This article updates the results from evidence-based reviews on the management of patients with migraine and cluster headache: specifically, acute, preventive, and nonpharmacologic treatments for migraine, as well as the role of neuroimaging in patients with headache. There have also been some important updates to treatment of cluster headache, and information from the most recent studies will be presented. The full papers for these treatment guidelines are published elsewhere (02; 04; 12; 13; 18; 25), and only the specific treatment recommendations are summarized below (10; 24; 11; 21; 23).
In June 1998, Duke University's Center for Clinical Health Policy Research, in collaboration with the American Academy of Neurology, completed 4 Technical Reviews on migraine sponsored by the Agency for Health Care Policy and Research: self-administered drug treatments for acute migraine (Gray et al 1999a); parenteral drug treatments for acute migraine (Gray et al 1999b); drug treatments for the prevention of migraine (Gray et al 1999c); and behavioral and physical treatments for migraine (Goslin et al 1999). The Education and Research Foundation of the American Academy of Neurology later funded additional reports on diagnostic testing for headache patients, an update on sumatriptan and other 5-HT1 agonists, and a report on butalbital-containing compounds for migraine and tension-type headache, using the same methodology that was used in the original Technical Reviews. A multidisciplinary panel of professional organizations (The US Headache Consortium) produced 4 treatment guidelines, each related to a distinct set of management decisions: diagnostic testing (primarily neuroimaging studies), pharmacological management of acute attacks, migraine-preventive drugs, and behavioral and physical treatments for migraine.
In 2012, the American Academy of Neurology updated and published new preventive treatment guidelines for migraine (10; 24). For pharmacologic therapy, the authors analyzed published studies from June 1999 to May 2009, using a structured review process to classify the evidence relative to the various medications available in the United States for migraine prevention. The author panel reviewed 284 abstracts, which ultimately yielded 30 Class I or Class II articles that are reviewed herein.
The original search identified 179 articles. A supplemental search (2007 to 2009) yielded 105 additional articles. Of the total 284 articles, 30 were pharmacologic and were classified as Class I or Class II and are reviewed herein. In addition, 15 were classified as Class I or Class II and identified as relating to nonsteroidal anti-inflammatory drugs (NSAIDs) and complementary treatments.
Studies were excluded if they included any of the following factors:
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• Assessed the efficacy of therapeutic agents for headache other than episodic migraine in adults
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• Assessed acute migraine treatment, migraine aura treatment/prevention, or nonpharmacologic treatments (eg, behavioral approaches)
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• Used quality of life measures, disability assessment, or nonstandardized outcomes as primary efficacy endpoints
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• Tested the efficacy of drugs not available in the United States
Since the guideline publication in 2000, the AAN revised its evidence classification criteria to include study completion rates. Studies with completion rates below 80% were downgraded; thus, several studies in the original guideline have been downgraded.
They found no new Class I or II studies published for acebutolol, atenolol, bisoprolol, carbamazepine, clonazepam, clonidine, clomipramine, fluvoxamine, guanfacine, nabumetone, nadolol, nicardipine, nifedipine, or protriptyline. Recommendations for these agents are based on the evidence reviewed in the original guideline (denoted with an asterisk in Table 1). Currently, no Class I or Class II studies exist for anticoagulants (limited Class III and IV studies were identified; Table 1 includes anticoagulants). Of the total 284 articles, 15 were classified as Class I or Class II and identified as relating to NSAIDs and complementary treatments; they are reviewed herein.
Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) effectively prevent migraine and have been approved in the past few years since the last publication of preventive guidelines. The 4 currently available treatments are erenumab, eptinezumab, fremanezumab, and galcanezumab, and all have demonstrated efficacy in both episodic and chronic migraine treatment (22).
In 2015, a study by Marmura and colleagues provided an updated assessment of the evidence for individual pharmacological therapies for acute migraine treatment (11). This assessment is an update to the American Academy Neurology Guidelines that were published in 2000, which summarized the available evidence related to the efficacy of acute migraine medications. The review was conducted by members of the Guidelines Section of the American Headache Society.
A standardized literature search was performed to identify articles related to acute migraine treatment that were published between 1998 and 2013. The American Academy of Neurology Guidelines Development procedures followed. Two authors reviewed each abstract resulting from the search and determined whether the full manuscript qualified for review. Two reviewers studied each qualifying full manuscript for its level of evidence. Level A evidence required at least 2 Class I studies, and level B evidence required 1 Class I or 2 Class II studies.
Future guidelines will address the use of novel treatments for acute migraine including new formulations, lasmiditan, rimagepant, and ubrogepant.
In 2016, the American Headache Society convened an expert panel of authors who defined a search strategy and performed a search of Medline, Embase, the Cochrane database, and clinical trial registries from inception through 2015. The authors provided evidence-based treatment recommendations for adults with acute migraine who require treatment with injectable medication in an emergency department. Identified articles were rated using the American Academy of Neurology’s risk of bias tool. They identified 68 unique randomized controlled trials utilizing 28 injectable medications. Of these, 19 were rated Class I (low risk of bias), 21 were rated Class II (higher risk of bias), and 28 were rated Class III (highest risk of bias). Metoclopramide, prochlorperazine, and sumatriptan each had multiple Class I studies supporting acute efficacy, as did dexamethasone for prevention of headache recurrence. All other medications had lower levels of evidence.
In 2016, a systematic review by Robbins and colleagues looked at the available evidence for the acute and prophylactic treatment of cluster headache (21). This was updated from the 2010 American Academy of Neurology (AAN) endorsed systematic review.
Since the publication of the 2010 AAN review, there are no new data from randomized, double-blind, controlled trials that contribute to determining the efficacy or safety of the following acute treatments: sumatriptan, zolmitriptan, oxygen, octreotide, dihydroergotamine, prednisone, cocaine/lidocaine, and somatostatin. Thus, the assessment of the data and recommendations regarding these treatments have been carried forward from the 2010 AAN assessment.
Medline, PubMed, and EMBASE databases were searched for double-blind, randomized controlled trials that investigated treatments of cluster headache in adults. To be included, studies must have been double-blind, randomized trials of any treatment versus placebo or sham versus another treatment studying adult participants (at least 18 years of age). Studies of episodic cluster headache, chronic cluster headache, or a combination were included. Studies were excluded if they were not double-blind, if there was no randomization, if a treatment or placebo/sham comparator was not used, and if children were studied. Research published between 1950 and April 15, 2015 was considered for inclusion.
In 2016, Rajapakse and Pringsheim reviewed Guidelines from the AAN/AHS, Canadian Headache Society, and the European Federation of Neurological Sciences (EFNS), as well as highlighted randomized control trial evidence for use of the following nutraceuticals: riboflavin, coenzyme Q10, magnesium, butterbur, feverfew, and omega-3 polyunsaturated fatty acids (OPFA) (17). This review will summarize their results.
Multiple noninvasive neuromodulation devices are approved for acute or preventive migraine treatment: noninvasive vagus nerve stimulation, single-transcranial magnetic stimulation, external trigeminal nerve stimulation, and remote electrical neuromodulation. Noninvasive vagus nerve stimulation is also approved for cluster headache treatment (20). Future guidelines will further evaluate their effectiveness.
Reviews have addressed the best practices of pediatric migraine management. Oskoui and colleagues evaluated pharmacologic and cognitive behavioral therapy for migraine prevention (14). The most proven treatment appears to be the combination of amitriptyline and cognitive behavioral therapy (16). The majority of studies of migraine prevention with oral drugs lack sufficient evidence. The panel noted topiramate treatment is probably likely to result in fewer migraine or headache days and children treated with propranolol are possibly more likely to have a greater than 50% reduction in headache days compared to placebo. Specific drugs with no significant evidence of effectiveness included divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine. Many other commonly used migraine preventive treatments such as nortriptyline, metoprolol, and medical devices have not been evaluated as preventive treatment in children.
Clinical factors affect outcomes in trials for acute pediatric migraine treatment. Higher placebo response, more rapid onset and resolution, and nausea/vomiting complicate acute study designs for children (19). Medications with high confidence recommendations for pain-freedom at 2 hours include zolmitriptan nasal spray 5 mg and combinations of sumatriptan/naproxen. Sumatriptan nasal spray 20 mg and ibuprofen are probably effective and rizatriptan oral dissolvable tablets 5 and 10 mg are possibly effective. A large number of treatments are possibly effective based on single, lower-quality studies such as almotriptan 6.25 and 12.5 mg and acetaminophen (15).
Evans and colleagues evaluated the evidence for when to perform neuroimaging in patients with a diagnosis of migraine (03). Based on numerous large case series the authors concluded “there is no necessity to do neuroimaging in patients with headaches consistent with migraine.” This recommendation assumes a normal neurologic examination and no red flags present for other diseases. However, it is worthwhile to consider neuroimaging in those with prolonged or persistent aura, a change in clinical features, motor weakness, late-life migraine accompaniments, and posttraumatic headache, among other circumstances (03).