Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-Analysis

Project Summary Title and Description

Title
Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-Analysis
Description
Objectives. To evaluate the effectiveness and comparative effectiveness of pharmacologic and non-pharmacologic therapies for the acute treatment of episodic migraine in adults. Data source. MEDLINE, Embase, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Scopus and various grey literature sources from database inception to April 24, 2020. Comparative effectiveness evidence about triptans and nonsteroidal anti-inflammatory drugs (NSAIDs) were extracted from existing systematic reviews. Review methods. We included randomized controlled trials (RCTs) and comparative observational studies that enrolled adults who received an intervention to acutely treat episodic migraine. Pairs of independent reviewers selected and appraised studies. Results. Data on triptans were derived from 186 RCTs summarized in 9 systematic reviews (101,276 patients, most studied was sumatriptan, followed by zolmitriptan, eletriptan, naratriptan, almotriptan, rizatriptan, and frovatriptan). Compared with placebo, triptans resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (high strength of the body of evidence [SOE]). Data on NSAIDs were derived from 5 systematic reviews (13,214 patients, most studied was ibuprofen, followed by diclofenac and ketorolac). Compared with placebo, NSAIDs probably resolved pain at 2 hours and 1 day, and increased the risk of mild and transient adverse events (moderate SOE). For other interventions, we included 135 RCTs and 6 comparative observational studies (37,653patients). Compared with placebo, antiemetics (low SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE) and acetaminophen (moderate SOE) reduced acute pain. Opioids were evaluated in 15 studies (2,208 patients). Tramadol in combination with acetaminophen, butorphanol, meperidine, morphine and hydromorphone may reduce pain at 2 hours and 1 day, compared with placebo (low SOE). Some opioids may be less effective than some antiemetics or dexamethasone (low SOE). No studies evaluated instruments for predicting risk of opioid misuse, opioid use disorder or overdose, or evaluated risk mitigation strategies to be used when prescribing opioids for the acute treatment of episodic migraine. Calcitonin gene-related peptide (CGRP) receptor antagonists improved headache relief at 2 hours and increased the likelihood of being headache-free at 2 hours, at 1 day, and at 1 week (low to high SOE). Lasmiditan (the first approved 5-HT1F receptor agonist) restored function at 2 hours and resolved pain at 2 hours, 1 day, and 1 week (moderate to high SOE). Sparse and low SOE suggested possible effectiveness of dexamethasone, dipyrone, flunarazine, magnesium sulfate, octreotide, tezampanel, and tonabersat. Compared with placebo, several non-pharmacologic treatments may improve various measures of pain, including remote electrical neuromodulation (moderate SOE), magnetic stimulation (low SOE), acupuncture (low SOE), chamomile oil (low SOE), external trigeminal nerve stimulation (low SOE), and eye movement desensitization re-processing (low SOE). However, these interventions, including the noninvasive neuromodulation devices, have only been evaluated by single or very few trials. Conclusions. A number of acute treatments for episodic migraine exist with varying degrees of evidence for effectiveness and harms. Use of triptans, NSAIDs, antiemetics, dihydroergotamine, CGRP antagonists, and lasmiditan is associated with improved pain and function. The evidence base for many other interventions for acute treatment, including opioids, remains limited.
Attribution
N/A
Authors of Report
N/A
Methodology description
We developed an analytic framework to guide the process of the systematic review. We followed the established methodologies of systematic reviews as outlined in Agency for Healthcare Research and Quality (AHRQ) Methods Guide for Comparative Effectiveness Reviews. The reporting complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. The study protocol is published on AHRQ website and registered in the international prospective register of systematic reviews (PROSPERO #: CRD42020163262). The full report details our literature search strategy, inclusion and exclusion criteria, data synthesis, assessments of risk of bias, and strength of evidence (SOE). We assigned SOE rating as high, moderate, low, or ‘insufficient evidence to estimate an effect’. High was rated when we were very confident that the estimate of effect lies close to the true effect (the body of evidence has few or no deficiencies and is judged to be stable). Moderate was rated if we were moderately confident that the estimate of effect lies close to the true effect (the body of evidence has some deficiencies and is judged to be likely stable). Low, we had limited confidence that the estimate of effect lies close to the true effect (the body of evidence has major or numerous deficiencies and is likely unstable), and insufficient if we had no evidence, are unable to estimate an effect, or have no confidence in the estimate of effect.
PROSPERO
CRD42020163262
DOI
N/A
Notes
Web address: https://doi.org/10.23970/AHRQEPCCER239 Data in this report is presented retrospectively. Data can be found in the following links: https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-+Risk+of+Bias.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-KQ1-+Characteristics+of+Included+Studies.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-KQ1-+Results+from+Included+studies.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-KQ2-+Characteristics+of+Included+Studies.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-KQ2-+Results+from+Included+Studies.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-KQ3-+Characteristics+of+Included+Studies.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR+-KQ3-+Results+from+Included+Studies.docx https://srdr.s3.amazonaws.com/uploads/01-08-2021/SRDR-KQ2-+Summary+of+Systematic+Reviews+Evaluating+Triptans+and+NSAIDs.docx
Funding Source
AHRQ

Key Questions

1. KQ1a. What is the comparative effectiveness of opioid therapy versus: 1) nonopioid pharmacologic therapy (e.g. acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], triptans, ergots alkaloids, combination analgesics, muscle relaxants, anti-nausea medications, and cannabis) or 2) nonpharmacologic therapy (e.g. exercise, cognitive behavioral therapy, acupuncture, biofeedback, noninvasive neuromodulation devices) for outcomes related to pain, function, pain relief satisfaction, and quality of life and after followup at the following intervals: < 1 day; 1 day to <1 week; 1 week to <2 weeks; 2 weeks to 4 weeks? KQ1b. How does effectiveness of opioid therapy vary depending on: (1) patient demographics (e.g. age, race, ethnicity, gender, socioeconomic status (SES)); (2) patient medical comorbidities (previous opioid use, body mass index (BMI); (3) dose of opioids; (4) duration of opioid therapy, including number of opioid prescription refills and quantity of pills used? KQ1c. What are the harms of opioid therapy versus nonopioid pharmacologic therapy, or nonpharmacologic therapy with respect to: (1) misuse, opioid use disorder, and related outcomes; (2) overdose; (3) medication overuse headache (MOH), (4) other harms including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinologic harms, infections, cardiovascular events, cognitive harms, and psychological harms (e.g. depression)? KQ1d. How do harms vary depending on: (1) patient demographics (e.g. age, gender); (2) patient medical comorbidities; (3) the dose of opioid used; (4) the duration of opioid therapy? KQ1e. What are the effects of prescribing opioid therapy versus not prescribing opioid therapy for acute treatment of episodic migraine pain on 1) short-term (<3 months) continued need for prescription pain relief, such as need for opioid refills, and 2) long-term opioid use (3 months or greater)? KQ1f. For patients with episodic migraine being considered for opioid therapy for acute treatment, what is the accuracy of instruments for predicting risk of opioid misuse, opioid use disorder, or overdose? KQ1g. For patients with episodic migraine being considered for opioid therapy for acute treatment, what is the effectiveness of instruments for predicting risk of opioid misuse, opioid use disorder, or overdose? KQ1h. For patients with episodic migraine being considered for opioid therapy for acute treatment, what is the effect of the following risk mitigation strategies on the decision to prescribe opioids: (1) existing opioid management plans; (2) patient education; (3) clinician and patient values and preferences related to opioids; (4) urine drug screening; (5) use of prescription drug monitoring program data; (6) availability of close followup?
2. KQ1a. What is the comparative effectiveness of opioid therapy versus: 1) nonopioid pharmacologic therapy (e.g. acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], triptans, ergots alkaloids, combination analgesics, muscle relaxants, anti-nausea medications, and cannabis) or 2) nonpharmacologic therapy (e.g. exercise, cognitive behavioral therapy, acupuncture, biofeedback, noninvasive neuromodulation devices) for outcomes related to pain, function, pain relief satisfaction, and quality of life and after followup at the following intervals: < 1 day; 1 day to <1 week; 1 week to <2 weeks; 2 weeks to 4 weeks? KQ1b. How does effectiveness of opioid therapy vary depending on: (1) patient demographics (e.g. age, race, ethnicity, gender, socioeconomic status (SES)); (2) patient medical comorbidities (previous opioid use, body mass index (BMI); (3) dose of opioids; (4) duration of opioid therapy, including number of opioid prescription refills and quantity of pills used? KQ1c. What are the harms of opioid therapy versus nonopioid pharmacologic therapy, or nonpharmacologic therapy with respect to: (1) misuse, opioid use disorder, and related outcomes; (2) overdose; (3) medication overuse headache (MOH), (4) other harms including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinologic harms, infections, cardiovascular events, cognitive harms, and psychological harms (e.g. depression)? KQ1d. How do harms vary depending on: (1) patient demographics (e.g. age, gender); (2) patient medical comorbidities; (3) the dose of opioid used; (4) the duration of opioid therapy? KQ1e. What are the effects of prescribing opioid therapy versus not prescribing opioid therapy for acute treatment of episodic migraine pain on 1) short-term (<3 months) continued need for prescription pain relief, such as need for opioid refills, and 2) long-term opioid use (3 months or greater)? KQ1f. For patients with episodic migraine being considered for opioid therapy for acute treatment, what is the accuracy of instruments for predicting risk of opioid misuse, opioid use disorder, or overdose? KQ1g. For patients with episodic migraine being considered for opioid therapy for acute treatment, what is the effectiveness of instruments for predicting risk of opioid misuse, opioid use disorder, or overdose? KQ1h. For patients with episodic migraine being considered for opioid therapy for acute treatment, what is the effect of the following risk mitigation strategies on the decision to prescribe opioids: (1) existing opioid management plans; (2) patient education; (3) clinician and patient values and preferences related to opioids; (4) urine drug screening; (5) use of prescription drug monitoring program data; (6) availability of close followup?

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