Percutaneous closure of patent foramen ovale in migraine with aura, a randomized controlled trial.

AIMS: Migraine with aura and patent foramen ovale (PFO) are associated. The Percutaneous Closure of PFO in Migraine with Aura (PRIMA) trial is a multicentre, randomized trial to investigate the effect of percutaneous PFO closure in patients refractory to medical treatment. METHODS: Migraine with aura patients and PFO who were unresponsive to preventive medications were randomized to PFO closure or medical treatment. Both groups were given acetylsalicylic acid 75-100 mg/day for 6 months and clopidogrel 75 mg/day for 3 months. The primary endpoint was reduction in monthly migraine days during months 9-12 after randomization compared with a 3-month baseline phase before randomization. The committee reviewing the headache diaries were blinded to treatment assignment. RESULTS: One hundred and seven patients were randomly allocated to treatment with an Amplatzer PFO Occluder (N = 53) or control with medical management (N = 54). The trial was terminated prematurely because of slow enrolment. Eighty-three patients (40 occluder, 43 control) completed 12-month follow-up. Mean migraine days at baseline were 8 (±4.7 SD) in the closure group and 8.3 (±2.4) in controls. The primary endpoint was negative with -2.9 days after PFO closure vs. -1.7 days in control group (P = 0.17). Patent foramen ovale closure caused five adverse events without permanent sequelae. CONCLUSION: In patients with refractory migraine with aura and PFO, PFO closure did not reduce overall monthly migraine days.

Canadian Headache Society Guideline: acute drug therapy for migraine headache.

OBJECTIVES: The primary objective of this guideline is to assist the practitioner in choosing an appropriate acute medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. It is focused on patients with episodic migraine ( headache on ≤ 14 days a month). METHODS: A detailed search strategy was used to find a relevant meta-analyses, systematic reviews and randomized double-blind controlled trials. Recommendations were graded with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group. In addition, a general literature review and expert consensus were used for aspects of acute therapy for which randomized controlled trials were not available. RESULTS: Twelve acute medications received a strong recommendation for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zomitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four received a weak recommendation for use (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol- containing medications). Three of these were NOT recommended for routine use (ergotamine and codeine- and tramadol- containing medications). Strong recommendations were made to avoid use of butorphanol and butalbital- containing medications. Metoclopramide and domperidone were strongly recommended for use when necessary. Our analysis also resulted in the formulation of eight general acute migraine management strategies. These were grouped into: 1) two mild-moderate attack strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three refractory migraine strategies, and 4) a vasoconstrictor unresponsive-contraindicated strategy. Additional were developed for menstrual migraine during pregnancy, and migraine during lactation. CONCLUSION: This guideline provides evidence-based advice on acute pharmacological migraine therapy, and should be helpful to both health professionals and patients, The available medications have been organized into a series of strategies based on patient clinical features. These strategies may help practitioners make appropriate acute medication choices for patients with migraine.

Botulinum toxin type A and acute drug costs in migraine with triptan overuse.

BACKGROUND: Patients with chronic migraine and medication overuse are significant consumers of health care resources. OBJECTIVE: To determine whether botulinum toxin type A prophylaxis reduces the cost of acute migraine medications in patients with chronic migraine and triptan overuse. METHODS: In this multicenter, open-label study, patients with chronic migraine (≥ 15 headache days/month) who were triptan overusers (triptan intake ≥ 10 days/month for ≥ 3 months) received botulinum toxin type A (95-130 U) at baseline and month three. Headache (HA) frequency and medication use were assessed with patient diaries, and headache-related disability by means of the MIDAS and Headache Impact Test-6 questionnaires. RESULTS: Of 53 patients enrolled (mean age ± standard deviation, 46.5 years ± 8.4; 47 [88.7%] females), 48 (90.6%) completed the study at month six. Based on headache diaries, significant (P ≤ 0.0002) decreases from baseline were observed for days per month with headache/migraine, days with any acute headache medication use, days with triptan use, and triptan doses taken per month. A significant (P < 0.0001) increase from baseline in headache-free days per month was also observed. Prescription medication costs for acute headache medications decreased significantly, including significant reductions in triptan costs (mean reduction of -C$106.32 ± 122.87/month during botulinum toxin type A prophylaxis; P < 0.0001). At baseline, 78% of patients had severe disability (MIDAS score) and 86.8% had severe impact due to headache (HIT-6 scores); at month six, this decreased to 60% and 68%, respectively. CONCLUSIONS: Botulinum toxin type A prophylactic therapy markedly decreased costs related to acute headache medication use in patients with chronic migraine and triptan overuse.

HIT-6 and MIDAS as measures of headache disability in a headache referral population.

OBJECTIVE: The objective of this study was to compare the headache impact test (HIT-6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache-related disability. BACKGROUND: The degree of headache-related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. METHODS: We compared HIT-6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT-6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI-II) scores. RESULTS: A positive correlation was found between HIT-6 and MIDAS scores (r = 0.52). The BDI-II scores correlated equally with the HIT-6 and the MIDAS (r = 0.42). There was a non-monotonic relationship between headache frequency and the MIDAS, and a non-linear monotonic relationship between headache frequency and the HIT-6 (r = 0.24). The correlation was higher between the intensity and the HIT-6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy-nine percent of patients fell into the most severe HIT-6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT-6 than with the MIDAS (McNemar chi-square = 191 on 6 d.f., P < .0001). CONCLUSIONS: The HIT-6 and MIDAS appear to measure headache-related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT-6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT-6 and MIDAS together may give a more accurate assessment of a patient's headache-related disability.

Are statin medications safe in patients with ALS?

Statin medications for elevated cholesterol are one of the most commonly prescribed medications worldwide. The aim of this study was to determine if statin medications affect the rate of disease progression, the severity and frequency of muscle cramping, and serum CK levels in patients with ALS. We conducted a prospective cohort study in patients diagnosed with ALS with statin medication as the predetermined exposure variable and the rate of decline of the ALS Functional Rating Scale-Revised (ALSFRS-R) as the primary outcome. One hundred and sixty-four consecutive patients with laboratory supported probable, clinically probable, or clinically definite ALS were evaluated from January 2006 to September 2007. Thirty-two patients (20%) were taking statin medications and 132 were in the control group. After adjusting for covariates, we found a highly significant increase in the rate of decline in the ALSFRS-R for the statin group (1.71 units/month) compared to the control group (1.05 units/month, pB0.0001) representing a 63% increase in the rate of functional decline. Patients on statin therapy also reported a significant increase in muscle cramp frequency and severity (pB0.0001). This study has demonstrated a strong association between statin medications and an increased rate of functional decline and muscle cramping in patients with ALS. Although this association does not prove a causal relationship, it is prudent to exercise caution and discuss discontinuation or replacement of statin medications in patients with ALS.

Migraine treatment.

The goal of the Canadian Migraine Forum was to work towards improving the lives of Canadians with migraine by reducing their migraine-related disability. This paper focuses on migraine treatment in its many aspects, including symptomatic therapy of individual migraine headache attacks, prophylactic drug therapy, non-pharmacological interventions, and diagnosis and management of symptomatic medication overuse. Many patients with difficult migraine experience significant frustration in trying to obtain the help they need from our current medical system. Although many symptomatic medications are available for use in migraine, migraine specific medications are still underutilized. An ideal migraine preventative medication does not yet exist, but currently available preventatives do have utility, and are also thought to be underutilized. Behavioral approaches to migraine management as an adjunct to medication therapy show promise, but the availability of programs to bring these to patients is limited, and more research is needed on their efficacy. Symptomatic medication overuse in migraine sufferers remains a large problem in Canada, and better defined treatment paradigms and programs are needed both to prevent and to treat this problem. Such programs should include strong elements of public, patient, and health professional education. A potential solution to some of these problems may be to develop treatment approaches to migraine similar to those that are being developed for other chronic medical disorders. For patients with severe migraine, these would optimally include multidisciplinary teams so that the multiple facets of migraine management can be adequately addressed.

Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study.

OBJECTIVE: This exploratory trial evaluated the safety and efficacy of multiple treatments of botulinum toxin type A (BoNTA; BOTOX, Allergan, Inc., Irvine, CA, USA) as prophylactic treatment of episodic migraine headaches. DESIGN AND METHODS: This was an 11-month randomized, double-blind, placebo-controlled, exploratory study. Patients were screened during a 30-day baseline period, and eligible patients with 4 or more migraine episodes and < or =15 headache days entered a single-blind 30-day placebo run-in period. Patients were classified as placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine episodes and did not experience at least a 50% decrease from baseline in the frequency of migraine episodes following their placebo treatment. All other subjects were classified as placebo responders (PR). Patients were randomized within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA per treatment cycle) or placebo at 90-day intervals using a modified follow-the-pain treatment paradigm. The primary efficacy outcome measure was the mean change from baseline in the frequency of migraine episodes for the 30 days prior to day 180 in the PNR group. Secondary efficacy measures included the proportion of patients with a decrease from baseline of 50% or more migraine episodes per 30-day period. Patients were allowed to take concomitant acute and prophylactic headache medications. Adverse events were reported. RESULTS: A total of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years; range, 20 to 65 years) entered the placebo run-in period and were subsequently randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met. Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were observed (P > .999). From day 180 through the end of the study (day 270) at least 50% of all patients in each treatment group had a decrease from baseline of 50% or more migraine episodes per 30-day period. However, in the group of patients with > or =12 headache days at baseline (and < or =15 headache days), BoNTA patients experienced a mean change from baseline of -4.0 headache episodes at day 180 compared with -1.9 headache episodes in the placebo group (P= .048). The majority of treatment-related adverse events were transient and mild to moderate in severity. Only 7 patients (1.9%) discontinued the study due to adverse events (6 BoNTA, 1 placebo). CONCLUSION: There were no statistically significant between-group differences in the mean change from baseline in the frequency of migraine episodes per 30-day period. There were substantial, sustained improvements during the course of the study in all groups. Multiple treatments with BoNTA were shown to be safe and well tolerated over an active treatment period lasting 9 months.

A clinical study of migraine evolution.

BACKGROUND: The buildup time of migraine headaches has not been well delineated in publications to date and we are aware of patients whose migraines last well over 72 hours. More concentration on these factors in the assessment of patients might lead to more appropriate therapeutic choices. METHOD: Prospective ascertainment of such data through a questionnaire completed by 253 informed and willing patients with IHS migraine with or without aura consulting Canadian headache specialists. Data were electronically sent to a central computer from each center, tabulated and analyzed using standard statistical parameters. RESULTS: In 253 patients with migraine ascertained using applied IHS criteria, nausea was a feature in over 90% of cases, especially in those with aura. This inhibited the ingestion of oral medications in about a quarter of all subjects. The time to build from no pain to moderate/severe pain was shorter in subjects with auras and was less than 2 hours in 97% of those with and 86% of those without auras. However, we also identified a group of subjects with migraine (over 10% of all) in whom the build time to maximum pain is delayed for over 2 hours. Nausea was experienced by 91.7% of subjects, slightly but significantly later in those without auras. While most headaches in each group lasted from 4 to 72 hours, 24.3% of those with and 20.6% of those without aura expected to experience pain for more than 72 hours, while in untreated cases disability due to pain, nausea, or malaise usually persisted for over 3 days in 24.3% and 16.7% of those with and without aura, respectively. One-fifth of migraineurs may be in pain and/or disabled by accompanying symptoms for over 3 days in a typical migraine attack. Over half of our subjects reported that their medications worked well or excellently. CONCLUSIONS: Attacks of migraine in real-life clinical situations vary somewhat from the IHS criteria in that they are more often associated with nausea that interferes with oral therapy; can persist for over 72 hours; may have slow (>2 hours) buildup to maximum pain in 10% of cases; and may cause disability for over 3 days. Nevertheless, current therapeutic regimens (including prescribed medications) work well for a substantial majority.

Demographics and clinical features of patients referred to headache specialists.

OBJECTIVE: To examine demographic characteristics and clinical features of headache patients referred to neurologists specializing in headache in Canada. METHODS: Demographic and clinical data were collected at the time of consultation for 865 new headache patients referred to five headache-specialty clinics in Canada. The Headache Impact Test (HIT-6) and Migraine Disability Questionnaire (MIDAS) were used to measure headache impact and disability. Data were analyzed as part of the Canadian Headache Outpatient Registry and Database (CHORD) Project. RESULTS: The average age of the patients was 40 years and the majority were female (78%). Most were employed either full time (49%) or part time (13%). The majority of patients were diagnosed with either migraine or tension-type headache (78%). Over a third of patients experienced headache every day, and half had experienced a headache in the previous month which was of severe intensity. Most (80%) scored in the "very severe" category of the HIT-6 and over half (55%) were severely disabled as measured by the MIDAS. CONCLUSION: Patients referred to headache specialists in Canada are severely disabled by their headache disorders. These patients are in the most productive phase of their lives in terms of age and employment. It is important to provide the best available treatment to headache patients in order to minimize the disability and impact of their headache disorders.

Treatment satisfaction with zolmitriptan nasal spray for migraine in a real life setting: results from phase two of the REALIZE study.

In phase one of the REALIZE study, zolmitriptan nasal spray demonstrated a significant headache response from 10 min post-dose and total symptom relief from 30 min post-dose. The objective of phase two was to investigate patients' dosing patterns, satisfaction and preference following open-label treatment with the nasal spray. Up to 3 attacks were treated. The ITT population consisted of 851 patients. The median time from onset of symptoms to treatment was 1 h 15 min (primary endpoint). Most patients reported being satisfied or very satisfied with zolmitriptan nasal spray (75.7%). Furthermore, the majority of patients would be willing to use zolmitriptan nasal spray in the future (59.8%) and preferred zolmitriptan nasal spray over previous therapies (57.8%). Zolmitriptan nasal spray was well tolerated. Most patients were satisfied with zolmitriptan nasal spray, were willing to continue using it and preferred it to previous therapies.

An economic evaluation of rizatriptan in the treatment of migraine.

BACKGROUND: Migraine is a common, chronic, neurovascular disorder, generally characterised by attacks of severe headache and autonomic nervous system dysfunction. Triptans are selective serotonin 5-HT(1B/1D) receptor agonists that represent effective therapeutic options for moderate-to-severe migraine attacks but with higher acquisition costs relative to usual care therapies. OBJECTIVE: The objective of this study was to examine the cost effectiveness of rizatriptan treatment compared with 'Usual Care' or other triptans available in Canada for patients with moderate-to-severe migraine for whom other therapies (e.g. NSAIDs, simple analgesics) are insufficient or contraindicated. METHODS: A decision-analysis model was created to estimate migraine treatment costs over a 24-hour period in patients with a diagnosis of moderate-to-severe migraine as defined by the International Headache Society criteria. Costs and clinical outcomes were observed over a 24-hour period from therapy initiation. Efficacy measures consisted of 'pain-free response at 2 hours' and 'sustained pain free for 2-24 hours'. Oral rizatriptan 10 mg was compared with other oral triptans (i.e. sumatriptan 50 or 100 mg), naratriptan 2.5 mg and zolmitriptan 2.5 mg, based on a meta-analysis and compared with 'Usual Care' based on a naturalistic study of people who experience migraine and who were similar to the target population. 'Usual Care' was defined as an aggregate of medications prescribed for the Canadian population for the indication of migraine, weighted by the relative frequency of use of prescriptions over a 1-year period. Analyses were conducted from the Ontario (Canada) Ministry of Health and Long-Term Care (MOH

Intranasal zolmitriptan.

Intranasal zolmitriptan has recently been launched in the US and Canada and is a novel formulation of the antimigraine drug zolmitriptan. This drug has been used extensively in its oral formulation. The intranasal formulation offers a more rapid onset of action. Pharmacokinetic studies have demonstrated that it is absorbed rapidly into the systemic circulation and traces can be seen in the brain within 5 min. The onset of efficacy in the Real Life Intranasal Zolmitriptan Exposure (REALIZE) study was measurable at 10 min and at 15 min in the US 22 study, which demonstrates rapid absorption and effect at the 5-HT(1B/1D) receptors. This article reviews the initial studies of intranasal zolmitriptan; three of the most recent studies will be examined in detail.

Botulinum toxin type A (BOTOX) for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The objective of this study was to evaluate the safety and efficacy of botulinum toxin type A (BoNT-A; BOTOX, Allergan, Inc.) for the prophylactic treatment of chronic daily headache (CDH). BACKGROUND: Several open-label and small controlled trials suggest that BoNT-A may be effective in the prophylactic treatment of headache. DESIGN AND METHODS: This was an 11-month, randomized double-blind, placebo-controlled study of BoNT-A for the treatment of patients aged 18 to 65 years old with 16 or more headache days per 30 days conducted at 13 North American study centers. Following a 30-day screening period and a 30-day, single-blind, placebo-response period to identify placebo responders, eligible patients from both the placebo responder and placebo nonresponder groups were injected with BoNT-A or placebo every 90 days and assessed every 30 days for 9 months, a period encompassing three treatment cycles. The primary efficacy measure was the change from baseline in the frequency of headache-free days in a 30-day period for the placebo nonresponder group at day 180, the chosen efficacy time point. The secondary efficacy measure was the proportion of patients with a decrease from baseline of 50% or more in the frequency of headache days per 30-day period for the placebo nonresponder group at day 180. The change from baseline in the frequency of headaches (per 30-day period), the proportion of patients with a decrease from baseline of 50% or greater in the frequency of headaches per 30-day period, acute medication use, and adverse events were also assessed. RESULTS: Of 571 patients assessed over the baseline period, 355 (mean age, 43.5 years; 300/355 [84.5%] female) were enrolled and randomized. At the end of the placebo run-in period, 279 patients (79%) were classified as placebo nonresponders and 76 patients (21%) as placebo responders. Subsequently, patients were randomized within each group to receive either BoNT-A or placebo. In the placebo nonresponder stratum, the mean number of headache-free days at baseline was 5.8 (+/-4.7) for BoNT-A- versus 5.5 (+/-4.7) for placebo-treated patients. At day 180, placebo nonresponders treated with BoNT-A had an improved mean change from baseline of 6.7 headache-free days per 30-day period compared to a mean change from baseline of 5.2 headache-free days for placebo-treated patients. The between-group difference of 1.5 headache-free days favored BoNT-A treatment, although the difference between the groups was not statistically significant. However, a statistically significant difference was observed at day 180 endpoint for the secondary efficacy measure. A significantly higher percentage of BoNT-A patients had a decrease from baseline of 50% or greater in the frequency of headache days per 30-day period at day 180 (32.7% vs. 15.0%, P=.027). Also, the mean change from baseline in the frequency of headaches per 30-day period at day 180 was -6.1 for BoNT-A patients vs. -3.1 for the placebo patients (P=.013). Only 4 of 173 BoNT-A patients (2.3%) discontinued the study due to adverse events. The majority of treatment-related adverse events were transient and mild to moderate in severity. CONCLUSIONS: BoNT-A treatment resulted in patients having, on average, approximately seven more (1 week) headache-free days compared to baseline. Although at the primary time point (day 180) the BoNT-A treatment resulted in a 1.5 between-group difference compared to placebo, this difference was not statistically significant. The treatment met secondary efficacy outcome measures, including the percentage of patients experiencing a 50% or more decrease in the frequency of headache days, in addition to statistically significant reductions in headache frequency. BoNT-A was also well tolerated in patients with CDH.

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study.

OBJECTIVES: The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. BACKGROUND: Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. METHODS: In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. RESULTS: The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. CONCLUSIONS: These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.

Zolmitriptan nasal spray exhibits good long-term safety and tolerability in migraine: results of the INDEX trial.

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.

Newer formulations of the triptans: advances in migraine management.

Migraine is a common, frequently incapacitating, headache disorder that imposes a substantial burden on both the individual patient and society. The last two decades have witnessed an explosion in our understanding of the pathophysiology of migraine, and in our development of an efficacious and diverse therapeutic armamentarium. There are several routes of drug administration available to patients with migraine. All the serotonin 5-HT(1B/1D) receptor agonists (triptans) are available as oral tablets (sumatriptan, rizatriptan, zolmitriptan, naratriptan, almotriptan, frovatriptan and eletriptan). Only sumatriptan is available as a subcutaneous injection. Some triptans are also available via newer routes of administration, including orally disintegrating tablets (rizatriptan and zolmitriptan), rectal suppositories (sumatriptan) and intranasal sprays (sumatriptan and zolmitriptan). Oral disintegrating tablets and other non-oral triptan routes (subcutaneous, intranasal, rectal) are a useful alternative to conventional oral tablets for patients who have difficulty swallowing pills or prefer not to do so, and for patients whose nausea and/or vomiting precludes swallowing tablets and/or makes the likelihood of complete absorption unpredictable. This is important because epidemiological studies in migraine reveal that the vast majority of patients (>90%) have experienced nausea during a migraine attack and more than 50% have nausea with the majority of attacks. Similarly, most (almost 70%) have vomited at some time during an attack and of these patients, almost one-third vomit in the majority of attacks. The newer formulations, rapidly dissolving tablets and intranasal sprays, afford patients the opportunity to use abortive therapy without the need for liquids, at anytime and anywhere, at the onset of a migraine attack. Furthermore, the intranasal sprays are absorbed rapidly and have a prompt onset of action allowing for significant pain free rates versus placebo as early as 15 minutes post administration. The ability to administer treatment early in a migraine attack and have a rapid onset of action is particularly important in acute migraine treatment in order to prevent the development of central sensitisation. While many patients and physicians choose conventional oral tablets because of familiarity and ease of administration, the newer formulations, oral disintegrating tablets and intranasal sprays, should be given consideration as first-line agents in selected patients.

A headache diagnosis project.

BACKGROUND: Despite the availability of objective criteria, the diagnosis of migraine is thought to be missed frequently in primary practice. OBJECTIVE: To determine the most important questions assisting in the clinical diagnosis of migraine headache. METHODS: A cohort of 461 patients referred to headache specialists in Canada was assessed using a pro-forma questionnaire that was completed by the patients alone or administered by the physicians themselves. A final clinical diagnosis was recorded after a complete clinical evaluation. In a subsequent validation study, three questions derived from the results of the first phase of the study were administered to a new cohort of 128 patients, and diagnoses of "migraine" or "not migraine" were recorded according to the decision generated in the first part of the study. The final clinical diagnosis was taken as the "gold standard" for diagnosis, and the results from the two independently derived diagnostic methods were compared. RESULTS: Statistical analysis of the responses from part 1 of the study yielded three questions (related to daily occurrence, unilaterally, and functional impairment) that distinguished between pure migraine and other headache diagnoses with high reliability and validity. The sensitivity and selectivity of the three-question protocol exceeded 91%. CONCLUSIONS: The use of three questions related to headache frequency, laterality, and impact on functioning may represent an attractive screening instrument in primary care practice, alerting physicians to the diagnosis of migraine in patients or to the possibility of a second or alternative headache diagnosis in patients in whom their diagnosis of migraine previously has been made. The presence of multiple headache syndromes in individual patients, as is common in tertiary referral practice, may reduce the discriminating power of the three-question protocol.

Triptans: are they all the same?

The triptans have provided a major advance in the treatment of the pain and disability associated with migraine headache. With seven triptans in use or in clinical development, the clinician is faced with the decision of which triptan to prescribe to the patient with migraine. Although the triptans are pharmacologically similar, they each have unique attributes. This article focuses on the pharmacologic differences between triptans with regard to their pharmacokinetics and drug interactions, and provides some helpful tips on how to optimize migraine treatment with the triptans.