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.     

Switching patients with migraine from sumatriptan to other triptans increases primary care costs

Treatment of migraine with triptans is highly effective, although cost considerations may prompt a change in therapy. This retrospective database analysis of 3196 patients with migraine, established on sumatriptan therapy, found that 54% of the 292 experiencing a triptan switch returned to sumatriptan within 15 months, suggesting that the alternative was less acceptable. Excluding patients with unusually high use of triptans (> or = 208 tablets/year), switching therapy resulted in a significant increase of pounds sterling 53/patient in total costs, compared with patients continuing on sumatriptan (p = 0.014). Cost savings (pounds sterling 17/patient over 15 months) were observed only among the 41% of patients in whom the initial switch was successful and did not result in a further switch or return to sumatriptan. Among patients who were relatively low cost initially, switching resulted in increased costs, irrespective of the outcome. This study suggests that there is no economic justification for switching from sumatriptan to another triptan.     

Prediction of headache response in migraine treatment

Triptans are efficacious for the acute treatment of migraine attacks. Yet, defining a concentration-effect relation for these compounds is difficult as the dynamics of the migraine attack are not thoroughly understood. The objective of this investigation was to develop a disease model to predict measures of headache in randomized placebo-controlled clinical trials investigating oral sumatriptan as a paradigm compound. A hidden Markov model based on the states of response (no relief, relief, and pain free) and headache scores (observed variable) was used in conjunction with population pharmacokinetics. Model parameters were capable of predicting the course of headache relief, pain-free status and headache recurrence. It was shown that sumatriptan shortens mean transit times between states by up to 5 h. The potency of sumatriptan (EC(50)) was 9 ng/ml. These findings demonstrate the value of combining pharmacokinetic and efficacy information to model disease and characterize time-independent drug properties in a population of migraineurs.     

A within-patient comparison of subcutaneous and oral sumatriptan in the acute treatment of migraine in general practice

This study compared, for the first time in the United Kingdom, the efficacy and safety of oral 100 mg and subcutaneous 6 mg sumatriptan within a patient for the acute treatment of migraine. The patient's preference for the two formulations of sumatriptan were also recorded. The study was a multicentre, randomized, open, crossover design with an optional open parallel group extension. Individual attacks were treated with one formulation only. Over 10% of patients who treated attack 1 in both treatment periods of the crossover phase reported headache relief with each formulation at 4 h. Only 3% of patients failed to respond to at least one of the formulations at this time point. At the end of the crossover phase patient preference for the injection more than doubled from the pretreatment level in those patients who were previously naive to sumatriptan. During the optional phase of the study, 38% of patients chose to treat some attacks with oral and some with subcutaneous sumatriptan. The main reason for choosing injection was speed of relief, whilst convenience was the major reason for the use of the tablet.     

Subcutaneous sumatriptan provides symptomatic relief at any pain intensity or time during the migraine attack

Over the years the paradigm of treating early during the migraine attack has become well established in clinical practice. It is also recommended that the 5-HT(1B/1D) agonists be administered early during the migraine attack for efficacy. This is because it has been proposed that most migraineurs are less responsive to delayed treatment, owing to the development of central sensitization of the pain transmission. The main objective of this prospective, cross-over study at a specialist clinic was to evaluate if these recommendations should also apply to the subcutaneous formulation of sumatriptan. Results are based on 20 adult International Headache Society migraineurs. Two attacks (n=40) were treated with 6 mg subcutaneous sumatriptan as early as possible after the onset of migraine headache and two attacks (n=40) as late as the patients could bear. The median intra-individual difference between the two strategies in time from first occurrence of pain to injection was 5.7 h and the median intra-individual difference in pain intensity at the time of injection was 29 visual analogue units. No significant differences were found in time to freedom from pain, pain severity at 1 and 2 h, area under the curves from injection to pain free or in headache recurrence after injection. At the end of the study, most of the patients claimed that their medication was as effective when given early as when given late in the course of the attack. The discrepancy between our present findings and retrospective analyses of trials on oral triptans probably has more to do with the less disturbed pharmacokinetics early during the migraine attack than with central sensitization. Consequently, we recommend nonoral formulations of triptans, which do not necessarily have to be administered early during the migraine attack to provide efficacy. In conclusion, it is reassuring for migraineurs that it is worthwhile taking their medication in an appropriate formulation even if they have not been able to do so early in the course of the attack.     

Long-term tolerability of sumatriptan nasal spray in adolescent patients with migraine

OBJECTIVE: This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. METHODS: A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. RESULTS: A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n=4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). CONCLUSION: Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years.     

Focus on trial endpoints of clinical relevance and the use of almotriptan for the acute treatment of migraine

Almotriptan is a 5-HT(1B/1D) receptor agonist, or triptan, indicated for the acute treatment of migraine. It has been shown to be effective and well tolerated for the treatment of acute migraine in approximately 5000 patients enrolled in short-term placebo- and active-controlled trials and long-term open-label trials. A recent meta-analysis reported that almotriptan has the highest sustained pain-free (SPF) rate and lowest adverse-event (AE) rate of all oral triptans. Sustained pain free is a composite endpoint of pain freedom at 2 h, no recurrence of moderate-to-severe headache and no use of rescue medication from 2 to 24 h after dosing. Patient surveys have indicated that migraine sufferers consider complete pain relief, no recurrence, rapid onset and no side-effects to be the most important attributes of their acute treatment. Composite endpoints such as SPF and SPF with no AEs (SNAE) contain the attributes that migraine sufferers express as being the most important elements of an acute migraine therapy, and their use in future clinical trials should aid in the selection of agents that can offer patients the highest likelihood of consistent treatment success.     

Treatment choices and patterns in migraine patients with and without a cardiovascular risk profile

Treatment patterns in migraine patients with cardiovascular risk factors are largely unknown. A retrospective observational study was conducted to characterize the baseline cardiovascular risk profile of new users of specific abortive migraine drugs, and to investigate treatment choices and patterns in patients with and without a known cardiovascular risk profile. New users of a triptan, ergotamine or Migrafin^® ( n  = 36 839) from 1 January 1990 to 31 December 2006 were included. Approximately 90% of all new users did not have a clinically recognized cardiovascular risk profile. The percentage of new users with a cardiovascular risk profile did not differ between new users of a triptan, ergotamine or Migrafin^® and also did not change during the study period of 17 years. Differences in treatment choices and patterns between migraine patients with and without a known cardiovascular risk profile reveal a certain reticence in prescribing vasoconstrictive antimigraine drugs to patients at cardiovascular risk.     

The natural course of migraine attacks. A prospective analysis of untreated attacks compared with attacks treated with a triptan

This study was designed to document prospectively and explore scientifically the natural course of untreated migraine attacks in detail. A new, integrated, time-intensity method for self-assessment of the intensity of symptoms was tested on 18 adult International Headache Society migraineurs who volunteered to refrain from treatment during one attack. The area under the curves (AUC) during 72 h of untreated attacks was compared with attacks treated with a triptan. Migraine attacks are heterogeneous both inter- and intra-individually. In untreated attacks, the pain can stabilize and fluctuate around a plateau with a wavelength of hours. In general, the symptoms of each separate migraine attack follow a similar temporal course, with only moderate deviations. In some cases photo- and/or phonophobia (hyperexcitability) were not experienced at all, despite severe pain and nausea. Moreover, there was sometimes no nausea despite severe pain and hyperexcitability. Vomiting does not always correlate to the intensity of nausea and is not always followed by decreased headache intensity. Treatment with a triptan usually only temporarily distorts the basic pattern of attacks. Hyperexcitability can respond before pain to treatment. These genuine findings of the classic symptoms of migraine attacks support the notion of a mutual underlying pathophysiological mechanism.     

A review of evidence-based medicine and meta-analytic reviews in migraine

The following systematic reviews and meta-analyses are presented and the results discussed: the evidence-based American guidelines, five systematic reviews on naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a meta-analysis of triptans available in Canada and a large meta-analysis of oral triptans. The systematic reviews of several randomized trials of one drug overcome random effects in estimating treatment effect of the reviewed drug. The results from the large meta-analysis of several drugs are compared with head-to-head comparative trials. Results are generally the same in the meta-analysis and in the comparative trials, with some exceptions. Head-to-head comparisons should remain the 'gold standard' and meta-analyses are a useful supplement in cases when comparative trials are relatively small and when no comparative trials exist.     

An open preference study with sumatriptan 50 mg and zolmitriptan 2.5 mg in 100 migraine patients

Understanding factors influencing patients' preference will improve guidance to make rational choices in expanded symptomatic migraine treatment. The objective of this open-label, cross-over study was to explore patients' preferences for sumatriptan 50 mg vs. zolmitriptan 2.5 mg tablets, focusing on factors influencing this preference. One hundred consecutive migraine patients attending our clinics were asked to treat three attacks with each medication and then fill out a preference questionnaire. Ninety-four migraineurs completed the trial and 42 (44%, 95% CI 34-58%) reported that they preferred zolmitriptan 2.5 mg over sumatriptan 50 mg tablets and 27 (29%, 20-38%) preferred sumatriptan 50 mg. The remaining 25 (27%, 18-36%) did not show any preference. For the initial treatment of the attacks, there were more patients needing just one tablet of zolmitriptan 2.5 mg compared with sumatriptan 50 mg (67 vs. 39%). The reasons for preference among those 69 patients who had shown preference for either of the two triptans were: a faster onset of action (speed of onset) (73%), a longer duration of the effects (39%), fewer adverse events (35%) and lower price (13%). Only one-quarter of the studied migraine population thought that sumatriptan 50 mg and zolmitriptan 2.5 mg were equivalent, which suggests that most migraine patients differentiate between triptans. A faster onset of action (speed of onset) was the most important reason for preference.     

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.     

Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized,double-blind,placebo-controlled clinical trial

Almotriptan is a novel and specific serotonin 5-HT1B/1D agonist for the acute treatment of migraine. This randomized, single-dose, double-blind, multicentre, study assessed the efficacy and safety of oral almotriptan (12.5 mg and 25 mg) in patients with migraine, and compared it with the standard treatment (sumatriptan 100 mg) and placebo. A total of 668 patients treated one migraine attack of moderate or severe intensity with study medication. The primary efficacy assessment was migraine pain relief, improvement from severe or moderate pain to mild or no pain, at 2 h after treatment. Response rates, stratified for variation in baseline pain levels, for both almotriptan doses were equivalent to sumatriptan and significantly better than placebo. Other efficacy assessments confirmed the equivalence of the almotriptan groups with the sumatriptan group. Almotriptan 12.5 mg was as well tolerated as placebo (P=0.493) and significantly better tolerated than sumatriptan (P<0.001), in terms of the overall incidence of adverse events. There was no statistically significant difference in the incidence of adverse events between almotriptan 25 mg and sumatriptan 100 mg (P=0.376). The results from this large clinical study indicate that the new, specific 5-HT1B/1D agonist, almotriptan, is an effective and well-tolerated treatment for migraine pain.     

Responsiveness of non-IHS migraine and tension-type headache to sumatriptan

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT₁ receptors that spans a range of clinical presentations.     

Triptans in the treatment of basilar migraine and migraine with prolonged aura

OBJECTIVE: To report on the use of triptans in migraine with prominent neurologic symptoms. BACKGROUND: As stated in their package inserts, the triptans are contraindicated in patients with basilar or familial hemiplegic migraine, and physicians are reluctant to prescribe these drugs to other patients with prominent or prolonged aura. METHODS: We evaluated 13 patients with basilar migraine, familial hemiplegic migraine, or migraine with prominent or prolonged aura who had received triptans. RESULTS: Excellent; no adverse events. CONCLUSION: The contraindication of triptans in basilar migraine should be reconsidered. Similarly, prominent or prolonged aura may not represent a reasonable contraindication to triptan therapy.     

FRAMIG 2000: medical and therapeutic management of migraine in France

FRAMIG 2000 is a population-based survey of medical and therapeutic management of migraine in France. A total of 312 migraine sufferers were first identified from a representative sample of 4689 adult subjects using a validated questionnaire based on the IHS migraine diagnostic criteria and administered by telephone. Subjects were then interviewed using a branching questionnaire and a computer-assisted interview technique. Although 80% were self-aware of their migrainous state, 82% of migraine sufferers had no medical follow-up for migraine. The proportion of migraine sufferers who did not consult decreased slightly with increasing migraine-related disability (from 87% for subjects in MIDAS grade I to 68% for those in MIDAS grade IV). Migraine sufferers declared to effectively control only four attacks out of 10 after the first intake of the usual treatment. Only 6% of subjects in the survey received a prophylactic treatment for migraine whereas 22% were in MIDAS grade III or IV. These data show that the burden of migraine does not result from a deficit in diagnosis but instead from a deficit in patient information on the proper use of current effective treatments of migraine.     

红细胞压积与年龄以及红细胞沉降率的关系

目的探讨红细胞压积在不同年龄患者的分布情况以及其与红细胞沉降率之间的关系。方法收集大于40岁的患者红细胞压积、年龄、红细胞沉降率资料,统计不同压积组的x±s,并进行t检验。结果男性高压积组中,红细胞压积的均值和标准差为0.47±0.26,正常压积组为0.39±0.27,低压积组为0.30±0.36;女性高压积组的红细胞压积的均值和标准差为0.42±0.17,正常压积组为0.36±0.22,低压积组为0.27±0.45。男性高压积组年龄为(57.41±10.62)岁,低压积组为(67.23±12.75)岁;女性高压积组年龄为(60.70±11.60)岁,低压积组为(61.60±12.40)岁。男性高压积组的红细胞沉降率均值和标准差为(3.95±3.26)mm/h,低压积组为(61.61±40.04)mm/h;女性高压积组的红细胞沉降率均值和标准差为(28.26±28.62)mm/h,低压积组为(60.20±43.71)mm/h。结论男性随红细胞压积降低,年龄逐渐增加,红细胞沉降率逐渐增加;女性随红细胞压积降低,红细胞沉降率逐渐增加,但与年龄分布无明显相关性。结合年龄、红细胞沉降率对红细胞压积进行检测可提高其在心脑血管疾病中的预防和监测作用。     

New paradigms in the recognition and acute treatment of migraine

It would be ideal if clinical decisions regarding acute migraine treatment could be made on the basis of three parameters: a critical appraisal of available scientific evidence, clinical experience (including knowledge of the individual patient and his/her attack characteristics), and, of course, patient preferences. Patients are likely to prefer agents that offer rapid relief, pain-free status within 2 hours, no recurrence or need for rescue medication, extended time to recurrence (if present), consistency of therapeutic effect over multiple attacks, oral administration. good tolerability, safety, and minimal drug interactions. Fortunately, a number of specific therapies now are available which place these objectives within the patient's reach. Ongoing barriers to optimal migraine care include underrecognition, underconsultation, undertreatment, restrictions imposed by insurance companies, and exaggerated concerns regarding the safety of the triptans. Overcoming these barriers is likely to prove a more important contribution to patient care than endeavoring to establish the relative merits of one triptan over another. We have described in detail a number of strategies for improving recognition and treatment of migraine. Many headache specialists now believe that recurrent episodes of disabling headache, with a stable pattern over years, should be viewed as migraine until proven otherwise. In the end, this may represent the most useful paradigm in the primary care setting, where time is of the essence. Studies to validate this approach are needed. Acute treatment intervention that is based on scientific evidence, clinical experience, and patients' needs and desires will provide better outcomes than those presently obtained. Preliminary evidence favors early intervention with oral triptans, and randomized, prospective, double-blind, placebo-controlled studies, ideally employing a crossover design, are required to confirm this. The US Consortium's evidence-based guidelines, the National Headache Foundation's standards of care, and the Canadian guidelines have applied the standards of scientific inquiry to the field of headache management and "translation" of these guidelines into practical instruments for clinicians through vehicles such as the Primary Care Network's Patient-Centered Strategies for Effective Management of Migraine should raise the general standard of care for patients with migraine. Last, but far from least, initiatives undertaken by the World Health Organization (WHO) will add credibility to the many layfolk and professionals who have struggled to present headache as a disabling disorder worthy of scientific investigation and aggressive medical management. The WHO states: "These common complaints impose a significant health burden ... Despite this, both the public and the majority of healthcare professionals tend to perceive headache as a minor or trivial complaint. As a result, the physical, emotional, social and economic burdens of headache are poorly acknowledged in comparison with those of other, less prevalent, neurologic disorders." Migraine is finally out of the closet.     

Identification of negative predictors of pain-free response to triptans: analysis of the eletriptan database

Thirty to forty percent of migraineurs do not respond to any given triptan treatment. We identified clinical variables that significantly predict therapeutic non-response and evaluated the efficacy of eletriptan (20, 40 and 80 mg) and sumatriptan (100 mg) vs. placebo in a subgroup of patients with all predictor variables. First-attack data were pooled from 10 randomized, double-blind, placebo-controlled migraine trials ( n  = 8473). Multivariate regression analyses identified three significant baseline predictors of failure to achieve 2-h pain-free response: severe headache pain, presence of photophobia/phonophobia and presence of nausea. Time of dosing following headache onset did not influence 2-h pain-free response. Among patients with all three risk factors ( n  = 2010; 24% of total sample), 2-h pain-free response was significantly higher in patients receiving all three doses of eletriptan or sumatriptan vs. placebo (all P  < 0.01). Thus, eletriptan and sumatriptan are efficacious in difficult-to-treat patients at high risk for non-response to triptans.