Efficacy and safety of tonabersat, a gap-junction modulator, in the acute treatment of migraine: a double-blind, parallel-group, randomized study.

The ability of tonabersat to relieve the symptoms of migraine attacks with or without aura was evaluated in a randomized, double-blind, placebo-controlled, multicentre, parallel-group study. Patients received 20 or 40 mg of tonabersat, or 50 mg of sumatriptan (positive control), or placebo at the onset of a moderate or severe attack. Headache intensity, relief and recurrence were recorded for 24 h after dosing. On the basis of primary or secondary efficacy measures, tonabersat did not provide a clinically or statistically significant advantage over placebo. Tonabersat generally was well tolerated and had no effect on vital signs, electrocardiogram recordings or laboratory values. The lack of efficacy may be a function of the slow absorption of tonabersat. As a consequence of slow absorption, daily administration of tonabersat as prophylaxis for migraine attacks is under investigation in ongoing studies.

Almotriptan and zolmitriptan in the acute treatment of migraine.

OBJECTIVE: To compare almotriptan and zolmitriptan in the treatment of acute migraine. METHODS: This multicentre, double-blind trial randomized adult migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for the treatment of a single migraine attack. The primary end point was sustained pain free plus no adverse events (SNAE); other end points included pain relief and pain free at several time points, sustained pain free, headache recurrence, use of rescue medication, functional impairment, time lost because of migraine, treatment acceptability, and overall treatment satisfaction. RESULTS: No significant difference was seen in SNAE (almotriptan 29.2% vs zolmitriptan 31.8%) or the other efficacy end points measured. The incidence of triptan-associated AEs and triptan-associated central nervous system AEs was significantly lower for patients receiving almotriptan compared to zolmitriptan. CONCLUSIONS: Almotriptan and zolmitriptan were associated with similar efficacy and overall tolerability in the treatment of acute migraine. Almotriptan was associated with a significantly lower rate of triptan-associated AEs.

Efficacy, speed of action and tolerability of almotriptan in the acute treatment of migraine: pooled individual patient data from four randomized, double-blind, placebo-controlled clinical trials.

A meta-analysis of pooled individual patient data from four randomized, placebo-controlled, double-blind trials comparing several doses of almotriptan (n = 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of onset and tolerability of almotriptan in the acute treatment of migraine. As early as 30 min after dosing, almotriptan 12.5 mg was significantly more effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free (2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for placebo. All almotriptan dosages were significantly more effective than placebo in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained pain relief up to 24 h (P < 0.05). The incidence of adverse events after almotriptan 6.25 mg and 12.5 mg was not significantly different from that of placebo. This meta-analysis confirms the findings of individual clinical trials, while demonstrating for the first time, significant pain-free efficacy at 30 min compared with placebo.

Infrequent or non-response to oral sumatriptan does not predict response to other triptans--review of four trials.

A migraineur can claim to be an infrequent responder ('non-responder') to an oral triptan independent of which triptan he or she is presently using. Four trials of an alternative triptan (zolmitriptan/rizatriptan; eletriptan; naratriptan; almotriptan) in patients with a history of infrequent response to oral sumatriptan were compared and contrasted in terms of study design, patient characteristics, and efficacy and tolerability of the triptan under investigation. Unfortunately, none of the reported studies used an appropriate parallel design, which would have had the non-responding triptan (oral sumatriptan) in one arm and without encapsulation. While the four trials differed in terms of study design (open-label vs. placebo-controlled), definition of sumatriptan 'non-responder' (retrospective vs. prospective) and pain intensity at baseline (30% severe to 70% severe), all four demonstrated that lack of response to sumatriptan did not predict lack of response to an alternative triptan. Changing triptans resulted in 2-h pain-relief rates of 25-81% in patients with a history of poor response to sumatriptan. It can be concluded that migraine patients who respond infrequently to sumatriptan should be switched to a different triptan, as lack of response to one triptan does not predict likelihood of responsiveness to another. A review of the available evidence suggests that almotriptan may be one of the most appropriate choices for an alternative triptan.

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.

[Is migraine a progressive cerebral disease?]. / La migraña es una enfermedad cerebral progresiva?

Migraine is a primary neurovascular headache which affects approximately 12% of the adult population. Migraine particularly affects women of working age and is associated with significant disability and reduced quality of life. During migraine attacks, the capacity to engage in daily activities such as child care, work, and social activities is reduced, and relationships with family members and friends become strained. In this respect, migraine places a heavy economic burden on both the individual and society. It is also known migraine is a risk factor for ischemic stroke in young women with migraine with aura. Recently, it was reported that some individuals that experience migraine with and without aura may be at an increased risk for subclinical lesions in certain areas of the brain. Cerebral white matter lesions (WMLs) are a common finding on cerebral MRI scans. Although, it appears that cerebral WMLs are more common in migraineurs than in the general population, the nature, association and the clinical significance of cerebral WMLs in migraineurs are not yet conclusive. Furthermore, there is no good evidence to support the notion that cerebral WMLs in migraineurs can predict subclinical or clinical stroke in these individuals. Needless to say, the need for more longitudinal and prospective migraine research is immense. The aim of the future migraine research should be to obtain more information about the natural course of migraine as well as evaluate the association between migraine and cerebral WMLs and their consequences. In addition, continuing genetic identification of key proteins involved in migraine will improve our understanding of this common and sometimes most debilitating disorder, which can strike during the most productive years of a person's life.

¿La migraña es una enfermedad cerebral progresiva? / Is migraine a progressive cerebral disease?

La migraña es una cefalea de origen neurovascular sufrida por aproximadamente el 12 % de la población adulta. La migraña afecta particularmente a mujeres en edad laboral y condiciona una considerable carga económica tanto para el individuo que la padece como para la sociedad. El sufrimiento psicosocial y humano, tanto del individuo afectado como de su familia, como consecuencia de la migraña, es de una gran dimensión. Se ha demostrado que la migraña es un factor de riesgo para la isquemia cerebral en mujeres jóvenes y recientemente se ha establecido que aquellos individuos que sufren migraña con y sin aura tienen un mayor riesgo de presentar lesiones subclínicas en ciertas áreas del cerebro. Sin embargo, la asociación, naturaleza y la trascendencia clínica de las lesiones de la sustancia blanca (LSB) en enfermos de migraña no son todavía concluyentes y no hay pruebas definitivas que respalden la noción de que las LSB cerebrales en enfermos de migraña puedan pronosticar isquemia cerebral subclínica o clínica en estos individuos. Por tanto, es absolutamente necesaria una investigación longitudinal y prospectiva en la migraña. Esta futura investigación debe hacer un esfuerzo especial por obtener más información sobre el curso natural de la enfermedad y evaluar la asociación entre la migraña y LSB cerebrales y sus consecuencias. Además, la futura identificación genética de proteínas clave involucradas en la migraña mejorará nuestro conocimiento sobre esta enfermedad tan común y debilitante

Migraine is a primary neurovascular headache which affects approximately 12% of the adult population. Migraine particularly affects women of working age and is associated with significant disability and reduced quality of life. During migraine attacks, the capacity to engage in daily activities such as child care, work, and social activities is reduced, and relationships with family members and friends become strained. In this respect, migraine places a heavy economic burden on both the individual and society. It is also known migraine is a risk factor for ischemic stroke in young women with migraine with aura. Recently, it was reported that some individuals that experience migraine with and without aura may be at an increased risk for subclinical lesions in certain areas of the brain. Cerebral white matter lesions (WMLs) are a common finding on cerebral MRI scans. Although, it appears that cerebral WMLs are more common in migraineurs than in the general population, the nature, association and the clinical significance of cerebral WMLs in migraineurs are not yet conclusive. Furthermore, there is no good evidence to support the notion that cerebral WMLs in migraineurs can predict subclinical or clinical stroke in these individuals. Needless to say, the need for more longitudinal and prospective migraine research is immense. The aim of the future migraine research should be to obtain more information about the natural course of migraine as well as evaluate the association between migraine and cerebral WMLs and their consequences. In addition, continuing genetic identification of key proteins involved in migraine will improve our understanding of this common and sometimes most debilitating disorder, which can strike during the most productive years of a person's life

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.

Unpleasant sensory symptoms are commonly reported in association with the use of 5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the chest and neck have restricted the use of triptans in the acute treatment of migraine. The cause of these triptan induced side-effects is still unidentified. We have now tested the hypothesis that sumatriptan influences the perception of tactile and thermal stimuli in humans in a randomized, double-blind, placebo-controlled cross-over study. Two groups were tested; one consisted of 12 (mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous allodynia in association with sumatriptan treatment. Twelve healthy subjects (mean age 38.7 years, 10 women) without migraine served as control group. During pain- and medication-free intervals tactile directional sensibility, perception of dynamic touch (brush) and thermal sensory and pain thresholds were studied on the dorsal side of the left hand. Measurements were performed before, 20, and 40 min after injection of 6 mg sumatriptan or saline. Twenty minutes after injection, sumatriptan caused a significant placebo-subtracted increase in brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain threshold in all participants pooled (P = 0.031), and a reduction of cold pain threshold in controls only (P = 0.013). At 40 min after injection, no differences remained significant. There were no changes in ratings of brush intensity, tactile directional sensibility or cold or warm sensation thresholds. Thus, sumatriptan may cause a short-lasting allodynia in response to light dynamic touch and a reduction of heat and cold pain thresholds. This could explain at least some of the temporary sensory side-effects of triptans and warrants consideration in the interpretation of studies on migraine-induced allodynia.

A six-item short-form survey for measuring headache impact: the HIT-6.

BACKGROUND: Migraine and other severe headaches can cause suffering and reduce functioning and productivity. Patients are the best source of information about such impact. OBJECTIVE: To develop a new short form (HIT-6) for assessing the impact of headaches that has broad content coverage but is brief as well as reliable and valid enough to use in screening and monitoring patients in clinical research and practice. METHODS: HIT-6 items were selected from an existing item pool of 54 items and from 35 items suggested by clinicians. Items were selected and modified based on content validity, item response theory (IRT) information functions, item internal consistency, distributions of scores, clinical validity, and linguistic analyses. The HIT-6 was evaluated in an Internet-based survey of headache sufferers (n = 1103) who were members of America Online (AOL). After 14 days, 540 participated in a follow-up survey. RESULTS: HIT-6 covers six content categories represented in widely used surveys of headache impact. Internal consistency, alternate forms, and test-retest reliability estimates of HIT-6 were 0.89, 0.90, and 0.80, respectively. Individual patient score confidence intervals (95%) of app. +/-5 were observed for 88% of all respondents. In tests of validity in discriminating across diagnostic and headache severity groups, relative validity (RV) coefficients of 0.82 and 1.00 were observed for HIT-6, in comparison with the Total Score. Patient-level classifications based in HIT-6 were accurate 88.7% of the time at the recommended cut-off score for a probability of migraine diagnosis. HIT-6 was responsive to self-reported changes in headache impact. CONCLUSIONS: The IRT model estimated for a 'pool' of items from widely used measures of headache impact was useful in constructing an efficient, reliable, and valid 'static' short form (HIT-6) for use in screening and monitoring patient outcomes.

Sumatriptan: pharmacological basis and clinical results.

Sumatriiptan was the first selective serotonin (5-HT)1B/1D agonist for the acute treatment of migraine attacks. Apart from the subcutaneous and oral formulation, it is also available as nasal spray and suppository. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing relief or resolution of other symptoms associated with migraine, including nausea, photophobia and phonophobia. For patients who desire particularly rapid relief that cannot be provided by a tablet form, sumatriptan injection with a 10-minute onset of action may be an appropriate choice. Patients with very severe attacks and those with vomiting may also benefit from the injection. For patients with nausea who do not wish to take tablets or who fear injections, a sumatriptan nasal spray or a suppository may be appropriate options. New triptans, zolmitriptan, rizatriptan, and naratriptan began entering the market in 1997 but in clinical practice, in particular after dose adjustments have been made, all triptans appear to be very similar with respect to efficacy and tolerability as well as safety.

Within-patient consistency of response of rizatriptan for treating migraine.

OBJECTIVE: To determine the within-patient consistency of response for rizatriptan, a 5-HT(1B/1D) receptor agonist for the acute treatment of migraine. METHODS: Post hoc analysis was performed on data from a randomized, double-blind, placebo-controlled clinical trial. Four hundred seventy-three patients with migraine diagnosed according to the criteria of the International Headache Society were randomly assigned to one of five sequence groups in which each patient was scheduled to treat four separate moderate or severe migraine attacks. Patients in four groups received 10 mg of rizatriptan for three of four attacks and placebo for the remaining attack; patients in the fifth group received 10 mg of rizatriptan for all four attacks. Headache severity, functional disability, and associated migraine symptoms were measured immediately before dosing and at regular intervals up to 4 hours after the dose. The analysis was based on efficacy at 2 hours after dosing, the last time point before escape medications were allowed. The percentages of patients who responded in a specified number of attacks after treatment with rizatriptan were calculated. The analysis was descriptive, and no formal statistical testing was performed. RESULTS: Of the evaluable patients who treated three migraine attacks with 10 mg of rizatriptan (with an additional interspersed placebo-treated attack in most patients), 216 of 252 (86%) had pain relief (reduction of pain to mild or none), 122 of 252 (48%) were pain free, 211 of 250 (84%) had no nausea, 163 of 251 (65%) had no photophobia, 182 of 252 (72%) had no phonophobia, 136 of 249 (55%) had no functional disability, and 233 of 252 (92%) had no need for escape medications at 2 hours after dosing in at least two of three attacks. CONCLUSION: The response to 10 mg of oral rizatriptan within individual patients was consistent over three attacks on a range of measures.

Rizatriptan in the treatment of migraine.

Rizatriptan is a selective 5-hydroxytriptamine1B/1D receptor agonist that was launched in 1998 for the acute treatment of migraine in adults. Based on data from 6 large clinical trials in patients > or =18 years of age in whom migraine was diagnosed according to International Headache Society criteria, the marketed 10-mg and 5-mg oral doses of rizatriptan are effective in relieving headache pain and associated migraine symptoms. The 10-mg dose is more effective than the 5-mg dose. At 2 hours after dosing, up to 77% of patients taking rizatriptan 10 mg had pain relief compared with 37% of those taking placebo, up to 44% were completely pain free compared with 7% of those taking placebo, and up to 77% were free of nausea compared with 58% of those taking placebo (P < 0.05 for all 3 comparisons). Both doses of rizatriptan are generally well tolerated. In placebo-controlled studies involving treatment of a single migraine attack, the most common side effects (incidence > or =2%) occurred in <10% of patients, typically were transitory (2 to 3 hours), and were mild or moderate. Rizatriptan is an effective and well-tolerated acute treatment for migraine.

[New triptan preparations can help the migraine patient. Pharmacodynamic and pharmacokinetic progresses]. / Nya triptanpreparat kan hjälpa migränpatienten. Farmakodynamiska och farmakokinetiska framsteg.

Migraine is an idiopathic, recurrent neurovascular headache disorder characterised by attacks of debilitating pain associated with photophobia, phonophobia, nausea and vomiting. It is apparently a global disorder, occurring in all races, cultures and geographical locations. Migraine has a hereditary component, and its life-time prevalence is about 16%. About a third of migraine patients in Sweden seem to be particularly sorely afflicted having 1-6 severe attacks a month and accounting for more than 80 per cent of the annual total of about 14 million attacks in the country as a whole. In general, these migraine sufferers do not obtain satisfactory relief from simple analgesice or NSAIDs (non-sterodial antiinflammatory drugs only), and thus require additional migraine-specific treatment. Selective 5-HT1B/1D-agonists, the so-called triptans, have become an invaluable addition to the therapeutic arsenal for treating this category of patients.

Safety trial with the 5HT1B/1D agonist avitriptan (BMS-180048) in patients with migraine who have experienced pressure, tightness, and/or pain in the chest, neck, and/or throat following sumatriptan.

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of all attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients (n = 51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patients, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.

How does sumatriptan nasal spray perform in clinical practice?

Migraineurs (94F, 24M) with previous experience of subcutaneous sumatriptan and/or sumatriptan tablets were asked their opinion on sumatriptan nasal spray treatment particularly with respect to onset of action, total efficacy, tolerability, and user friendliness. The information was obtained by means of a self-administered questionnaire handed out at the time of prescription of the nasal spray. The results are based on the patients' cumulative experience of having treated at least two migraine attacks with the spray (20 mg). Sumatriptan nasal spray (20 mg) was perceived to have a faster onset of action and, with the exception of a bad taste, to have a better tolerability than the tablets. Compared with subcutaneous sumatriptan, the nasal spray was claimed to be less effective in reducing symptoms of migraine attacks but to cause fewer adverse events. A bitter taste was the most commonly reported side effect of sumatriptan nasal spray--reported by 68% (80 out of 118) of the migraineurs. The user friendliness of sumatriptan nasal spray was rated better than that of subcutaneous sumatriptan and/or sumatriptan tablets. The overall impression of sumatriptan nasal spray was reported to be better or equal to that of the tablet and the injection by 57% and 46%, respectively. It is concluded that the results obtained in clinical practice are very much in line with those obtained in controlled clinical trials. The overall impression of sumatriptan nasal spray is that it is user friendly and useful in the acute treatment of migraine attacks of moderate intensity.

Pathophysiology and pharmacology of migraine. Is there a place for antiemetics in future treatment strategies?

This article reviews the pathophysiology and pharmacology of emesis in relation to migraine pathogenesis. Also, the place of antiemetic and gastrointestinal prokinetic agents in current and future acute migraine treatment strategies is reviewed. The mechanisms of action of current and novel acute migraine therapies are considered with respect to the neurogenic and vascular hypothesis. Control of migraine-associated nausea and vomiting is often achieved with the benzamide dopamine D2 receptor antagonist metoclopramide. This drug also has 5HT3 receptor antagonist activity and reproducibly stimulates gastric motility to increase the availability of orally administered drugs. Other antiemetic and gastroprokinetic agents with potential value for the treatment of migraine-associated nausea and vomiting could speed absorption of oral antimigraine therapies without central nervous system side effects. Domperidone, a dopamine D2 receptor antagonist that does not cross the blood brain barrier is relatively free of the central side-effect liability of metoclopramide. Cisapride, a benzamide 5HT4 receptor agonist gastrointestinal prokinetic drug, lacks dopamine antagonist activity. A controlled comparison of these agents as migraine co-therapies could provide information on the importance of peripheral and central mechanisms in migraine-associated nausea and vomiting and improve antimigraine treatment options.

Sumatriptan injection and tablets in clinical practice: results of a survey of 707 migraineurs.

This report from the Gothenburg Migraine Clinic in Sweden describes the results of a telephone survey of over 700 patients using open-label sumatriptan tablets or sumatriptan injection for the treatment of migraine. The information is based on the patients' cumulative experience of more than 76,000 subcutaneous injections, 56,000 tablets 100 mg, and 20,000 tablets 50 mg. The results demonstrate that sumatriptan tablets were preferred by a greater proportion of patients than sumatriptan injection. However, sumatriptan injection was perceived as the most effective dosing form by the greatest proportion of patients. Among patients who found sumatriptan injection to be the most effective dosing form, the most frequently cited reasons were efficacy and speed of action. Among patients who found sumatriptan tablets to be the most effective dosing form, the most frequently cited reasons were fewer side effects and lack of experience with other dosing forms. Approximately half of sumatriptan users indicated that sumatriptan use was associated with decreases in the numbers of days with migraine, days at work with migraine, and days off work/normal activities due to migraine. When they worked during a migraine attack, patients estimated that they were 76% effective after taking sumatriptan compared with 47% effective with other medications and 49% effective with no medication. In general, side effects were reported less frequently among sumatriptan tablet users compared with injection users. Asked to compare sumatriptan with the best migraine treatment that they had used before, 94% of patients indicated that sumatriptan was better or much better than their previous therapies. These data provide important information from the clinical practice setting to complement the data from sumatriptan clinical trials.

Alniditan in the acute treatment of migraine attacks: a subcutaneous dose-finding study. Subcutaneous Alniditan Study Group.

Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p = 0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine.