The course of frequent episodic migraine in a large headache clinic population: a 12-year retrospective follow-up study.

BACKGROUND: Despite its high prevalence, little is known about the clinical course of migraine. Presented here are the findings of a 12-year follow-up study involving patients diagnosed at baseline with frequent episodic migraine. OBJECTIVE: The main objectives were to determine the long-term outcome of patients with frequent episodic migraine and to identify factors predictive of a favorable vs less favorable prognosis. METHODS: A total of 374 subjects (200 women, 174 men) were selected randomly from a total population of 2812 patients initially diagnosed before December 31, 1996, with episodic migraine and at baseline experiencing 1 to 6 attacks per month. Their subsequent migraine course was evaluated via telephone interviews conducted between 2005 and 2006. RESULTS: Migraine attacks had ceased in 110 (29%) of the 374 patients (57 women and 53 men). The remaining 264 subjects continued to experience migraine attacks at follow-up, and a change in attack frequency was reported by 80% (of whom 80% reported fewer attacks). Sixty-six percent reported a change in pain intensity over time, and of these 83% reported milder pain. Only 6 subjects (6/374 = 1.6%) had developed chronic migraine. CONCLUSION: These data from a headache clinic population suggest that migraine has a favorable prognosis in most patients. Whether the findings reflect the natural history of the disorder or interval improvements in headache management remains conjectural.

Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets.

BACKGROUND: The gastric stasis that commonly accompanies migraine headache may impair absorption of conventional oral tablets in the stomach. A fast-disintegrating/rapid-release formulation of sumatriptan has been developed to enhance tablet disintegration and drug dispersion and potentially improve absorption. OBJECTIVE: Two studies were conducted comparing the time to onset of relief from moderate or severe migraine pain with the fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100 mg and placebo. METHODS: These were 2 identically designed randomized, double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was taken on an outpatient basis to treat a single moderate or severe migraine attack. Using a personal digital assistant, patients recorded the time of dosing and the time at which pain severity reached none or mild (ie, pain relief) or none (ie, pain free) in real time so that the time to onset of relief could be measured as a continuous variable. Onset of relief was defined as the earliest time point at which a statistically significant difference in pain relief compared with placebo was achieved and maintained through 2 hours after dosing. Before dosing and at pre-determined time points after dosing, patients also provided an assessment of migraine pain as none, mild, moderate, or severe. At a clinic visit within 1 week after treatment of the migraine attack, patients were queried about adverse events. For each adverse event, investigators recorded whether study medication was considered the cause. Data analyses were undertaken for each study individually and, in post hoc analyses of the primary and key secondary end points, on pooled data from both studies. RESULTS: The 2 studies comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan 100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8 years across treatment groups, and most patients were female (83%-87%) and white (92%-93%). In the analysis of pooled data, sumatriptan tablets provided significantly more effective pain relief compared with placebo as early as 20 minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing with the 50-mg dose (P < or = 0.05). Similar results were observed for the individual studies: in study 1, sumatriptan tablets were significantly more effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). The cumulative percentages of patients with a pain-free response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the individual studies, significantly more patients receiving either sumatriptan dose were migraine free 2 hours after dosing and had sustained pain relief and a sustained pain-free response over 24 hours compared with placebo (P < or = 0.001, both sumatriptan doses vs placebo). The only drug-related adverse events reported in >2% of patients in any treatment group in either study were nausea (both studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia (study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo). CONCLUSIONS: In these studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation were effective for the acute treatment of moderate to severe migraine pain, were generally well tolerated, and achieved an onset of pain relief as early as 20 minutes for 100 mg and as early as 30 minutes for 50 mg.

Non-oral formulations of triptans and their use in acute migraine.

The introduction of triptans (5-HT (1B/1D) agonists) into clinical practice has expanded the therapeutic options for doctors treating migraine sufferers. The triptans are available in several different formulations such as conventional oral tablets, orally disintegrating wafers, subcutaneous injections, nasal sprays, and suppositories, which provide an excellent opportunity to tailor therapy to individual patients' needs. Although the oral formulations are the most popular with patients, they are not the most appropriate route of administration for drug delivery during the migraine attack. Due to gastrointestinal dysmotility, the intestinal absorption of any triptan administered orally may be impaired and treatment effects become inconsistent. For this reason, triptans preferably should be prescribed in a non-oral formulation (injection, nasal spray, or suppository). Parenteral administration of a triptan is more likely to provide relief of symptoms, even when it is used later in the course of the migraine attack.

[Can migraine cause subclinical brain lesions? A Dutch study shows a connection--but more research is required]. / Kan migrän ge subklinisk hjärnskada? Holländsk studie visar samband--men mer forskning behövs.

There is general agreement that migraine a primary disease of the central nervous system with secondary vascular effects. In a recent study by Kruit and co-authors (JAMA 2004;291(4):427-34) it is 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. The results are very interesting but have to be interpreted with caution. Needless to say, it is imperative that in the absence of scientific evidence, we do not further burden individuals with migraine with frightening information on the potentially poor prognosis of their disease. At the same time, it is equally important that we do not miss the opportunity to avoid possible risks for brain lesions by means of optimized symptomatic treatment of migraine attacks as well as preventive therapies. Accordingly, 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. The results generated in future studies may prove very important, not least with respect to future allocation of health care resources. Future studies will hopefully provide correct answers to most questions about migraine and constitute a basis for improved care of migraine sufferers with optimal use of the different treatment options as well as offer promising treatment strategies to prevent disease progression, including risk factor modification, optimized symptomatic treatment of migraine attacks and preventive therapies.

Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study.

CONTEXT: Headache experts have suggested that to improve the recognition of migraine, patients with a stable pattern of episodic, disabling headache and a normal physical exam should be considered to have migraine in the absence of contradictory evidence. The premise upon which this approach is based-that is, that episodic, recurrent primary headache in the clinic is usually migraine-has not been evaluated in prospective clinical studies. OBJECTIVES: To (1) evaluate the diagnoses of patients consulting their physician with primary episodic headache and (2) compare clinic diagnoses and patient self-diagnoses with International Headache Society (IHS) headache diagnoses assigned on the basis of longitudinal data from patient diaries. DESIGN: Prospective, open-label study. During the screening visit, patients self-reported a headache diagnosis and then were assigned a headache diagnosis by their physician following his or her customary practice. Patients with a new physician diagnosis of migraine or nonmigraine primary headache were given diaries to record headache symptoms for up to 3 months or 6 attacks. Members of an expert panel, unaware of the clinic diagnosis, used diary data to assign a headache diagnosis to each attack and to each patient. SETTING: One hundred twenty-eight (128) practices in 15 countries including the United States. PATIENTS: A total of 1203 male and female patients between 18 and 65 years of age who consulted their physician with headache as a primary or secondary complaint. RESULTS: Overall, 94% of patients with a physician diagnosis of nonmigraine primary headache or a new clinic diagnosis of migraine had IHS-defined migraine (76%) or probable migraine (migrainous) (18%) headache on the basis of longitudinal diary data. A new clinic diagnosis of migraine was almost always correct: 98% of patients with a clinic diagnosis of migraine had IHS-defined migraine (87% of patients) or probable migraine (11% of patients) headache on the basis of longitudinal diary data. On the other hand, review of diaries of patients with a clinic diagnosis of nonmigraine revealed that 82% of these patients had IHS-defined migraine (48%) or probable migraine (34%) headache. Altogether, one in four patients (25%) with IHS-defined migraine according to longitudinal diary data did not receive a clinic diagnosis of migraine. CONCLUSIONS: These findings support the diagnostic approach of considering episodic, disabling primary headaches with an otherwise normal physical exam to be migraine in the absence of contradictory evidence. If in doubt of diagnosis or when assigning a nonmigraine diagnosis, strong consideration should be given to the use of a diary to confirm primary headache diagnosis.

Applications of computerized adaptive testing (CAT) to the assessment of headache impact.

OBJECTIVE: To evaluate the feasibility of computerized adaptive testing (CAT) and the reliability and validity of CAT-based estimates of headache impact scores in comparison with 'static' surveys. METHODS: Responses to the 54-item Headache Impact Test (HIT) were re-analyzed for recent headache sufferers (n = 1016) who completed telephone interviews during the National Survey of Headache Impact (NSHI). Item response theory (IRT) calibrations and the computerized dynamic health assessment (DYNHA) software were used to simulate CAT assessments by selecting the most informative items for each person and estimating impact scores according to pre-set precision standards (CAT-HIT). Results were compared with IRT estimates based on all items (total-HIT), computerized 6-item dynamic estimates (CAT-HIT-6), and a developmental version of a 'static' 6-item form (HIT-6-D). Analyses focused on: respondent burden (survey length and administration time), score distributions ('ceiling' and 'floor' effects), reliability and standard errors, and clinical validity (diagnosis, level of severity). A random sample (n = 245) was re-assessed to test responsiveness. A second study (n = 1103) compared actual CAT surveys and an improved 'static' HIT-6 among current headache sufferers sampled on the Internet. Respondents completed measures from the first study and the generic SF-8 Health Survey; some (n = 540) were re-tested on the Internet after 2 weeks. RESULTS: In the first study, simulated CAT-HIT and total-HIT scores were highly correlated (r = 0.92) without 'ceiling' or 'floor' effects and with a substantial reduction (90.8%) in respondent burden. Six of the 54 items accounted for the great majority of item administrations (3603/5028, 77.6%). CAT-HIT reliability estimates were very high (0.975-0.992) in the range where 95% of respondents scored, and relative validity (RV) coefficients were high for diagnosis (RV = 0.87) and severity (RV = 0.89); patient-level classifications were accurate 91.3% for a diagnosis of migraine. For all three criteria of change, CAT-HIT scores were more responsive than all other measures. In the second study, estimates of respondent burden, item usage, reliability and clinical validity were replicated. The test-retest reliability of CAT-HIT was 0.79 and alternate forms coefficients ranged from 0.85 to 0.91. All correlations with the generic SF-8 were negative. CONCLUSIONS: CAT-based administrations of headache impact items achieved very large reductions in respondent burden without compromising validity for purposes of patient screening or monitoring changes in headache impact over time. IRT models and CAT-based dynamic health assessments warrant testing among patients with other conditions.

Measuring disability and quality of life in migraine.

Although eight out of ten people suffer from different types of headaches, the severity of their pain is often not communicated properly to their doctors. Research shows that when doctors understand exactly how headaches are affecting their patients, they are able to provide a better and fully successful treatment program. The magnitude of impact of migraine is generally measured through self-administered questionnaires. Two reliable questionnaires for measuring patients' disability and quality of life in migraine are the Migraine Disability Assessment Questionnaire (MIDAS) and the new Internet-based Headache Impact Test (HIT).

How does almotriptan compare with other triptans? A review of data from placebo-controlled clinical trials.

Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral bioavailability than any other triptan, with more than two thirds of the administered dose absorbed within the first hour both inside and outside of a migraine attack. Gender or the presence of food in the stomach does not affect its pharmacokinetic profile, and the compound has no clinically relevant interactions with other drugs. Among the available triptans, response rates at 2 hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan 12.5 mg provides similar efficacy, with significant advantage over placebo at 30 minutes and a reliable consistency (75% in two of three attacks). Headache typically recurs in 25% to 45% of patients with most triptans. The recurrence rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The tolerability of almotriptan 12.5 mg is close to that of placebo with a low incidence of central nervous system side effects and chest symptoms. In conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in combination with excellent tolerability, make it an attractive choice in the acute treatment of migraine attacks.