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

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

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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.

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Contributor(s)

Juliana VanderPluym, MD, Rashmi Halker Singh, MD, Allison S. Morrow, BA, Meritxell Urtecho, MD, Tarek Nayfeh, MD, Victor D. Torres Roldan, MD, Magdoleen H. Farah, MBBS, Bashar Hasan, MD, Samer Mohir, MD, Sahrish Shah, MBBS, Rami Abd-Rabu, MBBS, Lubna Daraz, PhD, Larry J. Prokop, MLS, Mohammad Hassan Murad, MD, MPH, Zhen Wang, PhD

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Methodology

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.

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DOI

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Funding Source

AHRQ

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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

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Key Questions

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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KQ2a. What is the comparative effectiveness of nonopioid pharmacologic therapy (e.g. acetaminophen, NSAIDs, triptans, ergots alkaloids, combination analgesics, muscle relaxants, anti-nausea medications, and cannabis) versus: 1) other nonopioid pharmacologic treatments, such as those in a different medication class; or 2) nonpharmacologic therapy for outcomes related to pain, function, pain relief satisfaction, and quality of life after followup at the following intervals: < 1 day; 1 day to <1 week; 1 week to <2 weeks; 2 weeks to 4 weeks? KQ2b. How does effectiveness of nonopioid pharmacologic therapy vary depending on: (1) patient demographics (e.g. age, race, ethnicity, gender); (2) patient medical comorbidities; (3) the type of nonopioid medication; (4) dose of medication; (5) duration of treatment? KQ2c. What are the harms of nonopioid pharmacologic therapy versus other nonopioid pharmacologic therapy, or nonpharmacologic therapy with respect to: (1) misuse, (2) overdose; (3) MOH, (4) other harms including gastrointestinal-related harms, cardiovascular-related harms, kidney-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cognitive harms, and psychological harms (e.g. depression)? KQ2d. How do harms vary depending on: (1) patient demographics (e.g. age, gender); (2) patient medical comorbidities; (3) the type of nonopioid medication; (4) dose of medication; (5) the duration of therapy?

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KQ3a. What is the comparative effectiveness of nonpharmacologic therapy versus sham treatment, waitlist, usual care, attention control, and no treatment after followup at the following intervals: < 1 day; 1 day to <1 week; 1 week to <2 weeks; 2 weeks to 4 weeks? KQ3b. What is the comparative effectiveness of nonpharmacologic treatments (e.g. exercise, cognitive behavioral therapy, acupuncture, biofeedback, noninvasive neuromodulation devices) for outcomes related to pain, function, pain relief satisfaction, and quality of life? KQ3c. How does effectiveness of nonpharmacologic therapy vary depending on: (1) patient demographics (e.g. age, gender); (2) patient medical comorbidities? KQ3d. How do harms vary depending on: (1) patient demographics (e.g. age, gender); (2) patient medical comorbidities; (3) the type of treatment used; (4) the frequency of therapy; (5) the duration of therapy?

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Associated Extraction Forms

Title	Created by	Key Questions Addressed
Key Question 1	Meritxell Urtecho Suarez	1
Key Question 2	Meritxell Urtecho Suarez	2
Key Question 3	Meritxell Urtecho Suarez	3

Associated Studies (each link opens a new tab)

Title	Author	Year
The acute treatment of migraine with transnasal butorphanol (TNB)	Freitag F.	1993
Single-dose intravenous tramadol for acute migraine pain in adults: a single-blind, prospective, randomized, placebo-controlled clinical trial.	Alemdar M., Pekdemir M., Selekler HM.	2007
Double-blind comparison of an acetaminophen 400 mg-codeine 25 mg combination versus aspirin 1000 mg and placebo in acute migraine attack.	Boureau F., Joubert JM., Lasserre V., Prum B., Delecoeuillerie G.	1994
Double-blind, multicenter trial to compare the efficacy of intramuscular dihydroergotamine plus hydroxyzine versus intramuscular meperidine plus hydroxyzine for the emergency department treatment of acute migraine headache.	Carleton SC., Shesser RF., Pietrzak MP., Chudnofsky CR., Starkman S., Morris DL., Johnson G., Rhee KJ., Barton CW., Chelly JE., Rosenberg J., Van Valen MK.	1998
Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine.	Friedman BW., Irizarry E., Solorzano C., Latev A., Rosa K., Zias E., Vinson DR., Bijur PE., Gallagher EJ.	2017
Metoclopramide versus hydromorphone for the emergency department treatment of migraine headache.	Griffith JD., Mycyk MB., Kyriacou DN.	2008
Transnasal butorphanol in the treatment of acute migraine.	Hoffert MJ., Couch JR., Diamond S., Elkind AH., Goldstein J., Kohlerman NJ., Saper JR., Solomon S.	1995
Current emergency treatment of severe migraine headaches.	Klapper JA., Stanton J.	-- Not Found --
Comparative efficacy of chlorpromazine and meperidine with dimenhydrinate in migraine headache.	Lane PL., McLellan BA., Baggoley CJ.	1989
A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache.	Richman PB., Allegra J., Eskin B., Doran J., Reischel U., Kaiafas C., Nashed AH.	2002
Comparison of dihydroergotamine with metoclopramide versus meperidine with promethazine in the treatment of acute migraine.	Scherl ER., Wilson JF.	1995
Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a randomized, placebo-controlled trial.	Silberstein SD., Freitag FG., Rozen TD., Kudrow DB., Hewitt DJ., Jordan DM., Fisher AC., Rosenthal NR.	-- Not Found --
Methotrimeprazine versus meperidine and dimenhydrinate in the treatment of severe migraine: a randomized, controlled trial.	Stiell IG., Dufour DG., Moher D., Yen M., Beilby WJ., Smith NA.	1991
Intravenous dexamethasone versus morphine in relieving of acute migraine headache.	Taheraghdam AA., Amiri H., Shojaan H., Shamsvahdati S., Houshyar Y.	2011
Narcotic analgesics for acute migraine in the emergency room: are we meeting Headache Societies' guidelines?	Wasay M., Zaki KS., Khan SU., Rehmani R.	2006
A Randomized, Double-Blinded, Placebo-Controlled, Cross Over Study Evaluating the Efficacy and Safety of Timolol Ophthalmic Solution as an Acute Treatment of Migraine.	Aggarwal D., Heim AJ., Bittel B., Ford D., Dubinsky R., Gronseth G., Hairston V., Landazuri P., Sachen F., Herbelin L., Barohn RJ.	2020
Comparison of granisetron and metoclopramide in the treatment of pain and emesis in migraine patients: A randomized controlled trial study.	Amiri H., Ghodrati N., Nikuyeh M., Shams-Vahdati S., Jalilzadeh-Binazar M.	2017
MAP0004, orally inhaled DHE: a randomized, controlled study in the acute treatment of migraine.	Aurora SK., Silberstein SD., Kori SH., Tepper SJ., Borland SW., Wang M., Dodick DW.	2011
A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine.	Aurora SK., Rozen TD., Kori SH., Shrewsbury SB.	2009
Intranasal Lidocaine in Acute Treatment of Migraine: A Randomized Controlled Trial.	Avcu N., Doğan NÖ., Pekdemir M., Yaka E., Yılmaz S., Alyeşil C., Akalın LE.	2017
Propranolol in the treatment of acute migraine attacks.	Banerjee M., Findley L.	1991
Intravenous caffeine citrate vs. magnesium sulfate for reducing pain in patients with acute migraine headache; a prospective quasi-experimental study.	Baratloo A., Mirbaha S., Delavar Kasmaei H., Payandemehr P., Elmaraezy A., Negida A.	2017
A comparative trial of three agents in the treatment of acute migraine headache.	Bell R., Montoya D., Shuaib A., Lee MA.	1990
Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized, double blind, placebo controlled study.	Bigal ME., Bordini CA., Tepper SJ., Speciali JG.	2002
Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial.	Bigal ME., Bordini CA., Speciali JG.	2002
Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study.	Bigal ME., Bordini CA., Tepper SJ., Speciali JG.	2002
Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic tension-type headache--a placebo-controlled study.	Bigal ME., Bordini CA., Speciali JG.	2001
Intranasal lidocaine for the treatment of migraine headache: a randomized, controlled trial.	Blanda M., Rench T., Gerson LW., Weigand JV.	2001
Interim results of a prospective, randomized, open-label, Phase 3 study of the long-term safety and efficacy of lasmiditan for acute treatment of migraine (the GLADIATOR study).	Brandes JL., Klise S., Krege JH., Case M., Khanna R., Vasudeva R., Raskin J., Pearlman EM., Kudrow D.	2019
A controlled study of dihydroergotamine in the treatment of acute migraine headache.	Callaham M., Raskin N.	1986
Intravenous chlorpromazine vs intravenous metoclopramide in acute migraine headache.	Cameron JD., Lane PL., Speechley M.	1995
A randomized prospective placebo-controlled study of intravenous magnesium sulphate vs. metoclopramide in the management of acute migraine attacks in the Emergency Department.	Cete Y., Dora B., Ertan C., Ozdemir C., Oktay C.	2005
Zatosetron, a 5-HT3 receptor antagonist in a multicenter trial for acute migraine.	Chappell AS., Bay JM., Botzum GD., Cohen ML.	-- Not Found --
Randomized, controlled trial of telcagepant for the acute treatment of migraine.	Connor KM., Shapiro RE., Diener HC., Lucas S., Kost J., Fan X., Fei K., Assaid C., Lines C., Ho TW.	2009
Randomized, placebo-controlled evaluation of prochlorperazine versus metoclopramide for emergency department treatment of migraine headache.	Coppola M., Yealy DM., Leibold RA.	1995
Randomized clinical trial of intravenous magnesium sulfate as an adjunctive medication for emergency department treatment of migraine headache.	Corbo J., Esses D., Bijur PE., Iannaccone R., Gallagher EJ.	2001
Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial.	Croop R., Goadsby PJ., Stock DA., Conway CM., Forshaw M., Stock EG., Coric V., Lipton RB.	2019
Efficacy and safety of tonabersat, a gap-junction modulator, in the acute treatment of migraine: a double-blind, parallel-group, randomized study.	Dahlöf CG., Hauge AW., Olesen J.	2009
Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks.	Demirkaya S., Vural O., Dora B., Topçuoğlu MA.	2001
Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study.	Derosier F., Sheftell F., Silberstein S., Cady R., Ruoff G., Krishen A., Peykamian M.	2012
Double-blind controlled study of paramax in the acute treatment of common and classical migraine.	Dexter SL., Graham AN., Johnston ES., Ratcliffe DM., Wilkinson MI., Rose AJ.	1985
Intranasal civamide for the acute treatment of migraine headache.	Diamond S., Freitag F., Phillips SB., Bernstein JE., Saper JR.	2000
Treatment of migraine with isometheptene, acetaminophen, and dichloralphenazone combination: a double-blind, crossover trial.	Diamond S.	1976
BI 44370 TA, an oral CGRP antagonist for the treatment of acute migraine attacks: results from a phase II study.	Diener HC., Barbanti P., Dahlöf C., Reuter U., Habeck J., Podhorna J.	2011
RPR100893, a substance-P antagonist, is not effective in the treatment of migraine attacks.	Diener HC.	2003
Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double-blind, placebo-controlled comparison.	Diener HC., Jansen JP., Reches A., Pascual J., Pitei D., Steiner TJ.	2002
Ubrogepant for the Treatment of Migraine.	Dodick DW., Lipton RB., Ailani J., Lu K., Finnegan M., Trugman JM., Szegedi A.	2019
Intravenous metoclopramide in the treatment of acute migraines: A randomized, placebo-controlled trial.	Doğan NÖ., Pekdemir M., Yılmaz S., Yaka E., Karadaş A., Durmuş U., Avcu N., Koçkan E.	2019
Intravenous dexamethasone vs placebo as adjunctive therapy to reduce the recurrence rate of acute migraine headaches: a multicenter, double-blinded, placebo-controlled randomized clinical trial.	Donaldson D., Sundermann R., Jackson R., Bastani A.	2008
Low-dose Ketamine Does Not Improve Migraine in the Emergency Department: A Randomized Placebo-controlled Trial.	Etchison AR., Bos L., Ray M., McAllister KB., Mohammed M., Park B., Phan AV., Heitz C.	2018
Efficacy and tolerability of lasmiditan, an oral 5-HT(1F) receptor agonist, for the acute treatment of migraine: a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study.	Färkkilä M., Diener HC., Géraud G., Láinez M., Schoenen J., Harner N., Pilgrim A., Reuter U.	2012
Buccally absorbed vs intravenous prochlorperazine for treatment of migraines headaches.	Fernando T., Lumanauw DD., Youn S., Shimada M., Yadav K., Chappell B., Horeczko T., Tanen DA.	2019
Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.	Ferrari MD., Färkkilä M., Reuter U., Pilgrim A., Davis C., Krauss M., Diener HC.	2010
Randomized clinical trial of intravenous valproate (orifil) and dexamethasone in patients with migraine disorder.	Foroughipour M., Ghandehari K., Khazaei M., Ahmadi F., Shariatinezhad K., Ghandehari K.	2013
A Randomized, Sham-Controlled Trial of Bilateral Greater Occipital Nerve Blocks With Bupivacaine for Acute Migraine Patients Refractory to Standard Emergency Department Treatment With Metoclopramide.	Friedman BW., Mohamed S., Robbins MS., Irizarry E., Tarsia V., Pearlman S., John Gallagher E.	2018
Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial.	Friedman BW., Cabral L., Adewunmi V., Solorzano C., Esses D., Bijur PE., Gallagher EJ.	2016
Metoclopramide for acute migraine: a dose-finding randomized clinical trial.	Friedman BW., Mulvey L., Esses D., Solorzano C., Paternoster J., Lipton RB., Gallagher EJ.	2011
A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine.	Friedman BW., Esses D., Solorzano C., Dua N., Greenwald P., Radulescu R., Chang E., Hochberg M., Campbell C., Aghera A., Valentin T., Paternoster J., Bijur P., Lipton RB., Gallagher EJ.	2008
Randomized trial of IV dexamethasone for acute migraine in the emergency department.	Friedman BW., Greenwald P., Bania TC., Esses D., Hochberg M., Solorzano C., Corbo J., Chu J., Chew E., Cheung P., Fearon S., Paternoster J., Baccellieri A., Clark S., Bijur PE., Lipton RB., Gallagher EJ.	2007
Symptomatic relief of migraine: multicenter comparison of Cafergot P-B, Cafergot, and placebo.	Friedman AP., Di Serio FJ., Hwang DS.	1989
A Randomized Controlled Trial of Intravenous Haloperidol vs. Intravenous Metoclopramide for Acute Migraine Therapy in the Emergency Department.	Gaffigan ME., Bruner DI., Wason C., Pritchard A., Frumkin K.	2015
Acute treatment of migraine with dihydroergotamine nasal spray. Dihydroergotamine Working Group.	Gallagher RM.	1996
Postdischarge secobarbital after ED migraine treatment decreases pain and improves resolution.	Gerhardt RT., Hermstad E., Crawford DM., Rayfield J., Pfaff J., Hunter CJ.	2011
Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine.	Goadsby PJ., Wietecha LA., Dennehy EB., Kuca B., Case MG., Aurora SK., Gaul C.	2019
Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study.	Goldstein DJ., Wang O., Saper JR., Stoltz R., Silberstein SD., Mathew NT.	1997
Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with acute migraine.	Gomez-Mancilla B., Cutler NR., Leibowitz MT., Spierings EL., Klapper JA., Diamond S., Goldstein J., Smith T., Couch JR., Fleishaker J., Azie N., Blunt DE.	2001
Randomized, multicenter trial to assess the efficacy, safety and tolerability of a single dose of a novel AMPA receptor antagonist BGG492 for the treatment of acute migraine attacks.	Gomez-Mancilla B., Brand R., Jürgens TP., Göbel H., Sommer C., Straube A., Evers S., Sommer M., Campos V., Kalkman HO., Hariry S., Pezous N., Johns D., Diener HC.	2014
Ergotamine vs. metoclopramide vs. their combination in acute migraine attacks.	Hakkarainen H., Allonen H.	1982
Randomized controlled study of telcagepant plus ibuprofen or acetaminophen in migraine.	Hewitt DJ., Martin V., Lipton RB., Brandes J., Ceesay P., Gottwald R., Schaefer E., Lines C., Ho TW.	2011
Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine.	Hewitt DJ., Aurora SK., Dodick DW., Goadsby PJ., Ge YJ., Bachman R., Taraborelli D., Fan X., Assaid C., Lines C., Ho TW.	2011
Randomized, controlled study of telcagepant in patients with migraine and coronary artery disease.	Ho TW., Ho AP., Chaitman BR., Johnson C., Mathew NT., Kost J., Fan X., Aurora SK., Brandes JL., Fei K., Beebe L., Lines C., Krucoff MW.	2012
Randomized, controlled trial of telcagepant over four migraine attacks.	Ho AP., Dahlöf CG., Silberstein SD., Saper JR., Ashina M., Kost JT., Froman S., Leibensperger H., Lines CR., Ho TW.	2010
Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial.	Ho TW., Ferrari MD., Dodick DW., Galet V., Kost J., Fan X., Leibensperger H., Froman S., Assaid C., Lines C., Koppen H., Winner PK.	2008
Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine.	Ho TW., Mannix LK., Fan X., Assaid C., Furtek C., Jones CJ., Lines CR., Rapoport AM.	2008
A double-blind controlled study of nifedipine as an abortive treatment in acute attacks of migraine with aura.	Hoffert MJ., Scholz MJ., Kanter R.	1992
Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study.	Honkaniemi J., Liimatainen S., Rainesalo S., Sulavuori S.	2006
The nitric oxide synthase inhibitor and serotonin-receptor agonist NXN-188 during the aura phase of migraine with aura: A randomized, double-blind, placebo-controlled cross-over study.	Hougaard A., Hauge AW., Guo S., Tfelt-Hansen P.	2013
Intravenous Fluid for the Treatment of Emergency Department Patients With Migraine Headache: A Randomized Controlled Trial.	Jones CW., Remboski LB., Freeze B., Braz VA., Gaughan JP., McLean SA.	2019
Safety and efficacy of rectal prochlorperazine for the treatment of migraine in the emergency department.	Jones EB., Gonzalez ER., Boggs JG., Grillo JA., Elswick RK.	1994
Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache.	Jones J., Pack S., Chun E.	1996
Ketoprofen and ergotamine in acute migraine.	Kangasniemi P., Kaaja R.	1992
Treatment of migraine attacks with a long-acting somatostatin analogue (octreotide, SMS 201-995).	Kapicioğlu S., Gökce E., Kapicioğlu Z., Ovali E.	1997
Single-dose intravenous sodium valproate (Depakine) versus dexamethasone for the treatment of acute migraine headache: a double-blind randomized clinical trial.	Karimi N., Tavakoli M., Charati JY., Shamsizade M.	2017
Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study.	Kuca B., Silberstein SD., Wietecha L., Berg PH., Dozier G., Lipton RB.	2018
Octreotide is not effective in the acute treatment of migraine.	Levy MJ., Matharu MS., Bhola R., Meeran K., Goadsby PJ.	2005
Rimegepant, an Oral Calcitonin Gene-Related Peptide Receptor Antagonist, for Migraine.	Lipton RB., Croop R., Stock EG., Stock DA., Morris BA., Frost M., Dubowchik GM., Conway CM., Coric V., Goadsby PJ.	2019
Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials.	Lipton RB., Stewart WF., Ryan RE., Saper J., Silberstein S., Sheftell F.	1998
Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial.	Lipton RB., Dodick DW., Ailani J., Lu K., Finnegan M., Szegedi A., Trugman JM.	2019
Effects on migraine headache of MDL 72,222, an antagonist at neuronal 5-HT receptors. Double-blind, placebo-controlled study.	Loisy C., Beorchia S., Centonze V., Fozard JR., Schechter PJ., Tell GP.	1985
Intranasal lidocaine for migraine: a randomized trial and open-label follow-up.	Maizels M., Geiger AM.	1999
Intranasal lidocaine for treatment of migraine: a randomized, double-blind, controlled trial.	Maizels M., Scott B., Cohen W., Chen W.	-- Not Found --
BMS-927711 for the acute treatment of migraine: a double-blind, randomized, placebo controlled, dose-ranging trial.	Marcus R., Goadsby PJ., Dodick D., Stock D., Manos G., Fischer TZ.	2014
Effect of intravenous sodium valproate vs dexamethasone on acute migraine headache: a double blind randomized clinical trial.	Mazaheri S., Poorolajal J., Hosseinzadeh A., Fazlian MM.	2015
Treatment of migraine with intramuscular chlorpromazine.	McEwen JI., O'Connor HM., Dinsdale HB.	1987
Randomized evaluation of octreotide vs prochlorperazine for ED treatment of migraine headache.	Miller MA., Levsky ME., Enslow W., Rosin A.	2009
Clinical trial of flupirtine maleate in patients with migraine.	Million R., Finlay BR., Whittington JR.	1984
The effect of intravenous verapamil on acute migraine headache.	Molaie M., Olson CM., Koch J.	1987
Flunarizine (10 and 20 mg) i.v. versus placebo in the treatment of acute migraine attacks: a multi-centre double-blind study.	Pfaffenrath V., Oestreich W., Haase W.	1990
A randomized, placebo-controlled trial of acetaminophen for treatment of migraine headache.	Prior MJ., Codispoti JR., Fu M.	2010
Comparing the Effect of Intranasal Lidocaine 4% with Peppermint Essential Oil Drop 1.5% on Migraine Attacks: A Double-Blind Clinical Trial.	Rafieian-Kopaei M., Hasanpour-Dehkordi A., Lorigooini Z., Deris F., Solati K., Mahdiyeh F.	2019
Efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine. Dihydroergotamine Nasal Spray Multicenter Investigators.	-- Not Found --	1995
Is intravenous lidocaine clinically effective in acute migraine?	Reutens DC., Fatovich DM., Stewart-Wynne EG., Prentice DA.	1991
A double-blind comparison of granisetron and placebo for the treatment of acute migraine in the emergency department.	Rowat BM., Merrill CF., Davis A., South V.	1991
Double-blind clinical evaluation of the efficacy and safety of ergostine-caffeine, ergotamine-caffeine, and placebo in migraine headache.	Ryan RE.	1970
Metoclopramide as an analgesic in severe migraine attacks: an open, single-blind, parallel control study.	Salazar G., Fragoso M., Vergez L., Sergio P., Cuello D.	2011
LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine.	Sang CN., Ramadan NM., Wallihan RG., Chappell AS., Freitag FG., Smith TR., Silberstein SD., Johnson KW., Phebus LA., Bleakman D., Ornstein PL., Arnold B., Tepper SJ., Vandenhende F.	2004
Comparison of therapeutic effects of magnesium sulfate vs. dexamethasone/metoclopramide on alleviating acute migraine headache.	Shahrami A., Assarzadegan F., Hatamabadi HR., Asgarzadeh M., Sarehbandi B., Asgarzadeh S.	2015
Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine.	Sharma S., Prasad A., Nehru R., Anand KS., Rishi RK., Chaturvedi S., Bapna JS., Sharma DR.	2002
Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial.	Silberstein SD., Young WB., Mendizabal JE., Rothrock JF., Alam AS.	2003
Tonabersat, a gap-junction modulator: efficacy and safety in two randomized, placebo-controlled, dose-ranging studies of acute migraine.	Silberstein SD., Schoenen J., Göbel H., Diener HC., Elkind AH., Klapper JA., Howard RA.	2009
Effectiveness of intravenous dexamethasone versus propofol for pain relief in the migraine headache: a prospective double blind randomized clinical trial.	Soleimanpour H., Ghafouri RR., Taheraghdam A., Aghamohammadi D., Negargar S., Golzari SE., Abbasnezhad M.	2012
Flunarizine i.v. in the acute treatment of common or classical migraine attacks--a placebo-controlled double blind trial.	Soyka D., Taneri Z., Oestreich W., Schmidt R.	1989
Flunarizine i.v. in the acute treatment of the migraine attack. A double-blind placebo-controlled study.	Soyka D., Taneri Z., Oestreich W., Schmidt R.	1988
Efficacy of intravenous diphenhydramine versus intravenous DHE-45 in the treatment of severe migraine headache.	Swidan SZ., Lake AE., Saper JR.	2005
Intravenous sodium valproate versus prochlorperazine for the emergency department treatment of acute migraine headaches: a prospective, randomized, double-blind trial.	Tanen DA., Miller S., French T., Riffenburgh RH.	2003
A prospective, double-blind study of metoclopramide hydrochloride for the control of migraine in the emergency department.	Tek DS., McClellan DS., Olshaker JS., Allen CL., Arthur DC.	1990
Dihydroergotamine nasal spray in the treatment of acute migraine.	Treves TA., Kuritzky A., Hering R., Korczyn AD.	1998
The efficacy and safety of dipyrone (Novalgin) tablets in the treatment of acute migraine attacks: a double-blind, cross-over, randomized, placebo-controlled, multi-center study.	Tulunay FC., Ergün H., Gülmez SE., Ozbenli T., Ozmenoğlu M., Boz C., Erdemoglu AK., Varlikbas A., Göksan B., Inan L.	-- Not Found --
Dihydroergotamine nasal spray during migraine attacks. A double-blind crossover study with placebo.	Tulunay FC., Karan O., Aydin N., Culcuoglu A., Guvener A.	1987
A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine.	Voss T., Lipton RB., Dodick DW., Dupre N., Ge JY., Bachman R., Assaid C., Aurora SK., Michelson D.	2016
Dihydroergotamine nasal spray for the acute treatment of migraine.	Ziegler D., Ford R., Kriegler J., Gallagher RM., Peroutka S., Hammerstad J., Saper J., Hoffert M., Vogel B., Holtz N.	1994
Propofol for migraine in the emergency department: A pilot randomised controlled trial.	Mitra B., Roman C., Mercier E., Moloney J., Yip G., Khullar K., Walsh K., Smit V., Cameron PA.	2020
Cutaneous application of menthol 10% solution as an abortive treatment of migraine without aura: a randomised, double-blind, placebo-controlled, crossed-over study.	Borhani Haghighi A., Motazedian S., Rezaii R., Mohammadi F., Salarian L., Pourmokhtari M., Khodaei S., Vossoughi M., Miri R.	2010
Acute migraine therapy with external trigeminal neurostimulation (ACME): A randomized controlled trial.	Chou DE., Shnayderman Yugrakh M., Winegarner D., Rowe V., Kuruvilla D., Schoenen J.	2019
Pain Management Using Acupuncture Method in Migraine Headache Patients; A Single Blinded Randomized Clinical Trial.	Farahmand S., Shafazand S., Alinia E., Bagheri-Hariri S., Baratloo A.	2018
Treatment of acute migraine by a partial rebreathing device: A randomized controlled pilot study.	Fuglsang CH., Johansen T., Kaila K., Kasch H., Bach FW.	2018
Treatment of migraine attacks by transcutaneous electrical nerve stimulation in emergency department: A randomize controlled trial.	Hokenek NM., Erdogan MO., Hokenek UD., Algin A., Tekyol D., Seyhan AU.	2020
The effectiveness of greater occipital nerve blockade in treating acute migraine-related headaches in emergency departments.	Korucu O., Dagar S., Çorbacioglu ŞK., Emektar E., Cevik Y.	2018
Acupuncture for treating acute attacks of migraine: a randomized controlled trial.	Li Y., Liang F., Yang X., Tian X., Yan J., Sun G., Chang X., Tang Y., Ma T., Zhou L., Lan L., Yao W., Zou R.	2009
Single-pulse transcranial magnetic stimulation for acute treatment of migraine with aura: a randomised, double-blind, parallel-group, sham-controlled trial.	Lipton RB., Dodick DW., Silberstein SD., Saper JR., Aurora SK., Pearlman SH., Fischell RE., Ruppel PL., Goadsby PJ.	2010
Efficacy of topical Rose (Rosa damascena Mill.) oil for migraine headache: A randomized double-blinded placebo-controlled cross-over trial.	Niazi M., Hashempur MH., Taghizadeh M., Heydari M., Shariat A.	2017
Lavender essential oil in the treatment of migraine headache: a placebo-controlled clinical trial.	Sasannejad P., Saeedi M., Shoeibi A., Gorji A., Abbasi M., Foroughipour M.	2012
Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study.	Tassorelli C., Grazzi L., de Tommaso M., Pierangeli G., Martelletti P., Rainero I., Dorlas S., Geppetti P., Ambrosini A., Sarchielli P., Liebler E., Barbanti P.	2018
Nitrous oxide for the treatment of acute migraine headache.	Triner WR., Bartfield JM., Birdwell M., Raccio-Robak N.	1999
Efficacy of acupuncture for acute migraine attack: a multicenter single blinded, randomized controlled trial.	Wang LP., Zhang XZ., Guo J., Liu HL., Zhang Y., Liu CZ., Yi JH., Wang LP., Zhao JP., Li SS.	2012
A PET-CT study on the specificity of acupoints through acupuncture treatment in migraine patients.	Yang J., Zeng F., Feng Y., Fang L., Qin W., Liu X., Song W., Xie H., Chen J., Liang F.	2012
Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.	Yarnitsky D., Dodick DW., Grosberg BM., Burstein R., Ironi A., Harris D., Lin T., Silberstein SD.	2019
Nonpainful remote electrical stimulation alleviates episodic migraine pain.	Yarnitsky D., Volokh L., Ironi A., Weller B., Shor M., Shifrin A., Granovsky Y.	2017
Evaluation of the effect of topical chamomile (Matricaria chamomilla L.) oleogel as pain relief in migraine without aura: a randomized, double-blind, placebo-controlled, crossover study.	Zargaran A., Borhani-Haghighi A., Salehi-Marzijarani M., Faridi P., Daneshamouz S., Azadi A., Sadeghpour H., Sakhteman A., Mohagheghzadeh A.	2018
Phase 1 of integrated EMDR: An abortive treatment for migraine headaches	Marcus S	2008
Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials.	Ashcroft DM., Millson D.	2004
Zolmitriptan for acute migraine attacks in adults.	Bird S., Derry S., Moore RA.	2014
Meta-analysis examining the efficacy and safety of almotriptan in the acute treatment of migraine.	Chen LC., Ashcroft DM.	2007
Sumatriptan (oral route of administration) for acute migraine attacks in adults.	Derry CJ., Derry S., Moore RA.	2012
Sumatriptan (subcutaneous route of administration) for acute migraine attacks in adults.	Derry CJ., Derry S., Moore RA.	2012
Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials.	Ferrari MD., Loder E., McCarroll KA., Lines CR.	2001
Therapeutic benefit of eletriptan compared to sumatriptan for the acute relief of migraine pain--results of a model-based meta-analysis that accounts for encapsulation.	Mandema JW., Cox E., Alderman J.	2005
Intranasal sumatriptan for acute migraine attacks: a systematic review and meta-analysis.	Menshawy A., Ahmed H., Ismail A., Abushouk AI., Ghanem E., Pallanti R., Negida A.	2018
Efficacy and tolerability of frovatriptan in acute migraine treatment: systematic review of randomized controlled trials.	Poolsup N., Leelasangaluk V., Jittangtrong J., Rithlamlert C., Ratanapantamanee N., Khanthong M.	2005
Diclofenac with or without an antiemetic for acute migraine headaches in adults.	Derry S., Rabbie R., Moore RA.	2012
Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.	Derry S., Moore RA.	2013
Aspirin with or without an antiemetic for acute migraine headaches in adults.	Kirthi V., Derry S., Moore RA., McQuay HJ.	2010
Ibuprofen with or without an antiemetic for acute migraine headaches in adults.	Rabbie R., Derry S., Moore RA., McQuay HJ.	2010
Ketorolac in the treatment of acute migraine: a systematic review.	Taggart E., Doran S., Kokotillo A., Campbell S., Villa-Roel C., Rowe BH.	2013
Sumatriptan plus naproxen for acute migraine attacks in adults.	Law S., Derry S., Moore RA.	2013
Network meta-analysis of migraine disorder treatment by NSAIDs and triptans.	Xu H., Han W., Wang J., Li M.	2016

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Project: Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-Analysis Public Report Complete

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