproportionate prevalence of migraine among women in their reproductive years underscores the clinical significance of migraine during pregnancy. This paper discusses how migraine evolves during pregnancy, secondary headache disorders presenting in pregnancy and puerperium, and acute and preventive options for migraine management during pregnancy and lactation. Migraine is influenced by rising estrogen levels during pregnancy and their sharp decline in puerperium. Migraine, and migraine aura, can present for the first time during pregnancy and puerperium. There is also a higher risk for the development of preeclampsia and cerebrovascular headache during these periods. New or refractory headache, hypertension, and abnormal neurological signs are important "red flags" to consider. This paper reviews the diagnostic utility of neuroimaging studies and the risks of each during pregnancy. Untreated migraine can itself lead to preterm delivery, preeclampsia, and low birth weight infants. Behavioral interventions and lifestyle modifications are the cornerstone for migraine treatment during pregnancy. In addition, one should consider the risks and efficacy of each treatment during pregnancy on an individual basis. The protective nature of breastfeeding for migraine is debated, but there is no evidence to suggest breastfeeding worsens migraine. Acute and preventive migraine treatment options are available for nursing mothers. Neuromodulation and neurostimulation devices are additional options for treatment during pregnancy and lactation, while the safety of using calcitonin gene-related peptide receptor antagonists during these times remains to be determined.
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Targeting the 5-HT1B/1D and 5-HT1F receptors for acute migraine treatment.
Huang, PC, Yang, FC, Chang, CM, Yang, CP
Progress in brain research. 2020;:99-121
Abstract
Migraine is a common and highly disabling headache disorder associated with a substantial socioeconomic burden. Migraine treatments can be categorized as preventive treatment, aimed at reducing the frequency and severity of migraine attacks, and acute therapy, intended to abort attacks. Traditionally, acute treatment can be classified as specific (ergot derivatives and triptans) or nonspecific (analgesics and nonsteroidal anti-inflammatory drugs). Triptans, a class of 5-HT1B/1D receptor agonists with some affinity for the 5-HT1F receptor subtype, have been proven to be efficacious for acute treatment of moderate to severe migraine and have been deemed the gold standard. The availability of triptans in non-oral formulations, such as subcutaneous (SC) and intranasal forms, can be beneficial for patients who suffer from prominent nausea or vomiting, have a suboptimal response to oral agents, and/or seek a more rapid onset of treatment effects. However, triptans are contraindicated in patients with preexisting cardiovascular and/or cerebrovascular diseases due to their 5-HT1B-mediated vasoconstrictive action. For this reason, studies have focused on the development of ditans, a group of antimigraine drugs targeting 5-HT1D and 5-HT1F receptors. Unfortunately, 5-HT1D receptor agonists have been shown to be ineffective in the acute treatment of migraine. Several ditans targeting the 5-HT1F receptor have been developed and have shown no vasoconstrictive effect in preclinical studies, but only two of them, lasmiditan and LY334370, have been tested in clinical trials for migraine, and only lasmiditan has reached to Phase III clinical trials. These Phase III trials have demonstrated the efficacy and safety of lasmiditan, a selective 5-HT1F receptor agonist, in acute migraine treatment. Lasmiditan might offer an alternative migraine therapy without cardiovascular risks. This review will summarize the development of agents targeting the 5-HT1B/1D and 5-HT1F receptors and the clinical evidence supporting the use of these agents for acute migraine treatment.
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Drugs for Acute Attack of Pediatric Migraine: A Network Meta-analysis of Randomized Controlled Trials.
Wang, G, Tan, T, Liu, Y, Hong, P
Clinical neurology and neurosurgery. 2020;:105853
Abstract
Migraine in pediatric is a common neurological disease, and its prevalence is varying widely. The medication for the acute attack of pediatric migraine is various. we take advantage of network meta-analysis to address the efficacy and rank of these medications. Database including Pubmed and Cochrane Library were queried using a specific searching strategy. The quality of trials enrolled was assessed according to the Cochrane collaboration'tool for assessing risk of bias. The data analysis was conducted by using the core software for Cochrane reviews (Rev Man 5.3) and the Aggregate Data Drug Information System (Addis v1.16.8). The outcomes were pain-free and pain relief at 2 hours post-dose. Totally, twenty trials with high quality including 6029 migraineurs with 6912 attacks randomly assigned to 14 different drugs. The data of ketorolac and prochlorperazine were missing. We found that sumatriptan nasal spray and zolmitriptan nasal spray were superior to placebo in the two efficacy outcomes, whereas almotriptan, rizatriptan, sumatriptan with naproxen sodium, ibuprofen and ibuprofen suspension were superior to placebo only in one of the efficacy outcomes. And in network meta-analysis, we found the best 3 treatments were ibuprofen, sumatriptan with naproxen sodium and ibuprofen suspension in achieving pain-free. Meanwhile, the best 3 treatments were ibuprofen suspension, ibuprofen, and rizatriptan in achieving pain relief. In conclusion, in acute treatments of pediatric migraine, most triptans and NSAIDS were effective to achieve pain-free or pain-relief. And the most effective treatment to achieve pain-free is sumatriptan with naproxen sodium. Ibuprofen and ibuprofen suspension were the most effective treatments to achieve pain-relief.
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Complementary and Integrative Health Treatments for Migraine.
Patel, PS, Minen, MT
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2019;(3):360-369
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Abstract
BACKGROUND Migraine is a chronic disabling neurologic condition that can be treated with a combination of both pharmacologic and complementary and integrative health options. EVIDENCE ACQUISITION With the growing interest in the US population in the use of nonpharmacologic treatments, we reviewed the evidence for supplements and behavioral interventions used for migraine prevention. RESULTS Supplements reviewed included vitamins, minerals, and certain herbal preparations. Behavioral interventions reviewed included cognitive behavioral therapy, biofeedback, relaxation, the third-wave therapies, acupuncture, hypnosis, and aerobic exercise. CONCLUSIONS This article should provide an appreciation for the wide range of nonpharmacologic therapies that might be offered to patients in place of or in addition to migraine-preventive medications.