Consistency of return to normal function, productivity, and satisfaction following migraine attacks treated with sumatriptan/naproxen sodium combination.

OBJECTIVES: To assess the consistency of improved functioning, productivity, and medication satisfaction in migraines treated with a single tablet of sumatriptan 85 mg/naproxen sodium 500 mg (S/NS) using an early intervention approach. METHODS: Two randomized, double-blind, placebo-controlled, 4-period crossover, multi-attack, multi-center, outpatient studies of moderate to severe adult migraineurs were conducted to compare S/NS with placebo. Participants recorded outcome assessments in a diary during the 24 hours following study medication. Analyses were conducted on the intent-to-treat population who treated at least 1 attack. Statistical significance between treatment groups used analysis of variance repeated measures models and the intent-to-treat population. There were no corrections for multiplicity. RESULTS: Almost half (48.5%) of migraineurs treated with S/NS returned to normal functioning at 2 hours and 73.3% at 4 hours postdose, compared with 28.7% (2 hours) and 43.3% (4 hours) of placebo-treated attacks. Total productivity loss over the 24 hours postdose was significantly reduced following S/NS treatment (2.5 hours on average) compared with placebo (4.0 hours). Sumatriptan/naproxen treatment resulted in significantly higher medication satisfaction scores on the efficacy, functionality, and total efficacy subscales compared with placebo in all attacks in both studies. Sumatriptan/naproxen treatment also provided significantly greater ease of use in 7 of the 8 attacks. Although tolerability was high in both treatment groups (over 90%), the placebo group was significantly less bothered by side effects in 6 of 8 attacks. CONCLUSION: Results from these 2 randomized, double-blind, placebo-controlled, multi-attack, crossover studies demonstrated the rapid and consistent restoration of patients' functioning, the consistent reduction in productivity loss, and high satisfaction ratings from patients treating multiple migraine attacks with S/NS using an early intervention approach.

Does health information exchange reduce unnecessary neuroimaging and improve quality of headache care in the emergency department?

BACKGROUND: Health information exchange (HIE) is advocated as an approach to reduce unnecessary testing and improve quality of emergency department (ED) care, but little evidence supports its use. Headache is a specific condition for which HIE has theoretical benefits. OBJECTIVE: To determine whether health information exchange (HIE) reduces potentially unnecessary neuroimaging, increases adherence with evidence-based guidelines, and decreases costs in the emergency department (ED) evaluation of headache. DESIGN: Longitudinal data analysis SUBJECTS: All repeat patient-visits (N = 2,102) by all 1,252 adults presenting with headache to a Memphis metropolitan area ED two or more times between August 1, 2007 and July 31, 2009. INTERVENTION: Use of a regional HIE connecting the 15 major adult hospitals and two regional clinic systems by authorized ED personnel to access the patient's record during the time period in which the patient was being seen in the ED. MAIN MEASURES: Diagnostic neuroimaging (CT, CT angiography, MRI or MRI angiography), evidence-based guideline adherence, and total patient-visit estimated cost. KEY RESULTS: HIE data were accessed for 21.8 % of ED patient-visits for headache. 69.8 % received neuroimaging. HIE was associated with decreased odds of diagnostic neuroimaging (odds ratio [OR] 0.38, confidence interval [CI] 0.29-0.50) and increased adherence with evidence-based guidelines (OR 1.33, CI 1.02-1.73). Administrative/nursing staff HIE use (OR 0.24, CI 0.17-0.34) was also associated with decreased neuroimaging after adjustment for confounding factors. Overall HIE use was not associated with significant changes in costs. CONCLUSIONS: HIE is associated with decreased diagnostic imaging and increased evidence-based guideline adherence in the emergency evaluation of headache, but was not associated with improvements in overall costs. Controlled trials are needed to test whether specific HIE enhancements to increase HIE use can further reduce potentially unnecessary diagnostic imaging and improve adherence with guidelines while decreasing costs of care.

An open-label trial of a sumatriptan auto-injector for migraine in patients currently treated with subcutaneous sumatriptan.

OBJECTIVE: To assess the ability of patients, during an acute migraine attack, to successfully self-inject a single dose of sumatriptan using a novel sumatriptan auto-injector (Alsuma(®)), and to evaluate the safety, tolerability, and effectiveness of this sumatriptan auto-injector during an acute migraine attack. BACKGROUND: This sumatriptan auto-injector is a single-use system for the rapid subcutaneous delivery of 6 mg of sumatriptan succinate in the acute management of migraine pain. This auto-injector was developed to address the clinical need for an easy-to-use and rapid-to-administer system that did not require any assembly during the time of an ongoing attack. METHODS: This was an open-label, phase 3 trial conducted at 10 sites in the USA. Male or female adults, ages 18-60 years old, were eligible for study entry if they met International Headache Society criteria for migraine with or without aura, with at least 2 attacks per month, and if they reported use of subcutaneous injectable sumatriptan on at least 2 occasions within the previous 2 months. During the onset of a migraine attack of moderate-to-severe intensity, patients were asked to administer a 6-mg subcutaneous dose of sumatriptan using the auto-injector. Patients returned to the study site within 72 hours of the migraine for the post-treatment assessment visit. RESULTS: A total of 63 patients met entry criteria and received a dose of study medication (the intent-to-treat sample). Sixty-one patients (96.8%) reported injection in the thigh, and 2 patients (3.2%) reported injection in the arm. On the patient questionnaire, 100% of patients (95% confidence interval [CI] 94.3-100%) "agreed" or "agreed strongly" that the written instructions for the auto-injector were clear and easy to follow (30.2% "agreed"; 69.8% "agreed strongly"); 95.2% of patients (95% CI 86.7-99.0%) found that the auto-injector was easy to use (36.5% "agreed"; 58.7% "agreed strongly"), and 65.1% of patients (95% CI 52.0-76.7%) stated that they preferred the new auto-injector to the traditional auto-injector that they were using prior to study entry (42.9% "agreed"; 22.2% "agreed strongly"). Headache response rate at 2 hours was 93.7% (95% CI 84.5-98.2%), and pain-free rate at 2 hours was 60.3% (95% CI 47.2-72.4%). Pain-free rates at 2 hours were similarly high (58.3%; 95% CI 36.6-77.9%) in the subgroup of patients reporting severe baseline headache pain. Only 1 patient reported use of rescue medication after use of the auto-injector, a single oral dose of sumatriptan 100 mg on the same day. The most frequent adverse event was injection site bruising, reported by 15.9% of patients, and rated in all instance as mild in intensity. The second most frequent adverse event was injection site pain, reported by 6.3% of patients, and rated as mild by all patients except 1, who rated it as moderate in intensity. CONCLUSION: The majority of injection-experienced patients reported the pre-assembled, single-use sumatriptan auto-injector to be an easy-to-use, preferred treatment for an acute migraine attack. The study found the auto-injector to be safe and well tolerated, with levels of injection site reactions that were mild and infrequent.

A cross-sectional survey to assess the migraineur's medication decision-making beliefs: determining when a migraine is triptan-worthy.

OBJECTIVES: To investigate the factors that influence a migraineur's beliefs regarding oral triptans for the acute treatment of migraines and to provide further insight into patients' decision-making process when faced with migraine. METHODS: A multicenter, cross-sectional, observational study of subjects currently prescribed an oral triptan medication for the acute treatment of migraine headaches. Subjects were recruited from 6 headache clinics and one primary care practice in the United States. Enrolled subjects completed a questionnaire that could be completed either at the site as part of the visit or at home. The questionnaire comprised 27 questions assessing demographic characteristics, migraine history, migraine frequency and severity, and general beliefs about migraine treatments. The study population was stratified into 2 cohorts (Early Treatment and Delayed Treatment) based on how they typically use their oral triptan to treat a typical migraine. RESULTS: A total 506 subjects were enrolled in the study, of which 502 were stratified into the Early Treatment cohort (41.2%) and Delayed Treatment cohort (58.8%). Demographic and clinical characteristics were generally similar between the 2 cohorts. In terms of general treatment patterns, there were notable differences between the Delayed and Early Treatment cohorts, with the Delayed Treatment cohort significantly more likely to take an over-the-counter (OTC) or non-triptan medication first (P ≤ .001) and only take a triptan if the OTC or non-triptan medication did not work (P ≤ .001). Furthermore, 55% of the Delayed Treatment cohort delayed taking a triptan to be certain that the headache was a migraine (vs 32% of the Early Treatment cohort; P ≤ .001). When asked to specify the reasons for delaying treatment with a triptan, the Delayed Treatment cohort had, in general, greater concerns about using their oral triptan in comparison with the Early Treatment cohort. In particular, respondents were primarily concerned with running out of their triptan medication with 35% of the Delayed Treatment cohort expressing this concern compared with 22% of the Early Treatment cohort (P ≤ .001). Statistically significant differences were also noted for concerns about taking medications (P ≤ .001), side effects (P ≤ .05), expense (P ≤ .01), and taking prescription medications (P ≤ .001). CONCLUSIONS: Results build upon previously published studies and suggest that patient beliefs directly influence how migraineurs manage their migraines and have implications for patient outcomes. Such insights should be used to facilitate physician-patient communication and reinforce the need for patient-centered care to improve patient outcomes.

Examining the interrelationship of migraine onset, duration, and time to treatment.

OBJECTIVE: The objective of this study is to investigate migraines, both longitudinally and cross-sectionally, to understand the impact that time of treatment has on migraine duration and the patients' return to daily functioning. BACKGROUND: Several studies have explored the relationship between migraine treatment and its impact on migraine duration; however, the interrelationship of migraine onset and impact of treatment timing on migraine resolution is not completely understood. DESIGN/METHODS: Five hundred and nine migraineurs completed 1 online baseline survey and a diary survey after each of their next 3 migraines. All subjects were 18 or older and were employed full time. RESULTS: Migraine episodes treated within 1 hour were significantly shorter on average than those treated after 1 hour (9.1 hours vs 12.3 hours) (P < .05). Over-the-counter medication was the most frequently reported first-line treatment (44%) followed by an oral triptan (30%), another prescription medication (14%), and combination therapy (4%). Rescue treatment was reported in 57% of attacks. The majority of over-the-counter (69%) and another prescription (55%) treated attacks required rescue whereas only 39% of first-line triptan attacks required rescue. CONCLUSIONS: Treating migraines early with an oral triptan-containing therapy appears to be a very effective method for reducing migraine duration and preventing the need for additional medication. Our findings also suggest that physicians should spend more time educating patients how to identify migraines early. Understanding the relationship between these key factors will provide insight into appropriate treatment and management of migraines, and more importantly, equip patients with the tools necessary to improve their outcomes and overall impact on functioning.

Multi-center comparison of response to a single tablet of sumatriptan 85 mg and naproxen 500 mg vs usual therapy treating multiple migraine attacks as measured by the completeness of response survey.

OBJECTIVE: To investigate a broad definition of migraine resolution that extends beyond specific migraine-associated diagnostic symptoms as measured by the Completeness of Response Survey. METHODS: Conducted at 8 sites, 135 subjects treated migraines with SumaRT/Nap over 2 months. To measure subjects' experiences with SumaRT/Nap compared to their usual migraine medication, the Headache Impact Test, Revised Patient Perception of Migraine Questionnaire, and Completeness of Response Survey were administered at baseline and at 2 months. RESULTS: The effects of the study medicine compared to the subjects' usual migraine medicine reached statistical significance in decreasing headache severity, lessening of associated symptoms, and attaining complete relief with a single dose (60.04% of attacks resolved at 2 hours post-treatment). CONCLUSION: Compared to a subject's usual treatment, SumaRT/Nap used early and consistently for treatment of acute migraine offers important clinical improvements, including lessening of associated symptoms beyond International Headache Society criteria. CLINICAL TRIAL REGISTRATION NUMBER: NCT00893737.

Migraine: a better way to recognize and treat it.

Consider using the Headache Assessment Quiz, which 76% of providers in this study said enabled patients to adequately convey headache severity/symptoms, compared with just 20% of providers at baseline who thought patients communicated clearly. Use the quiz also to better understand the impact of migraine on a patient's life, and to help determine which patients need migraine-specific therapy.

Challenging or difficult headache patients.

This article addresses interesting and enigmatic presentations of headache from a diagnostic and treatment perspective. The emphasis is on migraineurs and other headache patients who represent a significant burden for the primary care provider. In particular, the author focuses on undiagnosed migraine, menstrual migraine, migraine in pregnancy, intractable migraine and status migrainosus,transformed migraine, hemiplegic migraine, basilar migraine, "triptan syndrome," sudden onset of severe headache, post-traumatic headache, and headache in elderly patients.

Divalproex ER prophylaxis in migraineurs with probable chronic migraine and probable medication-overuse headache: a case series.

This case series prospectively evaluated divalproex ER in 15 headache clinic migraine patients fulfilling International Headache Society criteria for probable chronic migraine and probable medication-overuse headache. Divalproex ER was initiated at 500 mg QHS and increased after Week 2 to 1000 mg QHS for a total treatment period of 2 months. Mean headache days per month dropped from 21.6 to 10.4 at month 1 and 8.9 at month 2. All 10 patients who completed the study rated their satisfaction with treatment as changed from unsatisfied at baseline to satisfied at study completion. The results of this study support the prophylactic efficacy of divalproex ER in migraine patients with probable chronic migraine and probable medication-overuse headache.

Assessing the impact of migraine onset on work productivity.

OBJECTIVE: Examine the impact of migraine on work productivity, and particularly the association between time of migraine onset and lost productivity as measured by absenteeism and presenteeism. METHODS: A total of 509 people with migraine completed one online baseline survey and a diary survey after each of their next three migraines. All subjects were 18 or older and employed full time. RESULTS: Sixty-four percent of migraines occurred on a workday. Of these, 68% resulted in some work productivity impact in the form of absenteeism or presenteeism. Migraines occurring during usual sleeping hours or prior to the start of work had the greatest impact on productivity. CONCLUSIONS: Findings indicate that absenteeism and presenteeism are both substantial contributors to work productivity loss. Primary factors associated with lost productivity include pain severity, migraine symptoms, and sleep disturbance.

The impact of migraine and the effect of migraine treatment on workplace productivity in the United States and suggestions for future research.

Evidence suggests that migraine is associated with decreased productivity. This article describes the results of a systematic literature review of peer-reviewed publications that measured the impact of migraine on workplace productivity in the United States and provides recommendations for future research. A MEDLINE search was conducted from January 1, 1990 to July 31, 2008. Articles were included if the results were from a prospective or retrospective study that reported work-specific productivity outcomes in adults with migraine in the United States. Twenty-six studies were included. Nine studies found that diagnosed and/or undiagnosed migraine had a negative impact on worker productivity. Although one migraine prophylactic study found a statistically significant improvement in worker productivity for topiramate-treated patients, another found an insignificant difference in lisinopril-treated patients. Fifteen studies compared the impact of triptan therapy with a control group. The control groups in these studies differed with regard to recall periods, time to follow-up, and types of questionnaires used. Almost all studies found that triptan therapy was associated with a statistically significant improvement in loss in worker productivity vs the control group. Health care professionals can reduce the impact of migraine on worker productivity with appropriate therapy. Researchers should collect presenteeism and absenteeism data, report results in units of time, use a validated instrument, carefully consider recall periods, and report worker productivity separately. In addition, patients with undiagnosed migraine should be included in disease burden studies. When evaluating effects of treatment on productivity, researchers should target well-controlled, double-blind studies and conduct productivity research for new treatments.

Clarification of developing and established clinical allodynia and pain-free outcomes.

OBJECTIVE: The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief questionnaire. BACKGROUND: Using quantitative sensory testing (QST) recent studies demonstrate that the presence of cutaneous allodynia, a clinical manifestation of central sensitization, can be detrimental to the success of migraine therapy with sumatriptan. QST is costly and requires much time, therefore it is not feasible to use in clinical practice. METHODS: In this prospective study, migraineurs completed a questionnaire about their skin sensitivity during migraine. Each migraineur treated 2 migraine headaches with sumatriptan (100 mg): 1 headache at the earliest sign of migraine pain (mild, within 1 hour of onset) and 1 headache at least 4 hours after the onset of pain while moderate or severe. RESULTS: Thirty-six migraine headaches were evaluated in 18 migraineurs. A total of 44% of the headaches were not associated with allodynia at any time. Irrespective of allodynic status, headaches were more likely to become pain-free with early versus late treatment (2 hours; 78% vs. 33%, respectively). Headaches were equally likely to become pain-free when allodynia was reported before treatment but not 2 and 4 hours after treatment (2 hours; 67 vs. 63%, respectively, 4 hours 80 vs. 81%, respectively). However, no headaches were pain-free when allodynia was reported at 2 and 4 hours after treatment. CONCLUSIONS: Headaches without allodynia were aborted when treated early or late, and headaches with allodynia were aborted only when allodynia was not present after treatment. These findings suggest that different mechanisms account for allodynia before and after treatment; a developing phase in which central sensitization depends on incoming pain signals from the peripheral nociceptors and an established phase in which the sensitization becomes independent of the pain signals that come from the dura.

Migraine treatment throughout the lifecycle.

The treatment of migraine headache is often suboptimal despite significant advances in our understanding of the pathophysiology and treatment of migraine. Children, adolescents, women and the elderly are particularly at risk of receiving inadequate or inappropriate therapy. In this review, the reader is brought up-to-date with changes to the International Headache Society diagnostic criteria for migraine. The pathophysiology of migraine is also reviewed, with a special emphasis on the evolving concept of central sensitization and cutaneous allodynia since this concept has led to a paradigm shift in the way migraines are managed. A review of the evidence supporting the benefits of early treatment before pain becomes moderate-to-severe is provided. Recommendations for acute and prophylactic treatments throughout the lifecycle are made in light of clinical practice guidelines and more recent evidence. Lastly, the current optimal treatment of migraine is provided and the potential role of calcitonin gene-related peptide antagonists in the future is discussed.

Pilot study evaluating preference for 3-mg versus 6-mg subcutaneous sumatriptan.

BACKGROUND: Subcutaneous sumatriptan (6 mg) is undeniably an excellent treatment of migraine. However, some patients have avoided using 6 mg sumatriptan because of unpleasant or unwanted side effects. OBJECTIVE: To evaluate the efficacy of subcutaneous sumatriptan (3 mg) during a moderate or severe migraine attack. METHODS: Thirty subcutaneous sumatriptan-naive patients with a history of migraine with and without aura treated their next two moderate or severe migraines with either 3-mg or 6-mg sumatriptan injection. The primary endpoint was whether patients preferred the low-dose (3 mg) or the high-dose (6 mg) subcutaneous sumatriptan. Other objectives included percentage of patients pain free at 15 and 30 minutes, 1 and 2 hours; a pain-free response lasting between 2 and 24 hours, patient satisfaction, and acceptability of formulation. A new combination endpoint (efficacy and lack of significant side effects) was also evaluated. RESULTS: Eighty percent of patients preferred 3-mg over 6-mg subcutaneous sumatriptan. At 1 hour postdose 57% of patients were pain free with 3 mg and 53% with 6 mg. At 2 hours postdose 87% were pain free with 3 mg and 80% with 6 mg. A sustained pain-free response was obtained by 70 to 80% of patients. When combining a pain-free response at 2 hours and a sustained pain-free response at 24 hours with no significant side effects, more patients met the endpoint with 3 mg (63 to 67%) than with 6 mg (33 to 50%). CONCLUSIONS: Combining efficacy and tolerability endpoints may be clinically meaningful and reflective of real-world expectations. In some patients, a lower dose of sumatriptan injection may be beneficial.

Oral transmucosal fentanyl citrate for the treatment of migraine headache pain in outpatients: a case series.

BACKGROUND: Migraine headache pain that does not respond to traditional antimigraine medications frequently requires treatment in the emergency department (ED) with parenteral opioids. Rapid onset of pain relief in an outpatient setting for migraine headache is the primary objective of patients and clinicians. Oral transmucosal fentanyl citrate (OTFC; ACTIQ) is a novel opioid product designed to deliver rapid analgesia to patients who experience breakthrough pain (BTP). OBJECTIVE: To evaluate the effectiveness, tolerability, and patient satisfaction with OTFC for the outpatient treatment of acute, refractory migraine headache pain. PATIENTS AND METHODS: Twenty patients with recurrent acute, refractory migraine headaches who had been referred to this headache clinic are reported in this case series. All patients had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. Patients were prescribed OTFC (400 microg) as rescue treatment for moderate or severe migraine headache pain as outpatients. Patients were instructed to self-administer OTFC at home and complete a diary recording: pain intensity (11-point scale; 10 = worst pain imaginable to 0 = no pain) before and 15, 30, 60, and 120 minutes after OTFC; satisfaction with the effectiveness of OTFC (selecting 1 of 7 categories ranging from "very dissatisfied" through "very satisfied") rated at 120 minutes; and adverse events. RESULTS: Eighteen patients (13 female) experienced a migraine and self-administered OTFC. OTFC successfully treated migraine episodes in all 18 outpatients; no patient went to an ED. OTFC rapidly reduced pain intensity, with significant improvement at 15 minutes that was sustained and provided progressively more pain relief at 30, 60, and 120 minutes (all P <.01). Mean (SEM) pain intensity significantly declined from 8.83 (0.35) pretreatment to 2.28 (0.67) at 120 minutes, an average reduction of 75% (P <.01). Patients' satisfaction ratings with OTFC were overwhelmingly positive, with 94% being satisfied and more than half (56%) being "very satisfied." Three (17%) patients experienced nausea, two (11%) somnolence, and one (6%) each itching, vomiting, and dry mouth. All adverse events were mild or moderate in severity. CONCLUSIONS: OTFC rapidly and significantly relieved acute, refractory migraine pain in outpatients, prevented the need for an ED visit, and was associated with high patient satisfaction ratings. The rapid onset of migraine headache pain relief in this case series is consistent with the analgesic effect reported with the use of OTFC in patients with BTP. OTFC was well tolerated in these patients who had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. OTFC may be effective for outpatient treatment of acute, refractory migraine headache pain. Further controlled studies are warranted.