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Notes: 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 (p0.002). 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 24h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine.

Notes: Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which mediates constriction of certain large cranial blood vessels and/or inhibits the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater following activation of the trigeminovascular system. The mode of action of this drug in migraine and cluster headache is discussed. On the basis of a detailed review of all published trials and available data from post-marketing studies, the efficacy, safety, tolerability and the place of oral and subcutaneous sumatriptan in the treatment of both conditions are assessed. A number of double-blind clinical trials have demonstrated that sumatriptan 100 mg administered orally is clearly superior to placebo in the acute treatment of migraine headache and achieves significantly greater response rates than ergotamine or aspirin. In other studies, 70 to 80% of patients receiving sumatriptan 6 mg sc experienced relief of migraine headaches by 1 or 2 h after administration, and patients consistently required less rescue medication for unresolved symptoms. Sumatriptan was also effective in relieving associated migraine symptoms like nausea and vomiting. Sumatriptan was equally effective regardless of migraine type or duration of migraine symptoms. Overall, approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache usually within 24 h, effectively treated by a further dose of this drug.In 75% of patients with cluster headache treated with sumatriptan 6 mg sc, relief was achieved within 15 min. Based on pooled study data, sumatriptan is generally well tolerated and most adverse events are transient. Adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. With the subcutaneous injection, injection site reactions occur in approximately 30%. Chest symptoms are reported in 3 to 5% but have been associated with myocardial ischaemia only in rare isolated cases. The recommended dosage of sumatriptan at the onset of migraine symptoms is 100 mg orally or 6 mg subcutaneously. The recommended dosage for cluster headache is 6 mg sumatriptan sc. Sumatriptan must not be given together with vascoconstrictive substances, e.g. ergotamines, or with migraine prophylactics with similar properties, e.g. methysergide. Sumatriptan should not be given during the migraine aura. It is contraindicated in patients with ischaemic heart disease, previous myocardial infarction, Prinzmetal (variant) angina and uncontrolled hypertension.

Notes: Antiphospholipid antibodies have occasionally been observed in small series of migraine patients, possibly signalling an immunological pathogenesis in a subgroup. We have measured anticardiolipin antibody levels in a series of 94 migraine patients (35 patients having migraine with aura, 59 without aura), during acute attacks and between attacks. Platelet counts were normal and VDRL was negative in all patients. A low positive anticardiolipin antibody level was found in only one patient, which was negative six months later. There appears to be no association between the presence of anticardiolipin antibodies and migraine. Antiphospholipid antibodies are unlikely to have a material pathogenetic role. Statistically, the incidence of significantly raised anticardiolipin antibody levels in this group of patients does not exceed 4% at a 95% probability level.

Notes: Patients with migraine who believed that chocolate could provoke their attacks were challenged with either chocolate or a closely matching placebo. In a double-blind parallel group study, chocolate ingestion was followed by a typical migraine episode in 5 out of 12 patients, while none of the 8 patients challenged with placebo had an attack (p = 0.051). The median time to the onset of the attack was 22 h. This brief study provides some objective evidence that chocolate is able to provoke a migraine attack in certain patients who believe themselves sensitive to it.

Notes: Antiphospholipid antibodies have occasionally been observed in migraine patients, but a recent study of a large series suggested the association was with other concurrent conditions, not specifically with migraine. We wondered about an association with other vascular headaches and measured anticardiolipin antibody levels in 20 cluster headache patients during the cluster period (three during an acute attack). Platelet counts were normal and VDRL negative in all patients. No elevated anticardiolipin antibody levels were found. There appears to be no important association between the presence of anticardiolipin antibodies and cluster headache, and we argue that there is no further rationale for seeking one.

Notes: Hepatic cytochrome P450 -dependent oxidation is deficient in 5% to 10% of the Caucasian population. A similar percentage seems to suffer from migraine. The hypothesis was tested that an oxidation deficiency possibly relevant to potential dietary triggers plays a role in the pathogenesis of migraine. In 37 migraine sufferers and 26 controls age- and sex-matched to 26 of these patients, debrisoquine hydroxylation following an oral dose of 10 mg was employed as a marker of oxidation status, determined by calculating the metabolic ratio (MR): urinary debrisoquineurinary 4-hydroxydebrisoquine. MR was similarly distributed in migraineurs and controls. Three subjects in each group were poor metabolizers (MR 〉 30, versus normal range, 0.1–12). MR in patients did not depend on type of migraine (common versus classic), attack frequency, the presence of trigger factors, smoking or a history of adverse reactions or sensitivity to medicines.

Notes: Whole blood 5HT levels were measured in seven female migraine sufferers with chronic daily headache due to medication abuse, before and after abrupt medication withdrawal. A statistically significant increase in 5HT levels, from mean 4.89 mmol/1 to mean 6.59 mmol/l (p 〈 0.05, Wilcoxon signed rank test), as well as a significant improvement in the number of headache-free days (p 〈 0.05, Wilcoxon signed rank test), occurred after 4 weeks of withdrawal. We conclude from this pilot study that 5HT may be important in the physiopathogenesis of chronic daily headache. Alternatively, reduced 5HT may be the result of chronic daily headache or else an epiphenomenon.

Notes: The principal reasons for a predominantly weekend incidence of migraine attacks are likely to be social or psychological in origin. There may be another factor. This study examines the use, and more importantly the way of use, of caffeine containing substances. We collected data by questionnaire from 151 consecutive Migraine Clinic patients with the diagnosis of migraine or tension type headache. Of the whole group, 21.9% claimed to have weekend attacks, with relatively more males than females. The males amongst these were all migraine patients, but 23% of the women suffered from tension-type headache. Patients with both a high daily caffeine intake and excessively delayed wakening at weekends (each defined as greater than the mean for the whole group) had a 69% risk of weekend headache. This compared with 4% in patients exceeding the mean in one only, and zero in those with moderate habits in both. These results support the idea that weekend attacks are linked to caffeine withdrawal. Sleeping in is not on its own a significant cause. We suggest that this possibility should be considered in clinical management of affected patients.