Abstract:ObjectivesOne of the irritating features of migraine is emesis that can compromise taking oral medications. We designed this study to compare the effectiveness of granisetron and metoclopramide in reducing pain and treating emesis in migraine patients.MethodsWe included a total of 148 patients with migraine headache presenting to two referral hospitals in a prospective, double-blinded randomized controlled trial. We compared the effect of granisetron (2 mg intravenous) with metoclopramide (10 mg intravenous). … Show more
“…Twenty-six RCTs with 2561 patients evaluated antiemetic medications. The overall risk of bias was moderate to high (4 RCTs with low risk; 8, moderate risk; and 14, high risk) (eTable 11 in the Supplement).…”
IMPORTANCEMigraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.OBJECTIVE To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.DATA SOURCES Multiple databases from database inception to February 24, 2021.STUDY SELECTION Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.DATA EXTRACTION AND SYNTHESIS Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.
MAIN OUTCOMES AND MEASURESThe main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.FINDINGS Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT 1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.CONCLUSIONS AND RELEVANCE There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.
“…Twenty-six RCTs with 2561 patients evaluated antiemetic medications. The overall risk of bias was moderate to high (4 RCTs with low risk; 8, moderate risk; and 14, high risk) (eTable 11 in the Supplement).…”
IMPORTANCEMigraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.OBJECTIVE To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.DATA SOURCES Multiple databases from database inception to February 24, 2021.STUDY SELECTION Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.DATA EXTRACTION AND SYNTHESIS Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.
MAIN OUTCOMES AND MEASURESThe main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.FINDINGS Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT 1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.CONCLUSIONS AND RELEVANCE There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.
“…After deleting duplicates and eliminating the papers that did not satisfy the eligibility criteria or presented one or more of the exclusion criteria, only 24 out of the 243 selected papers resulted in being eligible for further evaluation (13–36) (Figure 1, flow diagram). Figure 1.Data collection flow diagram.…”
Background The International Headache Society (IHS) has published four editions of Guidelines for acute clinical trials in migraine in the past 28 years. This continuous update process has been driven by the increasing amount of scientific data in the field of migraine and by the need to continuously improve the quality of trials. Objectives To illustrate: i) the results of the analysis on the adherence of published trials to the 3rd edition published in 2012, in order to identify the critical areas that needed to be addressed in the 4th edition and ii) the changes introduced in this latter edition for improving adherence and methodology robustness. Methods We searched and reviewed all controlled trials on acute treatment of migraine published in the period 2012–2018 and we assessed their adherence to the 3rd edition of the IHS Guidelines using a score system based on the most important recommendations. Afterwards, we compared the two editions of the Guidelines and assessed the changes between them. Results We included data from 24 controlled clinical trials. Most trials had a randomized double-blind controlled (RDB) design, while a minority (16.7%) were non-randomized double-blind trials. Less than half (44.6%) of the RDB trials used the recommended “pain-free at 2 hours” endpoint as the primary efficacy measure. Trial design and evaluation of results were the areas that diverged the most from the recommendations. Conclusion Adherence to IHS guidelines for clinical trials has been suboptimal so far. The new edition has been adapted and optimized to facilitate uptake and strengthen the quality of evidence.
“…We identified two studies of the serotonin 5HT 3 antagonist granisetron for migraine, which were not included in the AHS guideline. These studies, one of which compared granisetron with placebo and one granisetron with metoclopramide, 32 were of lower quality and came to different conclusions regarding granisetron's efficacy for migraine. Therefore, the available evidence does not indicate a role for intravenous 5HT 3 antagonists for migraine pain 33 …”
Objective
Millions of patients present to US emergency departments (ED) annually for the treatment of migraine. First‐line treatments, including metoclopramide, prochlorperazine, and sumatriptan, fail to provide sufficient relief in up to one‐third of treated patients. In this narrative review, we discuss the evidence supporting the use of injectable (intravenous, intramuscular, or subcutaneous) medications for patients in the ED who fail to improve sufficiently after treatment with first‐line medication.
Methods
We used the American Headache Society's guideline, “Management of Adults with Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies,” published in 2016, to identify first‐line medications for migraine. We then conducted a PubMed search to determine whether any evidence supported the use of these medications as second‐line therapy and whether any evidence existed to support the use of injectable therapies not discussed in the guideline as second‐line therapy.
Results
We identified only scant high‐quality randomized data of second‐line therapy. Therefore, we based our recommendations on medications that have reliably demonstrated efficacy as first‐line treatment of migraine. These medications include injectable non‐steroidal anti‐inflammatory drugs (NSAIDs) and acetaminophen. Dihydroergotamine and valproic acid have some data supporting efficacy. More recently, greater occipital nerve blocks (GONBs) have been shown to be efficacious. With the exception of meperidine, opioids have been shown to be not efficacious. Most data published to date demonstrate no role for propofol and ketamine.
Conclusions
There are no evidence‐based second‐line treatments of migraine in the ED setting. For patients with migraine, who fail to improve after treatment with a first‐line medication, it is reasonable to use an intravenous NSAID or intravenous acetaminophen. Alternatively, clinicians adept at performing a GONB may offer this treatment.
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