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In evaluating therapies for migraine prevention, emphasis is placed on frequency and less attention is paid to duration or severity. Total pain burden (TPB) combines frequency, duration, and severity of migraine headache, and has the potential to further characterize the benefit of preventive treatment using a single composite measure. TPB was previously used to characterize response to galcanezumab (GMB) in patients with migraine. In this post hoc analysis we assessed the impact of GMB in lowering TPB in patients who had previously not benefited from two to four categories of migraine preventive medication.CONQUER trial patients (N = 462), 18-75 years old who had previously not benefited from two to four categories of migraine preventive medication, were randomized (1:1) to monthly placebo or GMB 120 mg with 240 mg loading dose. For each patient, monthly TPB in severity-weighted hours was calculated by multiplying migraine headache duration (hours) by maximum severity for each migraine headache day, then summing these daily scores over the month for the monthly score. Changes from baseline in monthly TPB across months 1-3 were analyzed. Spearman correlations between TPB and scores on the Migraine-Specific Quality-of-Life Questionnaire (MSQ) total and Migraine Disability Assessment Scale (MIDAS) were assessed at baseline.Mean (SD) baseline monthly TPB was 192.1 (158.3) and 188.2 (197.4) severity-weighted hours for GMB-treated and placebo-treated patients, respectively. Across the 3-month double-blind period, GMB-treated patients experienced significantly greater mean reductions from baseline in monthly TPB compared with placebo-treated patients, both for mean change (GMB - 82.7, placebo - 15.8, p 0.001) and percentage change (GMB - 38.6%, placebo 9.4%, p 0.001). Furthermore, baseline TPB correlated with MSQ score (r = - 0.39) and MIDAS score (r = 0.40), suggesting good association of TPB with functional and disability outcomes.GMB reduced mean TPB in patients who had previously not benefited from two to four categories of migraine preventive medication.NCT03559257.

Objective: To provide a review of challenges in clinical trials for the preventive treatment of cluster headache (CH) and highlight considerations for future studies. Background: Current guidelines for preventive treatment of CH are largely based on off-label therapies supported by a limited number of small randomized controlled trials. Guidelines for clinical trial design for CH treatments from the International Headache Society were last issued in 1995. Methods/Results: Randomized controlled clinical trials were identified in the European and/or United States clinical trial registries with a search term of “cluster headache,” and manually reviewed. Cumulatively, there were 27 unique placebo-controlled prevention trials for episodic and/or chronic CH, of which 12 were either ongoing, not yet recruiting, or the status was unknown. Of the remaining 15 trials, 5 were terminated early and 7 of the 10 completed trials enrolled fewer patients than planned or did not report the planned sample size. A systematic search of PubMed was also utilized to identify published manuscripts reporting results from placebo-controlled preventive trials of CH. This search yielded 16 publications, of which 7 were registered. Through critical review of trial data and published manuscripts, challenges and complexities encountered in clinical trials for the preventive treatment of CH were identified. For example, the excruciating pain associated with CH demands a suitably limited baseline duration, rapid treatment efficacy onset, and poses a specific issue regarding duration of investigational treatment period and length of exposure to placebo. In episodic CH, spontaneous remission as part of natural history, and the unpredictability and irregularity of cluster periods across patients present additional key challenges. Conclusions: Optimal CH trial design should balance sound methodology to demonstrate efficacy of a potential treatment with patient needs and the natural history of the disease, including unique outcome measures and endpoint timings for chronic versus episodic CH.

Objective The objective of the study was to assess the tolerability and safety of galcanezumab in patients with chronic cluster headache (CH) with up to 15 months of treatment. Background Chronic CH is a highly debilitating disease with a substantial and unmet medical need. Methods Patients were randomized to receive placebo or galcanezumab (300 mg) monthly for 12 weeks, followed by an optional 52-week open-label extension and 16-week posttreatment follow-up (washout). This is a secondary analysis and long-term follow-up of a previously conducted clinical trial. The safety analysis included patients who received galcanezumab at any time during the study. Outcomes included adverse events (AEs), discontinuations, laboratory values, vital signs, electrocardiograms (ECGs), and suicidality ratings. Results A total of 233 patients received at least one galcanezumab dose. The mean exposure was 341 days. Galcanezumab-treated patients were mostly male (n = 169/233; 72.5%) with a mean age of 44.9 (±10.9) years. Treatment-emergent adverse events (TEAEs) were reported by 185 patients (n = 185/233; 79.4%), 23 patients (n = 23/233; 9.9%) reported serious adverse events (SAEs), and 18 patients (n = 18/233; 7.7%) discontinued due to AEs. The SAE CH was reported by three patients. The most common TEAEs (>10%) were nasopharyngitis (n = 41/233; 17.6%) and injection site pain (n = 33/233; 14.2%). 27.5% of patients (n = 64/233) had TEAEs related to injection sites. Likely hypersensitivity events, including injection site rash, injection site urticaria, and injection site hypersensitivity were reported (n = 14/233; 6.0%). There were past histories of suicidal ideation (n = 55/237; 23.2%) and suicidal behavior (n = 9/236; 3.8%). During the study, 15 patients (n = 15/230; 6.5%), seven with previous history, reported suicidal ideation. One patient had a nonfatal suicide attempt during the open-label extension and an aborted attempt during the washout. There were no new safety findings compared with the placebo-controlled treatment period in laboratory values, vital signs, or ECGs. Conclusions Galcanezumab 300 mg monthly had a favorable tolerability and safety profile in patients with chronic CH with up to 15 months of treatment.

Background CGAR, a Phase 3b open-label study, evaluated the long-term safety of galcanezumab in patients with cluster headache who completed one of two Phase 3 double-blind studies in chronic or episodic cluster headache. Methods Patients (N = 164) received galcanezumab 300 mg subcutaneously up to once a month. Primary endpoint was safety, as assessed by treatment-emergent adverse events, serious adverse events, and suicidality. Other endpoints included discontinuation rates, immunogenicity, efficacy as assessed by the Patient Global Impression of Improvement, and health values. Results At baseline, mean (standard deviation) age was 48.3 (9.8) years, 75.0% were men, and 85.4% were white. Treatment-emergent adverse events (n = 119 [72.6%]) were mostly mild-to-moderate, with nasopharyngitis the most commonly reported (22.0%). One of 18 serious adverse events was judged as treatment related (constipation). Two patients (1.2%) reported suicidal ideation. Five patients (3.1%) discontinued due to an adverse event. Eight patients were treatment-emergent anti-drug antibody positive, two of whom were not treatment-emergent anti-drug antibody positive in the parent studies. On the Patient Global Impression of Improvement, ≥81% reported their cluster headache status as very much, much, or a little better at Months 1, 6, and 12. Health value scores generally improved from baseline. Conclusions In this open-label study, galcanezumab was generally well tolerated and improved patient-reported cluster headache status. Trial registration number: NCT02797951; https://clinicaltrials.gov/ct2/show/NCT02797951

Background Cluster headache (CH) is a highly disabling primary headache disorder. To date, characterization of outcomes in the preventive treatment of episodic CH, including precise definitions of clinically meaningful attack frequency reduction and impact on acute treatment management, is lacking. Methods This was a Phase 3, randomized, double-blind, placebo-controlled study in patients (men or women aged 18-65 years) diagnosed with episodic CH as defined by the International Classification of Headache Disorders-3 beta criteria. In this post hoc analysis, we evaluated the median time-to-first occurrence of ≥50, ≥75, or 100% reduction from baseline in CH attack frequency, and impact on acute medication use. An anchor-based assessment of clinically relevant attack frequency reduction using the Patient Global Impression of Improvement (PGI-I) scores at Week 4 was also assessed. Results The median time-to-first occurrence of ≥50, ≥75, or 100% reduction from baseline in CH attacks was consistently shorter (9-10 days sooner) with galcanezumab vs placebo (median [95% confidence interval, 95% CI]: ≥50%, 5 days [4.0 to 7.0] vs 14 days [6.0 to 19.0]; ≥75%, 11 days [7.0 to 16.0] vs 21 days [13.0 to 26.0]; 100%, 22 days [16.0 to 37.0] vs 32 days [23.0 to 34.0]). Mean reduction from baseline in the overall frequency of weekly pooled acute medication use across Weeks 1-3 was significantly greater with galcanezumab vs placebo (11.0 vs 5.5; odds ratio, OR [95% CI]: 5.52 [1.02, 10.01]; P value = .017). Patients reporting "much better" on the PGI-I experienced a median weekly CH attack reduction of approximately 43% from baseline across Weeks 1-3. The overall odds of achieving an attack reduction threshold of 43% across Weeks 1-3 was significantly higher with galcanezumab vs placebo (Weeks 1-3: OR [95% CI], 2.60 [1.3 to 5.3]). Conclusions Faster median time-to-first occurrence of response rates, lower frequency of pooled acute medications use, and a greater proportion of patients achieving a response anchored by patient-reported improvement were observed for galcanezumab vs placebo.

Oralee J Varnado,1 Janna Manjelievskaia,2 Wenyu Ye,1 Allison Perry,2 Kory Schuh,1 Richard Wenzel1 1Value, Evidence, and Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Watson Health Life Sciences, Research & Analytics, IBM Watson Health, Cambridge, MA, USACorrespondence: Oralee J Varnado, Value, Evidence, and Outcomes, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46285, USA, Tel +1 317 277 0599, Email varnado_oralee_johnson@lilly.comBackground: Most conventional, oral, preventive treatments for migraine are non-specific and ∼ 50% of patients discontinue them within six months. In 2018, the Food and Drug Administration approved three preventive migraine treatments: monoclonal antibodies (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway implicated in migraine; galcanezumab and fremanezumab which target CGRP ligand; and erenumab which targets CGRP receptor. Real-world treatment patterns for CGRP mAb are limited.Purpose: To compare real-world treatment patterns for CGRP mAb, specifically galcanezumab versus standard-of-care (SOC) migraine preventive treatments.Patients and methods: This retrospective, observational study included 12-month baseline and 6- and 12-month follow-up analyses using IBM® MarketScan® databases. Patients identified were aged ≥ 18 years with ≥ 1 claim (first claim=index) for CGRP mAb (erenumab, fremanezumab, or galcanezumab) or SOC preventives (eg, antiepileptics, beta-blockers, antidepressants, or onabotulinumtoxinA) as index drugs between May/01/2018 and June/30/2019. Propensity score matching was used to address confounding by observed covariates. Outcomes analyzed included proportion of days covered (PDC), persistence (≤ 60-day gap), and first non-index drug switch. Descriptive, chi-square (categorical), and t-test (continuous) analyses were conducted.Results: The study included 3082 (CGRP mAb versus SOC) and 421 (galcanezumab versus SOC) matched patient pairs with 12-month follow-up. Mean age across cohorts ranged 43.2– 44.4 years (females: 85.7– 88.6%). Compared with SOC, the CGRP mAb cohort had higher mean persistence (212.5 vs 131.9 days), adherence (PDC: 55.1% vs 35.2%), and more patients were adherent with PDC ≥ 80% (32.7% vs 18.7%) (all p < 0.001). During 12-month follow-up, fewer patients discontinued CGRP mAb versus SOC (58.8% vs 77.6%, p < 0.001). Galcanezumab versus SOC comparisons yielded similar results. In the CGRP mAb cohort, most switchers (28.3%) used galcanezumab as subsequent treatment. Largely similar results were observed for 6-month follow-up cohorts.Conclusion: Patients on CGRP mAb and specifically galcanezumab showed higher adherence and persistence than patients on SOC migraine preventive treatments.Keywords: CGRP, persistence, adherence, discontinuation, switch

J Scott Andrews,1 David Kudrow,2 Mallikarjuna Rettiganti,1 Tina Oakes,1 Jennifer N Bardos,1 Richard Wenzel,1 Dulanji K Kuruppu,1 Charly Gaul,3 James M Martinez1 1Eli Lilly and Company, Indianapolis, IN, USA; 2California Medical Clinic for Headache, Santa Monica, CA, USA; 3Headache Center, Frankfurt, GermanyCorrespondence: Mallikarjuna RettigantiEli Lilly and Company, Lilly Corporate Center, 893 Delaware St., Indianapolis, IN, 46285, USATel +1 3176519378Email rettiganti_mallikarjuna@lilly.comPurpose: In a phase 3 study, galcanezumab significantly reduced the frequency of episodic cluster headache attacks across weeks 1– 3 (primary endpoint) compared with placebo. However, multiple pain dimensions may contribute to the total burden of episodic cluster headache pain. This post hoc analysis assessed the impact of galcanezumab on the total pain burden of episodic cluster headache using a composite measure.Patients and Methods: Patients with episodic cluster headache were randomized 1:1 to galcanezumab 300 mg or placebo once monthly for 8 weeks. Mean weekly total pain burden was calculated (daily cluster headache attack frequency × average duration × average pain severity summed over 7 days) using data collected in an electronic patient-reported outcomes diary. Change from baseline in weekly total pain burden across weeks 1– 3 was compared between galcanezumab and placebo. To explore construct validity, mean weekly total pain burden scores were stratified by Patient Global Impression of Improvement (PGI-I) responses at the week 4 clinic visit.Results: The reduction from baseline in mean weekly total pain burden was significantly greater with galcanezumab (N=49) than with placebo (N=57): the least squares mean difference was − 11.18 severity-weighted hours (p=0.035). Median weekly total pain burden decreased as PGI-I ratings improved, from 33.6 to 5.0 severity-weighted hours for patients who felt “very much worse” and “very much better,” respectively.Conclusion: Galcanezumab significantly reduced mean weekly total pain burden compared with placebo in patients with episodic cluster headache. The composite pain measure demonstrated construct validity. Total pain burden may provide a holistic measure of the pain of episodic cluster headache.Clinical Trials: ClinicalTrials.gov, NCT02397473.Keywords: composite pain, frequency, severity, duration, CGRP

Objective: The efficacy of galcanezumab was evaluated in patients with episodic cluster headache and history of preventive treatment failure. Methods: In the randomized, 8-week, double-blind study (CGAL), patients with episodic cluster headache received once-monthly subcutaneous injections of galcanezumab 300 mg or placebo. Patients who completed CGAL and enrolled in an open-label study were queried for preventive treatment history. In a subset of patients with a known history of failure of verapamil or any other prior preventive treatment, a post hoc analysis of least square mean change from baseline in weekly cluster headache attack frequency across Weeks 1 to 3 was assessed. Results: Fifteen patients provided data for known history of prior preventive treatment failure (6 placebo, 9 galcanezumab), of whom 11 failed verapamil. The mean reduction in the weekly frequency of cluster headache attacks was greater with galcanezumab compared to placebo among patients with prior preventive treatment failure (8.2 versus 2.4); mean difference 5.8 (95% confidence interval [CI] 2.0, 13.6) and among patients with verapamil failure (10.1 versus 1.6); mean difference 8.5 (95% CI 0.4, 16.7). Conclusion: In this exploratory analysis of patients with a known history of prior preventive treatment failures, treatment with galcanezumab resulted in greater mean reductions in weekly cluster headache attacks compared with placebo. ClinicalTrials.gov: NCT02397473 (I5Q-MC-CGAL) NCT02797951 (I5Q-MC-CGAR)

Cluster headache (CH) is a primary headache (PH) disorder characterized by recurrent attacks of severe/extremely severe unilateral pain and associated symptoms. While less prevalent than other PHs such as migraine, CH impact is substantial given the agonizing pain, negative effect on daily productivity, impaired mental health, and increased costs. Cluster headache is not optimally treated and few clinical trials are available to model therapy, especially dosing and administration. Pharmacists are well positioned to help prescribers and CH individuals with several key opportunities. Subcutaneous sumatriptan (SC SM) lower than the FDA-approved 6 mg per attack, specifically 2 mg and 3 mg, can be considered; literature describes these doses’ benefits. Moreover, lower doses may improve patient access to this treatment-of-choice. Despite the SC SM’s FDA-approved dose limit of 12 mg per 24 hours, the maximum CH dose has not been examined; this limit merits reevaluation since literature and clinical experience illustrate treatment exceeding this limit. Oxygen therapy for CH remains unfamiliar to, and under-utilized by, clinicians and CH individuals. Pharmacists can facilitate prescribing, distribution, and administration of oxygen via education. Patient education for the various CH medication devices, including oxygen, is paramount. Narcotics remain widely prescribed for CH, without supporting evidence, but with considerable abuse and diversion risks. Pharmacists are positioned to help guard against narcotic usage and to direct care toward medications endorsed by CH guidelines. Since the optimal method to initiate and discontinue drugs which may decrease CH attacks’ remains unknown, pharmacists can educate clinicians and individuals with CH to make fully informed decisions.

A continuous-flow isotope-ratio mass spectrometer (CF-IRMS, custom-made GasBenchII and Delta(plus)Advantage, ThermoFinnigan) was installed on a grassland site and interfaced with a closed-path infrared gas analyser (IRGA). The CF-IRMS and IRGA were housed in an air-conditioned travel van. Air was sampled at 1.5 m above the 0.07-m tall grassland canopy, drawn through a 17-m long PTFE tube at a rate of 0.25 L s(-1), and fed to the IRGA and CF-IRMS in series. The IRMS was interfaced with the IRGA via a stainless steel capillary inserted 0.5 m into the sample air outlet tube of the IRGA (forming an open split), a gas-tight pump, and a sample loop attached to the eight-port Valco valve of the continuous-flow interface. Air was pumped through the 0.25-mL sample loop at 10 mL s(-1) (a flushing frequency of 40 Hz). Air samples were analysed at intervals of approx. 2.8 min. Whole system precision was tested in the field using air mixed from pure CO2 and CO2-free air by means of mass flow controllers. The standard deviation of repeated single measurements was 0.21-0.07 per thousand for delta13C and 0.34-0.14 per thousand for delta18O of CO2 in air with mixing ratios ranging between 200-800 micromol mol(-1). The CO2 peak area measured by the IRMS was proportional to the CO2 mixing ratio (r2 = 1.00), allowing estimation of sample air CO2 mixing ratio from IRMS data. A 1-day long measurement cycle of CO2, delta13C and delta18O of air sampled above the grassland canopy was used to test the system for Keeling plot applications. Delta18O exhibited a clear diurnal cycle (4 per thousand range), but short-term (1-h interval) variability was small (average SD 0.38 per thousand). Yet, the correlation between delta18O and CO2 mixing ratio was relatively weak, and this was true for both the whole data set and 1-h subsets. Conversely, the delta13C of all 541 samples measured during the 25.2-h interval fitted well the Keeling regression (r2 = 0.99), yielding an intercept of -27.40 per thousand (+/-0.07 per thousand SE). Useful Keeling regressions (r2 > 0.9, average r2 = 0.96) also resulted from data collected over 1-h intervals of the 12-h long twilight and dark period. These indicated that 13C content of ecosystem respiration was approx. constant near -27.6 per thousand. The precision of the present system is similar to that of current techniques used in ecosystem studies which employ flask sampling and a laboratory-based CF-IRMS. Sampling (and measurement) frequency is greatly increased relative to systems based on flask sampling, and sampling time (0.025 s per sample) is decreased. These features increase the probability for sampling the entire CO2 range which occurs in a given time window. The system obviates sample storage problems, greatly minimises handling needs, and allows extended campaigns of high frequency sampling and analysis with minimal attendance.

Migraines affect 28 million people in the United States, and most of these individuals experience attack-related morbidity. Six of every 10 patients with migraine treat their headache exclusively with over-the-counter (OTC) products. Overreliance on OTC agents contributes to preventable morbidity and drug-induced headaches. To evaluate the role of OTC drugs in the management of migraine headaches, we performed a qualitative systematic literature search by using MEDLINE (January 1966-April 2002), analyzed the references of articles returned by the MEDLINE search, and reviewed other pertinent literature. In the studied populations, acetaminophen, aspirin, ibuprofen, and an aspirin-acetaminophen-caffeine combination product were shown to be more effective than placebo at reducing moderate or severe migraine pain to mild or no pain by 2 hours after administration. However, published trials of OTC agents have systematically excluded patients enduring morbidity with 50% or more of attacks and/or vomiting with 20% or more of attacks. Patients who experience disability during the predominance of their attacks are poor candidates for OTC-exclusive therapy and should seek a physician's help for migraine-specific prescription drugs. For those with migraine who encounter disability with less than 50% of attacks and/or vomiting with less than 20% of attacks, sole treatment with OTC products is a feasible option. Patients who fail to obtain acceptable relief after an adequate trial of OTC agents also should be referred to a physician. Pharmacists are well positioned to assess whether patients could benefit from OTC agents or should seek a physician's assistance.

Patient satisfaction with pharmacist-conducted weekly medication-education classes and the underlying factor structure of the evaluation items are described. The pharmacist service consisted of weekly, one-hour classes for headache sufferers in a tertiary headache clinic's hospital unit. One pharmacist taught all of the classes and conducted them in the same manner each week, using the Indian Health Service patient-counseling technique. The classes included both lecture and one-on-one interactions. Any patient admitted to the hospital's headache unit was eligible to participate in the study. Patients were asked to complete a survey at the end of the class, evaluating the service in terms of performance, disconfirmation of expectations, affect, equity, and self-efficacy by rating three statements about each of these on a 7-point scale, where 1 = very strongly disagree and 7 = very strongly agree. Exploratory factor analysis was used to investigate the degree to which these five evaluation areas were distinct constructs. A total of 157 patients attended a medication-education class during the study period. Of these, 153 (97%) provided usable data. Respondents favorably evaluated the pharmacist service, as the means were significantly greater than the scales' midpoint scores (p < 0.001). Factor analysis results suggested that covariation in the data was best described by four factors rather than five: (1) performance, (2) disconfirmation of expectations, (3) equity, and (4) self-efficacy. Inpatients attending pharmacist-conducted weekly medication-education classes favorably evaluated the pharmacist service. Four different conceptualizations of patients' evaluations were identified.

A continuous-flow isotope-ratio mass spectrometer (CF-IRMS, custom-made GasBenchII and Delta(plus)Advantage, ThermoFinnigan) was installed on a grassland site and interfaced with a closed-path infrared gas analyser (IRGA). The CF-IRMS and IRGA were housed in an air-conditioned travel van. Air was sampled at 1.5 m above the 0.07-m tall grassland canopy, drawn through a 17-m long PTFE tube at a rate of 0.25 L s(-1), and fed to the IRGA and CF-IRMS in series. The IRMS was interfaced with the IRGA via a stainless steel capillary inserted 0.5 m into the sample air outlet tube of the IRGA (forming an open split), a gas-tight pump, and a sample loop attached to the eight-port Valco valve of the continuous-flow interface. Air was pumped through the 0.25-mL sample loop at 10 mL s(-1) (a flushing frequency of 40 Hz). Air samples were analysed at intervals of approx. 2.8 min. Whole system precision was tested in the field using air mixed from pure CO2 and CO2-free air by means of mass flow controllers. The standard deviation of repeated single measurements was 0.21-0.07 per thousand for delta13C and 0.34-0.14 per thousand for delta18O of CO2 in air with mixing ratios ranging between 200-800 micromol mol(-1). The CO2 peak area measured by the IRMS was proportional to the CO2 mixing ratio (r2 = 1.00), allowing estimation of sample air CO2 mixing ratio from IRMS data. A 1-day long measurement cycle of CO2, delta13C and delta18O of air sampled above the grassland canopy was used to test the system for Keeling plot applications. Delta18O exhibited a clear diurnal cycle (4 per thousand range), but short-term (1-h interval) variability was small (average SD 0.38 per thousand). Yet, the correlation between delta18O and CO2 mixing ratio was relatively weak, and this was true for both the whole data set and 1-h subsets. Conversely, the delta13C of all 541 samples measured during the 25.2-h interval fitted well the Keeling regression (r2 = 0.99), yielding an intercept of -27.40 per thousand (+/-0.07 per thousand SE). Useful Keeling regressions (r20.9, average r2 = 0.96) also resulted from data collected over 1-h intervals of the 12-h long twilight and dark period. These indicated that 13C content of ecosystem respiration was approx. constant near -27.6 per thousand. The precision of the present system is similar to that of current techniques used in ecosystem studies which employ flask sampling and a laboratory-based CF-IRMS. Sampling (and measurement) frequency is greatly increased relative to systems based on flask sampling, and sampling time (0.025 s per sample) is decreased. These features increase the probability for sampling the entire CO2 range which occurs in a given time window. The system obviates sample storage problems, greatly minimises handling needs, and allows extended campaigns of high frequency sampling and analysis with minimal attendance.

Migraine headaches affect 12% of the adult population in the United States and cause a significant economic loss due to decreased workplace productivity Although interactions between pharmacists and individuals with headache are common, few pharmacists receive adequate training regarding migraine therapy. We refute several misconceptions that hinder effective care, such as that migraine is a vascular disease, triptans cause rampant cardiacrelated morbidity and even mortality, a best oral triptan exists, sinus and tension headaches are prevalent, and migraine is a minor economic problem. Our pathophysiologic understanding demonstrates that migraine is a neurologic process of the trigeminovascular system, of which vascular effects are secondary. This process can result in a myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus or tension headache. The last decade's experience with triptans in more than half a billion people worldwide reveals a benign adverse-effect profile, particularly when taken early in an attack. Published reports and real-world experiences illustrate that these drugs do not merit fears of triptan-induced cardiac consequences in appropriately selected individuals. Society's productivity loss due to migraine is measured in billions of dollars. Restoring a patient's ability to function normally is now recognized as the primary treatment goal, not merely relieving pain. Thus, the overreliance on "pain killer" drugs such as butalbital-containing products and the continued underutilization of migraine-specific drugs need to be addressed. Opportunities exist for pharmacists and other health care providers to dispel continually propagated migraine misconceptions and familiarize themselves with advances in therapy. Such actions will benefit patients, the health care system, and society as a whole.

Study Objective. To evaluate the role of butalbital-containing products in the management of migraine. Methods. Qualitative systematic search using MEDLINE (January 1966–November 2001), review of the United States Headache Consortium's evidence-based guidelines for migraine treatment, and review of other pertinent literature. Results. Over 28 million people suffer with migraine, yet this illness is less than optimally diagnosed and managed. Between 14% and 36% of diagnosed migraineurs are prescribed butalbital-containing products, often as initial therapy. However, the only identified controlled trial of these drugs for migraine treatment showed that butalbital-containing products were inferior to butorphanol. The consortium's guidelines specifically discourage administration of butalbital-containing products for migraine. In addition, other published literature highlights the frequent adverse consequences of butalbital-containing products for migraineurs, such as poor migraine control, disability, drug-induced headaches, and withdrawal symptoms. Conclusion. Although butalbital-containing products commonly are prescribed for migraine, no evidence in the literature demonstrates their benefit over other agents or placebo. Drugs with proven migraine efficacy, as listed in the consortium's evidence-based guidelines, should be prescribed instead.

OBJECTIVE: To assess primary headache education in colleges of pharmacy during the 2000–2001 academic year. DESIGN: A survey seeking to quantify students' primary headache education was mailed to all 82 American Association of Colleges of Pharmacy member schools. RESULTS: A usable response was obtained from 65 of 74 answering schools. Per professional year, the average pharmacy student receives 1 headache core course contact hour and no headache elective course contact hours. Two schools offer clerkships devoted exclusively to headaches. Six schools offer clerkships in which a student could expect to focus on headache therapy at least 25% of the time. Seven schools plan to alter their current curriculum to include more headache education, all via additional lectures. CONCLUSIONS: Few opportunities exist for students to learn about primary headaches in colleges of pharmacy. Given the high prevalence and poor medical management of primary headache disorders along with the commonality of pharmacist—headache patient interactions occurring in practice, pharmacy schools should evaluate and alter their curriculum to include more primary headache education.

CNS Drugs. 2002;16(6):385-403 Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact pathophysiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause. Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications. Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT(1B/1D) agonists (the Atriptans') and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids. Preventative medication therapy is indicated for patients experiencing frequent and/or refractory attacks. Comment: A nicely written, practical review article which I recommend for medical students, residents, and primary care physicians. SJT