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Structured Abstract
Objectives:
To evaluate the effectiveness and comparative effectiveness of pharmacologic and nonpharmacologic therapies for the acute treatment of episodic migraine in adults.
Data sources:
MEDLINE®, Embase®, Cochrane Central Registrar of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO®, Scopus, and various grey literature sources from database inception to July 24, 2020. Comparative effectiveness evidence about triptans and nonsteroidal anti-inflammatory drugs (NSAIDs) was 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 nine 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 five 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 (37,653 patients). 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). Butorphanol, meperidine, morphine, hydromorphone, and tramadol in combination with acetaminophen 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, magnesium sulfate, and octreotide. Compared with placebo, several nonpharmacologic 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 been evaluated only 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.
Contents
- Preface
- Acknowledgments
- Technical Expert Panel
- Peer Reviewers
- Evidence Summary
- Introduction
- Methods
- Results
- Discussion
- References
- Abbreviations and Acronyms
- Appendixes
- Appendix A. Search Strategy
- Appendix B. Flow Chart
- Appendix C. Excluded Studies
- Appendix D. Characteristics of Included Studies
- Appendix E. Risk of Bias
- Appendix F. Results From Included Studies
- Appendix G. Summary of Systematic Reviews Evaluating Triptans and NSAIDs
- Appendix H. Adverse Events
- Appendix I. Subgroup Analysis by Dosage
- Appendix J. Adverse Events: Subgroup Analysis by Dosage
- Appendix K. Subgroup Analysis by Study Settings and Routes of Administration
- Appendix L. Sensitivity Analysis
- Appendix M. Appendix References
Suggested citation:
Halker Singh RB, VanderPluym JH, Morrow AS, Urtecho M, Nayfeh T, Torres Roldan VD, Farah MH, Hasan B, Saadi S, Shah S, Abd-Rabu R, Daraz L, Prokop LJ, Murad MH, Wang Z. Acute Treatments for Episodic Migraine. Comparative Effectiveness Review No. 239. (Prepared by the Mayo Clinic Evidence-based Practice Center under Contract No. 290-2015-00013-I.) AHRQ Publication No. 21-EHC009. Rockville, MD: Agency for Healthcare Research and Quality; December 2020. DOI: https://doi.org/10.23970/AHRQEPCCER239. Posted final reports are located on the Effective Health Care Program search page.
This report is based on research conducted by the Mayo Clinic Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00013-I). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.
None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.
The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.
This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders.
AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.
AHRQ appreciates appropriate acknowledgment and citation of its work. Suggested language for acknowledgment: This work was based on an evidence report, Acute Treatments for Episodic Migraine, by the Evidence-based Practice Center Program at the Agency for Healthcare Research and Quality (AHRQ).
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