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.

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.

[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.