Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study.

Objective: To evaluate the feasibility, safety, and tolerability of noninvasive vagus nerve stimulation (nVNS) for the prevention of chronic migraine (CM) attacks.

Methods: In this first prospective, multicenter, double-blind, sham-controlled pilot study of nVNS in CM prophylaxis, adults with CM (≥15 headache d/mo) entered the baseline phase (1 month) and were subsequently randomized to nVNS or sham treatment (2 months) before receiving open-label nVNS treatment (6 months). The primary endpoints were safety and tolerability.

Managing migraine by patient profile: role of frovatriptan.

For the last quarter of a century, triptans have been available for acute treatment of migraine but with little guidance on which of the different triptan products to use for which patient or which attack of migraine. In this article, we propose a structured approach to analysis of individual migraine attacks and patient characteristics as a means of defining and optimizing acute intervention. Assessment of patient and attack profiles includes the "5-Ps": pattern, phenotype, patient, pharmacology, and precipitants.

Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention.

Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system.

The pharmacokinetics and clinical efficacy of AVP-825: a potential advancement for acute treatment of migraine.

Introduction: Oral triptans have dominated the prescription market for acute treatment of migraine for nearly 25 years. Today, patients often express dissatisfaction with prescribed acute treatment in part because they do not have confidence that the therapy will provide consistent efficacy over time. Major limitations to sustained successful use of oral triptans are their relatively slow onset of meaningful clinical benefit and variable absorption/efficacy due to impaired gastrointestinal function during migraine.

A novel intranasal breath-powered delivery system for sumatriptan: a review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine.

Introduction: AVP-825, formerly 'OptiNose Sumatriptan,' is an investigational Breath-Powered(TM) Bi-Directional(TM) intranasal delivery system containing low-dose sumatriptan (22 mg intranasal powder) that avoids limitations of other types of intranasal administration by taking advantage of unique features of nasal anatomy and physiology.

Areas Covered: This review summarizes intranasal drug delivery for migraine, how the breath-powered technology works, and AVP-825 pharmacokinetic, efficacy and safety/tolerability findings. To identify AVP-825 clinical studies, a PubMed/MEDLINE database search was conducted with the terms AVP-825, OptiNose, OptiNose Sumatriptan, Breath-Powered Nasal Delivery or sumatriptan powder.

AVP-825 breath-powered intranasal delivery system containing 22 mg sumatriptan powder vs 100 mg oral sumatriptan in the acute treatment of migraines (The COMPASS study): a comparative randomized clinical trial across multiple attacks.

Objective: The objective of this study was to compare the efficacy, tolerability, and safety of AVP-825, an investigational bi-directional breath-powered intranasal delivery system containing low-dose (22 mg) sumatriptan powder, vs 100 mg oral sumatriptan for acute treatment of migraine in a double-dummy, randomized comparative efficacy clinical trial allowing treatment across multiple migraine attacks.

Background: In phases 2 and 3, randomized, placebo-controlled trials, AVP-825 provided early and sustained relief of moderate or severe migraine headache in adults, with a low incidence of triptan-related adverse effects.

Methods: This was a randomized, active-comparator, double-dummy, cross-over, multi-attack study (COMPASS; NCT01667679) with two ≤12-week double-blind periods.

Long-term efficacy of a double-blind, placebo-controlled, randomized study for repetitive sphenopalatine blockade with bupivacaine vs. saline with the Tx360 device for treatment of chronic migraine.

Background: This study aims to determine if repetitive sphenopalatine ganglion (SPG) blockades with 0.5% bupivacaine delivered with the Tx360 device results in long-term improvement in chronic migraine (CM). The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve.

Acupuncture in the treatment of headache: a traditional explanation of an ancient art.

Background: Over the past 4000 years, acupuncture has survived the test of time. Recent scientific studies posit acupuncture is an effective intervention for back and joint pain and headache, including migraine.

Methods: The process of acupuncture is explained, including the role of Qi, the integration of Yang and Yin, the 5 elements, the 8 trigrams, and the metaphors that help the acupuncturist understand the patient, interpret symptoms, and determine acupuncture points in the meridians used to prevent or treat disease.

Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine.

Objective: To test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM).

Methods: In the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment.

A randomized, double-blind, placebo-controlled study of breath powered nasal delivery of sumatriptan powder (AVP-825) in the treatment of acute migraine (The TARGET Study).

Objective: To evaluate the efficacy and safety of AVP-825, a drug-device combination of low-dose sumatriptan powder (22 mg loaded dose) delivered intranasally through a targeted Breath Powered device vs an identical device containing lactose powder (placebo device) in the treatment of migraine headache.

Background: Early treatment of migraine headaches is associated with improved outcome, but medication absorption after oral delivery may be delayed in migraineurs because of reduced gastric motility. Sumatriptan powder administered with an innovative, closed-palate, Bi-Directional, Breath Powered intranasal delivery mechanism is efficiently absorbed across the nasal mucosa and produces fast absorption into the circulation.

A double-blind, placebo-controlled study of repetitive transnasal sphenopalatine ganglion blockade with tx360(®) as acute treatment for chronic migraine.

Objective: To determine if repetitive sphenopalatine ganglion (SPG) blocks with 0.5% bupivacaine delivered through the Tx360(®) are superior in reducing pain associated with chronic migraine (CM) compared with saline.

Background: The SPG is a small concentrated structure of neuronal tissue that resides within the pterygopalatine fossa (PPF) in close proximity to the sphenopalatine foramen and is innervated by the maxillary division of the trigeminal nerve.

Symptomatic Overlap and Therapeutic Opportunities in Primary Headache.

Headache, a nearly universal experience, remains costly, disabling, and often suboptimally managed. The most common presentations in the United States are migraine, tension-type headache (TTH) and "sinus" headache, but their extensive symptomatic overlap suggests that these conditions can be approached as variations in the same underlying pathology and managed accordingly. We use case studies of patients with varying prior diagnoses (none, migraine, TTH, and sinus headache), as well as a 4-question diagnostic screening tool, to illustrate how pharmacists can use this conceptual framework to simplify identification, management, and referral of patients with primary headache conditions of uncertain etiology.

Randomized controlled trial of the orexin receptor antagonist filorexant for migraine prophylaxis.

Background: This study explored whether antagonism of orexin receptors might be an effective mechanism for migraine prevention.

Methods: We conducted a randomized, double-blind, placebo-controlled, pilot trial. Patients experiencing four to 14 days with migraine during a one-month baseline period were randomized to the orexin receptor antagonist filorexant 10 mg nightly or placebo for three months.

Red flags and comfort signs for ominous secondary headaches.

Secondary headaches are classified by the cause of the underlying disease process that is causing the headache. There are hundreds of secondary headache diagnoses and this article is not an exhaustive discussion of secondary headache disorders. Maintaining a high level of virulence and having a structured approach to evaluating all patients with headache is the key to timely diagnosis of secondary headache disorders.

Effect of noninvasive vagus nerve stimulation on acute migraine: an open-label pilot study.

Background: We sought to assess a novel, noninvasive, portable vagal nerve stimulator (nVNS) for acute treatment of migraine.

Methods: Participants with migraine with or without aura were eligible for an open-label, single-arm, multiple-attack study. Up to four migraine attacks were treated with two 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve within a six-week time period.

Chronic migraine in women.

Chronic migraine is a frequent, severely disabling headache that often evolves from EM. Treatment should be individualized with consideration of the patient as a whole person rather than just the headaches. Many options have been used for acute and preventive pharmacologic management, although good scientific and clinical evidence is limited to a few options.

[Societal impact of migraine chronification].

Migraine is a common neurological disorder that produces substantial disability for sufferers. Chronic migraine (≥ 15 headache days/month; CM) was significantly more disabling than episodic migraine (< 15 headache days/month; EM). CM was associated with greater impairment of occupational and social aspects of quality of life.

An exploratory study of salivary calcitonin gene-related peptide levels relative to acute interventions and preventative treatment with onabotulinumtoxinA in chronic migraine.

Objective: To determine if baseline/interictal saliva calcitonin gene-related peptide (CGRP) levels would be lower in subjects with chronic migraine receiving onabotulinumtoxinA compared with those receiving saline.

Background: CGRP is considered central to the pathogenesis of episodic migraine, but its relationship to chronic migraine is less understood. OnabotulinumtoxinA is an effective treatment for chronic migraine and has been demonstrated to inhibit the vesicular release of CGRP.

SumaRT/Nap vs naproxen sodium in treatment and disease modification of migraine: a pilot study.

Objective: This pilot study explored the potential for 2 recognized acute migraine medications, 85 mg of sumatriptan plus 500 mg of naproxen sodium in a combination tablet (SumaRT/Nap) and 500 mg of naproxen sodium, to treat and modify the disease progression of migraine. In other words, can these medications both abort an acute attack of migraine and reduce the number of future migraine attacks?

Background: Patients suffering with moderate to severe attacks of migraine desire acute treatment. As migraine frequency increases, so does the need for more frequent relief of acute attacks.

Treatment of chronic migraine: a 3-month comparator study of naproxen sodium vs SumaRT/Nap.

Objective: To compare the use of a combination of 85 mg sumatriptan plus 500 mg naproxen sodium in a combination tablet with 500 mg naproxen sodium in an identically appearing tablet when used as a daily preventative and acute treatment for 1 month and episodic acute treatment for an additional 2 months in patients with chronic migraine.

Background: To date, there has been minimal study of acute medications for patients with chronic migraine. Consequently, there is a paucity of study methodology or evidence-based guidance on the use of acute treatment medications in patients with chronic migraine.

Public policy and headache: observations of health care policy in the US congress from a legislative fellow's perspective.

Many neurologists and headache specialists are befuddled by inside the Beltway wheelings and dealings as they follow health care politics. A few of us join lobbying efforts, and even fewer become strangers in a strange land.

The bowel and migraine: update on celiac disease and irritable bowel syndrome.

This article explores possible relationships between migraine, irritable bowel syndrome (IBS), celiac disease (CD), and gluten sensitivity. These seemingly distinct medical entities curiously share many common epidemiological, psychosocial, and pathophysiological similarities. Considerable evidence is emerging to support a concept that experiencing significant threatening adverse events creates a state of hypervigilance in the nervous system, which associates with exaggerated response to future threats and episodic attacks of migraine and IBS.

Two center, randomized pilot study of migraine prophylaxis comparing paradigms using pre-emptive frovatriptan or daily topiramate: research and clinical implications.

Objective: To compare the efficacy and clinical benefit of 2 paradigms of migraine prevention using pre-emptive frovatriptan and daily topiramate. The study compares the paradigms of pre-emptive use of frovatriptan, a drug approved for acute migraine, and the daily use of topiramate, a Federal Drug Administration-approved and -accepted standard for migraine prophylaxis.

Background: Traditionally, preventive treatment of migraine required daily medication.

Satisfaction with and confidence in needle-free subcutaneous sumatriptan in patients currently treated with triptans.

Objective: To evaluate patient satisfaction with and confidence in Sumavel® DosePro® (needle-free subcutaneous sumatriptan) among current triptan users administering Sumavel DosePro for up to 4 migraine attacks.

Background: Sumavel DosePro is a needle-free, single-use device that facilitates subcutaneous injection of sumatriptan 6 mg and confers relief as early as 10 minutes after dosing.

Design/methods: In this open-label, multicenter study, Sumavel DosePro was self-administered for ≤4 migraine attacks (over a ≤60-day period) involving moderate or severe baseline pain by adult migraineurs who currently were using triptans (any form, any dosage) and reported being less than very satisfied with their current therapy (i.