Acute Treatment Of Episodic Migraine Research Articles

Predictors of treatment-response to caffeine combination products, acetaminophen, acetylsalicylic acid (aspirin), and nonsteroidal anti-inflammatory drugs in acute treatment of episodic migraine.

To identify predictors of acute treatment optimization for migraine with "over-the-counter" (OTC) or prescription nonsteroidal anti-inflammatory drugs (NSAIDs) as well as other widely used OTCs including acetaminophen, caffeine combination products (CCP), and acetylsalicylic acid (ASA, aspirin) among people with episodic migraine and to develop models that predict treatment response to each class of OTCs. Efficacy of acute OTC medications for migraine varies greatly. Identifying predictors of treatment response to particular classes of medication is a step toward evidence-based personalized therapy. For this prediction model development study, we used data from 2224 participants from the American Migraine Prevalence and Prevention (AMPP) study who were aged ≥18 years, met criteria for migraine, had <15 monthly headache days, and reported being on monotherapy for acute migraine attacks with one of the following classes medications: CCP (N=711), acetaminophen (N=643), ASA (N=110), and prescription or OTC NSAIDs (N=760). The primary outcome measures of treatment optimization were adequate 2-h pain freedom (2hPF) and adequate 24-h pain relief (24hPR), which were defined by responses of half the time or more to the relevant items on the Migraine Treatment Optimization Questionnaire-6. The mean (SD) age of the participants was 46.2(13.1)years, 79.4% (1765/2224) were female, 43.7% (972/2224) reported adequate 2hPF, and 46.1% (1025/2224) reported adequate 24hPR. Those taking CCP had better 2hPF and 24PR outcomes. For those taking NSAIDs, better outcomes were associated with lower average pain intensity (2hPF: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.80-0.99; 24PR: OR 0.86, 95% CI 0.77-0.96), cutaneous allodynia (2hPF: OR 0.92, 95% CI 0.89-0.96; 24PR: OR 0.91, 95% CI 0.87-0.95), depressive symptoms (2hPF: OR 0.95, 95% CI 0.92-0.98; 24PR: OR 0.95, 95% CI 0.91-0.99), and Migraine Disability Assessment Scale (MIDAS) grade (2hPF: OR 0.76, 95% CI 0.64-0.90; 24PR: OR 0.79, 95% CI 0.65-0.95). Adequate 2hPF for those taking CCP was associated with male gender (OR 1.83, 95% CI 1.21-2.77), lower average pain intensity (OR 0.80, 95% CI 0.70-0.91), lower cutaneous allodynia (OR 0.94, 95% CI 0.90-0.97), and lower Migraine Symptom Severity Scale Score (MSSS; OR 0.91, 95% CI 0.86-0.97). Adequate 24hPR for those taking CCP was associated with lower average pain intensity (OR 0.85, 95% CI 0.75-0.96), lower cutaneous allodynia (OR 0.92, 95% CI 0.89-0.96), and lower MIDAS grade (OR 0.81, 95% CI 0.68-0.96). Participants who were married (OR 1.51, 95% CI 1.05-2.19), had lower average pain intensity (OR 0.79, 95% CI 0.70-0.89), lower MSSS (OR 0.93, 95% CI 0.88-0.99), less depression (OR 0.96, 95% CI 0.93-0.99), and lower MIDAS grade (OR 0.72, 95% CI 0.59-0.87) had adequate 2hPF after taking acetaminophen. Participants who were married (OR 1.50, 95% CI 1.02-2.21), had lower pain intensity (OR 0.78, 95% CI 0.69-0.88), less depression (OR 0.95, 95% CI 0.91-0.98) and lower MIDAS grade (OR 0.53, 95% CI 0.42-0.67) had higher 24hPR following use of acetaminophen. A lower MSSS was the only factor associated with higher 2hPF and 24PR after using ASA (OR 0.78, 95% CI 0.67-0.92 and OR 0.79, 95% CI 0.67-0.93). Predictive models had modest performance in identifying responders to each class of OTC. A large subgroup of people with migraine had an inadequate response to their usual acute OTC migraine treatment 2- and 24-h after dosing. These findings suggest a need to improve OTC treatment for some and to offer prescription acute medications for others. Predictive models identified several factors associated with better treatment-response in each OTC class. Selecting OTC treatment based on factors predictive of treatment optimization might improve patient outcomes.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Tolerability, and Safety of Celecoxib Oral Solution (ELYXYB) in Acute Treatment of Episodic Migraine with or without Aura.

BackgroundSafe, effective, oral therapies are needed for acute treatment of migraine. This clinical trial assessed the efficacy, tolerability, and safety of celecoxib oral solution (ELYXYB) in a single migraine attack associated with moderate-to-severe pain.MethodsThis was a phase III, randomized (1:1), double-blind, placebo-controlled trial, conducted at 41 US centers from December 2016 to October 2017. Adults with episodic migraine (with or without aura) for ≥1 year were treated with a single 4.8 mL dose of 120-mg celecoxib oral solution or placebo. Co-primary endpoints were the proportion of patients who were pain-free and free from the most bothersome migraine symptom (MBS) at 2 hours post-dose. The MBS was identified at screening from among nausea, photophobia, or phonophobia.ResultsSix hundred thirty-one patients were randomized (celecoxib oral solution, n=316; placebo, n=315; mean age 41 years, range 18–75; 84.3% female). One study site met prespecified outlier criteria (defined as a treatment effect estimate that was at least twice as large as all other sites) and was excluded from efficacy analyses. This site had a mean 2-hour pain freedom placebo response rate of 75% vs a combined mean of 23.5% for all other sites. In subsequent analysis, 2-hour post-dose pain freedom response rates were significantly higher in the celecoxib oral solution group vs placebo (32.8%, [27.2%, 38.8%]) vs 23.5%, [18.5%, 29.2%]; P=0.020). For 2-hour post-dose MBS freedom, response rates were significantly higher in the celecoxib oral solution group vs placebo (58.1% [51.4%, 64.5%] vs 43.9% [37.2%, 50.7%]; P=0.003). A total of 10.7% (31/289) of patients treated with celecoxib oral solution and 9.9% (28/283) of placebo-treated patients reported a treatment-emergent adverse event (TEAE). Study drug-related TEAEs were reported by 7.3% (21/289) and 7.4% (21/283) of celecoxib oral solution and placebo patients, respectively; the most common were nausea (celecoxib oral solution: 1.4% [4/289] vs placebo: 1.8% [5/283]) and dysgeusia (celecoxib oral solution: 1.7% [5/289] vs placebo: 1.1% [3/283]). No serious TEAEs, deaths, or drug-related TEAEs leading to withdrawal were reported.ConclusionCelecoxib oral solution is a safe, effective COX-2-selective nonsteroidal anti-inflammatory drug for the treatment of acute migraine. In this analysis, celecoxib oral solution was significantly more effective than placebo and was also associated with a low rate of gastric TEAEs. Celecoxib oral solution may provide a convenient, alternate option to currently available treatments.Trial RegistrationClinicalTrials.gov Identifier: NCT03009019; registered January 4, 2017; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03009019.

Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials.

Ubrogepant is a small molecular calcitonin gene-related peptide receptor antagonist that is used for the acute treatment of migraine. The aim was to conduct a meta-analysis to systematically evaluate the efficacy and safety of ubrogepant for the treatment of episodic migraine compared with placebo in the adult population. We systematically searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials for relevant randomized clinical trials, from the earliest available date to November 10, 2019, to evaluate the efficacy and safety of short-term ubrogepant use. Inclusion criteria were (1) randomized clinical trial; (2) enrolled adult participants diagnosed with episodic migraine; (3) compared ubrogepant with placebo at doses that were evaluated in phase III clinical trials; (4) enrolled more than 100 patients in each group; and (5) provided any information on primary or secondary outcomes. Trials were excluded if their participants were diagnosed with chronic migraine. A total of three multicenter, randomized clinical trials with 3326 patients were included. Ubrogepant use was associated with a significantly higher percentage of patients with pain freedom (ubrogepant 20.8%; placebo 12.6%; relative risk [RR] 1.65, 95% confidence interval [CI] 1.38-1.98) and absence of the most bothersome migraine-associated symptoms (ubrogepant 37.3%; placebo 27.6%; RR 1.35, 95% CI 1.20-1.53) at 2 h post-dose compared with placebo. Ubrogepant increased the rate of absence of migraine-associated symptoms at 2 h post-dose compared with placebo (photophobia: RR 1.30 [95% CI 1.18-1.44], I2 = 49%; phonophobia: RR 1.20 [95% CI 1.11-1.29]; nausea: RR 1.07 [95% CI 1.02-1.13]), and patients were more likely to function normally at 2 h post-dose compared with placebo (RR 1.30 [95% CI 1.16-1.45]). No significant difference was found for treatment-related adverse events within 48 h or 30 days for ubrogepant compared with placebo (48 h: RR 1.07 [95% CI 0.85-1.35]; 30 days: RR 1.03 [95% CI 0.79-1.34]). Subgroup analysis demonstrated that compared to placebo, ubrogepant led to greater rates of freedom from pain at 2 h with 25-mg, 50-mg, and 100-mg doses and absence of the most bothersome symptoms with 50-mg and 100-mg doses. The use of ubrogepant as an acute treatment of episodic migraine in adults led to a greater percentage of freedom from pain and absence of the most bothersome symptoms at 2 h post-dose. Short-term use of ubrogepant was not related to an increased risk for adverse events. Further studies are needed to evaluate efficacy and safety for long-term use and in specific subgroups of patients.

Efficacy, Tolerability, and Safety of DFN‐15 (Celecoxib Oral Solution, 25 mg/mL) in the Acute Treatment of Episodic Migraine: A Randomized, Double‐Blind, Placebo‐Controlled Study

ObjectiveThe objective of this study was to evaluate the efficacy, tolerability, and safety of 120 mg DFN‐15 vs placebo for the acute treatment of migraine.BackgroundCertain nonsteroidal anti‐inflammatory drugs (NSAIDs) are guideline‐recommended therapies for the acute treatment of migraine, but patients who use them may have issues with gastrointestinal tolerability. Celecoxib, a selective inhibitor of cyclooxygenase‐2, produces analgesia similar to nonselective NSAIDs. DFN‐15 is an oral, ready‐made liquid solution of celecoxib being investigated for the acute treatment of migraine.MethodsA randomized, double‐blind, placebo‐controlled, efficacy, tolerability, and safety study in adults with migraine was conducted. Subjects treated a single migraine attack with 120 mg DFN‐15 or placebo as soon as possible after the onset of pain of moderate to severe intensity. The 2 independent coprimary efficacy endpoints were the proportion of subjects with freedom from pain and the absence of the most bothersome symptom (MBS) at 2 hours postdose. A second double‐blind treatment period followed the first, but did not contribute to the primary outcomes and will be reported elsewhere.ResultsThere were 622 subjects randomized (1:1) to double‐blind treatment with either 120 mg DFN‐15 or placebo, and 567 (91.2%) treated a migraine with study drug (n = 285 DFN‐15; n = 282 placebo). Groups were balanced in demographic characteristics; the mean age was 40, and most subjects were female (87% [494/567]). At 2 hours postdose, DFN‐15 was significantly superior to placebo for pain freedom (35.6% [98/275] vs 21.7% [57/263], P < .001), with an odds ratio (95% CI) of 2.00 (1.36, 2.94) and for freedom from the MBS (57.8% [134/232] vs 44.8% [104/232], P = .007), with an odds ratio (95% CI) of 1.68 (1.17, 2.43). A total of 13.3% (38/285) of DFN‐15‐treated subjects and 8.9% (25/282) of placebo‐treated subjects reported a treatment‐emergent adverse event (TEAE). Study drug‐related TEAEs were reported by 9.1% (26/285) of DFN‐15 subjects and 6.0% (17/282) of placebo subjects, the most common of which were dysgeusia (4.2% [12/285] vs 1.4% [4/282]) and nausea (3.2% [9/285] vs 1.8% [5/282]). No subjects treated with DFN‐15 reported TEAEs that were severe or led to withdrawal, and no serious TEAEs or deaths were reported in the study.ConclusionsDFN‐15 was significantly more effective than placebo for the acute treatment of migraine, with a generally favorable tolerability and safety profile.

DFN-02 (Sumatriptan 10 mg With a Permeation Enhancer) Nasal Spray vs Placebo in the Acute Treatment of Migraine: A Double-Blind, Placebo-Controlled Study.

The objective of this study was to evaluate the efficacy, safety, and tolerability of DFN-02 - a nasal spray comprising sumatriptan 10 mg and a permeation-enhancing excipient (0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside [DDM]) - for the acute treatment of migraine with or without aura in adults. Prior work has shown that DFN-02, which contains only half the recommended adult dose of sumatriptan found in the original formulation (10 mg vs 20 mg), is more rapidly absorbed than commercial nasal spray of sumatriptan, with favorable pharmacokinetic and safety profiles. The efficacy of DFN-02 in the acute treatment of migraine has not been previously assessed. This was a multicenter, randomized, 2-period, double-blind, placebo-controlled efficacy, safety, and tolerability phase 2 study of DFN-02. Subjects with at least a 12 month history of episodic migraine, who averaged 2-8 attacks per month, with no more than 14 headache days per month and a minimum of 48 headache-free hours between attacks, were randomized (1:1) to receive DFN-02 or a matching placebo. Subjects were instructed to treat a single migraine attack of moderate to severe pain intensity. The primary efficacy endpoint, the proportion of subjects who were pain-free at 2 hours postdose in the first double-blind treatment period, was assessed with 2 protocol prespecified primary analyses: last observation carried forward (LOCF) and observed cases (OC). Secondary efficacy endpoints at 2 hours included pain relief; absence of the most bothersome symptom (MBS) among nausea, photophobia, and phonophobia; freedom from nausea, photophobia, and phonophobia. Sustained pain freedom from 2 through 24 hours postdose was also assessed. Of 107 subjects randomized, 86.9% (N = 93 [DFN-02, n = 50; placebo, n = 43]) had data in the first double-blind treatment period. The study met its primary endpoint; the proportion of subjects who were free from headache pain at 2 hours postdose, was statistically significantly higher in the DFN-02 group than in the placebo group in both prespecified primary analyses: LOCF (DFN-02, n = 21/48; placebo, n = 9/40; 43.8% vs 22.5%, P = .044) and OC (DFN-02, n = 21/48; placebo, n = 8/39; 43.8% vs 20.5%, P = .025). For secondary efficacy endpoints, at 2 hours postdose, DFN-02 was also statistically significantly superior to placebo for the proportion of subjects who had pain relief (83.3% vs 55.0%, P = .005); who were free of their MBS (70.7% vs 39.5%, P = .007); and who were free of nausea (78.3% vs 42.1%, P = .026), photophobia (71.8% vs 38.9%, P = .005), and phonophobia (78.1% vs 40.0%, P = .004). Compared with placebo, statistically significantly greater proportions of subjects who were treated with DFN-02 had sustained pain freedom from 2 through 24 hours postdose (38.9% vs 13.8%, P = .029). In total, 9.7% (9/93) of subjects reported a treatment-emergent adverse event during the study: 10.0% (5/50) of DFN-02 subjects in the first double-blind treatment period and 13.5% (5/37) of DFN-02 subjects in the second double-blind treatment period. The most common treatment-emergent adverse event with DFN-02 was dysgeusia (3/37 subjects in the second double-blind treatment period). DFN-02 was shown to be effective, well tolerated, and safe in the acute treatment of episodic migraine. Additional studies are needed to confirm these preliminary results. (ClinicalTrials.gov Identifier: NCT02856802).

A multicenter, open-label, long-term safety and tolerability study of DFN-02, an intranasal spray of sumatriptan 10\xa0mg plus permeation enhancer DDM, for the acute treatment of episodic migraine

BackgroundDFN-02 is a novel intranasal spray formulation composed of sumatriptan 10 mg and a permeation-enhancing excipient comprised of 0.2% 1-O-n-Dodecyl-β-D-Maltopyranoside (DDM). This composition of DFN-02 allows sumatriptan to be rapidly absorbed into the systemic circulation and exhibit pharmacokinetics comparable to subcutaneously administered sumatriptan. Rapid rate of absorption is suggested to be important for optimal efficacy. The objective of this study was to evaluate the safety and tolerability of DFN-02 (10 mg) in the acute treatment of episodic migraine with and without aura over a 6-month period based on the incidence of treatment-emergent adverse events and the evaluation of results of clinical laboratory tests, vital signs, physical examination, and electrocardiograms.MethodsThis was a multi-center, open-label, repeat-dose safety study in adults with episodic migraine with and without aura. Subjects diagnosed with migraine with or without aura according to the criteria set forth in the International Classification of Headache Disorders, 2nd edition, who experienced 2 to 6 attacks per month with fewer than 15 headache days per month and at least 48 headache-free hours between attacks, used DFN-02 to treat their migraine attacks acutely over the course of 6 months.ResultsA total of 173 subjects was enrolled, 167 (96.5%) subjects used at least 1 dose of study medication and were evaluable for safety, and 134 (77.5%) subjects completed the 6-month study. A total of 2211 migraine attacks was reported, and 3292 doses of DFN-02 were administered; mean per subject monthly use of DFN-02 was 3.6 doses. Adverse events were those expected for triptans, as well as for nasally administered compounds. No new safety signals emerged. Dysgeusia and application site pain were the most commonly reported treatment-emergent adverse events over 6 months (21% and 30.5%, respectively). Most of the treatment-emergent adverse events were mild. There were 5 serious adverse events, all considered unrelated to the study medication; the early discontinuation rate was 22.5% over the 6-month treatment period.ConclusionDFN-02 was shown to be well tolerated when used over 6 months to treat episodic migraine acutely.

Non-invasive Neuromodulation in Primary Headaches.

There is growing interest in neuromodulation for primary headache conditions. Invasive modalities such as occipital nerve stimulation, deep brain stimulation and sphenopalatine ganglion stimulation are reserved for the most severe and intractable patients. Non-invasive options such as vagal nerve stimulation (nVNS), supraorbital nerve stimulation (nSONS) and transcranial magnetic nerve stimulation (TMS) have all emerged as potentially useful headache treatments. This review examines the evidence base for non-invasive neuromodulation in trigeminal autonomic cephalalgias and migraine. Although a number of open-label series of non-invasive neuromodulation devices have been published, there is very little controlled evidence for their use in any headache condition. Open-label evidence suggests that nVNS may have a role in the prophylactic treatment of cluster headache and there is limited evidence to suggest it may be useful in the acute treatment of cluster and potentially migraine attacks. There is limited controlled evidence to suggest a role for nSONS in the prophylactic treatment of episodic migraine but there is no evidence to support its use in cluster headache. TMS may be efficacious in the acute treatment of episodic migraine has no controlled evidence to support its use as a preventative in any headache condition. Non-invasive neuromodulation techniques are an attractive treatment option with excellent safety profiles but their use is not yet supported by high-quality randomised controlled trials.

Ineffective acute treatment of episodic migraine is associated with new-onset chronic migraine.

To test the hypothesis that ineffective acute treatment of episodic migraine (EM) is associated with an increased risk for the subsequent onset of chronic migraine (CM). In the American Migraine Prevalence and Prevention Study, respondents with EM in 2006 who completed the Migraine Treatment Optimization Questionnaire (mTOQ-4) and provided outcome data in 2007 were eligible for analyses. The mTOQ-4 is a validated questionnaire that assesses treatment efficacy based on 4 aspects of response to acute treatment. Total mTOQ-4 scores were used to define categories of acute treatment response: very poor, poor, moderate, and maximum treatment efficacy. Logistic regression models were used to examine the dichotomous outcome of transition from EM in 2006 to CM in 2007 as a function of mTOQ-4 category, adjusting for covariates. Among 5,681 eligible study respondents with EM in 2006, 3.1% progressed to CM in 2007. Only 1.9% of the group with maximum treatment efficacy developed CM. Rates of new-onset CM increased in the moderate treatment efficacy (2.7%), poor treatment efficacy (4.4%), and very poor treatment efficacy (6.8%) groups. In the fully adjusted model, the very poor treatment efficacy group had a more than 2-fold increased risk of new-onset CM (odds ratio = 2.55, 95% confidence interval 1.42-4.61) compared to the maximum treatment efficacy group. Inadequate acute treatment efficacy was associated with an increased risk of new-onset CM over the course of 1 year. Improving acute treatment outcomes might prevent new-onset CM, although reverse causality cannot be excluded.

Beta-Blockers, a Spanner in the Works for Acute Management of Migraine?

Many patients suffer with migraine and do not feel their therapeutic needs are met, particularly in acute treatment. Betablockers are inexpensive, well-tolerated medications licensed for prophylaxis of migraine but not for acute treatment of episodic migraine (EM). However, this is based on trials that are possibly too narrow. A known association exists between migraine and various psychological disorders. In particular, anxiety disorder is implicated as a trigger and a pain modulator affecting experience and reporting of migraine. This case report highlights the need for a larger randomizedcontrolled trial assessing the efficacy of beta-blockers for the acute treatment of migraines, and in particular reviewing their effect in those patients with an associated anxiety disorder.

Orally Inhaled Dihydroergotamine: A Review

Orally inhalable dihydroergotamine (iDHE), before the US Food and Drug Administration in 2013 for consideration for approval for acute treatment of episodic migraine in adults, is a user-friendly formulation of an older medication. Dihydroergotamine (DHE) has a heterogeneous receptor profile, central penetration, and persistent receptor binding that may account for its clinical prolonged benefits in acute treatment of migraine. The same features may result in the ability of DHE to reverse central sensitization and allodynia and to maintain efficacy deep into attacks. These characteristics make DHE particularly useful in treating migraine upon awakening, prolonged migraine and status migrainosus, menstrually related migraine, and for bridging patients out of medication-overuse headache/chronic migraine. The inhalable formulation has helpful pharmacokinetics, with a lower maximal serum concentration than intravenous DHE which may account for minimal nausea, and less binding to the potentially toxic serotonin2B receptor. The inhaler itself is designed for delivery of reproducible aliquots of intrapulmonary DHE with only nominal need for patient coordination. The inhalable form allows for bypassing the gastrointestinal tract in the setting of migraine nausea or vomiting, and greatly reduces first-pass effect. No drug-related serious adverse events were reported during the Phase 3 study of iDHE. Product taste and nausea were the most common side effects in both the Phase 3 regulatory trial and in the safety extension trial. Limitations for use of iDHE are those for any ergot or triptan, ie, contraindication in the setting of vascular disease. In addition, iDHE is metabolized by the cytochrome P450 3A4 liver enzymatic system. Inhalable DHE provides the promise of a new formulation of a valued medication with important clinical features, useful deep into attacks in a variety of situations.

Targeted Review: Medications for Acute Migraine Treatment

Objective:To assess the evidence base for drugs used for acute treatment of episodic migraine (headache on &lt; 14 days a month) in Canada.Methods:A detailed search strategy was employed to find relevant published clinical trials of drugs used in Canada for the acute treatment of migraine in adults. Primarily meta-analyses and systematic reviews were included. Where these were not available for a drug or were out of date, individual clinical trial reports were utilized. Only double-blind randomized clinical trials with placebo or active drug controls were included in the analysis. Recommendations and levels of evidence were graded according to the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group.Results:Eighteen acute migraine medications and two adjunctive medications were evaluated. Twelve acute medications received a strong recommendation with supporting high quality evidence for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four acute medications received a weak recommendation for use with low or moderate quality evidence (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing combination analgesics). Three of these medications were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing medications), and strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Both metoclopramide and domperidone received a strong recommendation for use with acute migraine attack medications where necessary.Conclusion:Our targeted review formulated recommendations for the available acute medications for migraine treatment according to the GRADE method. This should be helpful for practitioners who prescribe medications for acute migraine treatment.

Targeted Review: Medications for Acute Migraine Treatment

ABSTRACT:Objective:To assess the evidence base for drugs used for acute treatment of episodic migraine (headache on &lt; 14 days a month) in Canada.Methods:A detailed search strategy was employed to find relevant published clinical trials of drugs used in Canada for the acute treatment of migraine in adults. Primarily meta-analyses and systematic reviews were included. Where these were not available for a drug or were out of date, individual clinical trial reports were utilized. Only double-blind randomized clinical trials with placebo or active drug controls were included in the analysis. Recommendations and levels of evidence were graded according to the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, using a consensus group.Results:Eighteen acute migraine medications and two adjunctive medications were evaluated. Twelve acute medications received a strong recommendation with supporting high quality evidence for use in acute migraine therapy (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and acetaminophen). Four acute medications received a weak recommendation for use with low or moderate quality evidence (dihydroergotamine, ergotamine, codeine-containing combination analgesics, and tramadol-containing combination analgesics). Three of these medications were NOT recommended for routine use (ergotamine, and codeine- and tramadol-containing medications), and strong recommendations were made to avoid use of butorphanol and butalbital-containing medications. Both metoclopramide and domperidone received a strong recommendation for use with acute migraine attack medications where necessary.Conclusion:Our targeted review formulated recommendations for the available acute medications for migraine treatment according to the GRADE method. This should be helpful for practitioners who prescribe medications for acute migraine treatment.

Calcitonin Gene‐Related Peptide (CGRP) and Migraine Current Understanding and State of Development

Calcitonin gene-related peptide (CGRP) is a ubiquitous neuropeptide found at the very centers of the migraine process, both centrally and peripherally. It has been under careful study for approximately 25 years. Several CGRP-receptor antagonists are being evaluated for acute treatment of episodic migraine. Three monoclonal antibodies are being studied for prevention of episodic migraine, and 1 monoclonal antibody is being studied for prevention of chronic migraine. In this review, we discuss the role of CGRP in normal physiology and the consequences of CGRP inhibition for human homeostasis. We then review the current state of development for CGRP-receptor antagonists and CGRP monoclonal antibodies. We close by speculating on the potential clinical role of CGRP antagonism in the acute and preventive treatment of episodic and chronic migraine.