OnabotulinumtoxinA Reduces Health Resource Utilization in Chronic Migraine: PREDICT Study.

BACKGROUND: PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use. METHODS: OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study. RESULTS: A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

Current state of headache training within Canadian Neurology Residency program: a national survey.

BACKGROUND: Headache disorders are the most common neurological disorders worldwide. Despite their widespread prevalence and importance, the topic of headache is inconsistently taught at both the undergraduate and postgraduate levels. The goal of this study is to establish a better picture of the current state of Headache Medicine (HM) training in Neurology postgraduate programs in Canada and describe the impact of the current pandemic on training in this domain. METHODS: Online surveys were sent to senior residents of adult Neurology programs in Canada. We also conducted telephone interviews with Neurology Program Directors. Descriptive statistics were analyzed, and thematic analysis was used to review free text. RESULTS: A total of 36 residents, and 3 Program Directors participated in the study. Most of the teaching in HM is done by headache specialists and general neurology faculty. Formal teaching is mainly given during academic half day. Most of the programs expose their residents to Onabotulinum toxin A injections and peripheral nerve blocks, but they don't offer much formal teaching regarding these procedures. Residents consider HM teaching important and they would like to have more. They don't feel comfortable performing interventional headache treatments, despite feeling this should be part of the skillset of a general neurologist. CONCLUSION: Our study is the first to establish the current state of headache teaching in post-graduate neurology programs as perceived by trainees and program directors in Canada. The current educational offerings leave residents feeling poorly prepared to manage headaches, including procedural interventions. There is a need to diversify the source of teaching, so the educational burden doesn't lie mostly upon Headache specialists who are already in short supply. Neurology Residency programs need to adapt their curriculum to face the current need in HM.

Network meta-analysis of therapies for cluster headache: Effects of acute therapies for episodic and chronic cluster.

OBJECTIVE: We used network meta-analysis (NMA) to characterize the relative effectiveness and harms of acute treatment options for cluster headache. BACKGROUND: There are few evidence-based acute treatments available for cluster headache. As most treatments were compared only against placebos in clinical trials, few head-to-head comparisons of treatments are available. METHODS: An a priori registered scoping review was performed to identify randomized controlled trials evaluating treatments in adult patients (>18 years old) with cluster headache per accepted diagnostic criteria. Bayesian NMAs were performed to compare treatments in terms of headache relief at 15 or 30 min, and also the occurrence of adverse events. We report odds ratios (ORs) of relative treatment effects along with corresponding 95% credible intervals (CrIs), as well as measures of treatment ranking. RESULTS: A total of 13 randomized controlled trials informed NMAs. We found high flow oxygen to be the most effective therapy for headache response at 15 and 30 min (OR 9.0, 95% CrI 5.3 to 15.9 vs. placebo), with injectable sumatriptan demonstrating the next highest effect (OR 6.4, 95% CrI 3.75 to 11.1 vs. placebo). High flow oxygen was also more effective than low flow oxygen (OR 2.55, 95% CrI 1.13 to 5.8), nasal spray zolmitriptan (OR 3.75, 95% CrI 1.72 to 8.4), octreotide (OR 4.5, 95% CrI 1.64 to 12.5), and non-invasive vagal nerve stimulation (nVNS; OR 5.2, 95% CrI 2.29 to 11.9). Sumatriptan injectable was also effective for headache relief and was found to be better than nasal spray zolmitriptan (OR 2.67, 95% CrI 1.21 to 5.9), octreotide (OR 3.20, 95% CrI 1.17 to 8.8), and nVNS (OR 3.69, 95% CrI 1.63 to 8.4). Octreotide (OR 4.1, 95% CrI 1.71 to 10.5) and sumatriptan (OR 2.40, 95% CrI 1.39 to 4.2) were associated with greater risk of adverse events compared to placebo, while other treatments did not demonstrate increased risk. When focusing on patients with episodic cluster headache, nVNS was significantly better than placebo (OR 4.9, 95% CrI 1.89 to 14.1). CONCLUSIONS: Our findings suggest that high flow oxygen is more efficacious when compared to low flow oxygen for headache relief. When low flow oxygen fails in patients who can tolerate oxygen, increased flow rates should be tried. Additionally, high flow oxygen is likely more effective than zolmitriptan nasal spray, nVNS, and octreotide. Sumatriptan injectable is more likely to be effective when compared to zolmitriptan nasal spray, octreotide, and nVNS.

Effects of acute and preventive therapies for episodic and chronic cluster headache: A scoping review of the literature.

BACKGROUND: Cluster headache is the most common primary headache disorder of the trigeminal autonomic cephalalgias, and it is highly disabling. OBJECTIVE: We undertake a scoping review to characterize therapies to prevent and acutely treat cluster headache, characterize trial methodology utilized in studies, and recommend future trial "good practices." We also assess homogeneity of studies and feasibility for future network meta-analyses (NMAs) to compare acute and preventive treatments for cluster headache. METHODS: A priori protocol for this scoping review was registered and available on Open Science Forum. We sought studies that enrolled adult patients with cluster headache as identified by accepted diagnostic criteria. Both randomized controlled trials (RCTs) and observational studies (with a control group) were included. The interventions of interest were medications, procedures, devices, surgeries, and behavioral/psychological interventions, whereas comparators of interest were placebo, sham, or other active treatments. Outcomes were predefined; however, we did not exclude studies lacking these outcomes. A systemic search was conducted in Ovid Medline, Embase, and Cochrane. We performed a targeted search for conference abstracts from journals prominent in the field. RESULTS: We identified 56 studies: 45 RCTs, four studies only available in clinical trial registries, and seven observational studies. Of the 45 RCTs, 20 focused on acute therapies and 25 on preventive therapies. Overall, we determined that it is feasible to pursue a NMA for acute therapy focusing on 15 or 30-min headache reduction for acute trials, as we identified 11 trials in the combined population of patients with either episodic or chronic cluster headache (2 trials in populations with chronic cluster headache were also found). For preventive therapy of cluster headache, we identified trials with common outcomes that may be considered for NMA, however, as these trials had differences in treatment effect modifiers that could not be corrected, NMAs appear infeasible for this indication. We identified new studies looking at noninvasive vagal nerve stimulation, sphenopalatine ganglion stimulation, prednisone, and oxygen published since the most recent systematic review in the field, although these acute treatments were previously identified as effective. However, for calcitonin gene-related peptide (CGRP) monoclonal antibodies, galcanezumab demonstrated effectiveness in episodic cluster headache, but a lack of effectiveness in chronic cluster headache, and fremanezumab was not effective for episodic nor chronic cluster headache. This finding highlights that CGRP monoclonal antibodies may not show a class effect in cluster headache prevention and need to be considered individually. CONCLUSIONS: We describe the treatment landscape of cluster headache for both acute and preventive treatments. Last, we present the NMAs we will undertake in acute therapies of cluster headache.

A real-world, observational study of erenumab for migraine prevention in Canadian patients.

OBJECTIVES: To assess real-world effectiveness, safety, and usage of erenumab in Canadian patients with episodic and chronic migraine with prior ineffective prophylactic treatments. BACKGROUND: In randomized controlled trials, erenumab demonstrated efficacy for migraine prevention in patients with ≤4 prior ineffective prophylactic migraine therapies. The "Migraine prevention with AimoviG: Informative Canadian real-world study" (MAGIC) assessed real-world effectiveness of erenumab in Canadian patients with migraine. METHODS: MAGIC was a prospective open-label, observational study conducted in Canadian patients with chronic migraine (CM) and episodic migraine (EM) with two to six categories of prior ineffective prophylactic therapies. Participants were administered 70 mg or 140 mg erenumab monthly based on physician's assessment. Migraine attacks were self-assessed using an electronic diary and patient-reported outcome questionnaires. The primary outcome was the proportion of subjects achieving ≥50% reduction in monthly migraine days (MMD) after the 3-month treatment period. RESULTS: Among the 95 participants who mostly experienced two (54.7%) or three (32.6%) prior categories of ineffective prophylactic therapies and who initiated erenumab, treatment was generally safe and well tolerated; 89/95 (93.7%) participants initiated treatment with 140 mg erenumab. At week 12, 32/95 (33.7%) participants including 17/64 (26.6%) CM and 15/32 (48.4%) EM achieved ≥50% reduction in MMD while 30/86 (34.9%) participants including 19/55 (34.5%) CM and 11/31 (35.5%) EM achieved ≥50% reduction in MMD at week 24. Through patient-reported outcome questionnaires, 62/95 (65.3%) and 45/86 (52.3%) participants reported improvement of their condition at weeks 12 and 24, respectively. Physicians observed improvement in the condition of 78/95 (82.1%) and 67/86 (77.9%) participants at weeks 12 and 24, respectively. CONCLUSION: One-third of patients with EM and CM achieved ≥50% MMD reduction after 3 months of erenumab treatment. This study provides real-world evidence of erenumab effectiveness, safety, and usage for migraine prevention in adult Canadian patients with multiple prior ineffective prophylactic treatments.

OnabotulinumtoxinA Improves Quality of Life in Chronic Migraine: The PREDICT Study.

BACKGROUND: The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA. METHODS: Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days. RESULTS: 184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: -3.5 [6.3]; Tx4: -6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

The Non-Inferiority Margins in Migraine Research (NIMM) Survey.

OBJECTIVES: To survey experts in Headache Medicine on their opinions regarding appropriate non-inferiority margins for outcomes commonly used in migraine research. METHODS: Members of the American Headache Society and the Canadian Headache Society were invited to participate in the Non-Inferiority Margins in Migraine Research (NIMM) survey. Adult and child neurologists with expertise in Headache Medicine were eligible to participate. The survey had a multiple choice format and comprised questions on respondent characteristics, eligibility, as well as expert opinion on non-inferiority margins for outcomes commonly used in trials of both prophylactic and acute interventions for migraine. RESULTS: Ninety-nine eligible respondents completed the survey. Most respondents were adult neurologists (84.9%) and 74% reported practicing in the USA. The following were the most commonly selected non-inferiority margins: (1) change in monthly migraine attacks comparing baseline to the treatment period: 1 attack (39.4% selecting), (2) change in monthly migraine days comparing baseline to the treatment period: 1 day (44.4%), (3) change in average migraine intensity on a 4-point scale comparing baseline to the treatment period: 1.0 (31.3%), (4) percentage of participants who are pain-free 2 hours after the intervention: 5% (41.4%), (5) percentage of participants who have a migraine recurrence within 48 hours of treatment: 5% (42.4%), and (6) percentage of participants with sustained pain freedom: 5% (42.4%). CONCLUSIONS: The results of the NIMM survey describe the opinions of a group of experts on appropriate non-inferiority margins for outcomes commonly used in migraine clinical trials. There was significant variability in responses and lack of consensus on the choice of non-inferiority margins. The survey did not incorporate the patient perspective and was not validated prior to distribution. Further work in this area is required in order to explore how to incorporate clinical considerations into the selection of non-inferiority margins for migraine research.

Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies.

OBJECTIVE: To provide evidence-based treatment recommendations for adults with acute migraine who require treatment with injectable medication in an emergency department (ED). We addressed two clinically relevant questions: (1) Which injectable medications should be considered first-line treatment for adults who present to an ED with acute migraine? (2) Do parenteral corticosteroids prevent recurrence of migraine in adults discharged from an ED? METHODS: The American Headache Society convened an expert panel of authors who defined a search strategy and then performed a search of Medline, Embase, the Cochrane database and clinical trial registries from inception through 2015. Identified articles were rated using the American Academy of Neurology's risk of bias tool. For each medication, the expert panel determined likelihood of efficacy. Recommendations were created accounting for efficacy, adverse events, availability of alternate therapies, and principles of medication action. RESULTS/CONCLUSIONS: The search identified 68 unique randomized controlled trials utilizing 28 injectable medications. Of these, 19 were rated class 1 (low risk of bias), 21 were rated class 2 (higher risk of bias), and 28 were rated class 3 (highest risk of bias). Metoclopramide, prochlorperazine, and sumatriptan each had multiple class 1 studies supporting acute efficacy, as did dexamethasone for prevention of headache recurrence. All other medications had lower levels of evidence. RECOMMENDATIONS: Intravenous metoclopramide and prochlorperazine, and subcutaneous sumatriptan should be offered to eligible adults who present to an ED with acute migraine (Should offer-Level B). Dexamethasone should be offered to these patients to prevent recurrence of headache (Should offer-Level B). Because of lack of evidence demonstrating efficacy and concern about sub-acute or long-term sequelae, injectable morphine and hydromorphone are best avoided as first-line therapy (May avoid-Level C).

Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings.

BACKGROUND: There is a considerable amount of practice variation in managing migraines in emergency settings, and evidence-based therapies are often not used first line. METHODS: A peer-reviewed search of databases (MEDLINE, Embase, CENTRAL) was carried out to identify randomized and quasi-randomized controlled trials of interventions for acute pain relief in adults presenting with migraine to emergency settings. Where possible, data were pooled into meta-analyses. RESULTS: Two independent reviewers screened 831 titles and abstracts for eligibility. Three independent reviewers subsequently evaluated 120 full text articles for inclusion, of which 44 were included. Individual studies were then assigned a US Preventive Services Task Force quality rating. The GRADE scheme was used to assign a level of evidence and recommendation strength for each intervention. INTERPRETATION: We strongly recommend the use of prochlorperazine based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a low level of evidence. We weakly recommend the use of chlorpromazine based on a moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine intranasal and meperidine, based on a low level of evidence. We found evidence to recommend strongly against the use of dexamethasone, based on a moderate level of evidence, and granisetron, haloperidol and trimethobenzamide based on a low level of evidence. Based on moderate-quality evidence, we recommend weakly against the use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we recommend weakly against the use of diclofenac, droperidol, lidocaine intravenous, lysine clonixinate, morphine, propofol, sodium valproate and tramadol.

Canadian Headache Society guideline for migraine prophylaxis.

OBJECTIVES: The primary objective of this guideline is to assist the practitioner in choosing an appropriate prophylactic medication for an individual with migraine, based on current evidence in the medical literature and expert consensus. This guideline is focused on patients with episodic migraine (headache on ≤ 14 days a month). METHODS: Through a comprehensive search strategy, randomized, double blind, controlled trials of drug treatments for migraine prophylaxis and relevant Cochrane reviews were identified. Studies were graded according to criteria developed by the US Preventive Services Task Force. Recommendations were graded according to the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. In addition, a general literature review and expert consensus were used for aspects of prophylactic therapy for which randomized controlled trials are not available. RESULTS: Prophylactic drug choice should be based on evidence for efficacy, side-effect profile, migraine clinical features, and co-existing disorders. Based on our review, 11 prophylactic drugs received a strong recommendation for use (topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan, butterbur, riboflavin, coenzyme Q10, and magnesium citrate) and 6 received a weak recommendation (divalproex sodium, flunarizine, pizotifen, venlafaxine, verapamil, and lisinopril). Quality of evidence for different medications varied from high to low. Prophylactic treatment strategies were developed to assist the practitioner in selecting a prophylactic drug for specific clinical situations. These strategies included: first time strategies for patients who have not had prophylaxis before (a beta-blocker and a tricyclic strategy), low side effect strategies (including both drug and herbal/vitamin/mineral strategies), a strategy for patients with high body mass index, strategies for patients with co-existent hypertension or with co-existent depression and /or anxiety, and additional monotherapy drug strategies for patients who have failed previous prophylactic trials. Further strategies included a refractory migraine strategy and strategies for prophylaxis during pregnancy and lactation. CONCLUSIONS: There is good evidence from randomized controlled trials for use of a number of different prophylactic medications in patients with migraine. Medication choice for an individual patient requires careful consideration of patient clinical features.

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.

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.

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.

Disability, Quality of Life, and Pain Coping in Pediatric Migraine: An Observational Study.

OBJECTIVES: The objective was to examine the relationship between disability, health-related quality of life (HrQoL), and pain coping in pediatric migraineurs. METHOD: Eighty-five patients with migraine were recruited from Pediatric Neurology clinics. Participants completed the Pediatric Migraine Disability Assessment Scale, the Pediatric Quality of Life Inventory, the Pain Coping Questionnaire, and the Pain Catastrophizing Scale. Means were compared to published norms using t-tests. Spearman correlations and logistic regression were used to explore the relationships between the variables. RESULTS: Mean HrQoL scores were lower than norms for controls and chronically ill pediatric patients ( P < .0001). Patients reported lower mean pain coping scores and higher mean pain catastrophizing scores than norms ( P < .0001). After controlling for age and sex, only the relationship between disability and HrQoL remained significant (OR = 0.91, 95% CI: 0.86-0.95). CONCLUSION: Pediatric patients with migraine report lower HrQoL, fewer pain coping strategies and more catastrophizing than controls, while disability is inversely associated with HrQoL.

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.

Pain free efficacy of sumatriptan in the early treatment of migraine.

BACKGROUND: There is evidence that headache response rates may be higher if triptans are used early when a migraine attack is still mild, as compared to when it is treated after pain has reached moderate or severe intensity. METHODS: In this randomized, double blind, placebo controlled, parallel group clinical trial, 361 patients took either placebo, sumatriptan 50 mg, or sumatriptan 100 mg in a single attack study. The primary outcome measure was pain-free status at two hours. RESULTS: In the intention to treat group, two hour pain free rates were 16%, 40%, and 50% in the placebo group, sumatriptan 50 mg group, and the sumatriptan 100 mg group respectively (p < 0.001, active treatment groups vs. placebo). CONCLUSIONS: Both sumatriptan 50 mg and 100 mg were significantly superior to placebo for the pain-free end point at two hours. The pain-free response rates in this trial where sumatriptan was taken while the headache was still mild were generally higher than in older clinical trials where headache was treated after reaching a moderate or severe intensity.

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

OBJECTIVES: To identify a treatment-responsive population for botulinum toxin type A (BoNTA) and to evaluate the safety and efficacy of 3 different doses of BoNTA as prophylactic treatment of chronic daily headache (CDH). PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled study of BoNTA in patients with CDH was conducted from July 6, 2001, through November 7, 2003, at 28 North American study centers. Eligible patients were injected with BoNTA at 225 U, 150 U, 75 U, or placebo and returned for additional masked treatments at day 90 and day 180. Patients were assessed every 30 days for 9 months. The primary efficacy end point was the mean change from baseline in the frequency of headache-free days at day 180 for the placebo nonresponder group. RESULTS: For this study, 702 patients were enrolled and randomized. The primary efficacy end point was not met. Mean improvements from baseline at day 180 of 6.0, 7.9, 7.9, and 8.0 headache-free days per month were observed in the placebo nonresponder group treated with BoNTA at 225 U, 150 U, 75 U, or placebo, respectively (P=.44). An a priori-defined analysis of headache frequency revealed that BoNTA at 225 U or 150 U had significantly greater least squares mean changes from baseline than placebo at day 240 (-8.4, -8.6, and -6.4, respectively; P=.03 analysis of covariance). Only 27 of 702 patients (3.8%) withdrew from the study because of adverse events, which generally were transient and mild to moderate. CONCLUSIONS: Although the primary efficacy end point was not met, all groups responded to treatment. The 225 U and 150 U groups experienced a greater decrease in headache frequency than the placebo group at day 240. The placebo response was higher than expected. BoNTA was safe and well tolerated. Further study of BoNTA prophylactic treatment of CDH appears warranted.

Topiramate prophylaxis and response to triptan treatment for acute migraine.

OBJECTIVE: To evaluate the effect of topiramate migraine prophylaxis on subject responsiveness to triptans used for acute symptomatic migraine treatment. BACKGROUND: Clinical experience suggests that prophylactic migraine treatment may enhance the efficacy of symptomatic medications used to treat acute migraine attacks. METHODS: This open-label, single-arm multicenter study consisted of a 6-week baseline period followed by a 16-week topiramate treatment period. Subjects meeting International Headache Society (IHS) criteria for migraine with and without aura signed consent and entered the baseline period. Those with 3 to 12 migraine periods per month during baseline received topiramate prophylactic treatment. Only patients who completed at least 12 weeks of topiramate treatment were included in the data analysis. RESULTS: Of 55 patients screened, 40 subjects entered the topiramate treatment period and 21 subjects received at least 12 weeks of treatment. Mean final dose of topiramate was 124 mg per day (range 50 to 200 mg per day). During the baseline period, the mean percentage of attacks rendered pain-free at 2 hours for the 21 subjects was 46.9% (SD = 31.9), while during the topiramate treatment period it was 44.6% (SD = 32.2) (P= .8). On topiramate, after the first 8 weeks of dosage titration, patients experienced a mean of 3.68 migraine attacks/month, compared to 4.31 during the baseline period (P < .03). Thirteen subjects discontinued because of adverse events. The most commonly reported adverse events were paresthesia, fatigue, anxiety, and dizziness. CONCLUSION: Although topiramate prophylaxis did reduce migraine attack frequency, in this pilot study topiramate prophylactic migraine treatment did not increase the proportion of patients pain-free 2 hours after symptomatic triptan therapy.

Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.

Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).