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1.
Effectiveness of coenzyme Q10 in prophylactic treatment of migraine headache: an open-label, add-on, controlled trial.
Shoeibi, A, Olfati, N, Soltani Sabi, M, Salehi, M, Mali, S, Akbari Oryani, M
Acta neurologica Belgica. 2017;(1):103-109
Abstract
Despite the huge health and economic burden of migraine headache, few medications have been approved for its prophylactic treatment, most of which can potentially induce serious adverse effects. Coenzyme Q10 (CoQ10) is a supplement and has shown preliminary benefits in migraine prophylaxis. We aimed to assess this effect in an adult population. This is an open-label, parallel, add-on, match-controlled trial. Eighty patients diagnosed with migraine headache based on International Headache Society criteria were allocated to receiving only their current preventive drugs or their current preventive drugs plus 100 mg CoQ10 daily, matching for their baseline characteristics, and were assessed for frequency and severity of attacks, and ≥50 % reduction in attack frequency per month. Thirty-six and 37 patients were analyzed in CoQ10 and control groups, respectively. Number of attacks per month dropped significantly in the CoQ10 group (mean decrease: 1.6 vs. 0.5 among CoQ10 and control groups, respectively, p < 0.001). A significant reduction was also evident in the severity of headaches (mean decrease: 2.3 vs. 0.6 among CoQ10 and control groups, respectively, p < 0.001). For ≥50 % reduction in the frequency of attacks per month, the number needed to treat was calculated as 1.6. No side effects for CoQ10 were observed. This study suggests that CoQ10 might reduce the frequency of headaches, and may also make them shorter in duration, and less severe, with a favorable safety profile.
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2.
Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.
Sun, H, Dodick, DW, Silberstein, S, Goadsby, PJ, Reuter, U, Ashina, M, Saper, J, Cady, R, Chon, Y, Dietrich, J, et al
The Lancet. Neurology. 2016;(4):382-90
Abstract
BACKGROUND The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. METHODS In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. FINDINGS From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was -3·4 (SE 0·4) days with AMG 334 70 mg versus -2·3 (0·3) days with placebo (difference -1·1 days [95% CI -2·1 to -0·2], p=0·021). The mean reductions in monthly migraine days with the 7 mg (-2·2 [SE 0·4]) and the 21 mg (-2·4 [0·4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54%) patients who received placebo, 54 (50%) patients in the AMG 334 7 mg group, 54 (51%) patients in the AMG 334 21 mg group, and 57 (54%) patients in the AMG 334 70 mg group. The most frequently reported adverse events were nasopharyngitis, fatigue, and headache. Serious adverse events were reported for one patient in the AMG 334 7 mg group (ruptured ovarian cyst) and one patient in the AMG 334 70 mg group (migraine and vertigo); these events were judged to be unrelated to AMG 334 treatment. Nine (3%) of 317 patients had neutralising antibodies. No apparent association was recorded between patients with positive anti-AMG 334 antibodies and adverse events. No clinically significant vital signs, laboratory, or electrocardiogram findings were recorded. INTERPRETATION These results suggest that AMG 334 70 mg might be a potential therapy for migraine prevention in patients with episodic migraine and support further investigation of AMG 334 in larger phase 3 trials. FUNDING Amgen.
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3.
Effect of vitamin D therapy in addition to amitriptyline on migraine attacks in pediatric patients.
Cayir, A, Turan, MI, Tan, H
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2014;(4):349-54
Abstract
The purpose of this study was to investigate the effect of supplementary vitamin D therapy in addition to amitriptyline on the frequency of migraine attacks in pediatric migraine patients. Fifty-three children 8-16 years of age and diagnosed with migraine following the International Headache Society 2005 definition, which includes childhood criteria, were enrolled. Patients were classified into four groups on the basis of their 25-hydroxyvitamin D [25(OH)D] levels. Group 1 had normal 25(OH)D levels and received amitriptyline therapy alone; group 2 had normal 25(OH)D levels and received vitamin D supplementation (400 IU/day) plus amitriptyline; group 3 had mildly deficient 25(OH)D levels and received amitriptyline plus vitamin D (800 IU/day); and group 4 had severely deficient 25(OH)D levels and was given amitriptyline plus vitamin D (5000 IU/day). All groups were monitored for 6 months, and the number of migraine attacks before and during treatment was determined. Calcium, phosphorus alkaline phosphatase, parathormone, and 25(OH)D levels were also determined before and during treatment. Results were compared between the groups. Data obtained from the groups were analyzed using one-way analysis of variance. The number of pretreatment attacks in groups 1 to 4 was 7 ± 0.12, 6.8 ± 0.2, 7.3 ± 0.4, and 7.2 ± 0.3 for 6 months, respectively (all P > 0.05). The number of attacks during treatment was 3 ± 0.25, 1.76 ± 0.37 (P < 0.05), 2.14 ± 0.29 (P < 0.05), and 1.15 ± 0.15 (P < 0.05), respectively. No statistically significant differences in calcium, phosphorus, alkaline phosphatase, or parathormone levels were observed (P > 0.05). Vitamin D given in addition to anti-migraine treatment reduced the number of migraine attacks.
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4.
Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium.
Gallelli, L, Avenoso, T, Falcone, D, Palleria, C, Peltrone, F, Esposito, M, De Sarro, G, Carotenuto, M, Guidetti, V
Headache. 2014;(2):313-24
Abstract
AIM: The purpose of this study was to evaluate both the effects of ibuprofen and/or acetaminophen for the acute treatment of primary migraine in children in or out prophylactic treatment with magnesium. METHODS Children ranging from the ages of 5 to 16 years with at least 4 attack/month of primary migraine were eligible for participation the study. A visual analog scale was used to evaluate pain intensity at the moment of admission to the study (start of the study) and every month up to 18 months later (end of the study). RESULTS One hundred sixty children of both sexes aged 5-16 years were enrolled and assigned in 4 groups to receive a treatment with acetaminophen or ibuprofen without or with magnesium. Migraine pain endurance and monthly frequency were similar in the 4 groups. Both acetaminophen and ibuprofen induced a significant decrease in pain intensity (P < .01), without a time-dependent correlation, but did not modify its frequency. Magnesium pretreatment induced a significant decrease in pain intensity (P < .01) without a time-dependent correlation in both acetaminophen- and ibuprofen-treated children and also significantly reduced (P < .01) the pain relief timing during acetaminophen but not during ibuprofen treatment (P < .01). In both acetaminophen and ibuprofen groups, magnesium pretreatment significantly reduced the pain frequency (P < .01). CONCLUSIONS Magnesium increased the efficacy of ibuprofen and acetaminophen with not age-related effects.
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5.
Dexketoprofen trometamol in the acute treatment of migraine attack: a phase II, randomized, double-blind, crossover, placebo-controlled, dose optimization study.
Mainardi, F, Maggioni, F, Pezzola, D, Zava, D, Zanchin, G
The journal of pain. 2014;(4):388-94
Abstract
UNLABELLED Migraine is a disabling disease that can significantly affect a person's quality of life. This study assessed the efficacy and tolerability of the 2 doses of dexketoprofen trometamol (DKP) compared to placebo for migraine treatment. Ninety-three patients with at least 1 migraine attack per month in the preceding 6 months were enrolled and randomized to 25 mg DKP, 50 mg DKP, and placebo in a randomized, double-blind, single-center, crossover, placebo-controlled study. Primary endpoint was pain-free episodes 2 hours after drug intake. The presence of accompanying symptoms and adverse effects was also recorded. Seventy-six patients (mean age 40.5 ± 10.9 and 61% female) completed the study. At baseline, mean number of attacks/month was 3.7 ± 1.3, with a mean duration of 15.4 ± 13.5 hours. Prevalence of pain-free episodes after drug intake was significantly reduced by 50 mg DKP vs placebo (33.8 vs 14.7%, P = .0065) whereas the dose of DKP 25 mg was better than placebo but did not reach statistical significance (23 vs 14.7%, P = .1182). Both 25 mg DKP (56.8 vs 25.3%, P = .0002) and 50 mg DKP improved headache relief compared to placebo. Furthermore, both doses of DKP increased the absence of functional disability (25 mg DKP, 39.7 vs 24%, P = .045; and 50 mg DKP, 45.9 vs 24%, P < .0004). Both doses of DKP were effective and well tolerated for acute migraine treatment. PERSPECTIVE This article demonstrates the efficacy and tolerability of DKP in the treatment of migraine without and with aura attacks. Its rapid absorption rate with higher maximum plasma concentrations and shorter time to maximum values suggest that this drug is a good option for acute migraine treatment.
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[A comparative study of the effectiveness of topiramate and flunarizine in independent series of chronic migraine patients without medication abuse].
Gracia-Naya, M, Ríos, C, García-Gomara, MJ, Sánchez-Valiente, S, Mauri-Llerda, JÁ, Santos-Lasaosa, S, Artal-Roy, J, Latorre-Jiménez, AM
Revista de neurologia. 2013;(8):347-53
Abstract
INTRODUCTION Topiramate and onabotulinumtoxin A have proven to be effective in chronic migraine with or without medication abuse according to recent criteria of the International Headache Society's Headache Classification. AIMS To show that flunarizine is as effective as topiramate in cases of chronic migraine without medication abuse. PATIENTS AND METHODS We conducted a prospective, non-randomised, comparative study of two groups of patients paired by age and sex, with chronic migraine without abuse, who had been treated preventively for the first time with topiramate or flunarizine. RESULTS Forty patients treated with flunarizine were assigned a patient of their same sex and age who was being treated with topiramate. The mean rate of reduction in intense migraines in the topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the responder rate at four months of treatment did not show any significant differences either, the figures being 75% for topiramate and 70% for flunarizine (p = 0.6236). The mean reduction of other headaches in the topiramate group was 57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four months of treatment was similar in the two groups: 76%. The percentage of dropouts from treatment was higher with topiramate (19.5%) than with flunarizine (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In all, 78.9% of the patients who took topiramate said they were satisfied with the drug versus 75% of those in the flunarizine group (p = 0.7903). CONCLUSIONS Flunarizine proved to be as effective as topiramate in the treatment of chronic migraine without medication abuse.
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7.
Iron deposition in pain-regulatory nuclei in episodic migraine and chronic daily headache by MRI.
Tepper, SJ, Lowe, MJ, Beall, E, Phillips, MD, Liu, K, Stillman, MJ, Horvat, M, Jones, SE
Headache. 2012;(2):236-43
Abstract
BACKGROUND Progression of migraine toward a more disabling chronic form of at least 15 days/month is linked with frequency of attacks. Magnetic resonance imaging (MRI) findings of iron accumulation in the brain, especially in periaqueductal gray and red nucleus, have been correlated with both duration of illness and frequency of attacks. METHODS This study therefore evaluated iron deposition as measured with MRI in basal ganglia and pain regulatory nuclei in neurologically healthy control volunteers and in patients with various migraine subtypes: episodic migraine (n = 10) with (n = 4) or without aura (n = 6), and chronic daily headache (n = 11), including medication overuse headache (MOH, n = 8), chronic tension-type headache (n = 1), and primary chronic migraine (n = 2). The goal was to assess differences in iron deposition among migraine subtypes and controls in the hopes of linking the by-products of frequent attacks or long duration of illness with these changes. RESULTS The study sought to evaluate the tradeoff between sensitivity and specificity in T2 imaging of patients with migraine, and found that only T2 imaging in the globus pallidus was able to distinguish between episodic and chronic migraine, suggesting that this technique may be the most appropriate to assess migraine frequency. Patients with MOH did not demonstrate T2' shortening. CONCLUSIONS Because iron accumulation should cause shortening of both T2 and T2', although the lack of significance in observed T2' difference could be due to increased variance in T2' the measurement, these results suggest that a mechanism other than increased iron deposition may play a role in the genesis or pathophysiology of MOH.
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8.
Intranasal ketorolac tromethamine (SPRIX(R)) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: safety and efficacy data from a phase II clinical trial.
Pfaffenrath, V, Fenzl, E, Bregman, D, Färkkila, M
Cephalalgia : an international journal of headache. 2012;(10):766-77
Abstract
OBJECTIVE Ketorolac is a non-triptan, non-opioid, mixed cyclooxygenase (COX)1/2-inhibitor for short-term management of moderate-to-severe acute pain. This trial evaluated an intranasal formulation of ketorolac tromethamine (SPRIX®) containing 6% lidocaine (ROX-828) for the acute treatment of migraine with and without aura as defined by the International Headache Society. METHODS Patients were randomly assigned 1:1 to self-treat with intranasal ROX-828 (31.5 mg ketorolac tromethamine/200 µL, containing 6% of lidocaine) or placebo (with 6% lidocaine) within four hours of a new migraine attack rated ≥ moderate in pain intensity. Assessments included headache intensity and associated migraine symptoms (nausea, vomiting, phonophobia, photophobia) measured at baseline and at regular intervals through 48 hours post-dosing, and global impression of efficacy (seven-point scale) measured at two hours. RESULTS Randomized patients who had a migraine attack (N = 140) were evaluable (ROX-828, N = 68; placebo, N = 72). Patients receiving ROX-828 showed a significant (p < 0.05) improvement in pain relief at all time points except 0.5 and 24 hours compared with those who received placebo. More patients achieved pain-free status with ROX-828 than with placebo at 1.5, 3, 4, 24 and 48 hours (p < 0.05); significance at the two-hour time point, which was the primary endpoint, was not met. Patients' global impression of efficacy showed statistically significantly better results for patients receiving ROX-828 than for those receiving placebo. Associated migraine symptoms were significantly improved (p < 0.05) with ROX-828 relative to placebo at several time points throughout the observation period. The most frequently reported adverse events in both groups were associated with nasal discomfort. CONCLUSION Self-administered intranasal ROX-828 was well tolerated. While the primary endpoint was not met, the results provide preliminary evidence that ROX-828 improves migraine pain.
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9.
Lack of drug interaction between the migraine drug MAP0004 (orally inhaled dihydroergotamine) and a CYP3A4 inhibitor in humans.
Kellerman, D, Kori, S, Forst, A, Chang, J, Febbraro, S, Wutann, L, Thomas, T, Taylor, G, Dodick, D
Cephalalgia : an international journal of headache. 2012;(2):150-8
Abstract
BACKGROUND Dihydroergotamine (DHE), a proven migraine treatment, currently has product labeling warning against concomitant use of CYP3A4 inhibitors because of potential drug interactions. However, no reported studies of such interactions with DHE administered by any route are available. METHODS The pharmacokinetics (PK) of MAP0004, an investigative inhaled DHE formulation, were assessed in human subjects with and without CYP3A4 inhibition by ketoconazole to evaluate the potential for drug interaction, elevation of DHE levels, and increased adverse effects. RESULTS After MAP0004 alone vs. MAP0004 plus ketoconazole, the DHE maximum concentrations (C(max)) and area-under-the-curve (AUC(0-48) and AUC(0-∞)) were not statistically significantly different nor was the C(max) of the primary metabolite, 8'-OH-DHE. A difference in 8'-OH-DHE AUCs was observed between MAP0004 with and without ketoconazole; however, the concentrations were very low. MAP0004 was well tolerated after both treatments. CONCLUSIONS This study demonstrated that CYP3A4 inhibition had little to no effect on DHE PK after MAP0004 administration, apparently because of its high systemic and low gastrointestinal bioavailability. CYP3A4 inhibition slowed elimination of the metabolite 8'-OH-DHE, but concentrations were too low to be pharmacologically relevant.
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10.
Lavender essential oil in the treatment of migraine headache: a placebo-controlled clinical trial.
Sasannejad, P, Saeedi, M, Shoeibi, A, Gorji, A, Abbasi, M, Foroughipour, M
European neurology. 2012;(5):288-91
Abstract
UNLABELLED Lavender essential oil has been used as an anxiolytic drug, a mood stabilizer, a sedative, spasmolytic, antihypertensive, antimicrobial, analgesic agent as well as a wound healing accelerator. We have studied for the first time the efficacy of lavender essential oil inhalation for the treatment of migraine in a placebo-controlled clinical trial. METHODS Forty-seven patients with definite diagnosis of migraine headache were divided into cases and controls. Cases inhaled lavender essential oil for 15 min, whereas the control group used liquid paraffin for the same time period. Patients were asked to record their headache severity and associated symptoms in 30-min intervals for a total of 2 h. We matched the two groups for key confounding factors. RESULTS The mean reduction of headache severity in cases was 3.6 ± 2.8 based on Visual Analogue Scale score. The reduction was 1.6 ± 1.6 in controls. This difference between the controls and cases was statistically significant with p < 0.0001. From 129 headache attacks in cases, 92 responded entirely or partially to lavender. In the control group, 32 out of 68 recorded headache attacks responded to placebo. The percentage of responders was significantly higher in the lavender group than the placebo group (p = 0.001). CONCLUSION The present study suggests that inhalation of lavender essential oil may be an effective and safe treatment modality in acute management of migraine headaches.