Objective: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults. Design: Systematic review and network meta-analysis. Data sources: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, as well as websites of regulatory agencies and pharmaceutical companies without language restrictions until 24 June 2023. Methods: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Random effects network meta-analyses were conducted for the primary analyses. The primary outcomes were the proportion of participants who were pain-free at two hours post-dose and the proportion of participants with sustained pain freedom from two to 24 hours post-dose, both without the use of rescue drugs. Certainty of the evidence was graded using the confidence in network meta-analysis (CINeMA) online tool. Vitruvian plots were used to summarise findings. An international panel of clinicians and people with lived experience of migraine co-designed the study and interpreted the findings. Eligibility criteria for selecting studies: Double blind randomised trials of adults (≥18 years) with a diagnosis of migraine according to the International Classification of Headache Disorders. Results: 137 randomised controlled trials comprising 89 445 participants allocated to one of 17 active interventions or placebo were included. All active interventions showed superior efficacy compared with placebo for pain freedom at two hours (odds ratios from 1.73 (95% confidence interval (CI) 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan), and most of them also for sustained pain freedom to 24 hours (odds ratios from 1.71 (1.07 to 2.74) for celecoxib to 7.58 (2.58 to 22.27) for ibuprofen). In head-to-head comparisons between active interventions, eletriptan was the most effective drug for pain freedom at two hours (odds ratios from 1.46 (1.18 to 1.81) to 3.01 (2.13 to 4.25)), followed by rizatriptan (1.59 (1.18 to 2.17) to 2.44 (1.75 to 3.45)), sumatriptan (1.35 (1.03 to 1.75) to 2.04 (1.49 to 2.86)), and zolmitriptan (1.47 (1.04 to 2.08) to 1.96 (1.39 to 2.86)). For sustained pain freedom, the most efficacious interventions were eletriptan and ibuprofen (odds ratios from 1.41 (1.02 to 1.93) to 4.82 (1.31 to 17.67)). Confidence in accordance with CINeMA ranged from high to very low. Sensitivity analyses on Food and Drug Administration licensed doses only, high versus low doses, risk of bias, and moderate to severe headache at baseline confirmed the main findings for both primary and secondary outcomes. Conclusions: Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant. Although cost effectiveness analyses are warranted and careful consideration should be given to patients with a high risk cardiovascular profile, the most effective triptans should be considered as preferred acute treatment for migraine and included in the WHO List of Essential Medicines to promote global accessibility and uniform standards of care. Systematic review registration: Open Science Framework https://osf.io/kq3ys/.
INTRODUCTION: The ideal dose of lasmiditan for migraine is not clear. This meta-analysis aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients.
METHODS: We have searched several databases including PubMed, Embase, Web of Science, EBSCO, and Cochrane Library Databases and selected the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model.
RESULTS: Five randomized controlled trials were included in this meta-analysis. Compared with lasmiditan 100-mg group in migraine patients, lasmiditan 200-mg group was associated with substantially increased pain free at 2 hours (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.12-1.44; P = 0.0002) and pain free at 24 hours (OR, 1.31; 95% CI, 1.08-1.60; P = 0.007) but demonstrated no obvious impact on pain relief at 2 hours (OR, 1.02; 95% CI, 0.91-1.16; P = 0.72) or MBS free at 2 hours (OR, 0.94; 95% CI, 0.77-1.14; P = 0.52). In addition, the incidence of adverse events was higher in lasmiditan 200-mg group than that in lasmiditan 100-mg group (OR, 1.29; 95% CI, 1.15-1.45; P < 0.0001).
CONCLUSIONS: Lasmiditan 200 mg is better for the treatment of migraine patients than lasmiditan 100 mg.
OBJECTIVE: Calcitonin gene-related peptide (CGRP) receptor antagonists have been suggested as novel treatments for acute migraine. This study aimed to use meta-analysis to compare the safety and tolerability of five existing oral CGRP receptor antagonists (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant) with that of a placebo or triptans against acute migraine.
METHODS: Five prominent databases were searched to identify randomized controlled trials on this topic. The primary safety outcomes of interest were any adverse events (AEs) and treatment-related adverse events (TRAEs), and secondary outcomes were individual events, namely diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting.
RESULTS: Fifteen studies met the eligibility criteria and were examined in detail. Although, compared to placebo, oral CGRP receptor antagonists significantly increased the incidence of any AEs (risk ratio [RR] = 1.15; 95% confidence interval [CI] = 1.07-1.23), there was no difference in the incidence of TRAEs (RR = 1.18; 95% CI = 1.00-1.38). Moreover, CGRP receptor antagonists were safer than triptans with respect to primary safety outcomes, such as any AEs (RR = 0.78; 95% CI = 0.63-0.98) and TRAEs (RR = 0.68; 95% CI = 0.58-0.79).
CONCLUSION: Despite oral CGRP receptor antagonists posing a significantly higher risk of AEs when compared to placebo, CGRP receptor antagonists have a favorable safety profile compared to triptans. Our findings inform strategies to enhance safety and tolerability in the treatment of acute migraine.
BACKGROUND: Migraine has a great impact on public health. Current acute therapies do not satisfy all migraineurs. The novel serotonin 5-HT<sub>1F</sub> receptor agonist appears more promising for aborting migraine attacks.
OBJECTIVE: To evaluate the clinical efficacy and safety of lasmiditan in treating acute migraine attacks.
METHODS: The literature search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) which assessed the effect and safety of lasmiditan on migraine. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool. Results were extracted and pooled as risk ratios (RRs) with a fixed or random-effects model.
RESULTS: Based on the four included RCTs, pooled estimates showed that lasmiditan with the 50 mg, 100 mg, and 200 mg doses was superior to placebo at 2 h after the first dose in terms of pain freedom, absence of migraine-associated symptoms, headache relief, no/mild disability, and global impression of change (very much/much better) (RRs ranged from 1.13 to 1.96), except for nausea-free and vomiting-free. Both lasmiditan 100 mg and 200 mg resulted in significantly fewer patients using rescue medication (100 mg: RR = 0.75, 95% CI (0.61, 0.92), P = 0.007; 200 mg: RR = 0.81, 95% CI (0.66, 0.99), P = 0.04) at 2-24 h postdose, compared with placebo. Safety data showed that the proportion of patients reporting at least one treatment-emergent adverse event (TEAE) and the incidence of most common TEAEs such as dizziness, paresthesia, fatigue, somnolence, and nausea was higher in the lasmiditan groups (50 mg, 100 mg, and 200 mg), compared with placebo. There was no significant difference between lasmiditan and placebo in terms of cardiovascular-related TEAEs (RR = 2.75, 95% CI (0.81, 9.37), P = 0.11). Compared with lasmiditan 100 mg, lasmiditan 200 mg was more effective in pain freedom at 2 h after the first dose (RR = 0.83, 95% CI (0.74, 0.94), P = 0.004) but associated with a higher risk of reporting at least one TEAE (RR = 0.88, 95% CI (0.81, 0.96), P = 0.006).
CONCLUSIONS: Lasmiditan with the 50 mg, 100 mg, and 200 mg doses are effective and safe in acute migraine treatment. Lasmiditan 200 mg is more effective than lasmiditan 100 mg in pain freedom, while lasmiditan 100 mg is better tolerated in the short-term follow-up. Further larger sample-size RCTs are required to verify the applicability and tolerability in the long term.
Report»In: Systematic Review on Acute Treatments for Episodic Migraine: Surveillance Reports [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 Jul.
This report is the second surveillance report for the Agency for Healthcare Research and Quality (AHRQ) 2020 report Acute Treatments for Episodic Migraine (available at https://effectivehealthcare.ahrq.gov/products/migraine-treatments/research) and covers the time period from September 2, 2021, through December 30, 2021. The original 2020 report examined the evidence on the comparative effectiveness and harms of opioids as well as nonopioid pharmacologic and nonpharmacologic treatments to provide the full range of evidence to inform clinical decision making about the acute treatment of migraine. The objectives of this surveillance report are to identify the latest evidence published since the last surveillance report as of September 2, 2021 (Surveillance Report 1), and to determine how the new evidence impacts the findings of the 2020 report and surveillance report. Another update is planned for June 2022 (based on evidence published from January to March 2022).
Report»In: Systematic Review on Acute Treatments for Episodic Migraine: Surveillance Reports [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 Jul.
This report is the first update for the Agency for Healthcare Research and Quality (AHRQ) 2020 report Acute Treatments for Episodic Migraine (available at https://effectivehealthcare.ahrq.gov/products/migraine-treatments/research) and covers the time period from July 2020 through September 2021. The original 2020 report examined the evidence on the comparative effectiveness and harms of opioids as well as nonopioid pharmacologic and nonpharmacologic treatments to provide the full range of evidence to inform clinical decision making about the acute treatment of migraine. The objective of this update is to identify the latest evidence published since the 2020 report and to determine how the new evidence impacts the findings of the 2020 report. Subsequent updates are planned for March 2022 (based on evidence published from October to December 2021) and June 2022 (based on evidence published from January to March 2022).
Background: As one of the novel therapeutic drugs that targets Calcitonin gene-related peptide (CGRP), 75 mg rimegepant has been used for the acute management of migraine, which is one of the most common neurological diseases worldwide. Several clinical trials have been conducted to investigate the efficacy and safety of rimegepant for the acute management of migraine, but no systematic review of existing literature has been performed. We therefore performed a meta-analysis to investigate the efficacy and safety of rimegepant in treatment of patients with migraine. Method: Pubmed, Embased, and Cochrane Library were searched from January 2001 to August 2019 for randomized controlled trials (RCTs). Four RCTs with 3,827 patients were finally included in our study. Result: We pooled 3,827 patients from four RCTs, and the primary endpoints were freedom from pain, most bothersome symptom, and pain relief at 2 hr post dose. We found that 75 mg rimegepant led to significant freedom from pain (P < 0.001), pain relief (P < 0.001), and freedom from the most bothersome symptom (P < 0.001) at 2 hr post dose compared with the placebo. In addition, there was no statistically significant increase in adverse events compared with the placebo. Conclusions: 75 mg rimegepant had good efficacy and safety for acute treatment of migraine. Further studies are needed to compare the efficacy of rimegepant with traditional drugs for acute management of migraine.
TEMA: Esta é uma versão atualizada da revisão original Cochrane publicado em Outubro de 2013, sobre 'sumatriptan e naproxen para crises agudas de enxaqueca em adultos ".A enxaqueca é uma doença incapacitante comum e um fardo para o indivíduo, serviços de saúde e da sociedade. Ela afeta duas a três vezes mais mulheres do que homens, e é mais comum na faixa etária de 30 a 50 anos. abortivos tratamentos eficazes incluem o triptano e não esteróides anti-inflamatórias as classes de fármacos. Estes fármacos têm mecanismos de ação diferentes e combiná-los pode fornecer melhor alívio. Sumatriptan e naproxen está agora disponível em forma de combinação para o tratamento agudo da enxaqueca.
OBJETIVOS: determinar a eficácia e tolerabilidade de sumatriptan e naproxen, administrados em conjunto, como comprimidos separados ou tomado como uma combinação comprimido de dose fixa, em comparação com placebo e outras intervenções ativas no tratamento de crises agudas de enxaqueca em adultos.
PESQUISA MÉTODOS: Para esta actualização que procurou o Cochrane Central Register de Ensaios Controlados (CENTRAL) via The Cochrane Register de Estudos Online (CRSO) a 28 de Outubro de 2015, MEDLINE (via Ovídio) 1946-28 2015 outubro, e EMBASE (via Ovid ) 1974-28 2015 outubro, e duas bases de dados on-line (www.gsk-clinicalstudyregister.com e www.clinicaltrials.gov). Nós também procurou as listas de referência dos estudos incluídos e comentários relevantes.
Critério de seleção: Foram incluídos randomizado, duplo-cego, placebo ou estudos com controlo activo, com pelo menos 10 participantes por grupo de tratamento, utilizando sumatriptan e naproxen para tratar um episódio de enxaqueca dor de cabeça.
COLETA DE DADOS E ANÁLISE: Dois revisores independentemente avaliaram a qualidade dos estudos e dados extraídos. Usamos números de participantes que alcançaram cada resultado para calcular relação risco e números necessários para tratar de um resultado benéfico adicional (NNT) ou para um resultado prejudicial adicional (NNH) em comparação com placebo ou um tratamento ativo diferente.
PRINCIPAIS RESULTADOS: Para esta actualização identificamos um novo estudo (43 participantes), mas não contribuiu quaisquer dados para análise. A revisão incluiu 13 estudos que utilizam sumatriptan 85 mg ou 50 mg mais 500 mg de naproxeno para tratar ataques de intensidade da dor leve, moderada ou grave. Doze estudos contribuíram com dados para as análises: 3663 participantes receberam tratamento de combinação, 3682 placebo, 964 sumatriptan e naproxen 982. Nós julgado apenas um pequeno estudo para estar em alto risco de viés para qualquer um dos critérios avaliados; não contribuir para quaisquer análises.No geral, a combinação foi melhor do que placebo para os resultados primários de alívio da dor-livre e dor de cabeça em duas horas. O NNT para a duas horas sem dor foi de 3,1 (IC 95% 2,9-3,5) quando a dor da linha de base era suave (resposta de 50% com sumatriptan e naproxen em comparação com 18% com placebo) e 4,9 (4,3-5,7) quando dor de linha de base foi moderada ou grave (28% com sumatriptan e naproxen em comparação com 8% com placebo) (evidência de alta qualidade). Usando 50 mg de sumatriptano, em vez de 85 mg, em combinação a não se alterou significativamente o resultado. Tratar cedo, quando a dor ainda era suave, foi significativamente melhor do que tratar uma vez dor era moderada ou grave para respostas sem dor em duas horas e durante o pós-dose 24 horas. Os eventos adversos foram principalmente ligeira ou moderada em termos de gravidade e raramente levou à retirada; eles foram mais comuns com a combinação do que com placebo (evidência de qualidade moderada).Onde os dados permitiram a comparação direta, tratamento de combinação foi superior a qualquer monoterapia, mas os eventos adversos foram menos frequentes com o naproxeno do que com sumatriptan (evidência de qualidade moderada).
Conclusão dos autores: As conclusões desta avaliação não foram alteradas. O tratamento de combinação foi eficaz no tratamento agudo de enxaqueca. O efeito foi maior do que para a mesma dose de sumatriptano ou naproxeno, quer sozinho, mas benefícios adicionais ao longo do sumatriptano isoladamente não foram grandes. Mais participantes conseguiram um bom alívio quando a medicação foi tomada no início do ataque, quando a dor ainda era suave. Os eventos adversos foram mais comuns com a combinação e sumatriptan sozinho do que com placebo ou naproxeno sozinho.
OBJETIVO: Fornecer recomendações de tratamento baseadas em evidências para adultos com enxaqueca aguda que necessitem de tratamento com medicação injetável em um departamento de emergência (ED). Abordamos duas questões clinicamente relevantes: (1) Quais medicamentos injetáveis devem ser considerados como tratamento de primeira linha para adultos que apresentam uma ED com enxaqueca aguda? (2) Os corticosteróides parenterais impedem a recorrência de enxaqueca em adultos descarregados de um ED? MÉTODOS: A American Headache Society convocou um painel experiente de autores que definiu uma estratégia de busca e depois realizou uma pesquisa do Medline, Embase, banco de dados Cochrane e registros de ensaios clínicos desde o início até 2015. Os artigos identificados foram classificados usando o risco da American Academy of Neurology De ferramenta de desvio. Para cada medicamento, o painel de especialistas determinou a probabilidade de eficácia. Foram criadas recomendações que comprovem eficácia, eventos adversos, disponibilidade de terapias alternativas e princípios de ação de medicação. RESULTADOS / CONCLUSÕES: A pesquisa identificou 68 ensaios clínicos randomizados únicos utilizando 28 medicamentos injetáveis. Destes, 19 foram classificados como classe 1 (baixo risco de viés), 21 foram classificados como classe 2 (maior risco de viés) e 28 foram classificados como classe 3 (maior risco de viés). A metoclopramida, a proclorperazina e o sumatriptano apresentaram vários estudos de classe 1 que apoiam a eficácia aguda, assim como a dexametasona para a prevenção da recorrência da dor de cabeça. Todos os outros medicamentos apresentaram níveis mais baixos de evidência. RECOMENDAÇÕES: A metoclopramida intravenosa e a proclorperazina e o sumatriptano subcutâneo devem ser oferecidos aos adultos elegíveis que apresentam uma ED com enxaqueca aguda (deve oferecer-nível B). A dexametasona deve ser oferecida a esses pacientes para prevenir a recorrência da dor de cabeça (deve oferecer-nível B). Devido à falta de evidências que demonstram eficácia e preocupação com seqüelas sub-agudas ou de longo prazo, a morfina e a hidromorfona injetáveis são melhor evitadas como terapia de primeira linha (pode evitar-nível C).
Embora triptanos são amplamente utilizados para o tratamento de enxaqueca aguda, são contraindicado ou não eficaz em uma grande proporção de pacientes. Assim, são necessários tratamentos alternativos. Os antagonistas dos receptores da calcitonina peptídeo relacionado ao gene, tais como telcagepant, estiveram sob investigação como um tratamento para a enxaqueca aguda. Uma meta-análise da eficácia da telcagepant vs placebo e triptanos (zolmitriptano ou rizatriptan) foi realizada. Ensaios clínicos randomizados foram identificados a partir de bancos de dados com os seguintes termos de pesquisa: enxaqueca; calcitonina peptídeo relacionado ao gene; antagonistas dos receptores da calcitonina peptídeo relacionado ao gene; eficácia, segurança e telcagepant. O desfecho primário foi a liberdade dor 2 horas após o primeiro tratamento. O desfecho secundário foi o alívio da dor 2 horas após o primeiro tratamento. Oito estudos foram incluídos na meta-análise (telcagepant = 4011 participantes). A diferença de liberdade dor em 2 horas favoreceu significativamente telcagepant em relação ao placebo (odds ratio = 2,70, intervalo de confiança de 95% = 2,27-3,21, P <0,001) e triptanos mais telcagepant (odds ratio = 0,68, intervalo de confiança de 95% = 0,56-0,83 , P <0,001). A diferença no alívio da dor em 2 horas favoreceu significativamente telcagepant em relação ao placebo (odds ratio = 2,48, 95% intervalo de confiança = 2,18-2,81, P <0,001). A diferença no alívio da dor em 2 horas não favoreceu significativamente telcagepant sobre triptanos ou vice-versa (odds ratio = 0,76, 95% intervalo de confiança = 0,57-1,01, P = 0,061). Estes resultados indicam que o telcagepant pode ser eficaz para o tratamento de enxaqueca aguda. Antagonistas dos receptores de peptídeo relacionado ao gene da calcitonina representam um potencial importantes meios alternativos de tratamento da enxaqueca aguda.
Objective: To compare all licensed drug interventions as oral monotherapy for the acute treatment of migraine episodes in adults. Design: Systematic review and network meta-analysis. Data sources: Cochrane Central Register of Controlled Trials, Medline, Embase, ClinicalTrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, as well as websites of regulatory agencies and pharmaceutical companies without language restrictions until 24 June 2023. Methods: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Random effects network meta-analyses were conducted for the primary analyses. The primary outcomes were the proportion of participants who were pain-free at two hours post-dose and the proportion of participants with sustained pain freedom from two to 24 hours post-dose, both without the use of rescue drugs. Certainty of the evidence was graded using the confidence in network meta-analysis (CINeMA) online tool. Vitruvian plots were used to summarise findings. An international panel of clinicians and people with lived experience of migraine co-designed the study and interpreted the findings. Eligibility criteria for selecting studies: Double blind randomised trials of adults (≥18 years) with a diagnosis of migraine according to the International Classification of Headache Disorders. Results: 137 randomised controlled trials comprising 89 445 participants allocated to one of 17 active interventions or placebo were included. All active interventions showed superior efficacy compared with placebo for pain freedom at two hours (odds ratios from 1.73 (95% confidence interval (CI) 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan), and most of them also for sustained pain freedom to 24 hours (odds ratios from 1.71 (1.07 to 2.74) for celecoxib to 7.58 (2.58 to 22.27) for ibuprofen). In head-to-head comparisons between active interventions, eletriptan was the most effective drug for pain freedom at two hours (odds ratios from 1.46 (1.18 to 1.81) to 3.01 (2.13 to 4.25)), followed by rizatriptan (1.59 (1.18 to 2.17) to 2.44 (1.75 to 3.45)), sumatriptan (1.35 (1.03 to 1.75) to 2.04 (1.49 to 2.86)), and zolmitriptan (1.47 (1.04 to 2.08) to 1.96 (1.39 to 2.86)). For sustained pain freedom, the most efficacious interventions were eletriptan and ibuprofen (odds ratios from 1.41 (1.02 to 1.93) to 4.82 (1.31 to 17.67)). Confidence in accordance with CINeMA ranged from high to very low. Sensitivity analyses on Food and Drug Administration licensed doses only, high versus low doses, risk of bias, and moderate to severe headache at baseline confirmed the main findings for both primary and secondary outcomes. Conclusions: Overall, eletriptan, rizatriptan, sumatriptan, and zolmitriptan had the best profiles and they were more efficacious than the recently marketed drugs lasmiditan, rimegepant, and ubrogepant. Although cost effectiveness analyses are warranted and careful consideration should be given to patients with a high risk cardiovascular profile, the most effective triptans should be considered as preferred acute treatment for migraine and included in the WHO List of Essential Medicines to promote global accessibility and uniform standards of care. Systematic review registration: Open Science Framework https://osf.io/kq3ys/.