Severe headache and migraine remain important public health problems that are more common and burdensome for women, particularly women of childbearing age, and other historically disadvantaged segments of the population. These inequities could be exacerbated if new high-cost treatments are inaccessible to those who need them most.

Background.-Updated guidelines for the preventive treatment of episodic migraine have been issued by the American Headache Society (AHS) and the American Academy of Neurology (AAN). We summarize key 2012 guideline recommendations and changes from previous guidelines. We review the characteristics, methods, consistency, and quality of the AHS/AAN guidelines in comparison with recently issued guidelines from other specialty societies.Methods.-To accomplish this, we reviewed the AHS/AAN guidelines and identified comparable recent guidelines through a systematic MEDLINE search. We extracted key data, and summarized and compared the key recommendations and assessed quality using the Appraisal of Guidelines Research and Evaluation-II (AGREE-II) tool. We identified 2 additional recent guidelines for migraine prevention from the Canadian Headache Society and the European Federation of Neurological Societies. All of the guidelines used structured methods to locate evidence and linked recommendations with assessment of the evidence, but they varied in the methods used to derive recommendations from that evidence.Results.-Overall, the 3 guidelines were consistent in their recommendations of treatments for first-line use. All rated topiramate, divalproex/sodium valproate, propranolol, and metoprolol as having the highest level of evidence. In contrast, recommendations diverged substantially for gabapentin and feverfew. The overall quality of the guidelines ranged from 2 to 6 out of 7 on the AGREE-II tool.Conclusion.-The AHS/AAN and Canadian guidelines are recommended for use on the basis of the AGREE-II quality assessment. Recommendations for the future development of clinical practice guidelines in migraine are provided. In particular, efforts should be made to ensure that guidelines are regularly updated and that guideline developers strive to locate and incorporate unpublished clinical trial evidence.

Background and Objectives: Accurate, up-to-date estimates of the burden of migraine and severe headache are important for evidence-based decision-making

Headache, an almost universal human experience, is one of the most common complaints encountered in medicine and neurology. Described and categorized since antiquity, with the first classification by Aretaeus of Cappadocia, other classifications followed. The evaluation of this condition may be straightforward or challenging, and, though often benign, headache may prove to be an ominous symptom. This review discusses the current diagnosis and classification of headache disorders and principles of management, with a focus on migraine, tension-type headache, trigeminal autonomic cephalgias, and various types of daily headache.

Background We assessed the safety profile of lasmiditan, a selective 5-HT1F receptor agonist without vasoconstrictive activity being developed as an acute therapy for migraine. Methods SAMURAI and SPARTAN were Phase 3 double-blind studies of patients with migraine, randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo to be taken within 4 hours of onset of migraine pain. Safety data from the studies were integrated. Treatment-emergent adverse events (occurring within 48 hours of first dose) were considered in the analyses. Results The safety population comprised 1262 patients assigned placebo, and 654, 1265, and 1258 assigned lasmiditan 50 mg, 100 mg, and 200 mg, respectively. There were no deaths; serious adverse events were reported for seven patients (placebo, n = 2 [0.2%]; lasmiditan 50 mg, n = 1 [0.2%]; lasmiditan 100 mg, n = 1 [0.2%]; lasmiditan 200 mg, n = 3 [0.2%]). Patients reporting ≥ 1 treatment-emergent adverse events were: Placebo, n = 174 (13.5%); lasmiditan 50 mg, n = 166 (25.4%); lasmiditan 100 mg, n = 458 (36.2%); and lasmiditan 200 mg, n = 510 (40.6%). Treatment-emergent adverse events were generally mild or moderate in severity. The most common treatment-emergent adverse events with lasmiditan were dizziness, paresthesia, somnolence, fatigue, nausea, muscular weakness and hypoesthesia. There were no ischemic events. Conclusions As a centrally-penetrant drug, lasmiditan use was associated with neurologic treatment-emergent adverse events; most were mild or moderate in severity and self-limiting. Trial registration at clinicaltrials.gov SAMURAI (NCT02439320) and SPARTAN (NCT02605174).

This paper describes current non-antibody pharmacologic approaches to the prevention of migraine in adults. Preventive therapy should be considered for patients with migraine who routinely have more than 6 headache days per month or in other special circumstances. Choices for preventive therapy are based on patient preferences about side effects and evidence of efficacy. The evidence level and commonly used doses for selected categories of migraine preventive medication are reviewed, including antiepileptic drugs, antihypertensive drugs, and antidepressants. Propranolol, timolol, topiramate, and divalproex sodium are approved for migraine prevention by the US FDA. OnabotulinumtoxinA is approved for prevention of chronic migraine. Several off-label drugs, especially lisinopril, candesartan, and amitriptyline also have good evidence of benefit. The spectrum of response to preventive therapy varies; in general, complete cessation of headaches is uncommon, although there are "super-responders" to every therapy, as illustrated by patient reports of dramatic responses to treatment. Preventive treatment should be started at a low dose and doses increased slowly until therapeutic benefit is achieved or side effects preclude continued use.

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This article reviews several options for managing acute attacks, including information on expected efficacy, dosing, and adverse effects. Strategies for effective application of acute therapies are discussed. Prevention can be added to acute therapy depending on headache characteristics such as frequency, severity, disability, and the presence of comorbid conditions. The mechanisms of action of preventive medications and strategies for their most effective use are discussed.