Should women suffering from migraine with aura be screened for biological thrombophilia?: results from a cross-sectional French study.

INTRODUCTION: Migraine, particularly migraine with aura (MA), is associated with a higher risk for ischemic stroke (IS). A procoagulant state may predispose to IS. Whether inherited biological thrombophilia are associated with migraine risk remains controversial. OBJECTIVE: To assess the risk of migraine without or with aura related to inherited biological thrombophilia adjusted for the main potential confounders. MATERIAL AND METHODS: A cross-sectional study was conducted in 1456 French women aged 18 to 56years, referred for biological coagulation check-up because of personal or familial venous thrombosis history. Between April 2007 and December 2008, all women answered a self-administered questionnaire to determine whether they had headache. RESULTS: There were 294 (20%) migrainous sufferers (including 71 [5%] with MA), 975 (67%) non migrainous women and 187 (13%) non migrainous headache women. Inherited thrombophilia were detected in 576 (40%) women, including 389 (40%) non migrainous women, 90 (40%) migraine without aura (MWA), 33 (46%) MA women and 64 (34%) non migrainous headache women. Factor V Leiden (FVL) i.e. F5rs6025 or Factor II G20210A (FIIL) i.e. F2rs1799963 mutation was detected in 296 (30%) non migrainous women and in 100 (34%) migrainous women of which 27 had MA. There was a significant association between MA and FVL or FIIL mutations (adjusted OR=1.76 [95% CI 1.02-3.06] p=0.04) whereas this association in MWA and in non migrainous headache women was not significant. There was no significant association between migraine and other biological thrombophilia. CONCLUSION: FVL or FIIL mutations were more likely among patients suffering from MA. Whether biological thrombophilia screening should be systematically performed in women suffering from MA remains to be determined.

The GRIM2005 study of migraine consultation in France. III: Psychological features of subjects with migraine.

The objective of this analysis was to describe psychological and cognitive variables in subjects with migraine and to identify those associated with chronicity. Data were collected from 10 000 subjects during face-to-face interview. Subjects with episodic migraine (n = 1127) or chronic daily headache (n = 407) with migrainous features were identified using an algorithm based on the International Classification of Headache Disorders, 2nd edn classification. Data on headache impact was obtained with the Headache Impact Test-6, on psychological distress with the Hospital Anxiety and Depression Scale, on coping with the Coping Strategy Questionnaire catastrophizing score and the Brief COPE inventory, on illness perception with the Brief Illness Perception Questionnaire and on locus of control. Psychological variables associated with chronicity include perceived headache impact, psychological distress, the use of catastrophizing and avoidance coping strategies and an externalized locus of control. In conclusion, maladaptive coping strategies should be taken into account in the management of patients with migraine. Longitudinal studies will be necessary to address the causality of the relationship observed.

Evaluation and registration of adverse events in clinical drug trials in migraine.

Tolerability of a drug should be regarded as important as its efficacy. In all four phases of drug development evaluation of adverse events is important. Recommendations for assessment of adverse events in acute and prophylactic clinical drug trials in migraine are given. Tolerability may be indirectly assessed using measures of general well-being and eight such tools are presented. Finally, recommendations for reporting of adverse events are given.

The GRIM2005 study of migraine consultation in France II. Psychological factors associated with treatment response to acute headache therapy and satisfaction in migraine.

The objective of this analysis was to identify variables associated with treatment response in subjects with migraine. Data were collected from a sample of 10,000 subjects. A battery of questionnaires assessing clinical and psychological variables was completed. Migraine diagnosis was attributed using an algorithm based on the IHS criteria and treatment response using the ANAES criteria. We identified 1534 subjects, of whom 1443 were treated. For 54.2%, at least one ANAES criterion for treatment response was unfulfilled. Non-response was associated with female gender, high HIT-6 impact scores and high HAD psychological distress scores. The strongest associations with non-response were identified for four psychological variables: elevated scores on the CSQ catastrophization subscale and the 'Consequences' and 'Acceptance' dimensions of the Brief COPE, and low scores on the 'Positive Reinterpretation' Brief COPE dimension. In conclusion, many individuals with migraine respond inadequately to treatment. Behavioural interventions aimed at modifying coping strategies may improve outcome.

The GRIM2005 study of migraine consultation in France I. Determinants of consultation for migraine headache in France.

The aim of this study was to evaluate determinants of consultation for migraine in a representative sample of the French general adult population. We interviewed 10,032 subjects, of whom 1534 fulfilled the International Headache Society diagnostic criteria for migraine. These were categorized into migraine, probable migraine and chronic migraine. Information was collected on consultation experience; 436 subjects (28.4%) had never consulted for headache, 473 (30.8%) were in active consultation and 625 (40.7%) had previously consulted but lapsed. Subjects with chronic migraine showed the highest active consultation rates (51.8%). All subjects completed rating instruments for headache [Headache Impact Test (HIT)-6], psychiatric (Hospital Anxiety and Depression Scale scale) and psychological [Brief Illness Perception Questionnaire (BIPQ), Brief COPE Inventory and Coping Strategy Questionnaire] variables. The strongest determinants of active consultation were BIPQ scores, HIT-6 scores and migraine type. Consultation was associated with maladaptive coping strategies (social support, emotional expression and acceptance). Determinants of remaining in consultation were catastrophizing coping scores and previous consultation experience.

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 of oral naratriptan in the treatment of menstrually related migraine.

The aim of this study was to investigate the efficacy of orally administered 2.5 mg naratriptan in the treatment of menstrually related migraine (MRM). A high percentage of women suffering from migraine report increased frequency of attacks in association with menstruation that may be more severe, of longer duration and more difficult to treat than at other times. This was a phase IIIb, randomized, double-blind, placebo-controlled clinical trial. Subjects were given either 2.5 mg naratriptan or placebo to treat a single MRM episode, defined as starting between days -2 and +4 relative to the start of menstruation. The primary efficacy measure was the percentage of subjects who were free of pain 4 h after treatment, the absence of pain at 30 min, 1 and 2 h being secondary efficacy measures. Other secondary measures were the absence of associated symptoms, sustained headache relief 24 h after a single dose of the study medication, recourse to a second dose of study medication or escape medication, pain intensity 4-24 h after first treatment, the ability to carry out work or daily activities, and patient satisfaction. Adverse events were also monitored. A total of 275 women were enrolled in the trial and 229 (115 naratriptan group, 114 placebo group) provided data on the effects of the study medication on MRM. A higher percentage of subjects in the naratriptan group (58%) reported complete pain relief 4 h after medication than in the placebo group (30%) (P<0.001). Significant differences between the naratriptan and placebo groups and in favor of naratriptan were also found for: total pain relief at 2 h (P=0.004), sustained pain-free response within 4-24 h (P<0.001), absence of all associated symptoms at 2 and 4 h (P=0.004), ability to work and carry out daily activities at 2 h (P=0.036), and patient overall satisfaction (P<0.001). Three adverse events were recorded that might potentially be attributable to naratriptan. Naratriptan given orally at a dose of 2.5 mg is effective in the acute treatment of MRM as early as 2 h after treatment.

[Prophylactic drug treatment of migraine]. / Traitement médicamenteux de fond de la migraine.

Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks. Based on the results of published controlled trials, the main prophylactic drugs are some beta-blockers, methysergide, pizotifene, oxetorone, flunarizine, amitriptyline, NSAIDs, sodium valproate and topiramate. With these drugs, the frequency of attacks can be reduced by half in 50 percent of patients. Some less evaluated substances such as aspirin, DHE, indoramine, and angiotensin II inhibitors may be useful. The decision to treat with drugs and the choice of a prophylactic drug are made together with the patient. The superiority of one major drug over another has never been demonstrated in a comparative trial, thus the choice of the drug to start with depends on the possible side effects and contraindications, the characteristics of the migraine attacks, and the associated morbidities and possible interactions with abortive medications. Doses should be increased gradually, in order to reach the recommended daily dose, only if tolerance permits. Treatment efficacy has to be assessed after 2 or 3 months, and in case of failure or poor tolerance, another treatment should be started. If the treatment is successful, it should be continued for 6 to 12 months, and then tapered off. The moderate efficacy and the frequency of the side effects observed with prophylactic drugs explain the high rate of withdrawals. Some patients nevertheless dramatically improve, warranting trying several drugs successively in order to find the most appropriate one.

Almotriptan improves response rates when treatment is within 1 hour of migraine onset.

BACKGROUND: Results from open-label trials with almotriptan and sumatriptan have shown higher response rates when treatment was initiated early after acute migraine onset. OBJECTIVE: To investigate the temporal component of early intervention by measuring 2-hour pain-free and sustained pain-free responses to almotriptan and sumatriptan when the study drug was taken within 1 hour of onset of moderate to severe pain. METHODS: This was a post hoc analysis from a double-blind, randomized, placebo-controlled trial of almotriptan and sumatriptan. Men and women, 18 to 65 years of age, who met International Headache Society criteria for migraine with or without aura were eligible. Patients were randomized to receive a single oral dose of almotriptan 12.5 or 25 mg, sumatriptan 100 mg, or placebo at the onset of a severe or moderate migraine attack. For this post hoc analysis, the almotriptan 25-mg dose was excluded because 12.5 mg is the recommended dose. The primary efficacy assessment was sustained pain-free, defined as pain-free at 2 hours postdose with no recurrence from 2 to 24 hours and no use of rescue medication. Only patients who took study medication within 1 hour of migraine onset were included in the analysis. RESULTS: Of the 475 patients involved in the original study, 253 (53.3%) initiated treatment within the 0- to 1-hour interval. For these patients, 2-hour pain-free rates were 37.9% for almotriptan 12.5 mg (P=.016 versus placebo), 35.7% for sumatriptan 100 mg (P=.028 versus placebo), and 18.9% for placebo. Only almotriptan was significantly higher than placebo on the sustained pain-free rate-34.7% (P=.022 versus placebo); the sustained pain-free rate for sumatriptan was 29.6% and for placebo, 17.0%. CONCLUSION: Initiation of treatment with almotriptan 12.5 mg within the first hour after acute migraine onset resulted in a significantly higher sustained pain-free response compared with placebo. There was no significant difference in sustained pain-free rates between sumatriptan and placebo. These results are consistent with those from a previous open-label trial, and suggest that early intervention with almotriptan can improve clinical outcome.

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.

Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical trial.

BACKGROUND: Certain nonsteroidal anti-inflammatory drugs are effective in the acute treatment of migraine attacks. The authors report a double-blind, placebo-controlled, randomized cross-over trial of a dual-release formulation of oral ketoprofen in the acute treatment of migraine attacks. METHODS: The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized patients) with migraine with or without aura. The principal efficacy outcome was headache relief (reduction in headache severity from severe or moderate to mild or absent at 2 hours). RESULTS: Results are based on 838 attacks with a severe or moderate headache that were evaluable at 2 hours. Relief was reported for 62.6% of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and 66.8% with zolmitriptan. The difference between the three active treatments and placebo (27.8% relief) was highly significant, both tests of ketoprofen vs placebo being globally controlled at a 5% level for the type I error (primary analysis). Headaches at 2 hours disappeared more frequently for the active treatments than for placebo. The authors also demonstrated efficacy on most other secondary outcomes. The tolerance of ketoprofen was good (similar to that of placebo). CONCLUSIONS: Oral ketoprofen (75 mg or 150 mg) in a dual-release formulation is an effective and well-tolerated drug in the acute treatment of migraine attacks.

A negative trial of sodium valproate in cluster headache: methodological issues.

We report the result of a double-blind placebo controlled study of sodium valproate (SV) (1000-2000 mg/day) in the prophylaxis of cluster headache CH. Episodic and chronic CH were defined according to the International Headache Society classification. Ninety-six patients were included, 50 in the SV group and 46 in the placebo group. After a 7-day run-in period, patients were treated for 2 weeks. The primary efficacy criterion was the percentage of patients successfully improved, i.e having an at least 50% reduction in the average number of attacks per week between the run-in period and the last week of treatment. Whatever the type of CH, there was no difference between the two groups: 50% of subjects in the SV group and 62% in the placebo group were successfully improved (P = 0.23). This high success rate observed in the placebo group, which is likely to be due to the spontaneous remission of the episode, does not allow us to draw any valid conclusion with regard to the true efficacy of SV in the prophylaxis of CH.

Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised placebo-controlled trial.

BACKGROUND: Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis. METHODS: We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency. RESULTS: 53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia. CONCLUSIONS: In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks.

Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine.

OBJECTIVE: To assess the efficacy and tolerability of oral almotriptan, a selective serotonin receptor (5-HT1B/1D) agonist, when used at different doses in the treatment of acute migraine. METHODS: This was a placebo controlled, double-blind, parallel-group, dose-finding study. Patients satisfying International Headache Society criteria for acute migraine were randomized to a single dose of placebo or oral almotriptan 2, 6.25, 12.5, or 25 mg at the onset of moderate or severe pain. Patients graded pain intensity on a 4-point verbal scale from 0 (no pain) to 3 (severe pain) and recorded adverse events. The primary efficacy variable was headache response at 2 hours. Data were analyzed on an intent-to-treat basis. RESULTS: Nine hundred and three patients were randomized, and 742 were included in the evaluation of the efficacy and tolerability. Headache response at 2 hours was 32.5% with placebo, and 30%, 56.3%, 58.5%, and 66.5% with almotriptan 2, 6.25, 12.5, and 25 mg doses (p < 0.05 for 6.25, 12.5, and 25 mg vs placebo). A dose-dependent decrease in the incidence of migraine-associated symptoms and the need for escape medication was observed. The incidence of adverse events with the almotriptan 2-mg, 6.25-mg, and 12.5-mg groups was comparable to that with the placebo group. CONCLUSION: Almotriptan 12.5 mg demonstrated the most favorable ratio between efficacy and tolerability, offering equivalent efficacy and better tolerability compared with the 25 mg dose. The minimum effective dose of almotriptan was 6.25 mg.

Effect of rizatriptan and other triptans on the nausea symptom of migraine: a post hoc analysis.

OBJECTIVE: To compare the effects of oral rizatriptan, sumatriptan, naratriptan, and zolmitriptan on the relief and emergence of nausea during a migraine attack. METHODS: Data from five randomized, placebo-controlled, double-blind clinical trials in which oral rizatriptan 10 mg was directly compared with oral sumatriptan 100 mg (N = 772), 50 mg (N = 1168), 25 mg (N = 1180), naratriptan 2.5 mg (N = 406), or zolmitriptan 2.5 mg (N = 571) for the acute treatment of a migraine attack were retrospectively analyzed. Migraine was diagnosed according to International Headache Society criteria. Presence or absence of nausea was recorded at baseline and at 0.5, 1, 1.5, and 2 hours after dosing. The end points analyzed were relief of nausea in those who had it at baseline and emergence of nausea in those who were free of it at baseline. Treatments were compared using odds ratios estimated from logistic regression models at 2 hours, and averaged odds ratios for the first 2 hours posttreatment. RESULTS: Approximately 60% of patients in each treatment group had nausea at baseline. In those patients with nausea at baseline, significantly more patients treated with rizatriptan 10 mg were free of nausea at 2 hours compared with sumatriptan 100 mg (66% versus 58%, P =.043), sumatriptan 50 mg (68% versus 57%, P =.010), sumatriptan 25 mg (68% versus 59%, P =.017), and naratriptan 2.5 mg (59% versus 45%, P =.014). Averaging over the four posttreatment time points in the first 2 hours, significantly more patients treated with rizatriptan 10 mg were free of nausea compared with sumatriptan 100 mg (P =.004), sumatriptan 50 mg (P =.001), and naratriptan 2.5 mg (P =.015). No significant differences in nausea relief were seen between rizatriptan 10 mg and zolmitriptan 2.5 mg, either at 2 hours (65% versus 61%, P =.210) or over the first 2 hours (P =.781). Rates of treatment-emergent nausea at 2 hours ranged from 11% to 18% with placebo, from 5% to 13% with rizatriptan 10 mg, and from 10% to 20% with other comparator triptans. CONCLUSIONS: Oral rizatriptan 10 mg was more effective than oral sumatriptan and naratriptan at eliminating nausea within 2 hours in patients who had it at baseline. Rates of emergent nausea in patients who were free of it at baseline were low, and no consistent differences were observed between active treatments.

[Idiopathic SUNCT (short lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating and rhinorrhea) syndrome: 2 new cases]. / Le syndrome SUNCT idiopathique: deux nouveaux cas.

The syndrome of short-lasting unilateral, neuralgiform attacks of pain in the peri orbital area associated with conjunctival injection and tearing (SUNCT) is a rare disorder affecting mainly males. We report two French patients (1 male and 1 female) with SUNCT syndrome, 27 and 28 years of age respectively. Both patients had short (30 sec), frequent (30-100/day) excruciating pain located at the peri orbital area, associated with conjunctival injection, tearing, rhinorrhea, ptosis and others vasomotor symptoms. Clinical examination and imaging were normal. Most drugs used in the treatment of migraine, cluster headache, trigeminal neuralgia, and other short-lasting headaches were not successful.

Naratriptan.

Naratriptan is a selective 5-HT(1B/1D) receptor agonist, with a high affinity at the 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor subtypes. Naratriptan contracts a number of large isolated cerebral arteries from several species, and has little contractile effect on peripheral blood vessels. It has an inhibitory effect on the cranial neurogenic inflammation model. The clinically recommended dose is 2.5 mg. It was found significantly superior to placebo on headache relief and pain free at 2 and 4 hours, and in relieving nausea, photophobia and phonophobia. It also has a good within-patient consistency, and a low recurrence rate. The side-effect profile is that of the triptan class, wih an incidence no different from placebo at the 25 mg dose. The contraindications are similar to any triptan, including coronary disease. Naratriptan is unlikely to affect metabolism of other drugs. In comparison sumatriptan 100 mg, naratriptan 2.5 mg has a slower onset of action and a lower response rate at 4 h, but it has a lower recurrence rate, and is better tolerated.