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Serum lipid abnormalities in migraine: A meta-analysis of observational studies.
Liampas, I, Mylonas, KS, Brotis, A, Dervenis, P, Siokas, V, Mentis, AA, Dastamani, M, Aloizou, AM, Tsouris, Z, Aslanidou, P, et al
Headache. 2021;(1):44-59
Abstract
BACKGROUND The association of migraine with vascular comorbidities is long-established. The contribution of the "traditional" cardiovascular risk factors to this connection remains unclear. OBJECTIVE To determine-quantify the differences in the serum lipid concentrations between lipid-lowering agents-naïve individuals with migraine and healthy controls (HC). METHODS The study protocol was not preregistered with an online systematic review-protocol registry. A literature search involving MEDLINE, EMBASE, CENTRAL, Google Scholar, and the OpenGrey database was performed. Case-control, cross-sectional, or cohort studies involving HC and participants with migraine (with and without aura regardless of the use of prophylactic treatment) that quantitatively assessed serum low-density lipoprotein cholesterol (LDL-C) (primary index) and/or total cholesterol (TC) and/or high-density lipoprotein cholesterol (HDL-C) and/or triglycerides (TG) (secondary indices) were retrieved. Articles including participants with known dyslipidemia (or under lipid-lowering medications) or with secondary causes of dyslipidemia (aside from the subjectively assessed lifestyle parameters) were excluded. Studies with abstracts and full texts not published in English and articles reporting the implementation of other study designs (reviews, meta-analyses, commentaries, case reports, etc.) were excluded as well. Conference abstracts and English abstracts from studies with full texts not published in English were evaluated as part of the gray literature. Each step of the review process was performed by two investigators independently, and relevant data were abstracted based on standardized extraction forms. Any discrepancies were resolved by a third investigator. RESULTS Seventeen studies (16 case-control and 1 cross-sectional) fulfilled the eligibility criteria. Retrieved articles involved adult participants, principally during the fourth decade of life. Results were compatible with higher LDL-C levels in migraine individuals (1370) than in HC (1215) [12 studies, mean difference (MD) = 10.4 mg/dl, 95% confidence interval (CI) = (1.6, 19.2)]. Similarly, higher TC levels were determined in migraine patients [14 studies, migraine = 1325, HC = 1213, MD = 10.6 mg/dl, 95% CI = (1.8, 19.3)], as were TG levels [15 studies, migraine = 1526, HC = 1262, MD = 11.8 mg/dl, 95% CI = (3.6, 20.0)]. HDL-C concentrations were not different between the two groups [14 studies, migraine = 1488, HC = 1328, MD = -0.4 mg/dl, 95% CI = (-2.2, 1.5)]. Prespecified sensitivity analysis following the exclusion of studies not presenting comparable body mass index values between the groups nullified the significant difference regarding LDL-C levels [MD = 5.3 mg/dl, 95% CI = (-0.1, 10.8)]. Subgroup analyses as well as the direct comparison of migraine with aura and migraine without aura individuals were compatible with no difference regarding lipid concentrations, but only a small fraction of the retrieved studies presented relevant figures. CONCLUSIONS Although our results are of limited generalizability, since most retrieved studies were performed in Turkey (nine studies), TC abnormalities may provide part of the explanation for the unfavorable cardiovascular profile of migraine patients. Lifestyle may be partly or entirely accountable for the determined increased serum TC. Additional studies that will completely address the effect that lifestyle parameters exert on lipid concentrations are required to better capture existing abnormalities.
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Effect of coenzyme Q10 supplementation on clinical features of migraine: a systematic review and dose-response meta-analysis of randomized controlled trials.
Parohan, M, Sarraf, P, Javanbakht, MH, Ranji-Burachaloo, S, Djalali, M
Nutritional neuroscience. 2020;(11):868-875
Abstract
Objective: Coenzyme Q10 is an antioxidant and an essential mitochondrial cofactor which has been suggested to improve the clinical features of migraine. Several randomized clinical trials have examined the effects of Coenzyme Q10 on migraine with inconclusive results. The aim of this systematic review and meta-analysis was to evaluate the impact of Coenzyme Q10 supplementation on the frequency, severity, and duration of migraine attacks. Methods: A systematic review of the literature was conducted using ISI Web of Science, PubMed, Cochrane library and Scopus to identify eligible studies up to April 2018. Studies included were randomized clinical trials of Coenzyme Q10 supplementation that reported the frequency, severity, or duration of migraine attacks as a primary outcome. A meta-analysis of eligible studies was performed using the fixed effects model or the random effects model to estimate pooled effect size. Results: Four randomized clinical trials with 221 participants were included. Coenzyme Q10 supplementation significantly reduced the frequency of migraine attacks (weighted mean difference: -1.87 attacks/month, 95% CI: -2.69 to -1.05, p < 0.001) without significant heterogeneity among the studies (I 2 = 36.6%, p = 0.192). Coenzyme Q10 supplementation had no significant effect on severity (weighted mean difference: -2.35 visual analog scale score, 95% CI: -5.19 to 0.49, p = 0.105) and duration of migraine attacks (weighted mean difference: -6.14 h, 95% CI: -13.14 to 0.87, p = 0.086) with high heterogeneity. Conclusion: Pooled analyses of available randomized clinical trials suggest that Coenzyme Q10 supplementation may reduce the frequency of migraine attacks per month without affecting the severity or duration of migraine attacks.
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Levetiracetam as preventive treatment in adults with migraine: an up-to-date systematic review and quantitative meta-analysis.
Tsaousi, G, Pourzitaki, C, Siafis, S, Kyrgidis, A, Grosomanidis, V, Kouvelas, D, Papazisis, G
European journal of clinical pharmacology. 2020;(2):161-174
Abstract
PURPOSE The aim of this systematic review was to evaluate current evidence on the efficacy and safety of levetiracetam as migraine prophylaxis in adult patients suffering from migraine attacks. METHODS PubMed, Scopus, Cochrane Central Register of Controlled Trials, and International Web of Science were searched (last search in August 2018) for studies investigating levetiracetam for migraine prophylaxis in adults. Both randomized and non-randomized trials were eligible. Efficacy was the primary outcome, but tolerability was also investigated. The study is registered on PROSPERO, number CRD42018088900. RESULTS Nine studies, enrolling 215 patients, were included. Levetiracetam decreased the frequency of attacks with headache in all studies, with a pooled mean difference of -3.02 (95% CI: -4.59 to -1.45; I2 = 0%), -4.65(-7 to -2.3; I2 = 0%), and -5.71 (-8.60 to -2.82; I2 = 0%) at 1, 3, and 6 months compared with baseline. Three randomized controlled trials were included, and levetiracetam was superior to placebo in two but was inferior to sodium valproate in reducing headache frequency. Similar results were found in the other indices of efficacy, and levetiracetam was generally well tolerated. CONCLUSION Levetiracetam may be a relatively safe and efficacious treatment for the prophylaxis of migraine based on limited evidence, most from uncontrolled studies. Further evidence from randomized controlled trials is necessary.
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Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.
Locher, C, Kossowsky, J, Koechlin, H, Lam, TL, Barthel, J, Berde, CB, Gaab, J, Schwarzer, G, Linde, K, Meissner, K
JAMA pediatrics. 2020;(4):341-349
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Abstract
IMPORTANCE Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking. OBJECTIVE To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability. DATA SOURCES Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018. STUDY SELECTION Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers. DATA EXTRACTION AND SYNTHESIS Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model. MAIN OUTCOMES AND MEASURES Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason). RESULTS Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention. CONCLUSIONS AND RELEVANCE Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.
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Intravenous sodium valproate for acute migraine in the emergency department: A meta-analysis.
Wang, F, Zhang, H, Wang, L, Cao, Y, He, Q
Acta neurologica Scandinavica. 2020;(6):521-530
Abstract
The role of intravenous sodium valproate (iVPA) in acute migraine attack has not been completely established. The aim of this updated review was to evaluate the efficacy and safety of iVPA in patients with acute migraine in the emergency department. We searched the PubMed, Web of Science, and Cochrane Library databases for relevant randomized controlled trials (RCTs). The primary outcome was improvement of headache intensity and headache relief. The need for rescue therapy, recurrence of headache, and number of adverse events was also assessed. Seven double-blinded RCTs involving 682 patients were analyzed. Overall, patients receiving iVPA had less improvement of headache intensity (SMD: -0.39, 95% CI: -0.73 to -0.06, P = .02) and lower rate of headache relief (OR: 0.51, 95% CI: 0.33 to 0.77, P = .002) than those receiving other active comparators. In addition, iVPA increased the odds of rescue therapy compared with other active drugs (OR: 3.76; 95% CI: 1.96 to 7.20, P < .0001). Subgroup analysis showed that iVPA was comparable to dexamethasone, with similar improvement of headache intensity, and recurrence of headache. For migraine without aura, we found no significant difference in headache intensity improvement when iVPA was compared with active comparators (SMD: -0.00, 95% CI: -0.54 to 0.54, P = 1.00). iVPA was inferior to the studied comparators and was comparable to dexamethasone for aborting migraine attack. Based on the available evidence, iVPA may be a reasonable alternative or salvage therapy. In particular, iVPA might be a promising agent for migraine with aura and migraine status.
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Genetic variants in migraine: a field synopsis and systematic re-analysis of meta-analyses.
Zhao, Y, Zhu, R, Xiao, T, Liu, X
The journal of headache and pain. 2020;(1):13
Abstract
OBJECTIVE Numerous genetic variants from meta-analyses of observational studies and GWAS were reported to be associated with migraine susceptibility. However, due to the random errors in meta-analyses, the noteworthiness of the results showing statistically significant remains doubtful. Thus, we performed this field synopsis and re-analysis study to evaluate the noteworthiness using a Bayesian approach in hope of finding true associations. METHODS Relevant meta-analyses from observational studies and GWAS examining correlation between all genetic variants and migraine risk were included in our study by a PubMed search. Identification of noteworthy associations were analyzed by false-positive rate probability (FPRP) and Bayesian false discovery probability (BFDP). Using noteworthy variants, GO enrichment analysis were conducted through DAVID online tool. Then, the PPI network and hub genes were performed using STRING database and CytoHubba software. RESULTS As for 8 significant genetic variants from observational studies, none of which showed noteworthy at prior probability of 0.001. Out of 47 significant genetic variants in GWAS, 36 were noteworthy at prior probability of 0.000001 via FPRP or BFDP. We further found the pathways "positive regulation of cytosolic calcium ion concentration" and "inositol phosphate-mediated signaling" and hub genes including MEF2D, TSPAN2, PHACTR1, TRPM8 and PRDM16 related to migraine susceptibility. CONCLUSION Herein, we have identified several noteworthy variants for migraine susceptibility in this field synopsis. We hope these data would help identify novel genetic biomarkers and potential therapeutic target for migraine.
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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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Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine.
Onderwater, GLJ, Ligthart, L, Bot, M, Demirkan, A, Fu, J, van der Kallen, CJH, Vijfhuizen, LS, Pool, R, Liu, J, Vanmolkot, FHM, et al
Neurology. 2019;(16):e1899-e1911
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Abstract
OBJECTIVE To identify a plasma metabolomic biomarker signature for migraine. METHODS Plasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses. RESULTS Decreases in the level of apolipoprotein A1 (β -0.10; 95% confidence interval [CI] -0.16, -0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β -0.10; 95% CI -0.15, -0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β -0.24; 95% CI -0.36, -0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status. CONCLUSIONS Metabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.
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The efficacy of dexketoprofen for migraine attack: A meta-analysis of randomized controlled studies.
Yang, B, Xu, Z, Chen, L, Chen, X, Xie, Y
Medicine. 2019;(46):e17734
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Abstract
BACKGROUND The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients. METHODS We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2019 for randomized controlled trials (RCTs) assessing the effect of dexketoprofen supplementation versus placebo on pain control for migraine attack patients. This meta-analysis is performed using the random-effect model. RESULTS Five RCTs involving 794 patients are included in the meta-analysis. Overall, compared with control group for migraine attack, dexketoprofen supplementation is associated with substantially increased pain free at 2 hours (RR = 1.90; 95% CI = 1.43-2.53; P < .0001), pain free at 48 hours (RR = 1.63; 95% CI = 1.07-2.49; P = .02), good or excellent treatment (RR = 1.48; 95% CI = 1.24-1.78; P < .0001) and pain relief at 2 hours (RR = 1.80; 95% CI = 1.17-2.77; P = .007), as well as reduced need for rescue drug (RR = 0.64; 95% CI = 0.43-0.94; P = .02), with no significant increase in adverse events (RR = 1.51; 95% CI = 0.87-2.62; P = .14). CONCLUSION Dexketoprofen supplementation benefits to improve pain control at 48 hours and reduce the need for rescue drug in migraine attack patients.