Predictors of outcome in patients consulting their general practitioners for headache: a prospective study.

Headache is the most common neurological symptom presenting to general practitioners (GPs). Identifying factors predicting outcome in patients consulting their GPs for headache may help GPs with prognosis and choose management strategies which would improve patient care. We followed up a cohort of patients receiving standard medical care, recruited from 18 general practices in the South Thames region of England, approximately 9 months after their initial participation in the study. Of the baseline sample (N=255), 134 provided both full baseline and follow-up data on measures of interest. We determined associations between patients' follow-up scores on the Headache Impact Test-6 and baseline characteristics (including headache impact and frequency scores, mood, attributions about psychological/medical causes of their headaches, satisfaction with GP care and illness perceptions). Greater impact and stronger beliefs about the negative consequences of headaches at baseline were the strongest predictors of poor outcome at follow-up.

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.

Review of clinical trials using early acute intervention with oral triptans for migraine management.

Most of the data on triptan use are from clinical trials in which patients were instructed to wait until migraine headache pain was moderate/severe in intensity. In the real world, patients may hesitate to use a triptan until headache pain is moderate/severe because of the cost of these agents or limited supply allowed by their health service organisation. However, accumulating data indicate that early intervention with an oral triptan when headache pain is still mild may be the most effective acute treatment strategy. Economic analyses also support early triptan intervention in migraine attacks. Tolerability is expected to be particularly important in early intervention, as patients treating mild migraine pain may be more reluctant to risk adverse events. Thus, an agent selected for use as early intervention should have both a demonstrated efficacy in treating mild migraine headache and placebo-like tolerability. This article reviews retrospective and prospective clinical trials which investigated the use of triptans for early acute migraine therapy.

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.

Clinical and economic issues associated with switching between triptans in clinical practice.

Seven oral triptans are now generally available for the acute treatment of migraine, and physicians may sometimes feel under pressure to switch patients from one triptan to another for nonclinical reasons. This commentary article provides advice on what information should be taken into account by the physician before they consider switching one triptan for another. We review recommendations on switching triptans from international guidelines for migraine management and relate these to data from a recently published study on the economic implications of switching triptans in the UK. Controlled clinical studies reveal that most of the oral triptans have broadly similar efficacy profiles. Switching triptans can therefore only be recommended if the patient experiences problems such as lack of efficacy or intolerable side effects following repeated use of the initial triptan. The retrospective database study revealed that most patients who had their triptan switched were subsequently switched again during a 15 month review period, most usually back to their original triptan. Overall, switching a patient's triptan led to increased costs (analysed as costs of medication and the GP consultation) to the healthcare provider. These data indicate that patients should only be switched from one triptan for another for clinical reasons and not for perceived economic reasons, i.e. cost of the medication.

Psychiatric morbidity and cognitive representations of illness in chronic daily headache.

OBJECTIVES: We studied patients with chronic daily headache (CDH) attending a headache clinic. Our hypothesis was that patients with anxiety or depression would have poorer functional status and differing cognitive representations of illness than would those without psychiatric morbidity. METHODS: The sample consisted of 144 consecutive new patients. Patients underwent a semistructured interview and completed a prospective headache diary, the Hospital Anxiety and Depression Scale (HADS) and other health-related questionnaires. RESULTS: Sixty patients (42%) were probable cases of anxiety or depression on the basis of their HADS score. These HADS-positive cases had longer, more severe headaches, were more worried about them, were more functionally impaired and believed that their illness would last longer. Principal components analysis revealed that the HADS-positive cases believed that psychological factors play a role in their headaches. CONCLUSIONS: Psychological morbidity is high amongst CDH patients who attend specialist clinics. In addition to identifying those with high levels of psychological distress, the HADS can be used to predict those likely to have worse headaches and poorer functional ability.

Identifying patients who require a change in their current acute migraine treatment: the Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire.

The aim of the study was to design and test a new, easy to use, assessment tool, the Migraine Assessment of Current Therapy (Migraine-ACT), for identifying patients who require a change in their acute treatment. A 27-item questionnaire was developed by an international advisory board including questions formulated in four domains: headache impact, global assessment of relief, consistency of response and emotional response. Migraine patients entered a multinational, prospective study to investigate the test-retest reliability and construct validity of the tool, which was completed by the patients on two occasions. Test-retest reliability was assessed by Pearson's and by Spearman correlation coefficients. Construct validity was assessed by correlating patients' answers to the 27-item questionnaire with those of well-reported measures: SF-36, MIDAS and Migraine Therapy Assessment Questionnaire (MTAQ). The test-retest reliability of the 27 initial questions ranged from good to excellent. Correlations of all items with SF-36, MIDAS and MTAQ scores--assessed by discriminatory t-tests--indicated that the following 4 were the most discriminating items: Does your migraine medication work consistently, in the majority of your attacks? Does the headache pain disappear within 2 hours? Are you able to function normally within 2 hours? Are you comfortable enough with your medication to be able to plan your daily activities? The 4-item Migraine-ACT is a brief, simple, and reliable assessment tool to identify patients who require a change in their acute migraine treatment, and can be recommended for primary care physicians, neurologists and headache clinicians.

Identifying patients who require a change in their current acute migraine treatment: the Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire.

BACKGROUND: Currently available measures of the efficacy of acute migraine medications are not frequently used in primary care. They may be too burdensome and complicated for routine use. OBJECTIVES: To design and test a new, easy to use, 4-item assessment tool, the Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire for use by clinicians, to quickly evaluate how a recently prescribed acute medication is working, and to identify patients who require a change of their current acute treatment. METHODS: A 27-item Migraine-ACT questionnaire was developed by an international advisory board of headache specialists. Questions were formulated in four domains: headache impact, global assessment of relief, consistency of response and emotional response. All these are clinically important measures of migraine severity and treatment outcome. All questions were dichotomous and answered by yes or no. Patients (n = 185) attending secondary care headache clinics who were diagnosed with migraine according to International Headache Society criteria entered a multinational, prospective, observational study to investigate the test-retest reliability and construct validity of the 27-item Migraine-ACT. Patients completed the Migraine-ACT on two occasions, separated by a 1-week interval, and test-retest reliability was assessed by Pearson product moment and Spearman rank measures. Construct validity was assessed by correlating patients' answers to the 27-item Migraine-ACT with those to other questionnaires (individual domains and total scores) conceptually related to it; the Short-Form 36 quality of life questionnaire (SF-36), the Migraine Disability Assessment (MIDAS) questionnaire and the Migraine Therapy Assessment Questionnaire (MTAQ). Discriminatory t-tests were used to identify the four Migraine-ACT questions (one in each domain) which discriminated best between the domains of the SF36, MIDAS, and MTAQ. These four items constituted the final 4-item Migraine-ACT. RESULTS: The test-retest reliability of the 27 Migraine-ACT questions ranged from good to excellent, and correlation coefficients were highly significant for all items. The consistency of reporting the yes and no answers was also excellent. Correlations of Migraine-ACT items with SF-36 and MIDAS items and SF-36, MIDAS and MTAQ total scores indicated that the following were the most discriminating items, in the respective four domains, and constitute the final Migraine-ACT questionnaire: Consistency of response: Does your migraine medication work consistently, in the majority of your attacks? Global assessment of relief: Does the headache pain disappear within 2 h? IMPACT: Are you able to function normally within 2 h? Emotional response: Are you comfortable enough with your medication to be able to plan your daily activities? The 4-item Migraine-ACT was shown to be highly reliable (Spearman/Pearson measure r = 0.82). The individual questions, and the total 4-item Migraine-ACT score, showed good correlation with items of the SF-36, MIDAS and MTAQ questionnaires, particularly with the total MTAQ and SF-36 scores. CONCLUSIONS: The 4-item Migraine-ACT questionnaire is an assessment tool for use by primary care physicians to identify patients who require a change in their current acute migraine treatment. It is brief and simple to complete and score, and has demonstrated reliability, accuracy and simplicity. Migraine-ACT can therefore be recommended for everyday clinical use by clinicians.

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.

Managing chronic headaches in the clinic.

Chronic daily headache (CDH), which is often linked to a history of migraine, tension-type headache and the abuse of headache medications, and cluster headache are the best known of the chronic headaches. These headaches may not be well recognised or well treated in primary care. This article outlines the development of management algorithms for these headache subtypes, designed for use by the primary care physician with an interest in headache. Principles of care for chronic headaches include implementation of screening procedures, differential diagnosis, tailoring of management to the individual's needs, proactive follow-up and a team approach to care. These principles can be customised to the headache subtype by the selection of appropriate therapies. The optimal treatments for CDH include physical therapy to the neck if there is any stiffness there, withdrawal of abused medications and treatment of any subsequent withdrawal symptoms and headache prophylaxis, together with the provision of acute medications as rescue therapy. Optimal treatments for cluster headache include short- and long-term prophylaxis to prevent the headaches developing and acute medications for use as rescue. If treatment is ineffective, alternative medications can be provided at follow-up, with the possibility of referral for refractory patients.

Patients with migraine prefer zolmitriptan orally disintegrating tablet to sumatriptan conventional oral tablet.

The Zolmitriptan Evaluation versus Sumatriptan Trial (ZEST) assessed patient preference for 2.5 mg zolmitriptan orally disintegrating tablet (ODT) or 50 mg sumatriptan conventional tablet in 218 patients with significant migraine disability. Significantly more patients preferred zolmitriptan ODT to sumatriptan conventional tablet (60.1% vs 39.9%; p = 0.0130). In terms of efficacy, significantly more patients considered zolmitriptan ODT to be an effective migraine treatment than sumatriptan conventional tablet (77% vs 63%; p = 0.0063). When asked about specific formulation attributes, significantly more patients selected zolmitriptan ODT as the least disruptive therapy (83.6% vs 16.4%), the easiest to take (85.5% vs 14.5%), the most convenient to take (86.1% vs 13.9%), and the one which enabled them to maintain an active lifestyle (65.5% vs 34.5%), compared with the sumatriptan conventional tablet (all comparisons p < 0.001). Zolmitriptan ODT is a convenient and beneficial alternative to conventional tablets and is preferred to sumatriptan conventional tablets by migraineurs.

Establishing principles for migraine management in primary care.

Published guidelines for the management of migraine in primary care were evaluated by an international advisory board of headache specialists, to establish evidence-based principles of migraine management that could be recommended for international use. Twelve principles of migraine management were identified, covering screening, diagnosis, management and treatments: Almost all headaches are benign/primary and can be managed by all practising clinicians. Use questions/a questionnaire to assess the impact on daily living and everyday activities, for diagnostic screening and to aid management decisions. Share migraine management between the clinician and the patient. Provide individualised care for migraine and encourage patients to manage their migraine. Follow up patients, preferably with migraine calendars or diaries. Regularly re-evaluate the success of therapy using specific outcome measures and monitor the use of acute and prophylactic medications regularly. Adapt migraine management to changes that occur in the illness and its presentation over the years. Provide acute medication to all migraine patients and recommend it is taken at the appropriate time, during the attack. Provide rescue medication/symptomatic treatment for when the initial therapy fails. Offer to prescribe prophylactic medications, as well as lifestyle changes, to patients who have four or more migraine attacks per month or who are resistant to acute medications. Consider concurrent co-morbidities in the choice of appropriate prophylactic medication. Work with the patient to achieve comfort with mutually agreed upon treatment and ensure that it is practical for their lifestyle and headache presentation. Using these principles, practising clinicians can screen and diagnose their headache patients effectively and manage their migraine patients over the long-term natural history of the migraine process. In this way, the majority of migraine patients can be well treated in primary care, ensuring a structured and individualised approach to headache management, and conserving valuable healthcare resources.

New guidelines for the management of migraine in primary care.

Despite repeated initiatives over the past decade, migraine remains under-recognised, under-diagnosed and under-treated in everyday clinical practice. The Migraine in Primary Care Advisors (MIPCA) group has produced new guidelines for migraine management to attempt to rectify this situation. MIPCA is a group of physicians, nurses, pharmacists and other healthcare professionals dedicated to the improvement of headache management in primary care, who have also worked closely with the Migraine Action Association (the UK patients' group) in the development of these guidelines. The principles of the new MIPCA guidelines are: To arrange specific consultations for headache. To institute a system of detailed history taking, patient education and buy-in at the outset of the consultation. To utilise a new screening algorithm for the differential diagnosis of headache, which can be confirmed by further questioning, if necessary. To institute a process of management that is individualised for each patient, using a new algorithm. Assessing the impact on the patient's daily life is a key aspect of diagnosis and management. To prescribe only treatments that have objective evidence of favourable efficacy and tolerability. To utilise prospective follow-up procedures to monitor the success of treatment. To organise a team approach to headache management in primary care.

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.

Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine.

A new formulation of zolmitriptan has been developed that dissolves on the tongue without the need for additional fluid intake. In this double-blind, parallel study, 471 patients were randomized to receive the zolmitriptan orally disintegrating tablet 2.5 mg (n=231) or matching placebo (n=240) to treat a single moderate or severe migraine. Headache relief following zolmitriptan 2.5 mg (63%) was significantly greater than with placebo (22%) at 2 h post-dose (primary endpoint; P < 0.0001). The zolmitriptan orally disintegrating tablet was also significantly more effective than placebo for 1-, 2- and 4-h pain-free response (8% vs. 3%, P=0.0207, 27% vs. 7%, P < 0.0001, and 37% vs. 11%, P < 0.0001, respectively). Of those patients stating a preference, 70% of patients preferred the orally disintegrating tablet to a conventional tablet. Zolmitriptan orally disintegrating tablets are an effective and convenient alternative to a conventional tablet, allowing migraine attacks to be treated anytime a migraine strikes, which can facilitate earlier treatment.

The cost effectiveness of stratified care in the management of migraine.

OBJECTIVE: To examine the cost effectivess of a stratified-care regimen for patients with migraine--in which patients are stratified by severity of illness, and then prescribed differing treatments according to level of severity--compared with a conventional stepped-care approach. DESIGN AND METHODS: A decision analytic model was constructed to simulate a controlled clinical trial in which patients with migraine receiving primary medical care were randomly assigned to treatment under a stepped-care or a stratified-care regimen. A health service payer perspective was adopted and the time horizon was 1 year. Data inputs were: (i) the frequency and disability of migraine, derived from population-based studies; (ii) disability level-specific treatment response rates for over-the-counter analgesics,aspirin/metoclopramide and zolmitriptan as the representative of high-end therapy obtained from an international consensus opinion enquiry; and (iii) unit costs of healthcare obtained from UK health service sources. MAIN OUTCOME MEASURES AND RESULTS: The estimated 1-year direct healthcare costs per primary care patient with migraine were pound sterling 156.82 for stepped care and sterling pound 151.57 for stratified care. Estimates of treatment response rates were 40 and 71% for stepped and stratified care, respectively. The cost per successfully treated attack was sterling pound 23.43 for stepped care and sterling pound 12.60 for stratified care. Stratified care remained cost effective when tested in a wide range of one-way sensitivity analyses, and probabilistic sensitivity analysis showed the cost effectiveness of stratified care to be significant at the 3% level. Conditional confidence analysis showed that the level of confidence in the cost effectiveness of stratified care varied positively with the case mix, i.e. in populations where the proportion of moderate and severely disabled patients with migraine was greater than 25%, the cost effectiveness of stratified care remained statistically significant. CONCLUSION: A stratified-care treatment strategy (including zolmitriptan as the representative of high-end therapy) is a highly cost-effective method of managing migraine in the primary care setting compared with stepped care, delivering improved clinical outcomes at no additional cost.

Development and testing of the Migraine Disability Assessment (MIDAS) Questionnaire to assess headache-related disability.

The MIDAS Questionnaire was developed to assess headache-related disability with the aim of improving migraine care. Headache sufferers answer five questions, scoring the number of days, in the past 3 months, of activity limitations due to migraine. The internal consistency, test-retest reliability, and validity (accuracy) of the questionnaire were assessed in separate population-based studies of migraine sufferers. In addition, the face validity, ease of use, and clinical utility of the questionnaire were evaluated in a group of 49 physicians who independently rated disease severity and need for care in a diverse sample of migraine case histories. The test-retest Pearson correlation coefficient for the total MIDAS score was approximately 0.8. The MIDAS score was valid when compared with a reference diary-based measure of disability; the overall correlation between MIDAS and the diary-based measure was 0.63. The MIDAS score was also correlated with physicians' assessments of need for medical care (r = 0.69). From studies completed to date, the MIDAS Questionnaire has been shown to be internally consistent, highly reliable, valid, and correlates with physicians' clinical judgment. These features support its suitability for use in clinical practice. Use of the MIDAS Questionnaire may improve physician-patient communication about headache-related disability and may favorably influence health-care delivery for migraine patients.

Assessing the impact of migraine.

Migraine is a remarkably disabling condition, although unpredictable and heterogeneous in frequency, duration and severity. It can be difficult to manage in primary care, where it is under-recognised, under-diagnosed and under-treated. Proposals have been made that migraine care could be improved by incorporating assessments of migraine impact into management strategies. Research has shown that measuring headache-related disability, together with assessments of pain intensity, headache frequency, tiredness, mood alterations and cognition can be used to assess the impact of migraine on sufferers' lives and society. From this research, two simple and brief impact tools were developed: the Migraine Disability Assessment (MIDAS) Questionnaire and the Headache Impact Test (HIT). Both tools are scientifically valid measures of migraine severity and have the potential to improve communication between patients and their physicians, assess migraine severity and act as outcome measures to monitor treatment efficacy. Each of these tools offers its own advantages. For example, HIT was designed for greater accessibility (on the Internet at www.headachetest.com and www.amlhealthy.com, and as a paper-based form known as HIT-6) and has a wider coverage of the spectrum of headache than MIDAS. Impact tools are also being increasingly recommended as part of generalised headache management guidelines to produce an individualised treatment plan for each patient in concert with other clinical assessments. It is not possible as yet to recommend unequivocally the optimal impact tool for use in primary care, but it should be usable by GPs, pharmacists, nurses and patients, and for research purposes.

Migraine: assessment and management.

Headaches occur at some time in the vast majority of the population. For most people headaches are a nuisance but for some they can be disabling. Two per cent of the population at any time have chronic daily headache, with or without analgesic dependence, but most disabling headaches are intermittent and migranous in nature. Before hoping to make an appropriate intervention, an accurate diagnosis must be made. The first part of this paper examines the differential diagnosis and in particular separates benign from sinister, acute from chronic and tension-type from migranous. The second half focuses on the management of migraine. An individualised approach is usually the most effective, with the patient drawing from the broad areas of attention to trigger factors and lifestyle, finding an acute or rescue medication that consistently returns them to normal activities within a few hours, and prophylaxis to reduce the rate of attack by 50% in those with high frequency migraine. The expession of migraine may well vary during an individual's life and in order to achieve the best lifelong control, adjustment of the blend of management options may be needed. The aim of the adviser is to enable patients to feel in control of their migraine rather than feeling that migraine controls them.