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1.
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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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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Association of diet and headache.
Razeghi Jahromi, S, Ghorbani, Z, Martelletti, P, Lampl, C, Togha, M, ,
The journal of headache and pain. 2019;(1):106
Abstract
The global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.
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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.
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SEEDS for success: Lifestyle management in migraine.
Robblee, J, Starling, AJ
Cleveland Clinic journal of medicine. 2019;(11):741-749
Abstract
Primary care physicians can help their patients with migraine modify their triggers, and thereby mitigate the severity and frequency of their symptoms, by offering lifestyle modification counseling based on the mnemonic SEEDS (sleep, exercise, eat, diary, and stress). The authors review evidence associated with each of these factors and provide best-practice recommendations.
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Caffeine in the management of patients with headache.
Lipton, RB, Diener, HC, Robbins, MS, Garas, SY, Patel, K
The journal of headache and pain. 2017;(1):107
Abstract
Caffeinated headache medications, either alone or in combination with other treatments, are widely used by patients with headache. Clinicians should be familiar with their use as well as the chemistry, pharmacology, dietary and medical sources, clinical benefits, and potential safety issues of caffeine. In this review, we consider the role of caffeine in the over-the-counter treatment of headache. The MEDLINE and Cochrane databases were searched by combining "caffeine" with the terms "headache," "migraine," and "tension-type." Studies that were not placebo-controlled or that involved medications available only with a prescription, as well as those not assessing patients with migraine and/or tension-type headache (TTH), were excluded. Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with TTH or migraine, with favorable tolerability in the vast majority of patients. The most common adverse events were nervousness (6.5%), nausea (4.3%), abdominal pain/discomfort (4.1%), and dizziness (3.2%). This review provides evidence for the role of caffeine as an analgesic adjuvant in the acute treatment of primary headache with over-the-counter drugs, caffeine doses of 130 mg enhance the efficacy of analgesics in TTH and doses of ≥100 mg enhance benefits in migraine. Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine.
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Family studies to find rare high risk variants in migraine.
Hansen, RD, Christensen, AF, Olesen, J
The journal of headache and pain. 2017;(1):32
Abstract
INTRODUCTION Migraine has long been known as a common complex disease caused by genetic and environmental factors. The pathophysiology and the specific genetic susceptibility are poorly understood. Common variants only explain a small part of the heritability of migraine. It is thought that rare genetic variants with bigger effect size may be involved in the disease. Since migraine has a tendency to cluster in families, a family approach might be the way to find these variants. This is also indicated by identification of migraine-associated loci in classical linkage-analyses in migraine families. A single migraine study using a candidate-gene approach was performed in 2010 identifying a rare mutation in the TRESK potassium channel segregating in a large family with migraine with aura, but this finding has later become questioned. The technologies of next-generation sequencing (NGS) now provides an affordable tool to investigate the genetic variation in the entire exome or genome. The family-based study design using NGS is described in this paper. We also review family studies using NGS that have been successful in finding rare variants in other common complex diseases in order to argue the promising application of a family approach to migraine. METHOD PubMed was searched to find studies that looked for rare genetic variants in common complex diseases through a family-based design using NGS, excluding studies looking for de-novo mutations, or using a candidate-gene approach and studies on cancer. All issues from Nature Genetics and PLOS genetics 2014, 2015 and 2016 (UTAI June) were screened for relevant papers. Reference lists from included and other relevant papers were also searched. For the description of the family-based study design using NGS an in-house protocol was used. RESULTS Thirty-two successful studies, which covered 16 different common complex diseases, were included in this paper. We also found a single migraine study. Twenty-three studies found one or a few family specific variants (less than five), while other studies found several possible variants. Not all of them were genome wide significant. Four studies performed follow-up analyses in unrelated cases and controls and calculated odds ratios that supported an association between detected variants and risk of disease. Studies of 11 diseases identified rare variants that segregated fully or to a large degree with the disease in the pedigrees. CONCLUSION It is possible to find rare high risk variants for common complex diseases through a family-based approach. One study using a family approach and NGS to find rare variants in migraine has already been published but with strong limitations. More studies are under way.
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Drugs for the acute treatment of migraine in children and adolescents.
Richer, L, Billinghurst, L, Linsdell, MA, Russell, K, Vandermeer, B, Crumley, ET, Durec, T, Klassen, TP, Hartling, L
The Cochrane database of systematic reviews. 2016;(4):CD005220
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Abstract
BACKGROUND Numerous medications are available for the acute treatment of migraine in adults, and some have now been approved for use in children and adolescents in the ambulatory setting. A systematic review of acute treatment of migraine medication trials in children and adolescents will help clinicians make evidence-informed management choices. OBJECTIVES To assess the effects of pharmacological interventions by any route of administration versus placebo for migraine in children and adolescents 17 years of age or less. For the purposes of this review, children were defined as under 12 years of age and adolescents 12 to 17 years of age. SEARCH METHODS We searched seven bibliographic databases and four clinical trial registers as well as gray literature for studies through February 2016. SELECTION CRITERIA We included prospective randomized controlled clinical trials of children and adolescents with migraine, comparing acute symptom relieving migraine medications with placebo in the ambulatory setting. DATA COLLECTION AND ANALYSIS Two reviewers screened titles and abstracts and reviewed the full text of potentially eligible studies. Two independent reviewers extracted data for studies meeting inclusion criteria. We calculated the risk ratios (RRs) and number needed to treat for an additional beneficial outcome (NNTB) for dichotomous data. We calculated the risk difference (RD) and number needed to treat for an additional harmful outcome (NNTH) for proportions of adverse events. The percentage of pain-free patients at two hours was the primary efficacy outcome measure. We used adverse events to evaluate safety and tolerability. Secondary outcome measures included headache relief, use of rescue medication, headache recurrence, presence of nausea, and presence of vomiting. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. MAIN RESULTS We identified a total of 27 randomized controlled trials (RCTs) of migraine symptom-relieving medications, in which 9158 children and adolescents were enrolled and 7630 (range of mean age between 8.2 and 14.7 years) received medication. Twenty-four studies focused on drugs in the triptan class, including almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, sumatriptan + naproxen sodium, and zolmitriptan. Other medications studied included paracetamol (acetaminophen), ibuprofen, and dihydroergotamine (DHE). More than half of the studies evaluated sumatriptan. All but one study reported adverse event data. Most studies presented a low or unclear risk of bias, and the overall quality of evidence, according to GRADE criteria, was low to moderate, downgraded mostly due to imprecision and inconsistency. Ibuprofen was more effective than placebo for producing pain freedom at two hours in two small studies that included 162 children (RR 1.87, 95% confidence interval (CI) 1.15 to 3.04) with low quality evidence (due to imprecision). Paracetamol was not superior to placebo in one small study of 80 children. Triptans as a class of medication were superior to placebo in producing pain freedom in 3 studies involving 273 children (RR 1.67, 95% CI 1.06 to 2.62, NNTB 13) (moderate quality evidence) and 21 studies involving 7026 adolescents (RR 1.32, 95% CI 1.19 to 1.47, NNTB 6) (moderate quality evidence). There was no significant difference in the effect sizes between studies involving children versus adolescents. Triptans were associated with an increased risk of minor (non-serious) adverse events in adolescents (RD 0.13, 95% CI 0.08 to 0.18, NNTH 8), but studies did not report any serious adverse events. The risk of minor adverse events was not significant in children (RD 0.06, 95% CI - 0.04 to 0.17, NNTH 17). Sumatriptan plus naproxen sodium was superior to placebo in one study involving 490 adolescents (RR 3.25, 95% CI 1.78 to 5.94, NNTB 6) (moderate quality evidence). Oral dihydroergotamine was not superior to placebo in one small study involving 13 children. AUTHORS' CONCLUSIONS Low quality evidence from two small trials shows that ibuprofen appears to improve pain freedom for the acute treatment of children with migraine. We have only limited information on adverse events associated with ibuprofen in the trials included in this review. Triptans as a class are also effective at providing pain freedom in children and adolescents but are associated with higher rates of minor adverse events. Sumatriptan plus naproxen sodium is also effective in treating adolescents with migraine.
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New advances in prevention of migraine. Review of current practice and recent advances.
Al-Quliti, KW, Assaedi, ES
Neurosciences (Riyadh, Saudi Arabia). 2016;(3):207-14
Abstract
Despite being one of the most common disabling primary headaches, migraine continues to be underdiagnosed and under-treated. A migraine challenges not only the patient suffering from the migraine, but also physicians; especially in recognizing candidates for prophylaxis and selecting the appropriate preventive medication. Recently, there have been major advances in the diagnosis and treatment of migraine, with different guidelines of migraine management across the world. Here, we review migraines abortive and prophylactic medications, based on their pharmacologic category, citing their recommended doses, efficacy, and side effects. Additionally, we highlight the prophylactic treatment of specific patient populations and present suggested treatment approaches in view of recent international treatment guidelines that consider factors other than drug efficacy when choosing the optimal preventive therapy. Finally, we introduce drugs in different stages of development, which have novel mechanisms of action or have new therapeutic targets.
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Spotlight on frovatriptan: a review of its efficacy in the treatment of migraine.
Allais, G, Benedetto, C
Drug design, development and therapy. 2016;:3225-3236
Abstract
Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours). Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (<1 hour after symptom onset) or late (>1 hour after onset). Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost-effectiveness advantages versus other triptans could drive selection of the most appropriate treatment for acute migraine attacks.