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European Journal of Pharmacology Aug 2024Migraine is a common and disabling primary headache disorder. Several drugs targeting calcitonin gene-related peptide (CGRP), such as erenumab (an anti-CGRP receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine is a common and disabling primary headache disorder. Several drugs targeting calcitonin gene-related peptide (CGRP), such as erenumab (an anti-CGRP receptor mAb), have been developed recently. However, the real-world effects of erenumab are not well understood.
OBJECTIVE
To assess the clinical effectiveness and safety of erenumab for reducing migraine intensity and frequency in the real world.
METHODS
A systematic search of PubMed, Scopus, Web of Science and the Cochrane Library was conducted from inception to December 2023. Studies estimating the real-world effect of erenumab on monthly migraine days (MMD), monthly headache days (MHD), headache impact test (HIT-6), number of days in medication (NDM), acute monthly intake (AMI), pain intensity (PI) and safety outcomes were included. Meta-analyses of proportions or mean differences were performed.
RESULTS
Fifty-three studies were included. At 3-months, the effect was -7.18 days for MMD, -6.89 days for MHD, -6.97 for HIT-6, -6.22 days for NDM, -15.75 for AMI, and -1.71 for PI. Generally, the effect at 6- and 12-months increased slightly and gradually. The MMD/MHD response rates revealed that approximately one-third of patients exhibited a response greater than 30%, while one-sixth demonstrated a response exceeding 50%. Additionally, 3-4% of patients achieved a response rate of 100%. Adverse event rates were 0.34 and 0.43 at 6- and 12-months, respectively.
CONCLUSION
This study provides strong evidence of the effectiveness and safety of erenumab in the real world; to our knowledge, this is the first real-world meta-analysis specific to erenumab. Erenumab represents a solid therapeutic option for physicians.
Topics: Humans; Migraine Disorders; Antibodies, Monoclonal, Humanized; Calcitonin Gene-Related Peptide Receptor Antagonists; Treatment Outcome
PubMed: 38823758
DOI: 10.1016/j.ejphar.2024.176702 -
Toxins May 2024Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in... (Observational Study)
Observational Study
Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients under 18 years old with CM treated with BTX-A (PREEMPT protocol) as compassionate use. Demographic, efficacy (monthly headache days-MHD; monthly migraine days-MMD; acute medication days/month-AMDM) and side effect data were collected. A ≥ 50% reduction in MHD was considered as a response. Effectiveness and safety were analyzed at 6 and 12 months. A systematic review of the use of BTX-A in children/adolescents was conducted in July 2023. In total, 20 patients were included (median age 15 years [14.75-17], 70% (14/20) females). The median basal frequencies were 28.8 [20-28] MHD, 18 [10-28] MMD and 10 [7.5-21.2] AMDM. Compared with baseline, at 6 months ( = 20), 11 patients (55%) were responders, with a median reduction in MHD of -20 days/month ( = 0.001). At 12 months ( = 14), eight patients (57.1%) were responders, with a median reduction in MHD of -17.5 days/month ( = 0.002). No adverse effects were reported. The literature search showed similar results. Our data supports the concept that BTX-A is effective, well tolerated, and safe in adolescents with CM resistant to oral preventatives.
Topics: Humans; Migraine Disorders; Botulinum Toxins, Type A; Adolescent; Female; Male; Prospective Studies; Chronic Disease; Treatment Outcome; Neuromuscular Agents
PubMed: 38787073
DOI: 10.3390/toxins16050221 -
Clinical NeuropharmacologyEvaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks.
METHODS
A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs.
RESULTS
Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72).
CONCLUSION
Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.
Topics: Migraine Disorders; Humans; Randomized Controlled Trials as Topic; Calcitonin Gene-Related Peptide Receptor Antagonists; Treatment Outcome
PubMed: 38743600
DOI: 10.1097/WNF.0000000000000588 -
Frontiers in Neurology 2024Extensive research on cluster headaches (CHs) has been conducted worldwide; however, there is currently no bibliometric research on CHs. Therefore, this study aimed to...
BACKGROUND
Extensive research on cluster headaches (CHs) has been conducted worldwide; however, there is currently no bibliometric research on CHs. Therefore, this study aimed to analyze the current research hotspots and frontiers of CHs over the past decade.
METHODS
Raw data on CHs was obtained from the Web of Science Core Collection database from 2014 to 2023. CiteSpace V6.2 R7 (64 bit) and Microsoft Excel were used to assess the annual publication volume, authors, countries, and references. VOSviewer 1.6.19 software was used to assess the institutions, cited authors, and keywords, and co-occurrence and clustering functions were applied to draw a visual knowledge map.
RESULTS
In the past decade, the overall annual publication volume of articles related to CHs has increased year by year, showing promising development prospects. The total 1909 articles contained six types of literature, among which the proportion of original research articles was the highest (1,270 articles, 66.53%), published in 201 journals. (439 articles, 23.00%) had the highest publication volume, and the was the journal with the highest impact factor (IF = 168.9). Furthermore, the United States of America was the country with the most published papers (584 articles, 30.60%), University of London was the research institution with the most published papers (142 articles, 7.44%), and Goodsby, Peter J was found to be the most prolific author (38 articles, 1.99%).
CONCLUSION
This study may provide some direction for subsequent researcher on CHs. The hotspots and frontiers of future research on CHs are suggested as follows: in basic medicine, more attention should be paid to pathophysiology, especially on increasing research on the pathogenesis mediated by CGRP; in clinical medicine, more attention should be paid to the design of evidence-based medicine methodology, especially the strict design, including double-blind, questionnaire, and follow-up, in randomized controlled trials, using high-quality articles for meta-analyses, and recommending high-level evidence; therapeutic techniques need to be further explored, suggesting the implementation of transcranial magnetic stimulation of the cortex, and stimulation of the sphinopalatine ganglia and occipital nerve to achieve peripheral neuromodulation. Furthermore, chronic migraine and insomnia are inextricably linked to CHs.
PubMed: 38725643
DOI: 10.3389/fneur.2024.1395770 -
Headache May 2024This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We...
BACKGROUND
This study reviewed migraine prevalence and disability gathered through epidemiologic survey studies in the United States conducted over the past three decades. We summarized these studies and evaluated changing patterns of disease prevalence and disability.
METHODS
We conducted a systematic review of US studies addressing the prevalence, disability, and/or burden of migraine, including both episodic migraine (EM) and chronic migraine (CM). A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol was used in conjunction with the PubMed search engine. Eligible studies were published before February 2022, were conducted in the United States, included representative samples, and used a case definition of migraine based on the International Classification of Headache Disorders (ICHD). The primary measure of disease burden was the Migraine Disability Assessment Scale (MIDAS). The MIDAS measures days lost due to migraine over 3 months in three domains and defines groups with moderate (Grade III) or severe disability (Grade IV) using cut-scores.
RESULTS
Of the 1609 identified records, 26 publications from 11 US population-based studies met eligibility criteria. The prevalence of migraine in the population has remained relatively consistent for the past 30 years: ranging from 11.7% to 14.7% overall, 17.1% to 19.2% in women, and 5.6% to 7.2% in men in the studies reviewed. CM prevalence is 0.91% (1.3% among women and 0.5% of men) in adults and 0.8% in adolescents. The proportion of people with migraine and moderate-to-severe MIDAS disability (Grades III-IV), has trended upward across studies from 22.0% in 2005 to 39.0% in 2012, to 43.2% in 2016, and 42.4% in 2018. A consistently higher proportion of women were assigned MIDAS Grades III/IV relative to men.
CONCLUSION
The prevalence of migraine in the United States has remained stable over the past three decades while migraine-related disability has increased. The disability trend could reflect changes in reporting, study methodology, social and societal changes, or changes in exacerbating or remediating factors that make migraine more disabling, among other hypotheses. These issues merit further investigation.
Topics: Humans; Migraine Disorders; United States; Prevalence; Cost of Illness; Disability Evaluation
PubMed: 38700185
DOI: 10.1111/head.14709 -
Nutrients Apr 2024L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal...
OBJECTIVE
L-carnitine (LC), a vital nutritional supplement, plays a crucial role in myocardial health and exhibits significant cardioprotective effects. LC, being the principal constituent of clinical-grade supplements, finds extensive application in the recovery and treatment of diverse cardiovascular and cerebrovascular disorders. However, controversies persist regarding the utilization of LC in nervous system diseases, with varying effects observed across numerous mental and neurological disorders. This article primarily aims to gather and analyze database information to comprehensively summarize the therapeutic potential of LC in patients suffering from nervous system diseases while providing valuable references for further research.
METHODS
A comprehensive search was conducted in PubMed, Web Of Science, Embase, Ovid Medline, Cochrane Library and Clinicaltrials.gov databases. The literature pertaining to the impact of LC supplementation on neurological or psychiatric disorders in patients was reviewed up until November 2023. No language or temporal restrictions were imposed on the search.
RESULTS
A total of 1479 articles were retrieved, and after the removal of duplicates through both automated and manual exclusion processes, 962 articles remained. Subsequently, a meticulous re-screening led to the identification of 60 relevant articles. Among these, there were 12 publications focusing on hepatic encephalopathy (HE), while neurodegenerative diseases (NDs) and peripheral nervous system diseases (PNSDs) were represented by 9 and 6 articles, respectively. Additionally, stroke was addressed in five publications, whereas Raynaud's syndrome (RS) and cognitive disorder (CD) each had three dedicated studies. Furthermore, migraine, depression, and amyotrophic lateral sclerosis (ALS) each accounted for two publications. Lastly, one article was found for other symptoms under investigation.
CONCLUSION
In summary, LC has demonstrated favorable therapeutic effects in the management of HE, Alzheimer's disease (AD), carpal tunnel syndrome (CTS), CD, migraine, neurofibromatosis (NF), PNSDs, RS, and stroke. However, its efficacy appears to be relatively limited in conditions such as ALS, ataxia, attention deficit hyperactivity disorder (ADHD), depression, chronic fatigue syndrome (CFS), Down syndrome (DS), and sciatica.
Topics: Humans; Carnitine; Dietary Supplements; Mental Disorders; Nervous System Diseases
PubMed: 38674921
DOI: 10.3390/nu16081232 -
Headache May 2024We conducted a systematic review and meta-analysis to explore the relationship between blood pituitary adenylate cyclase-activating polypeptide (PACAP) levels and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We conducted a systematic review and meta-analysis to explore the relationship between blood pituitary adenylate cyclase-activating polypeptide (PACAP) levels and migraine.
BACKGROUND
PACAP is involved in the onset of migraine, but the results from clinical studies on PACAP level variations across different periods of migraine are conflicting.
METHODS
We systematically searched for observational studies that reported PACAP levels in people with migraine and non-migraine controls published in English from the PubMed, Web of Science, and Ovid electronic databases, or in Chinese from the Chinese National Knowledge Infrastructure and the WanFang Med database. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The quality of evidence for each outcome was assessed according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines.
RESULTS
Of the 514 identified studies, 8 were eligible for inclusion. There was a "very low" level of evidence suggesting that the PACAP level is negatively correlated with migraine disease duration in adults with migraine (summary = -0.35, 95% confidence interval [CI] -0.49 to -0.22) and that the PACAP is higher in people with migraine during the ictal period than in the interictal period (standardized mean difference = 0.41, 95% CI 0.17 to 0.66) for both adults and children with migraine. Adult patients with episodic migraine (weighted mean difference [WMD] = -9.58 pg/mL, 95% CI -13.41 to -5.75 pg/mL) or chronic migraine (WMD = -10.93 pg/mL, 95% CI -15.57 to -6.29 pg/mL) had lower blood PACAP levels than non-migraine controls during the interictal period, supported by a "low" or "very low" quality of evidence, respectively, according to the GRADE rules.
CONCLUSION
There is a very low certainty of evidence suggesting that the PACAP level is negatively correlated with migraine disease duration of adults with migraine and it varies greatly among different periods of migraine of both adults and children with migraine.
Topics: Humans; Migraine Disorders; Observational Studies as Topic; Pituitary Adenylate Cyclase-Activating Polypeptide
PubMed: 38659322
DOI: 10.1111/head.14711 -
BMJ Neurology Open 2024Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications...
BACKGROUND
Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs.
METHOD
We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC).
RESULTS
Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs.
CONCLUSION
Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations.
PROSPERO REGISTRATION NUMBER
CRD42021265993.
PubMed: 38646505
DOI: 10.1136/bmjno-2023-000616 -
Headache Apr 2024To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine.
BACKGROUND
Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear.
METHODS
Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096).
RESULTS
A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics.
CONCLUSIONS
Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.
Topics: Humans; Analgesics; Emergency Service, Hospital; Metoclopramide; Migraine Disorders; Network Meta-Analysis; Pain Management; Randomized Controlled Trials as Topic
PubMed: 38644702
DOI: 10.1111/head.14704 -
Headache May 2024To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). (Meta-Analysis)
Meta-Analysis
Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: A systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs).
BACKGROUND
Insurers mandate step therapy with NOEPs before approving CGRP mAbs.
METHODS
Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days.
RESULTS
Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]).
CONCLUSIONS
There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.
Topics: Humans; Administration, Oral; Antibodies, Monoclonal; Calcitonin Gene-Related Peptide; Migraine Disorders; Randomized Controlled Trials as Topic; Topiramate; Valproic Acid
PubMed: 38634515
DOI: 10.1111/head.14693