Willingness to use a wearable device capable of detecting and reversing overdose among people who use opioids in Philadelphia.

BACKGROUND: The incidence of opioid-related overdose deaths has been rising for 30 years and has been further exacerbated amidst the COVID-19 pandemic. Naloxone can reverse opioid overdose, lower death rates, and enable a transition to medication for opioid use disorder. Though current formulations for community use of naloxone have been shown to be safe and effective public health interventions, they rely on bystander presence. We sought to understand the preferences and minimum necessary conditions for wearing a device capable of sensing and reversing opioid overdose among people who regularly use opioids. METHODS: We conducted a combined cross-sectional survey and semi-structured interview at a respite center, shelter, and syringe exchange drop-in program in Philadelphia, Pennsylvania, USA, during the COVID-19 pandemic in August and September 2020. The primary aim was to explore the proportion of participants who would use a wearable device to detect and reverse overdose. Preferences regarding designs and functionalities were collected via a questionnaire with items having Likert-based response options and a semi-structured interview intended to elicit feedback on prototype designs. Independent variables included demographics, opioid use habits, and previous experience with overdose. RESULTS: A total of 97 adults with an opioid use history of at least 3 months were interviewed. A majority of survey participants (76%) reported a willingness to use a device capable of detecting an overdose and automatically administering a reversal agent upon initial survey. When reflecting on the prototype, most respondents (75.5%) reported that they would wear the device always or most of the time. Respondents indicated discreetness and comfort as important factors that increased their chance of uptake. Respondents suggested that people experiencing homelessness and those with low tolerance for opioids would be in greatest need of the device. CONCLUSIONS: The majority of people sampled with a history of opioid use in an urban setting were interested in having access to a device capable of detecting and reversing an opioid overdose. Participants emphasized privacy and comfort as the most important factors influencing their willingness to use such a device. TRIAL REGISTRATION: NCT04530591.

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: a multicenter, randomized, double-blind, placebo-controlled study.

BACKGROUND: In a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6 mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2 h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed. RESULTS: A total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2 h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P  =  0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90 min postdose (P  ≤  0.0195). DFN-11 was significantly superior to placebo for pain relief at 60 min, 90 min, and 2 h postdose (P ≤ 0.0179). At 2 h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P  =  0.0056) and phonophobia (P  =  0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%). CONCLUSIONS: This study met its primary endpoint, pain freedom at 2 h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3 mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6 mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015).

Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with episodic migraine: an 8-week open-label extension study.

BACKGROUND: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute treatment of migraine, has not been assessed previously in multiple attacks. The objective of this study was to evaluate the efficacy, tolerability, and safety of DFN-11 in the acute treatment of multiple migraine attacks. METHODS: This was an 8-week open-label extension of multicenter, randomized, double-blind, placebo-controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per month were randomized to DFN-11 or placebo to treat a single attack of moderate-to-severe intensity and then entered the extension study to assess the efficacy, tolerability, and safety of DFN-11 in multiple attacks of any pain intensity. RESULTS: Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%) discontinued early. A total of 848 migraine episodes were treated with 1042 doses of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2 h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110), respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%, 86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6% (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most common of which were associated with the injection site: swelling (12.8%), pain (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw tightness). Five subjects (2.1%) discontinued due to adverse events, which included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection site swelling. There were no serious TEAEs and no new or unexpected safety findings. CONCLUSION: DFN-11 was effective, tolerable, and safe in the acute treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain and associated symptoms. Most TEAEs were mild, with a very low incidence of triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02569853 . Registered 07 October 2015.

Psychological flexibility in migraine: A study of pain acceptance and values-based action.

BACKGROUND: Studies of musculoskeletal pain patients confirm that acceptance of pain and values-based action are strong predictors of pain-related disability and that interventions fostering "psychological flexibility" confer positive outcomes. However, data on these processes in migraine remain limited. This cross-sectional study examined relations between components of psychological flexibility and headache among treatment-seeking migraineurs. METHODS: A total of 103 adults (M age = 41.5 (11.9) years; 88.2% female) with ICHD-confirmed migraine (71.8% episodic, 28.2% chronic) across three clinics completed measures of psychological flexibility and headache-related disability. Hierarchical regressions quantified relations between acceptance/values-based action and headache variables after first controlling for pain severity and gender. RESULTS: Acceptance of pain and values-based action accounted for 10% of unique variance in headache severity (ΔR(2) p = 0.006) and up to 20% in headache-related disability (ΔR(2) ps = 0.02 and < 0.001) but were weakly related to headache frequency. Psychological flexibility was more strongly associated with MIDAS-measured disability than was headache severity or headache frequency. Significant effects were typically of medium-to-large size and driven primarily by values-based action. CONCLUSIONS: Paralleling results from the broader chronic pain literature, pain acceptance and values-based action play significant roles in headache pain and disability. Further study of interventions targeting these processes may enhance existing treatments.

Consistency of eletriptan in treating migraine: Results of a randomized, within-patient multiple-dose study.

OBJECTIVE: The current study evaluated the consistency of eletriptan response. METHODS: Using a within-patient crossover design, patients with migraine completed a three-attack, open-label, lead-in period, before being treated, double-blind for four attacks, with either eletriptan 40 mg (ELE-40; N = 539) or eletriptan 80 mg (ELE-80; N = 432); placebo was randomly substituted for the treatment of one attack. RESULTS: On an A PRIORI analysis of within-patient consistency, double-blind treatment was associated with similar 2 hour headache response rates using a ≥2/3 response criterion for ELE-40 (77%) and ELE-80 (73%), and using a 3/3 response criterion for ELE-40 (46%) and ELE-80 (47%). Within-patient consistency in achieving pain-free status at 2 hours using a ≥2/3 criterion was slightly higher on ELE-40 (42%) compared with ELE-80 (38%), and was similar using the 3/3 criterion (18% on ELE-40, 17% on ELE-80). On a repeated measures logistic regression analysis across all treated attacks, the probability of achieving a headache response at 2 hours ranged from 71% to 74% on ELE-40 vs. 17% to 28% on placebo ( P < 0.0001), and from 66% to 74% on ELE-80 vs. 21% to 27% on placebo ( P < 0.0001). The incidence, per attack, of adverse events was low for both ELE-40 and ELE-80. Few adverse events occurred with incidence ≥10% on ELE-40 (asthenia, 5.0%) or ELE-80 (asthenia, 10%; nausea, 5.8%). Discontinuations because of adverse events were 0.2% on ELE-40, and 1.6% on ELE-80 CONCLUSION: In this multiple attack study, eletriptan was well-tolerated and demonstrated consistent and significant efficacy in the treatment of migraine.

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.

Multimodal Migraine Management and the Pursuit of Migraine Freedom: A Narrative Review.

Migraine is a neurologic disease with a complex pathophysiology that can be controlled with current treatment options but not cured. Therefore, treatment expectations are highly variable. The concept of migraine freedom was recently introduced and can mean different things, with some, for example, expecting complete freedom from headache and associated symptoms and others accepting the occasional migraine attack if it does not impact functioning. Therefore, migraine management should be optimized so that patients can have the best opportunity to achieve their optimal treatment goals. With migraine freedom as a goal and, given the complex pathophysiology of migraine and the high incidence of comorbidities among individuals with migraine, treatment with a single modality may be insufficient, as it may not achieve migraine freedom in those with more frequent or disabling attacks. In this clinical perspective article, we have identified four key, partially overlapping principles of multimodal migraine treatment: (1) manage common comorbidities; (2) control modifiable risk factors for progression by addressing medication and caffeine overuse; (3) diagnose and treat secondary causes of headache, if present; and (4) individualize acute and preventive treatments to minimize pain, functional disability, and allodynia. There are many barriers to pursuing migraine freedom, and strategies to overcome them should be optimized. Migraine freedom should be an aspirational goal both at the individual attack level and for the disease overall. We believe that a comprehensive and multimodal approach that addresses all barriers people with migraine face could move patients closer to migraine freedom.

Sumatriptan-naproxen migraine efficacy in allodynic patients: early intervention.

OBJECTIVE: This study evaluated the effectiveness of a single fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan-naproxen) using a very early treatment paradigm in migraine patients whose attacks were historically accompanied by cutaneous allodynia. BACKGROUND: Evidence suggests that allodynic migraineurs may demonstrate a better response when treated prior to developing central sensitization, and that these patients are treated more effectively with a compound of sumatriptan and naproxen sodium than either drug alone. This study targeted patients who have accompanying allodynia using a very early treatment paradigm where treatment was initiated while symptoms were still mild. METHODS: This was an open-label prospective, outpatient study of adult migraineurs who had screened positive for cutaneous allodynia and typically experienced moderate to severe pain preceded by an identifiable mild pain phase. Patients were treated with sumatriptan-naproxen using a very early intervention paradigm in 4 test migraines over 12 weeks where dosage occurred within 30 minutes of symptom onset. Data from diaries and questionnaires were used to evaluate the primary endpoints of sustained pain-free response at 24 hours post dose (using no second dose of study drug and no other rescue drugs), and overall satisfaction with sumatriptan-naproxen. RESULTS: Forty allodynic migraineurs enrolled in this study and reported a total of 160 migraines. Of these migraines, 78 (49%) achieved sustained pain-free at 24 hours and 94 (59%) were reported as pain-free at 2 hours. The number of patients who rated their Overall Satisfaction following treatment with sumatriptan-naproxen as "Satisfied" (satisfied or very satisfied) was 32 (80%) after the first migraine and 25 (63%) after 3 or more migraines. CONCLUSIONS: In this open-label study, allodynic patients reported that their migraine attacks responded well and they achieved a high degree of satisfaction following treatment with a fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg administered in a very early treatment paradigm.

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.

Fixed-dose sumatriptan and naproxen in poor responders to triptans with a short half-life.

OBJECTIVE: To evaluate efficacy and tolerability of a single, fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan/naproxen sodium) vs placebo in migraineurs who had discontinued treatment with a short-acting triptan because of poor response or intolerance. BACKGROUND: Triptan monotherapy is ineffective or poorly tolerated in 1 of 3 migraineurs and in 2 of 5 migraine attacks. In April, 2008, the Food and Drug Administration approved the combination therapy sumatriptan/naproxen sodium, developed specifically to target multiple migraine mechanisms. This combination product offers an alternative migraine therapy for patients who have reported poor response or intolerance to short-acting triptans. METHODS: Two replicate, randomized, multicenter, double-blind, placebo-controlled, 2-attack crossover trials evaluated migraineurs who had discontinued a short-acting triptan in the past year because of poor response or intolerance. Patients were instructed to treat within 1 hour and while pain was mild. RESULTS: Patients (n = 144 study 1; n = 139 study 2) had discontinued an average of 3.3 triptans before study entry. Sumatriptan/naproxen sodium was superior (P < .001) to placebo for 2- through 24-hour sustained pain-free response (primary end point) (study 1, 26% vs 8%; study 2, 31% vs 8%) and pain-free response 2 hours post dose (key secondary end point) (study 1, 40% vs 17%; study 2, 44% vs 14%). A similar pattern of results was observed for other end points that evaluated acute (2- or 4-hour), intermediate (8-hour), or 2- through 24-hour sustained response for migraine (ie, pain and associated symptoms), photophobia, phonophobia, or nausea (with the exception of nausea 2 and 4 hours post dose). The percentage of patients with at least 1 adverse event (regardless of causality) was 11% with sumatriptan/naproxen sodium compared with 4% with placebo in study 1 and 9% with sumatriptan/naproxen sodium compared with 5% with placebo in study 2. Only 1 adverse event in 1 study was reported in > or =2% of patients after treatment with sumatriptan/naproxen sodium and reported more frequently with sumatriptan/naproxen than placebo: chest discomfort was reported in 2% of subjects in study 1, and no events met this threshold in study 2. No serious adverse events attributed to study medication were reported in either study. CONCLUSION: In migraineurs who reported poor response to a short-acting triptan, sumatriptan/naproxen sodium was generally well tolerated and significantly more effective than placebo in conferring initial, intermediate, and sustained efficacy for pain and migraine-associated symptoms of photophobia and phonophobia.

Two double-blind, multicenter, randomized, placebo-controlled, single-dose studies of sumatriptan/naproxen sodium in the acute treatment of migraine: function, productivity, and satisfaction outcomes.

OBJECTIVE: To describe return to normal function, productivity, and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium, sumatriptan alone, naproxen sodium alone, or placebo. PATIENTS, DESIGN, AND SETTING: Patients in 2 identical, US, phase 3, randomized, double-blind, parallel-group, placebo-controlled, single-dose, multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium (85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation), sumatriptan, naproxen sodium, or placebo. MAIN OUTCOME MEASURES: Ability to function (not impaired, mildly impaired, severely impaired, or required bed rest) was collected in diary cards completed immediately prior to treatment, every 30 minutes for the first 2 hours, and hourly from 2 to 24 hours while awake. Patients completed the Productivity Assessment Questionnaire (PAQ) 24 hours after study drug administration. The Patient Perception of Migraine Questionnaire (PPMQ) was administered at screening and 24 hours post treatment to capture patient satisfaction. RESULTS: Compared with the other groups, the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing. They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies, and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications. CONCLUSIONS: Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly, and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups. Overall productivity loss was significantly reduced following use of sumatriptan/naproxen sodium.

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.

Central sensitisation and cutaneous allodynia in migraine: implications for treatment.

Cutaneous allodynia, pain resulting from application of a non-noxious stimulus to normal skin, is a recently described symptom of migraine, with a potential role in directing optimal treatment for migraine attacks. Manifestations of cutaneous allodynia include discomfort when combing the hair, shaving, and wearing glasses, contact lenses, earrings or tight clothing. The exact mechanism by which a migraine attack is triggered is not known, but it has been theorised that, in some patients, once the attack has begun, central neurons can propagate information about the pain process without the need for further external stimuli. This process is termed central sensitisation. The trigeminal nerves, which innervate intracranial and extracranial tissues, account for head pain and other symptoms in migraine. The first-order neurons in the trigeminal ganglion receive input from the dural blood vessels, which is transmitted to second-order neurons in the trigeminal brain stem nuclear complex and is finally sent to the third-order neurons in the thalamus. Studies in humans and animals have shown that migraine pain progresses along this neural pathway, with throbbing head pain occurring early in the attack (sensitisation of first-order neurons), followed by central sensitisation and cutaneous allodynia within the referred pain area (second-order) and finally extracephalic allodynia (third-order). The data also indicate that once central sensitisation is established in the second- and third-order neurons, migraine treatment designed to prevent the initiation of central sensitisation can lessen the pain to some extent but cannot reverse it. Thus, treatment affecting the initiation of central sensitisation should be administered immediately after the onset of migraine pain to prevent intracranial hypersensitivity and the establishment of allodynia. The serotonin 5-HT(1B/1D) agonist anti-migraine agents (the 'triptans') block meningeal nociceptor transmission at presynaptic sites in the dorsal horn. Studies have shown that triptan therapy can abort pain prior to the development of central sensitisation, but not after allodynia has been established. Therefore, in the subset of patients who report symptoms of cutaneous allodynia with migraine attacks, early initiation of triptan therapy is currently the best intervention to achieve rapid, complete and sustained pain relief.

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.