Migraine Disorders: Dowson AJ

Dowson AJ, Lipscombe S, Sender J, Rees T, Watson D, Anonymous00006. · King's Headache Service, King's College Hospital, London, UK. · Curr Med Res Opin. · Pubmed #12487508 No free full text.

Abstract: 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.

Dowson AJ, Tepper SJ. · No affiliation provided · Int J Clin Pract. · Pubmed #19166426 No free full text.

This publication has no abstract.

Dowson AJ, Fuat A, Gruffydd-Jones K. · King's Headache Service, King's College Hospital, London, UK. · Curr Med Res Opin. · Pubmed #15811206 No free full text.

Abstract: 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.

Dowson AJ, Mathew NT, Pascual J. · King's Headache Services, King's College Hospital, London, UK. · Int J Clin Pract. · Pubmed #16805756 No free full text.

Abstract: 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.

Dahlöf CG, Pascual J, Dodick DW, Dowson AJ. · Institute of Clinical Neuroscience, Gothenburg Migraine Clinic, Gothenburg, Sweden. · Cephalalgia. · Pubmed #16556240 No free full text.

Abstract: 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.

Dowson AJ, Tepper SJ, Dahlöf C. · King's Headache Service, King's College Hospital, Denmark Hill, London SE5 9RS, UK. · J Headache Pain. · Pubmed #16355291 No free full text.

Abstract: Oral triptans are effective and well tolerated acute treatments for migraine, but clinical differences between them are small and difficult to measure in conventional clinical trials. Patient preference assesses a global measure of efficacy and tolerability, and may be a more sensitive means of distinguishing between these drugs. In a series of studies, patients consistently expressed a clear preference for triptans over their usual non-triptan acute medications, e.g., analgesics and ergotamine. Direct comparator studies of patient preference with oral triptans showed that patients could distinguish between different triptans, and between different formulations of the same triptan. Patients could even distinguish between the three oral doses of sumatriptan. The most frequently provided reasons for preference were speed of response and overall effectiveness. Patient preference is a sensitive clinical trial endpoint and physicians should consider using it when reviewing the efficacy of acute migraine medications.

Dowson AJ, Almqvist P. · The King's Headache Services, King's College Hospital, London, UK. · Curr Med Res Opin. · Pubmed #16083519 No free full text.

Abstract: As part of an optimal strategy for the management of migraine, the individual needs and preferences of patients need to be considered when of patients need to be considered when prescribing treatments. Zolmitriptan has been available as a conventional oral tablet for more than seven years, and is established as a highly effective, well-tolerated compound for the acute treatment of migraine. A bioequivalent, orally disintegrating tablet (ODT) of zolmitriptan, which dissolves on the tongue without the need for additional fluid intake, has been developed. In a study designed to compare patient preference for zolmitriptan ODT and conventional oral sumatriptan tablets, > 60% of the 186 patients questioned had an overall preference for zolmitriptan ODT, with > 80% of patients reporting that this was the more convenient and less disruptive therapy to take. Approximately 90% of patients agreed that, unlike a conventional tablet, zolmitriptan ODT can be taken wherever and whenever a migraine occurs. When patient preference for zolmitriptan ODT and the ODT formulation of rizatriptan was compared in 171 migraineurs, 70% had an overall preference for zolmitriptan ODT to be superior to rizatriptan ODT with respect to taste and aftertaste, as well as packaging. In summary, not only is zolmitriptan ODT a convenient tablets, such as the sumatriptan oral tablet, but patients generally consider it to be a more attractive option for the acute treatment of migraine than the orally disintegrating version of rizatriptan.

Dowson AJ, Dodick DW, Limmroth V. · King's Headache Service, King's College Hospital, London, UK. · CNS Drugs. · Pubmed #15962999 No free full text.

Abstract: Medication overuse headache (MOH) is a common medical condition that is associated with considerable long-term morbidity and disability. Patients experiencing MOH have primary headache disorders (migraine, tension-type headache [TTH] or the combination of migraine and TTH) that change to a pattern of daily or near-daily headaches over a period of years or decades following the overuse of symptomatic headache medications. Overused drugs include analgesics, ergot alkaloids, serotonin 5-HT(1B/1D) receptor agonists ('triptans') and medications containing barbiturates, codeine, caffeine, tranquillisers and mixed analgesics. Affected patients usually have a long history of primary headache, overuse of medications and MOH before they consult a physician for care. Patients with MOH are usually managed in specialist centres by withdrawal of the overused drugs and treatment of withdrawal symptoms (on an inpatient or outpatient basis), headache prophylaxis and limited use of symptomatic acute medications. Most patients respond to this therapy, although the prognosis is not always good and >or=50% may lapse over an initial 5-year follow-up period. The best practical strategy at present is to prevent the overuse of drugs in the first place by patient education and formal management approaches conducted in primary care to treat the primary headache before it changes to MOH. The quality of the clinical evidence on MOH is suboptimal and further biological and clinical research is urgently required to help facilitate the management of these patients more effectively in the future.

Dowson AJ. · The King's Headache Service, King's College Hospital, Denmark Hill, London, SE5 9RS, UK. · Expert Rev Neurother. · Pubmed #15853532 No free full text.

Abstract: Almotriptan (Almogran, Lundbeck; Almirall Prodesfarma; Axert, Ortho-McNeil) is a novel 5-HT(1B/1D) receptor agonist (triptan) that is widely available on prescription for the acute treatment of migraine. Almotriptan has pharmacodynamic and pharmacokinetic profiles that make it suitable for use in this indication. It is a potent agonist at 5-HT(1B), (1D) and (1F) receptors, while having a low affinity for other 5-HT receptors. It is also a potent inhibitor of neurogenic inflammation. Almotriptan has a high oral bioavailability, is absorbed rapidly, has a relatively short plasma half-life and its route of elimination presents few potential problems. Placebo-controlled dose-finding studies have demonstrated that almotriptan tablets are effective and well-tolerated in the acute treatment of migraine, with a 12.5 mg dose providing the best balance between efficacy and tolerability. Large placebo-controlled studies show that the efficacy of oral almotriptan is comparable with that of the other oral triptans. In direct comparator-controlled studies, almotriptan was as effective as sumatriptan 50 and 100 mg but had a superior tolerability profile. Furthermore, the efficacy and tolerability of almotriptan is sustained in the long term following open-label administration. Meta-analyses and post hoc analyses of clinical data confirm these findings. In conclusion, almotriptan 12.5 mg is a good therapeutic choice for the symptomatic treatment of acute migraine attacks.

Dowson AJ, Bradford S, Lipscombe S, Rees T, Sender J, Watson D, Wells C. · King's College Hospital, London, UK. · Int J Clin Pract. · Pubmed #15646412 No free full text.

Abstract: 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.

Dowson AJ, Sender J, Lipscombe S, Cady RK, Tepper SJ, Smith R, Smith TR, Taylor FR, Boudreau GP, van Duijn NP, Poole AC, Baos V, Wöber C. · King's Headache Service, King's College Hospital, London, UK. · Int J Clin Pract. · Pubmed #12918889 No free full text.

Abstract: 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.

Dowson AJ. · King's Headache Service, King's College Hospital. · Practitioner. · Pubmed #12602225 No free full text.

Abstract: Headache alone rarely indicates a sinister underlying cause. However, if the red flags are flying -- that is, if the patient is over 30 years old when the first headache develops, has additional symptoms or signs or has a very acute onset, particularly involving vomiting, then suspicion should be raised (see table 4). Although migraine has a high impact on the sufferer and affects a large proportion of the population on a monthly basis, the problem of acute muscle contraction headache is far greater. Other forms of headache are actually uncommon in comparison to these two. However, chronic daily headache is the most common condition seen by the medical professional because of its impact on the patient's quality of life. The key to the management of this condition is the assessment of analgesic dependence including NSAIDs, and particularly the codeine-containing agents. These should be avoided while long-term aproached such as exercise and certain prophylactic agents are introduced. It is true to say that if a careful initial assessment is made leading to a correct diagnosis, then the chance of appropriate management is enormously increased. Patients undergoing the correct management should generally see a massive improvement in their quality of life. Headache can, therefore, be a very satisfying condition for the clinician to treat.

Dowson AJ, Charlesworth B. · Director, Kings Headache Services, Kings College Hospital, Denmark Hill, London, UK. · Expert Opin Pharmacother. · Pubmed #12083998 No free full text.

Abstract: Preclinical studies have shown that zolmitriptan is a selective serotonin 5-HT(1B/1D) receptor agonist (triptan). Randomised, placebo-controlled, double-blind trials in patients with migraine have shown that zolmitriptan has good efficacy measured using 2 h response and pain-free rates. Migraine-associated symptoms, including nausea, photophobia and phonophobia, are also improved with zolmitriptan. Oral zolmitriptan (2.5 and 5 mg) has an onset of action within 45 min and efficacy is sustained in most patients who respond at 2 h. The orally-disintegrating zolmitriptan tablet has the advantage that it may be taken immediately, without the need for additional fluids, any time a migraine headache occurs. Patients may benefit in terms of improved efficacy from the convenience of the disintegrating tablet, since there is evidence that taking triptan therapy as early as possible in an attack is advantageous. For similar reasons, as well as improved efficacy, a nasal spray formulation is in development. Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura. There is no tachyphylaxis following repeated doses for multiple attacks of migraine over a prolonged period of time. Compared to placebo, the incidence of persistent migraine headache is reduced by zolmitriptan and recurrent migraine headache occurs less frequently. Zolmitriptan has also shown efficacy in the treatment of persistent and/or recurrent migraine headache. Comparative clinical studies have shown overall that zolmitriptan has similar or superior efficacy to sumatriptan in the treatment of migraine. Specifically, zolmitriptan 2.5 mg was significantly more effective than sumatriptan 25 or 50 mg according to a number of end points, including headache response at 2 h. Oral zolmitriptan is also effective in the acute treatment of cluster headache. Zolmitriptan is generally well tolerated, with most adverse events being mild-to-moderate, transient and resolving without intervention or the need for treatment withdrawal. The consistent efficacy in treating all types of migraine and the choice of available formulations make zolmitriptan acceptable to patients and a suitable first-line therapy for the treatment of migraine.

Dahlöf CG, Dodick D, Dowson AJ, Pascual J. · Gothenburg Migraine Clinic, Sociala Huset, Sweden. · Headache. · Pubmed #12005302 No free full text.

Abstract: 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.

Dowson AJ. · King's Headache Service, King's College Hospital, London, UK. · Curr Med Res Opin. · Pubmed #11922404 No free full text.

Abstract: 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.

Dowson AJ. · King's Headache Service, London, UK. · Int J Clin Pract. · Pubmed #11777294 No free full text.

Abstract: 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.

Stewart WF, Lipton RB, Dowson AJ, Sawyer J. · Johns Hopkins School of Public Health, Baltimore, MD, USA. · Neurology. · Pubmed #11294956 No free full text.

Abstract: 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.

Dowson AJ, Kilminster SG, Salt R. · King's College Headache Service, King's College Hospital, London, UK. · Drugs R D. · Pubmed #18457467 No free full text.

Abstract: BACKGROUND AND OBJECTIVES: Some evidence for the efficacy of botulinum toxin A as a preventive treatment for chronic primary headaches has been reported in randomized, controlled clinical studies. This study investigated the clinical profile of botulinum toxin A in a naturalistic clinical practice setting in a population of patients with cervical dystonia associated with chronic headache and a history of migraine. METHODS: This was a prospective, open-label, longitudinal study. Following a prospective run-in period, eligible patients were given three sets of botulinum toxin A injections at 8- to 12-week intervals over a 16- to 24-week period and were monitored for 3 months after the final injections. Efficacy was assessed in terms of headache-related disability (using the Migraine Disability Assessment [MIDAS] questionnaire), pain and emotional function (using the Short Pain Inventory [SPI]), quality of life (QOL, using the Short-Form-36 [SF-36] questionnaire) and patient-assessed headache frequency and severity, and medication use and its effectiveness. Safety was assessed as adverse events. The primary endpoint was the change in MIDAS score from baseline following treatment with botulinum toxin A. RESULTS: Twenty-four patients took part in the study and 17 (71%) completed the study. There were significant improvements in headache-related disability (MIDAS score), pain and emotional function (SPI), QOL (SF-36), headache frequency and medication use following treatment with botulinum toxin A (p < 0.05 for all endpoints). An efficacy response occurred within 8 weeks of treatment initiation and was maintained throughout the study duration. Botulinum toxin A was generally well tolerated. CONCLUSIONS: This study demonstrated that botulinum toxin A is an effective and well tolerated preventive treatment for chronic headache in patients with cervical dystonia and a history of migraine. These results warrant further investigation in a large, randomized, controlled study.

Dowson AJ, Charlesworth BR, Green J, Färkkilä M, Diener HC, Hansen SB, Gawel M, Anonymous00025. · King's Headache Services, King's College Hospital, London, UK · Headache. · Pubmed #15663608 No free full text.

Abstract: BACKGROUND: Previous studies have shown that zolmitriptan 5 mg nasal spray has a fast onset of action, high efficacy, and good tolerability in the acute treatment of migraine. Objective.-This open-label, noncomparative, multicenter, multinational phase III study was designed to further evaluate the long-term safety and tolerability of zolmitriptan 5 mg nasal spray in a population of migraineurs largely naive to triptan nasal sprays who treated multiple migraine attacks over a 1-year period. METHODS: Patients were required to have an established diagnosis of migraine with or without aura (based on International Headache Society criteria), a high frequency of migraine attacks, and were allowed to treat migraine with any baseline headache intensity. A secondary objective of the study was to assess the long-term efficacy of zolmitriptan nasal spray. A subgroup analysis aimed to determine whether rhinitis had any influence on outcomes of treatment. RESULTS: The safety population consisted of 538 patients who treated 20,717 migraine attacks with zolmitriptan 5 mg nasal spray. Overall, adverse events occurred in 32.8% of attacks, and led to treatment withdrawal in 4.5% of patients. The most common adverse events were unusual taste (19.0%) and paresthesia (6.8%). Adverse events were generally of mild intensity, transient, and well tolerated, showing a decline in incidence over time. Serious adverse events were rare. The presence of rhinitis and use of a second dose of trial medication had no effect on the incidence of adverse events. At 2 hours, 53.8% of attacks treated with zolmitriptan nasal spray 5 mg were rendered pain free. The highest 2-hour pain free rates were seen for headaches of mild baseline intensity (83.3%), followed by headaches of moderate (56.5%), and severe (32.2%) baseline intensity. The 2-hour pain-free rate remained consistent throughout the study period. The presence of rhinitis had no effect on efficacy. CONCLUSIONS: Zolmitriptan 5 mg nasal spray demonstrated a well-tolerated and efficacious profile in the acute treatment of multiple migraine attacks over a 1-year period.

Dowson AJ, Massiou H, Lainez JM, Cabarrocas X. · King's Headache Services, King's College Hospital, London, UK. · Headache. · Pubmed #15109355 No free full text.

Abstract: 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.

Dowson AJ, Charlesworth BR. · King 's Headache Services, King's College Hospital, London, UK. · Int J Clin Pract. · Pubmed #14529055 No free full text.

Abstract: 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.

Dowson AJ, Charlesworth BR, Purdy A, Becker WJ, Boes-Hansen S, Färkkilä M. · The King's Headache Services, King's College Hospital, London, UK. · CNS Drugs. · Pubmed #12921494 No free full text.

Abstract: OBJECTIVES: To primarily assess the tolerability of zolmitriptan (Zomig) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). METHODS: This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1,093 patients aged 18-65 years with an established diagnosis of migraine with or without aura received intranasal zolmitriptan 5, 2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres.Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. RESULTS: Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1,093 patients who treated 13,806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with zolmitriptan nasal spray 5mg as good or excellent. CONCLUSION: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of zolmitriptan.

Charlesworth BR, Dowson AJ, Purdy A, Becker WJ, Boes-Hansen S, Färkkilä M. · AstraZeneca, Macclesfield, England. · CNS Drugs. · Pubmed #12828501 No free full text.

Abstract: OBJECTIVE: Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of zolmitriptan administered via a nasal spray with placebo and zolmitriptan oral tablet in the acute treatment of migraine. PATIENTS AND STUDY DESIGN: This was a randomised, double-blind, double-dummy, placebo-controlled, parallel-group, multicentre, dose-ranging study. 1547 patients aged 18-65 years with an established diagnosis of migraine with or without aura (as defined by International Headache Society criteria) who had at least a 1-year history of migraine and an age of onset <50 years were included. Patients were able to distinguish typical migraine from nonmigraine headaches and had experienced an average of one to six migraine headaches per month during the 2 months preceding the study. Patients were randomised to zolmitriptan (Zomig) The use of tradenames is for product identification purposes only and does not imply endorsement.) nasal spray (5.0, 2.5, 1.0 or 0.5 mg), zolmitriptan oral tablet (2.5mg) or placebo for the treatment of three moderate or severe migraine attacks. The primary outcome measure was headache response at 2 hours following treatment, defined as reduced intensity of migraine pain (using a scale of none, mild, moderate or severe) from severe or moderate at baseline to mild or no pain at 2 hours after treatment. Secondary outcome measures included early headache response at 15, 30 and 45 minutes and headache response at 1 and 4 hours postdose, as well as pain-free rates at 15, 30 and 45 minutes and 1, 2 and 4 hours postdose. Laboratory assessments, vital signs, 12-lead ECGs and nose and throat examinations were performed at screening and follow-up visits. Adverse events were recorded throughout the study using Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) terminology. RESULTS: Each dose of zolmitriptan nasal spray produced a greater 2-hour headache response rate than placebo (70.3%, 58.6%, 54.8% and 41.5% for zolmitriptan nasal spray 5.0, 2.5, 1.0 and 0.5mg, compared with 30.6% for placebo [all p < 0.001 vs placebo]). The 2-hour headache response rate for zolmitriptan nasal spray 5.0mg was significantly higher than that of the zolmitriptan 2.5mg oral tablet (61.3%; p < 0.05), while comparisons of nasal spray 0.5, 1.0 and 2.5mg with zolmitriptan 2.5mg oral tablet were not statistically significant. The nasal spray 5.0 and 2.5mg showed a rapid onset of action, with a significant difference in headache response compared with placebo from 15 minutes through 4 hours after administration and a significant difference between the nasal spray 5.0mg and 2.5mg oral tablet from 15 minutes through to 2 hours (the other nasal spray doses were not statistically significant compared with 2.5mg oral tablet). Zolmitriptan nasal spray resulted in pain-free rates that were dose dependent. While all doses from 1.0 mg upwards produced significant pain-free outcomes from 30 minutes versus placebo, only the 5.0mg dose produced pain-free rates significantly superior to both placebo and the 2.5mg oral tablet. Zolmitriptan nasal spray was well tolerated, with the most common adverse events being unusual taste and paresthesia. The majority of adverse events were of short duration and mild or moderate intensity. Only ten patients were withdrawn from the trial because of adverse events. Serious adverse events were reported by nine patients after taking study medication, but none was considered to be causally related to study medication. Zolmitriptan was not associated with any clinically significant changes in laboratory test values or vital signs. CONCLUSION: All doses of zolmitriptan nasal spray produced significant 2-hour headache response rates compared with placebo. The 5.0 and 2.5mg doses were also significantly more effective than placebo for the majority of secondary efficacy measures. Zolmitriptan nasal spray 5.0mg provided a headache response statistically superior to both placebo and the 2.5mg tablet as early as 15 minutes after administration, while demonstrating pain-free outcomes significantly superior to placebo and the 2.5mg tablet as early as 30 minutes after administration. All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.

Dowson AJ, Massiou H, Laínez JM, Cabarrocas X. · Kings Headache Service, Kings College Hospital, Denmark Hill, London SE5 9RS, UK. · Cephalalgia. · Pubmed #12133045 No free full text.

Abstract: 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.

Dowson AJ, MacGregor EA, Purdy RA, Becker WJ, Green J, Levy SL. · The Kings Headache Services, Kings College Hospital, London, UK. · Cephalalgia. · Pubmed #11972576 No free full text.

Abstract: 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.