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1.
Randomised trial of IV metoclopramide vs IV ketorolac in treatment of acute primary headaches.
Soltani, KM, Motamed, H, Eslami, K, Majdinasab, N, Kouti, L
The American journal of emergency medicine. 2021;:376-380
Abstract
INTRODUCTION Headache is one of the most common neurological conditions among emergency department visits (ED), although the best therapy has not been identified yet. Therefore, in the current study, we aimed to compare the pain-relieving effect of metoclopramide and ketorolac in acute primary headaches patients. METHODS This double-blind, randomised clinical trial was conducted at Golestan Hospital, Ahvaz, Iran. This research involved all adult patients with acute primary (migraine or tension-type) headaches presented to the ED. Pain intensity was assessed with 0 to 10 verbal Numeric Rating Scales (NRS). The subjects were randomised into 10 mg intravenous (IV) metoclopramide or 30 mg IV ketorolac groups. Pain score and drug adverse reactions were compared between the two groups at baseline, 15, 30, and 60 min after baseline. RESULTS 108 patients completed this trial and were equally divided into two groups (mean age of 34 ± 8.54 years; 57.4% female). Before treatment, the mean pain score was 6.9 and 6.8 in metoclopramide and ketorolac groups, respectively (p > 0.05). Metoclopramide failed to provide more improvement in pain score at 30 min (p = 0.55) and 60 min (p = 0.15) from baseline. There were no serious adverse events in this study. Only five patients required rescue medication which four of them were in ketorolac group. CONCLUSION We were unable to reject the null hypothesis that there would be no difference in pain outcomes between metoclopramide and ketorolac.
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2.
Applications of Ketogenic Diets in Patients with Headache: Clinical Recommendations.
Di Lorenzo, C, Ballerini, G, Barbanti, P, Bernardini, A, D'Arrigo, G, Egeo, G, Frediani, F, Garbo, R, Pierangeli, G, Prudenzano, MP, et al
Nutrients. 2021;(7)
Abstract
Headaches are among the most prevalent and disabling neurologic disorders and there are several unmet needs as current pharmacological options are inadequate in treating patients with chronic headache, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. Among these, the largest body of evidence supports the use of the ketogenic diet (KD). Exactly 100 years ago, KD was first used to treat drug-resistant epilepsy, but subsequent applications of this diet also involved other neurological disorders. Evidence of KD effectiveness in migraine emerged in 1928, but in the last several year's different groups of researchers and clinicians began utilizing this therapeutic option to treat patients with drug-resistant migraine, cluster headache, and/or headache comorbid with metabolic syndrome. Here we describe the existing evidence supporting the potential benefits of KDs in the management of headaches, explore the potential mechanisms of action involved in the efficacy in-depth, and synthesize results of working meetings of an Italian panel of experts on this topic. The aim of the working group was to create a clinical recommendation on indications and optimal clinical practice to treat patients with headaches using KDs. The results we present here are designed to advance the knowledge and application of KDs in the treatment of headaches.
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3.
A nationwide randomized, double-blind, placebo-controlled physicians' trial of loxoprofen for the treatment of fatigue, headache, and nausea after hangovers.
Hara, M, Hayashi, K, Kitamura, T, Honda, M, Tamaki, M
Alcohol (Fayetteville, N.Y.). 2020;:21-25
Abstract
Hangovers are associated with negative economic consequences due to decreased job performance or frequent visits to physicians. Thus, a new strategy for the alleviation of hangover-related symptoms is needed to avoid this detriment to society. The purpose of this nationwide randomized, double-blind, placebo-controlled physicians' trial was to evaluate the efficacy of loxoprofen sodium for the alleviation of fatigue, headache, and nausea after hangover. A total of 229 participants were randomized to receive loxoprofen sodium (60 mg once orally) or placebo. The study was closed when the first 150 participants (n = 74 in the loxoprofen vs. n = 76 in the placebo groups) experienced hangovers. The primary endpoint was set as the difference in severity of general fatigue before and 3 h after taking the test drugs and was evaluated using a visual analogue scale. Secondary endpoints included difference in severity of headache, nausea, and incidence of adverse events. The study participants were 34 (interquartile range; 30-39) years old, 92.0% were men, and both groups were comparable for baseline characteristics. The alleviation of general fatigue did not differ statistically between the loxoprofen and placebo groups (24 [14-49] vs. 19 [9-35], p = 0.07). However, the alleviation of headache was statistically greater in the loxoprofen group (25 [10-50] vs. 10 [2-30], adjusted difference 14, 95% confidence interval 8-21, p < 0.001), whereas, there was no difference in nausea (7 [0-27] vs. 10 [0-24], p = 0.68). The incidence of adverse symptoms such as epigastric discomfort was also comparable between groups (2.7% vs. 3.9%, p = 0.25). Loxoprofen sodium was effective for relieving headaches after hangovers but did not alleviate general fatigue or nausea.
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4.
Gastroprotective herbs for headache management in Persian medicine: A comprehensive review.
Naeimi, M, Gorji, N, Memariani, Z, Moeini, R, Kamalinejad, M, Kolangi, F
Journal of integrative medicine. 2020;(1):1-13
Abstract
The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal (GI) disorders. In Persian medicine (PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM. Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. PubMed, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family. Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose, apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer, antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities. However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.
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5.
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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6.
Effect of KATP channel blocker glibenclamide on levcromakalim-induced headache.
Al-Karagholi, MA, Ghanizada, H, Kokoti, L, Paulsen, JS, Hansen, JM, Ashina, M
Cephalalgia : an international journal of headache. 2020;(10):1045-1054
Abstract
INTRODUCTION Administration of ATP-sensitive potassium channel opener levcromakalim triggers headache in healthy volunteers and migraine attacks in migraine patients. Here, we investigated the effect of ATP-sensitive potassium channel blocker glibenclamide on levcromakalim-induced headache in healthy volunteers. METHODS In a randomized, double-blind, placebo-controlled, three-way cross-over study, 15 healthy volunteers aged 18-40 years were randomly allocated to receive glibenclamide and levcromakalim (day 1), glibenclamide and placebo (day 2), and placebo and placebo (day 3) on three different days separated by at least 1 week. The primary endpoints were the difference in incidence of headache and the difference in area under the curve for headache intensity scores (0-12 hours) between the days. RESULTS Fifteen healthy volunteers completed the 3 days of the study. More participants (12/15, 80%) developed headache on the glibenclamide-levcromakalim day compared to the glibenclamide-placebo day (5/15, 33%) (p = 0.01; mean difference 47%; 95% confidence interval 18-75%) and compared to the placebo-placebo day (1/15, 7%) (p = 0.001; mean difference 73%; 95% confidence interval 48-99%). We found no difference in headache incidence between glibenclamide-placebo day and placebo-placebo day (p = 0.12; mean difference 27%; 95% confidence interval 1.3-52%). The area under the curve for headache intensity was significantly larger on the glibenclamide-levcromakalim day compared to the glibenclamide-placebo day (p = 0.003); and compared to the placebo-placebo day (p = 0.001). We found no difference in the area under the curve between the glibenclamide-placebo day compared to the placebo-placebo day (p = 0.07). The median time to onset for headache after levcromakalim infusion with glibenclamide pretreatment was delayed (180 min) compared to levcromakalim without pretreatment (30 min) from a previously published study. CONCLUSION Glibenclamide administration did not cause headache, and glibenclamide pretreatment did not prevent levcromakalim-induced headache. However, glibenclamide delayed the onset of levcromakalim-induced headache. More selective blockers are needed to further elucidate the role of the ATP-sensitive potassium channel in headache initiation.Trial Registration: ClinicalTrials.gov NCT03886922.
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7.
Intravenous Magnesium Sulfate to Treat Acute Headaches in the Emergency Department: A Systematic Review.
Miller, AC, K Pfeffer, B, Lawson, MR, Sewell, KA, King, AR, Zehtabchi, S
Headache. 2019;(10):1674-1686
Abstract
INTRODUCTION Non-traumatic headaches comprise up to 4% of all emergency department (ED) visits. Current practice is moving toward multimodal analgesia regimens that limit narcotic use. OBJECTIVE The objective of this systematic review is to address the following research question: In patients with non-traumatic headaches (Population), does administration of intravenous magnesium sulfate (Intervention) compared to placebo, corticosteroids, dopamine antagonists, ergot alkaloids, non-steroidal anti-inflammatory drugs (NSAIDs), triptans, or usual care result in better pain control, lower rate of recurrence at 24 hours, lower requirements for rescue analgesia, and less adverse medication effects (Outcomes)? METHODS Scholarly databases and relevant bibliographies were searched, as were clinical trial registries and relevant conference proceedings to limit publication bias. Studies were not limited by date, language, or publication status. Inclusion criteria were: (1) randomized clinical trial (RCT), (2) patients age ≥18 years, (3) non-traumatic headache, (4) patients treated in ED or an outpatient acute care treatment center, and (5) magnesium sulfate administered intravenously (IV). Eligible comparison groups included: placebo, conventional therapy, dopamine antagonist, NSAID, corticosteroid, ergot alkaloid, or triptans. RESULTS Out of 4018 identified references, 7 RCTs (545 participants) that treated migraine headaches (n = 6) and benign non-traumatic headaches (n = 1) met inclusion criteria. Pain intensity was improved with magnesium sulfate vs comparators at 60-120 minutes, but not at earlier time points. Result for the endpoint of pain reduction by 50% were conflicting as 3 studies reported that headache was improved, unchanged, and less with magnesium sulfate. Complete pain relief was improved with magnesium sulfate in 1 study, and in the migraine with aura (MA) subgroup in another. The need for rescue analgesia at any point was improved with magnesium sulfate in 1 study, and in the MA subgroup in another. Twenty-four-hour headache recurrence was improved with magnesium sulfate in 1 study, but unchanged in a second. The intended meta-analysis was not performed due to the clinical heterogeneity among studies. CONCLUSION While we cannot draw a firm conclusion on the efficacy or benefit of intravenous magnesium sulfate in the treatment of acute non-traumatic headaches, the existing evidence indicates potential benefits in pain control beyond 1 hour, aura duration, and need for rescue analgesia.
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8.
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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9.
Peripheral edema and headache associated with amlodipine treatment: a meta-analysis of randomized, placebo-controlled trials.
Vukadinović, D, Scholz, SS, Messerli, FH, Weber, MA, Williams, B, Böhm, M, Mahfoud, F
Journal of hypertension. 2019;(10):2093-2103
Abstract
OBJECTIVE Use of amlodipine for treatment of arterial hypertension and stable coronary artery disease (CAD) is sometimes limited by occurrence of peripheral edema and headache. We aimed to explore the true magnitude of this phenomenon by determining the rate and placebo-adjusted rate of these side effects. METHODS We performed a meta-analysis by including all randomized, placebo-controlled trials reporting edema and headache with amlodipine in patients with arterial hypertension and CAD. Placebo-adjusted rate (%) was determined as follows: (SE amlodipine % - SE placebo %)/SE amlodipine %. RESULTS Data from 7226 patients of 22 trials were analyzed. Rate of edema was higher on amlodipine vs. placebo (16.6 vs. 6.2%, risk ratio: 2.9, 95% CI: 2.50-3.36, P < 0.0001). The placebo-adjusted rate was 63%, indicating that 37% of edema cases were unrelated to amlodipine. Treatment with low/medium doses (2.5-5 mg) resulted in lower rates of edema (risk ratio: 2.01, 95% CI: 1.41-2.88, P = 0.0001) vs. high dose (10 mg) (risk ratio: 3.08, 95% CI 2.62-3.60, P < 0.0001, Pforinteraction = 0.03). Incidence of headache was reduced using amlodipine vs. placebo (7.9 vs. 10.9%, risk ratio: 0.77, 95% CI: 0.65-0.90, P = 0.002) and was driven by use of low/medium doses (risk ratio: 0.52, 95% CI: 0.40-0.69, P < 0.00001 vs. risk ratio: 0.92, 95%-CI: 0.74-1.15, P = 0.45, for high doses, Pforinteraction = 0.002). CONCLUSION Although risks of peripheral edema are three-fold higher on amlodipine, up to one-third of edema cases on amlodipine might not be induced by amlodipine. Headache is reduced on amlodipine treatment, mainly driven by use of this drug at low/medium doses.
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10.
[Temporal bone cholesterol granuloma penetrating into the middle cranial fossa].
Jakab-Péter, K, Tóth, A, Barabás, MA, Gerlinger, I, Lujber, L
Orvosi hetilap. 2019;(52):2067-2072
Abstract
The authors present a case report of a patient who was treated conservatively for a non-specific headache for more than a decade, while an arachnoidal cyst in the middle cranial fossa, over the temporal bone tegmen was diagnosed, but ruled out as the cause of the headache. The patient was referred to our ENT department with left, purulent ear discharge. Besides a chronic purulent otitis media, a cholesterol granuloma occupying the antrum, eroding the tegmen of the pyramid bone and penetrating into the middle cranial fossa was diagnosed. Case presentation of a patient with cholesterol granuloma, surgical options, differential diagnostic problems, and a literature review are presented. Tympanoplasty with cortical mastoidectomy was carried out to treat the chronic purulent otitis media, and the cholesterol granuloma was removed during transmastoid craniotomy. The iatrogenic temporal meningo-encephalic tissue herniation was repaired and the bone defect of the tegmen was reconstructed with septal cartilage. The patient's headache diminished immediately after the surgery. The chronic ear discharge stopped, the cholesterol granuloma was excised completely and the cerebral herniation was repaired successfully. Neither CSF leak, nor further herniation or meningitis were noticed. Two years after the operation the patient is asymptomatic. A large cholesterol granuloma, eroding into the middle cranial fossa can cause serious complications, and needs a high level of attention besides individualized surgical treatment based on the surgeon's abilities and skills. Orv Hetil. 2019; 160(52): 2067-2072.