Ketorolac in the Treatment of Acute Migraine: A Systematic Review

This systematic review examined the effectiveness of parenteral ketorolac (KET) in acute migraine. Acute migraine headaches are common emergency department presentations, and despite evidence for various treatments, there is conflicting evidence regarding the use of KET. Searches of MEDLINE, EMBASE, Cochrane, CINAHL, and gray literature sources were conducted. Included studies were randomized controlled trials in which KET alone or in combination with abortive therapy was compared with placebo or other standard therapy in adult patients with acute migraine. Two reviewers assessed relevance, inclusion, and study quality independently, and agreement was measured using kappa (k). Weighted mean differences (WMD) and relative risks are reported with 95% confidence intervals (CIs). Overall, the computerized search identified 418 citations and 1414 gray literature citations. From a list of 34 potentially relevant studies (k = 0.915), 8 trials were included, involving over 321 (141 KET) patients. The median quality scores were 3 (interquartile range: 2‐4), and two used concealed allocation. There were no baseline differences in 10‐point pain scores (WMD = 0.07; 95% CI: ?0.39, 0.54). KET and meperidine resulted in similar pain scores at 60 minutes (WMD = 0.31; ?0.68, 1.29); however, KET was more effective than intranasal sumatriptan (WMD = ?4.07; 95% CI: ?6.02 to ?2.12). While there was no difference in pain relief at 60 minutes between KET and phenothiazine agents (WMD = 0.82; 95% CI: ?1.33 to 2.98), heterogeneity was high (I² = 70%). Side effect profiles were similar between KET and comparison groups. Overall, KET is an effective alternative agent for the relief of acute migraine headache in the emergency department. KET results in similar pain relief, and is less potentially addictive than meperidine and more effective than sumatriptan; however, it may not be as effective as metoclopramide/phenothiazine agents.     

Dose Range-Finding Studies With Frovatriptan in the Acute Treatment of Migraine

Objective.—To determine the optimum dose of frovatriptan for the acute treatment of migraine.
Background.—Frovatriptan is a new triptan developed for the acute treatment of migraine. The dose-response characteristics and safety of frovatriptan have been investigated across a broad range of doses from 0.5 to 40 mg.
Design.—Two randomized, placebo-controlled, double-blind, parallel-group trials, with a total of 1453 patients, were performed to determine the optimal dose of the 5-HT_1B/1D agonist, frovatriptan, for the acute treatment of migraine. The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg in the low-dose study.
Results.—At 2 hours postdosing for initial moderate or severe headache (International Headache Society grades 2 or 3), there was an approximate two-fold difference in the proportion of patients taking frovatriptan doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours postdose, and 2.5 mg was identified as the lowest effective dose for the relief of migraine and accompanying symptoms. Above 2.5 mg, no dose-response relationship was observed for any efficacy parameters. There was an increase in the incidence of adverse events from 10 mg and above, but the vast majority were rated as mild in severity and did not impact upon tolerability in a significant manner.
Conclusions.—Frovatriptan was well tolerated throughout the dose range of 0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and tolerability for the acute treatment of migraine.     

Rational Use of Lasmiditan for Acute Migraine Treatment in Adults: A Narrative Review

PurposeThis narrative review provides an update on the research that led to the development of ditans and lasmiditan for the acute treatment of migraine in adults and discusses the potential advantages and disadvantages of lasmiditan in clinical use.MethodsThe electronic databases PubMed, Scopus, and ClinicalTrials.gov were searched from database inception through January 9, 2021, to identify relevant studies. Search results were assessed for their overall relevance to this review.FindingsBecause part of the effect of the triptans is mediated by the serotonin 1F receptors, which are not present in the smooth muscle, a pure agonist of these receptors, lasmiditan, was developed. Lasmiditan is hypothesized to act on antinociceptive pathways and inhibit the calcitonin gene-related peptide release. Lasmiditan was approved by the US Food and Drug Administration in 2019 based on the results of 2 pivotal trials that found a significant difference from placebo in the percentage of patients who achieved freedom from pain and most bothersome symptom at 2 h. The main concern of lasmiditan derives from its central nervous system–related adverse effects, mainly dizziness and paraesthesia, probably attributable to its high blood brain barrier penetration. These central nervous system adverse effects impair driving performance for hours and might be suboptimal for individuals with migraine who want to quickly stop the migraine attack to resume their activities as soon as possible.ImplicationsDespite the advantage of being beneficial in the acute treatment of migraine without vasocostrictive action, lasmiditan also presents limitations, in particular the central nervous system adverse effects. Moreover, head-to-head trials against triptans and gepants are indispensable to determine the better option for patients.     

Acute Treatment of Basilar‐Type Migraine With Greater Occipital Nerve Blockade

(Headache 2010;50:1057‐1069) Basilar‐type migraine (BTM) precludes use of migraine‐specific medications such as triptans and ergots based on concerns originating from the vascular theory of migraine, although data supporting this contraindication are lacking. Availability of effective treatments for acute BTM is limited. We report a case of BTM aborted with greater occipital nerve (GON) blockade given in the setting of prominent suboccipital tenderness. GON blockade may provide an additional option in acute management of BTM. It may be particularly useful when associated with prominent ipsilateral suboccipital tenderness.     

How to Apply the AHS Evidence Assessment of the Acute Treatment of Migraine in Adults to your Patient with Migraine

The “Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies” provides levels of evidence for medication efficacy for acute treatment of migraine. The goal of this companion paper is to provide guidance on how to choose between evidence‐based treatment options, and, based on the clinical characteristics of the patient and their migraine attacks, to provide guidance on designing an individualized strategy for managing migraine attacks. The acute pharmacological treatments described in the American Headache Society evidence assessment can be divided into those initially taken by the patient during the headache phase of the migraine attack, those taken by the patient later in the attack when initial treatments fail, and those administered intravenously or intramuscularly in urgent care settings. Medications taken initially by patients in the headache phase include nonspecific analgesics such as acetaminophen and nonsteroidal anti‐inflammatory drugs (NSAIDs), triptans, and dihydroergotamine (DHE). A stratified approach to treatment is advised, with the choice of medication based on the patient's treatment needs, taking into consideration the attack severity, presence of associated symptoms such as nausea and vomiting, and the degree of migraine‐related disability. Individuals with migraine may find reassurance in having a “back‐up plan” in the event of an initial acute treatment failure. For those individuals who had a partial response to the initial acute treatment, a second dose might be indicated. When the initial treatment does not provide meaningful and sustained benefits, a treatment from a different medication class is typically chosen. Depending upon the initial treatment used, this might include NSAIDs, triptans, or DHE. Opioids or acetaminophen in combination with codeine or tramadol can be considered as part of the “back‐up plan,” provided they are used infrequently. When all patient administered treatments have failed and moderate to severe migraine symptoms remain, some individuals seek treatment in urgent care settings. The intravenous administration of antiemetics with or without an intravenous or intramuscular NSAID or DHE, or an intramuscular opioid can be considered. Patients with migraine should be encouraged to treat migraine pain early, and avoid overuse of medications.     

Migraine Treatment With Rizatriptan and Almotriptan: A Crossover Study

Background.— Rizatriptan and almotriptan are effective and well-tolerated triptans that have not been compared directly. Objective.— To evaluate the effectiveness of rizatriptan 10 mg and almotriptan for the acute treatment of migraine, in a real-world setting. Methods.— Of a large, multicenter, open-label, crossover study, we conducted a substudy to contrast the effectiveness of rizatriptan 10 mg and almotriptan 12.5 mg for the acute treatment of 2 migraine attacks in a sequential, crossover manner. Time to outcome was assessed using stopwatches. Mean and median times to onset of pain relief (PR) and pain freedom (PF) for rizatriptan and almotriptan were compared. The effect of rizatriptan on times to onset of PR and PF, adjusting for potential confounding factors (treatment sequence, treatment order, and use of rescue medication), was computed via a Cox proportional hazard model. Results.— Out of the 146 patients taking almotriptan as their usual care medication, 79 used stopwatch for both attacks. Significantly more patients taking rizatriptan achieved onset of PR within 2 hours after dosing than those taking almotriptan (88.6% vs 73.4%, P = .007). A higher proportion of patients taking rizatriptan achieved PF within 2 hours after dosing than those taking almotriptan (55.7% vs 45.6%, P = .10). Times to onset of PR and PF were significantly shorter with those patients taking rizatriptan than with those taking almotriptan (median time to PR: 45 vs 60 minutes, P = .002; median time to PF: 100 vs 135 minutes, P = .004). The adjusted proportional hazard ratios (rizatriptan vs almotriptan) for times to onset of PR and PF were 1.51 (95% confidence interval 1.20 to 1.88) and 1.42 (95% confidence interval 1.15 to 1.76), respectively. More patients were very satisfied when treating their attacks with rizatriptan than with almotriptan. Rizatriptan was preferred by most patients. Conclusions.— Times to achieve PR and PF were significantly shorter for patients using rizatriptan, as compared with those using almotriptan.     

Acute Migraine Treatment With Rizatriptan in Real World Settings – Focusing on Treatment Strategy, Effectiveness, and Behavior

Although randomized controlled trials (RCTs) are the gold standard for assessing efficacy of a drug intervention, because they are conducted in a highly selected group of patients, they do not necessarily reflect normal customary or optimized patient care. Accordingly, information from RCTs must be supplemented by outcomes research and by nonexperimental or quasi-experimental study designs. Herein, we discuss information that supplements the rigorous but sometimes rigid nature of RCTs in an effort to better understand the clinical utility of drug treatment for migraine with patient-centered outcomes in mind. We start by discussing several lessons we learned from RCTs on comparative triptan studies, followed by presenting data on outcomes studies for rizatriptan. We then briefly discuss migraine treatment behavior issues, including early treatment and adherence to treatment.     

Factors associated with triptan use in episodic migraine: results from the American Migraine Prevalence and Prevention Study

Background.— Though triptans are considered the standard of acute therapy for migraine attacks with headache‐related disability, they are used by the minority of potentially eligible persons. Understanding the socio‐demographic and headache features that predict triptan use may help to clarify barriers to optimal treatment. Objective.— To assess the sociodemographic and headache features associated with triptan use in a US population sample of persons with episodic migraine. Methods.— The American Migraine Prevalence and Prevention Study (AMPP) is a longitudinal study conducted in a representative sample of US headache sufferers. Episodic migraineurs (n = 11,388) who provided treatment data in 2005 were included in the current analyses. We assessed factors associated with triptan use through univariate and multivariate analyses. Multivariate analyses were adjusted for sociodemographic factors, headache‐related disability, cutaneous allodynia, depression, and preventive headache medication use. Results.— Among persons with episodic migraine, 18.31% reported current use of triptans for acute headache treatment. In univariate analyses, triptan use was most common in midlife (ages 30‐59), among females, and was more common in Caucasians than in African Americans. Triptan use increased with headache frequency, headache‐related disability and allodynia, but decreased among persons with depression. In multivariate analyses, female gender, Caucasian race, age 40‐49, higher levels of education (college or higher), annual household income of ≥$40,000, having health insurance, the presence of cutaneous allodynia, greater headache‐related disability, and preventive medication use for migraine were significantly associated with triptan use. Conclusions.— Less than 1 in 5 persons with migraine in the United States who were respondents to this survey used triptans for acute headache treatment over the course of a year. Several markers of severe headache, including disability and allodynia, were associated with increased triptan use. Groups less likely to get triptans included males, African Americans, older adults, and the uninsured. Predictors of use provide insight into groups with unmet treatment needs.