Sumatriptan and naproxen sodium for the acute treatment of migraine

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine. BACKGROUND: The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multi-mechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets were encapsulated in order to achieve blinding of the study. RESULTS: In the sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), and versus placebo (38%; P= .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common. CONCLUSIONS: This is among the first prospective studies to demonstrate that multi-mechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine. This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy.     

Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents

Objectives.— To evaluate the long‐term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents. Methods.— This 12‐month, multicenter, open‐label, safety study was conducted in adolescents (aged 12‐17 years) with an average of 2‐8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen‐containing product, over‐the‐counter pain reliever, or anti‐emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24‐hour headache‐free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction. Results.— Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment‐related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain‐free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study. Conclusion.— In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction.     

Acute migraine attack therapy: comparison of naproxen sodium and an ergotamine tartrate compound

The efficacy of safety of naproxen sodium and ergotamine tartrate were compared for the treatment of acute migraine attack in a randomized, parallel trial with 114 participating patients. At the start of symptoms, patients took either three tablets of naproxen sodium (275 mg each) or one of an ergotamine combination (containing 2 mg ergotamine tartrate, 91.5 mg caffeine, and 50 mg cyclizine chlorhydrate). Patients were followed for three months or until six attacks were monitored, whichever came first. Both medications substantially shortened the duration of migraine attacks and reduced the severity of symptoms. When the test medications were taken within 2 h of onset of attack, naproxen sodium was statistically significantly more effective than the ergotamine combination in reducing the severity of headache pain, nausea, and lightheadedness. The ergotamine combination was associated with significantly more vomiting, need for rescue medication, and side effects than was naproxen sodium. Four patients required discontinuation of the ergotamine combination and one of naproxen sodium. Both patients and investigators rated tolerance for naproxen sodium as superior to tolerance for the ergotamine combination. Naproxen sodium seems to be an effective and safe treatment for migraine attacks.     

Sumatriptan-naproxen sodium for menstrual migraine and dysmenorrhea: satisfaction, productivity, and functional disability outcomes

(Headache 2011;51:664‐673) Objective.— To evaluate the impact of a sumatriptan/naproxen sodium combination tablet on patient satisfaction, productivity, and functional disability in menstrual migraine treated during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea. Background.— Menstrual migraineurs with dysmenorrhea represent a unique patient population not previously studied. When health outcomes end points are analyzed alongside traditional efficacy end points in migraine studies, a more comprehensive and robust understanding of the many factors that may influence patients' choice of and adherence to pharmacological treatments for migraine is observed. Methods.— In 2 replicate, multicenter, randomized, double‐blind, placebo‐controlled trials, participants with menstrual migraine and dysmenorrhea treated a single menstrual migraine attack with a single fixed‐dose tablet of sumatriptan 85 mg formulated with RT Technology? and naproxen sodium 500 mg (sumatriptan–naproxen sodium) or placebo. Results.— Participants randomized to sumatriptan–naproxen sodium were significantly more satisfied than those randomized to placebo at 24 hours post dose, as demonstrated by higher satisfaction subscale scores for efficacy (P < .001 for both studies), functionality (P = .003 for study 1; P < .001 for study 2), and ease of use (P = .027 for study 1; P = .011 for study 2). There was little bothersomeness of side effects associated with either treatment. Use of sumatriptan–naproxen sodium was also associated with lower reported “lost‐time equivalents” in work and leisure time (pooled analysis, P = .003) and lower rates of functional disability (P = .05, study 1; P < .001, study 2) compared with placebo. Conclusion.— A fixed‐dose combination tablet containing sumatriptan and naproxen sodium significantly improved patient satisfaction, productivity, and restoration of normal functioning in menstrual migraineurs with dysmenorrhea.     

Pharmacological synergy: the next frontier on therapeutic advancement for migraine

The burden of migraine significantly impacts the individual sufferer, their families, the workplace, and society. The World Health Organization has identified migraine as an urgent public health priority and has initiated a global initiative to reduce the burden of migraine. Underlying the World Health Organization initiative is the need to discover means of optimizing migraine treatments and make them accessible to the broader portion of the world population. Development of acute migraine medications over the past several decades has largely centered on engineering highly specific receptor molecules that alter migraine pathophysiological mechanisms to abort or reverse the acute attack of migraine. The first product of this line of discovery was sumatriptan and heralded as a landmark therapeutic breakthrough. Sumatriptan is a 5-HT-1B/D receptor agonist considered to activate receptors involved in the pathophysiology specific to migraine. Large-scale regulatory/clinical studies demonstrated statistical superiority for sumatriptan over placebo in reduction or elimination of headache, nausea, photophobia, and phonophobia. Since the introduction of sumatriptan, 6 other triptan products have been released in the United States as acute treatments for migraine, all having the same mechanism of action and similar efficacy. Despite their utility as migraine abortive medications, the triptans do not successfully treat all attacks of migraine or necessarily treat all migraine associated symptoms. In fact, in less than 25% of attacks do subjects obtain and maintain a migraine-free response to treatment for at least beyond 24 hours. A wide range of non-triptan medications also have demonstrated efficacy in acute migraine. These include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, phenothiazines, and valproic acid to name a few. Given the distinctly different mechanisms of actions of these various medications, it is likely that several unique pathophysiological mechanisms are involved in terminating acute episodes of migraine. Clinicians now capitalize on this observation and use migraine medication in combination with another to improve patient outcomes, for example, using an antiemetic with an opioid or a triptan and NSAIDs. More recently, the Food and Drug Adminstration has approved a combination product containing 85mg of sumatriptan plus 500mg of naproxen sodium for acute treatment of migraine. Clinical trials conducted prior to approval demonstrated that the combination of sumatriptan and naproxen was more effective as a migraine abortive than either of its components but that each component and the combination were more effective than placebo. Exactly how sumatriptan and naproxen interact to create therapeutic synergism is unknown though its mere occurrence suggests that models assisting medical understanding and prediction of pharmacological synergism may improve clinical outcome over products acting through a single receptor mechanism. Migraine is a syndrome, meaning it is defined by observed symptoms rather than known pathophysiology. Multiple pathogenic mechanisms are likely involved in generating this diverse array of symptoms understood as the migraine symptom complex. Sumatriptan and naproxen have independent mechanisms of action and target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine. Sumatriptan acts on the 5-HT(1B) and 5-HT(1D) receptors, whereas naproxen inhibits the COX-1 and COX-2 enzymes. Sumatriptan has vasoconstricting effects as well as effects on neurogenic inflammation by decreasing the release of substance P and calcitonin gene-related peptide. In contrast, naproxen affects prostaglandins and other inflammatory mediators. Because sumatriptan and naproxen both relieve migraine yet interact with different cellular targets within the migraine pathway, it is reasonable to assume there is a unique synergy between these medications that improves treatment outcomes. Clinical trials supported this contention by demonstrating the combination of sumatriptan/naproxen alleviated migraine pain quickly (primarily based on the sumatriptan mechanism of action), and sustained the response longer (primarily based on the naproxen mechanism of action) than is possible when either drug is given alone. The working hypothesis is that when sumatriptan and naproxen are given at the same time, they affect different mechanisms of the migraine pathway and produce an enhanced therapeutic effect. The purpose of this article is to apply statistical analyses to data from phase II and phase III studies of the combination of sumatriptan and naproxen to determine if this enhanced therapeutic effect is synergistic. This methodology of accessing synergy can be used in the development of future combination migraine treatments to improve treatment outcomes.     

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 ≥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.     

Sumatriptan in the treatment of acute migraine with aura

The efficacy of the selective 5HT1-like agonist sumatriptan in acute treatment of classical migraine (i.e. migraine with aura) was assessed in a double-blind, placebo-controlled, parallel group randomized trial. An oral dose of 200 mg was chosen on the basis of the efficacy rates achieved (70-85%) with 70-280 mg in open studies (1, 2). The dose of 200 mg was also chosen for the study because preliminary data from an oral pilot study indicated that efficacy increased with increasing dose up to 200 mg. Each patient was treated for a maximum of three separate attacks of migraine with aura within a three months' period. Three attacks were treated so that we could examine consistency of response across more than one attack. For attack 1, 200 mg sumatriptan was significantly more effective, safe and well tolerated than placebo at relieving headache 2 h after treatment was given (p = 0.023). In subsequent attacks, i.e. in attacks 2 and 3, there was no such significant effect of sumatriptan compared with placebo in relieving headache. This reduced efficacy of sumatriptan in the second and third attacks may be due to a high incidence of vomiting induced by the high dose of dispersible formulation and also by the bitter taste of the tablets. In addition, there was an increase in placebo response in attacks 2 and 3 compared to the first attack.     

The efficacy of divalproex sodium in the prophylactic treatment of children with migraine

OBJECTIVE: To determine the beneficial use of divalproex sodium as a prophylactic treatment for migraine in children. BACKGROUND: Previous studies for treatment of migraine in adults have shown a greater than 50% reduction in migraine attack frequencies. Few data exist, however, regarding the efficacy and safety of divalproex sodium use in children with migraine. METHODS: We studied the incidence of headache relief in our patients with migraine aged 16 years and younger treated with divalproex sodium prophylactically at our institution from July 1996 to December 1998 to determine medication dosage used, concomitant headache medications, and possible adverse effects. RESULTS: A total of 42 patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated with divalproex sodium for headache. All had a history of migraine with or without aura. Baseline headache frequency during a minimum 6-month period was one to four headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to 45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their abortive medications. After 4 months' treatment, 50% headache reduction was seen in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients became headache-free. CONCLUSION: These results indicate divalproex sodium to be an effective and well-tolerated treatment for the prophylaxis of migraine in children.     

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

(Headache 2010;50:808‐818) Objective.— To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.— Non‐steroidal anti‐inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.— Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (1) double‐blind, randomized, placebo‐controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain‐free, relief of migraine‐associated symptoms, sustained headache relief, sustained pain‐free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.— We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta‐analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain‐free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41‐1.77, P < .00001), and 2.22 (95% CI 1.46‐3.37, P = .0002), respectively, for headache relief at 2 hours and pain‐free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine‐associated symptoms, sustained headache relief, and sustained pain‐free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04‐1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.— The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain‐free at 2 hours and improving migraine‐associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head‐to‐head clinical trials.     

Distinct Pharmacokinetic Profile and Safety of a Fixed‐Dose Tablet of Sumatriptan and Naproxen Sodium for the Acute Treatment of Migraine

(Headache 2010;50:357‐373) Objective.— To describe the pharmacokinetic and safety profiles of sumatriptan 85 mg formulated with RT Technology (RT) and naproxen sodium 500 mg in a fixed‐dose combination tablet (sumatriptan/naproxen sodium) that targets both serotonergic dysmodulation and inflammation in migraine. Methods.— Six open‐label, crossover studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients with migraine (Study 6). Results.— Consistently across studies, naproxen administered as a component of sumatriptan/naproxen sodium demonstrated a delayed‐release profile similar to that of an enteric‐coated product. Naproxen from the combination tablet showed a delayed time to peak plasma concentration and lower peak plasma concentration while exposures (area under the plasma concentration–time curve) were similar. The peak plasma concentration for naproxen was approximately 36% lower and the time to peak plasma concentration approximately 4 hours later when naproxen was administered as sumatriptan/naproxen sodium compared with a single naproxen sodium 550 mg tablet. Sumatriptan peak plasma concentration and area under the plasma concentration–time curve after administration of sumatriptan/naproxen sodium (containing sumatriptan 85 mg) were comparable to those after administration of a commercially available sumatriptan 100 mg (RT) tablet. Sumatriptan time to peak plasma concentration occurred, on average, 30 minutes earlier with sumatriptan/naproxen sodium compared with sumatriptan 100 mg (RT). No clinically significant differences between sumatriptan/naproxen sodium and sumatriptan tablets 100 mg (RT) were identified with respect to electrocardiograms, blood pressure, or heart rate. In addition, food had no significant effect on the bioavailability of naproxen or sumatriptan after administration of sumatriptan/naproxen sodium but slightly delayed the time to peak plasma concentration of sumatriptan by approximately 40 minutes. The pharmacokinetics of sumatriptan and naproxen did not differ according to whether sumatriptan/naproxen sodium was administered during a migraine attack or a migraine‐free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium tablets administered 2 hours apart were consistent with the pharmacokinetic predictions from a single dose of the combination tablet. The adverse‐event profile of the sumatriptan/naproxen sodium combination tablet did not appear to differ from that of the individual components of the same or similar dosage strengths administered alone or in combination. In addition, the incidence of adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours apart was lower than that with the single dose. Conclusion.— The combination tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The rapid absorption of sumatriptan with the delayed‐release properties of naproxen sodium from sumatriptan/naproxen sodium might contribute to its therapeutic advantage over monotherapy with either component. No clinically meaningful effects of food, administration during a migraine attack, or administration of a second tablet (2 hours after initial dose) on the pharmacokinetics or safety of sumatriptan/naproxen sodium were observed.     

Double-blind study of naproxen vs placebo in the treatment of acute migraine attacks

Naproxen was compared with placebo in a double-blind, crossover trial in classic and common migraine. The trial was terminated at a fixed date; 37 patients had entered, 5 of whom were excluded. Naproxen was given as 750 mg at the first symptom of the attack, a total of 1250 mg per 24 h was allowed. Patients were followed for six attacks or three months in each phase, whichever came first. The severity of the headache was significantly less with naproxen in the first 2 h of the attack (p = 0.047), whereas there was no difference when the whole attack was considered. Significantly more patients preferred naproxen (p = 0.042). Side effects occurred in five patients, causing withdrawal of one patient while on naproxen.     

甘露醇治疗96例偏头痛的临床观察

目的比较单用氟桂利嗪、丹参与加用甘露醇治疗偏头痛的疗效及副作用，旨在为偏头痛治疗寻找新途径。方法将96例偏头痛患者随机分两组：常规治疗对照组、加用甘露醇治疗组、观察临床疗效。结果甘露醇治疗组48例总有效率95，9％与对照组68．8％相比差异有显著性，不良反应差异无显著性。结论甘露醇做为常用的脱水剂及清楚自由基作用治疗偏头痛疗效显著。     

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.     

Intranasal civamide for the acute treatment of migraine headache

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 microg or 150 microg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.     

Lessons from placebo effects in migraine treatment

In medical research, the placebo effect is an important methodological tool. Placebo is given to participants in clinical trials, with the intention of mimicking an experimental intervention. The "nocebo" effect, on the other hand, is the phenomenon whereby a patient who believes that a treatment will cause harm actually does experience adverse effects. The placebo effect strongly influences the way the results of clinical trials are interpreted. Placebo responses vary with the choice of study design, the choice of primary outcome measure, the characteristics of the patients and the cultural setting in which the trial is conducted. In migraine trials, the placebo response is high, in terms of both efficacy and side effects. Although medical ethics committees are becoming increasingly resistant to the use of placebo in acute migraine trials, placebo nevertheless remains the pivotal comparator in trials of migraine medications.     

Preventive treatment of migraine: an overview

The pharmacologic treatment of migraine may be acute (abortive, symptomatic) or preventive (prophylactic). Most migraine preventive medications were designed to treat other disorders (e.g., propranolol for hypertension, valproate for epilepsy, etc.). Preventive medication is usually given daily for months or years; however, treatment can be episodic, subacute, or chronic. The medications can be divided into two major categories: (i) Alternatives of high efficacy, which include β- blockers , tricyclic antidepressants , and divalproex , and of lower efficacy, which include selective serotonin reuptake inhibitors, calcium channel antagonists, and non-steroidal antiinflammatory drugs and (ii) second-line choices of high efficacy, which include methysergide and monoamine oxidase inhibitors. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.     

MMPI profiles in migraine before and after biofeedback treatment

Migraine has been associated with specific personality traits. Typically, migraine patients show elevation on the "neurotic scales" on the MMPI, and the profiles usually reported can be classified as "psychosomatic". A crucial matter is whether certain personality traits predispose to headache problems or whether they are an effect of such problems. To elucidate this problem, common and classic migraine patients (n = 13) were evaluated with the MMPI before and 2 years after biofeedback treatment. Two subgroups were identified on the basis of degree of clinical improvement. The least improved patients were significantly older and had a significantly longer headache history than the patients showing most improvement. No relationships between age, headache history, and improvement were found within subgroups. Clinical improvement was correlated with significant "normalization" of the MMPI profiles. Thus, personality traits as measured by the MMPI seem to be secondary to headache problems and not a predisposing cause.     

顽固性偏头痛的血流动力学观察及治疗

目的 探讨顽固性偏头痛患者血流动力学状态及治疗。方法 用全自动血流动力学分析仪测定了32例顽固性偏头痛患者及发作间期血流动力学,同时应用降纤酶治疗。结果 顽固性偏头痛患者血流动力学部分指标明显升高,给予降纤酶能有效地减轻症状,血流动力学指标明显下降。结论 血流动力学指标及降纤酶治疗对判断顽固性偏头痛和预防缺血民生中风的发生具有明确的临床价值。