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American Family Physician Feb 2018Migraine is a primary headache disorder characterized by recurrent attacks. Acetaminophen, nonsteroidal anti-inflammatory drugs, triptans, antiemetics, ergot alkaloids,...
Migraine is a primary headache disorder characterized by recurrent attacks. Acetaminophen, nonsteroidal anti-inflammatory drugs, triptans, antiemetics, ergot alkaloids, and combination analgesics have evidence supporting their effectiveness in the treatment of migraine. Acetaminophen and nonsteroidal anti-inflammatory drugs are first-line treatments for mild to moderate migraines, whereas triptans are first-line treatments for moderate to severe migraines. Although triptans are effective, they may be expensive. Other medications such as dihydroergotamine and antiemetics are recommended for use as second- or third-line therapy for select patients or for those with refractory migraine. The pharmacologic properties, potential adverse effects, cost, and routes of administration vary widely, allowing therapy to be individualized based on the pattern and severity of attacks. Several treatment principles, including taking medication early in an attack and using a stratified treatment approach, can help ensure that migraine treatment is cost-effective.
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Curriculum; Education, Medical, Continuing; Humans; Lysergic Acid Diethylamide; Migraine Disorders; Tryptamines
PubMed: 29671521
DOI: No ID Found -
Drugs Jan 2022Cluster headache belongs to the group of trigeminal autonomic headaches. This review summarizes drug therapy of cluster attacks and prophylactic treatment.... (Review)
Review
Cluster headache belongs to the group of trigeminal autonomic headaches. This review summarizes drug therapy of cluster attacks and prophylactic treatment. Neurostimulation methods are not addressed. The therapy for acute cluster attacks includes inhalation of 100% oxygen, subcutaneous administration of sumatriptan, and intranasal application of sumatriptan or zolmitriptan. Bridging therapy, which is used until oral prophylactic therapy is effective, is performed either with oral prednisolone or with a pharmacological block of the major occipital nerves. Best documented drugs for preventive treatment of cluster headache are verapamil and lithium, and possibly effective drugs are gabapentin, topiramate, divalproex sodium, and melatonin. The efficacy of monoclonal antibodies to the calcitonin gene-related peptide so far has been only demonstrated for episodic cluster headache. Several drug therapies are being investigated including ketamine, onabotulinumtoxinA, lysergic acid, and sodium oxybate.
Topics: Cluster Headache; Drug Administration Routes; Humans; Lithium; Oxazolidinones; Oxygen Inhalation Therapy; Prednisolone; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Tryptamines; Verapamil
PubMed: 34919214
DOI: 10.1007/s40265-021-01658-z -
JAMA Jun 2021Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Migraine is common and can be associated with significant morbidity, and several treatment options exist for acute therapy.
OBJECTIVE
To evaluate the benefits and harms associated with acute treatments for episodic migraine in adults.
DATA SOURCES
Multiple databases from database inception to February 24, 2021.
STUDY SELECTION
Randomized clinical trials and systematic reviews that assessed effectiveness or harms of acute therapy for migraine attacks.
DATA EXTRACTION AND SYNTHESIS
Independent reviewers selected studies and extracted data. Meta-analysis was performed with the DerSimonian-Laird random-effects model with Hartung-Knapp-Sidik-Jonkman variance correction or by using a fixed-effect model based on the Mantel-Haenszel method if the number of studies was small.
MAIN OUTCOMES AND MEASURES
The main outcomes included pain freedom, pain relief, sustained pain freedom, sustained pain relief, and adverse events. The strength of evidence (SOE) was graded with the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews.
FINDINGS
Evidence on triptans and nonsteroidal anti-inflammatory drugs was summarized from 15 systematic reviews. For other interventions, 115 randomized clinical trials with 28 803 patients were included. Compared with placebo, triptans and nonsteroidal anti-inflammatory drugs used individually were significantly associated with reduced pain at 2 hours and 1 day (moderate to high SOE) and increased risk of mild and transient adverse events. Compared with placebo, calcitonin gene-related peptide receptor antagonists (low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (low SOE), butorphanol (low SOE), and tramadol in combination with acetaminophen (low SOE) were significantly associated with pain reduction and increase in mild adverse events. The findings for opioids were based on low or insufficient SOE. Several nonpharmacologic treatments were significantly associated with improved pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant difference in adverse events was found between nonpharmacologic treatments and sham.
CONCLUSIONS AND RELEVANCE
There are several acute treatments for migraine, with varying strength of supporting evidence. Use of triptans, nonsteroidal anti-inflammatory drugs, acetaminophen, dihydroergotamine, calcitonin gene-related peptide antagonists, lasmiditan, and some nonpharmacologic treatments was associated with improved pain and function. The evidence for many other interventions, including opioids, was limited.
Topics: Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antiemetics; Calcitonin Gene-Related Peptide Receptor Antagonists; Electric Stimulation Therapy; Ergot Alkaloids; Evidence-Based Medicine; Humans; Migraine Disorders; Pain Measurement; Serotonin Receptor Agonists; Tryptamines
PubMed: 34128998
DOI: 10.1001/jama.2021.7939 -
JAMA Network Open Oct 2021New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
New therapeutic classes of migraine-specific treatment have been developed, including 5-hydroxytryptamine1F receptor agonists (lasmiditan) and calcitonin gene-related peptide antagonists (rimegepant and ubrogepant).
OBJECTIVE
To compare outcomes associated with the use of lasmiditan, rimegepant, and ubrogepant vs triptans for acute management of migraine headaches.
DATA SOURCES
The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to March 5, 2020.
STUDY SELECTION
Double-blind randomized clinical trials examining current available migraine-specific acute treatments were included.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was applied to extract the data according to a predetermined list of variables of interest, and all network meta-analyses were conducted using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was the odds ratio (OR) for freedom from pain (hereafter referred to as pain freedom) at 2 hours after the dose, and the secondary outcomes were ORs for pain relief at 2 hours after the dose and any adverse events.
RESULTS
A total of 64 randomized clinical trials were included (46 442 participants; 74%-87% women; age range, 36-43 years). Most of the included treatments were associated with reduced pain at 2 hours compared with placebo. Most triptans were associated with higher ORs for pain freedom at 2 hours compared with lasmiditan (range: OR, 1.72 [95% CI, 1.06-2.80] to OR, 3.40 [95% CI, 2.12-5.44]), rimegepant (range: OR, 1.58 [95% CI, 1.07-2.33] to OR, 3.13 [95% CI, 2.16-4.52]), and ubrogepant (range: OR, 1.54 [95% CI, 1.00-2.37] to OR, 3.05 [95% CI, 2.02-4.60]). Most triptans were associated with higher ORs for pain relief at 2 hours compared with lasmiditan (range: OR, 1.46 [95% CI, 1.09-1.96] to OR, 3.31 [95% CI, 2.41-4.55]), rimegepant (range: OR, 1.33 [95% CI, 1.01-1.76] to OR, 3.01 [95% CI, 2.33-3.88]), and ubrogepant (range: OR, 1.38 [95% CI, 1.02-1.88] to OR, 3.13 [95% CI, 2.35-4.15]). The comparisons between lasmiditan, rimegepant, and ubrogepant were not statistically significant for both pain freedom and pain relief at 2 hours. Lasmiditan was associated with the highest risk of any adverse events, and certain triptans (rizatriptan, sumatriptan, and zolmitriptan) were also associated with a higher risk of any adverse events than the calcitonin gene-related peptide antagonists.
CONCLUSIONS AND RELEVANCE
For pain freedom or pain relief at 2 hours after the dose, lasmiditan, rimegepant, and ubrogepant were associated with higher ORs compared with placebo but lower ORs compared with most triptans. However, the lack of cardiovascular risks for these new classes of migraine-specific treatments may offer an alternative to triptans.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Tryptamines
PubMed: 34633423
DOI: 10.1001/jamanetworkopen.2021.28544 -
The Cochrane Database of Systematic... Apr 2023Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of... (Review)
Review
BACKGROUND
Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. The unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of pharmacological interventions have been used, or proposed to be used, at the time of a vestibular migraine attack to help reduce the severity or resolve the symptoms. These are predominantly based on treatments that are in use for headache migraine, with the belief that the underlying pathophysiology of these conditions is similar. OBJECTIVES: To assess the benefits and harms of pharmacological interventions used to relieve acute attacks of vestibular migraine.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing triptans, ergot alkaloids, dopamine antagonists, antihistamines, 5-HT3 receptor antagonists, gepants (CGRP receptor antagonists), magnesium, paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 2 hours, 2 to 12 hours, > 12 to 72 hours. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included two RCTs with a total of 133 participants, both of which compared the use of triptans to placebo for an acute attack of vestibular migraine. One study was a parallel-group RCT (of 114 participants, 75% female). This compared the use of 10 mg rizatriptan to placebo. The second study was a smaller, cross-over RCT (of 19 participants, 70% female). This compared the use of 2.5 mg zolmitriptan to placebo. Triptans may result in little or no difference in the proportion of people whose vertigo improves at up to two hours after taking the medication. However, the evidence was very uncertain (risk ratio 0.84, 95% confidence interval 0.66 to 1.07; 2 studies; based on 262 attacks of vestibular migraine treated in 124 participants; very low-certainty evidence). We did not identify any evidence on the change in vertigo using a continuous scale. Only one of the studies assessed serious adverse events. No events were noted in either group, but as the sample size was small we cannot be sure if there are risks associated with taking triptans for this condition (0/75 receiving triptans, 0/39 receiving placebo; 1 study; 114 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for interventions used to treat acute attacks of vestibular migraine is very sparse. We identified only two studies, both of which assessed the use of triptans. We rated all the evidence as very low-certainty, meaning that we have little confidence in the effect estimates and cannot be sure if triptans have any effect on the symptoms of vestibular migraine. Although we identified sparse information on potential harms of treatment in this review, the use of triptans for other conditions (such as headache migraine) is known to be associated with some adverse effects. We did not identify any placebo-controlled randomised trials for other interventions that may be used for this condition. Further research is needed to identify whether any interventions help to improve the symptoms of vestibular migraine attacks and to determine if there are side effects associated with their use.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Anti-Inflammatory Agents, Non-Steroidal; Vertigo; Headache; Tryptamines
PubMed: 37042545
DOI: 10.1002/14651858.CD015322.pub2 -
The Journal of Headache and Pain Oct 2022Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the... (Review)
Review
BACKGROUND
Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder.
MAIN BODY
The Consensus process included a preliminary literature review, a Delphi round and a subsequent open discussion. According to the Consensus Panel, effective treatment of a migraine attack is to be defined on patient well-being featured by a) improvement of headache, b) relief of non-pain symptoms and c) absence of adverse events. An attack is considered effectively treated if patient's well-being, as defined above, is restored within 2 hours and for at least 24 hours. An individual with migraine is considered as triptan-responder when the given triptan leads to effective acute attack treatment in at least three out of four migraine attacks. On the other hand, an individual with migraine is considered triptan non-responder in the presence of failure of a single triptan (not matching the definition of triptan-responder). The Consensus Panel defined an individual with migraine as triptan-resistant in the presence of failure of at least 2 triptans; triptan refractory, in the presence of failure to at least 3 triptans, including subcutaneous formulation; triptan ineligibile in the presence of an acknowledged contraindication to triptan use, as specified in the summary of product characteristics.
CONCLUSIONS
The novel definitions can be useful in clinical practice for the assessment of acute attack treatments patients with migraine. They may be helpful in identifying people not responding to triptans and in need for novel acute migraine treatments. The definitions will also be of help in standardizing research on migraine acute care.
Topics: Consensus; Headache; Humans; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Transcription Factors; Tryptamines
PubMed: 36224519
DOI: 10.1186/s10194-022-01502-z -
Headache Feb 2022The ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses...
OBJECTIVE
The ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses symptomatology, consulting, diagnosis, treatment, and impact of migraine in the United States.
BACKGROUND
Regularly updating population-based views of migraine in the United States provides a method for assessing the quality of ongoing migraine care and identifying unmet needs.
METHODS
The OVERCOME (US) 2018 migraine cohort involved: (I) creating a demographically representative sample of US adults using quota sampling (n = 97,478), (II) identifying people with active migraine in the past year via a validated migraine diagnostic questionnaire and/or self-reported medical diagnosis of migraine (n = 24,272), and (III) assessing consultation, diagnosis, and treatment of migraine (n = 21,143). The current manuscript evaluated whether those with low frequency episodic migraine (LFEM; 0-3 monthly headache days) differed from other categories on outcomes of interest.
RESULTS
Among the migraine cohort (n = 21,143), 19,888 (94.1%) met our International Classification of Headache Disorders, 3rd edition-based case definition of migraine and 12,905 (61.0%) self-reported a medical diagnosis of migraine. Respondents' mean (SD) age was 42.2 (15.0) years; 15,697 (74.2%) were women. Having at least moderate disability was common (n = 8965; 42.4%) and around half (n = 10,783; 51.0%) had consulted a medical professional for migraine care in the past year. Only 4792 (22.7%) of respondents were currently using a triptan. Overall, 8539 (40.4%) were eligible for migraine preventive medication and 3555 (16.8%) were currently using migraine preventive medication. Those with LFEM differed from moderate and high frequency episodic migraine and chronic migraine on nearly all measures of consulting, diagnosis, and treatment.
CONCLUSION
The OVERCOME (US) 2018 cohort revealed slow but steady progress in diagnosis and preventive treatment of migraine. However, despite significant impact among the population, many with migraine have unmet needs related to consulting for migraine, migraine diagnosis, and getting potentially beneficial migraine treatment. Moreover, it demonstrated the heterogeneity and varying unmet needs within episodic migraine.
Topics: Adult; Cohort Studies; Disabled Persons; Female; Humans; Longitudinal Studies; Male; Migraine Disorders; Referral and Consultation; Self Report; Serotonin 5-HT1 Receptor Agonists; Surveys and Questionnaires; Tryptamines; United States
PubMed: 35076091
DOI: 10.1111/head.14259 -
Cephalalgia : An International Journal... Feb 2023This post-hoc analysis from three phase 3 treatment trials of rimegepant 75 mg - an oral small molecule calcitonin gene-related peptide receptor antagonist for acute...
BACKGROUND
This post-hoc analysis from three phase 3 treatment trials of rimegepant 75 mg - an oral small molecule calcitonin gene-related peptide receptor antagonist for acute and preventive treatment of migraine - assessed efficacy in adults with migraine based on triptan treatment experience.
METHODS
Participants were assigned to one of four groups based on triptan treatment experience: insufficient response (e.g. lack of efficacy and/or poor tolerability) to 1 triptan, insufficient response to ≥2 triptans, current triptan users, and triptan-naïve participants. The co-primary efficacy endpoints were pain freedom and most bothersome symptom freedom at two hours postdose.
RESULTS
In the three trials (N = 3507; rimegepant n = 1749, placebo n = 1758), 1235 (35.2%) participants had a history of insufficient response to 1 triptan (n = 910 [25.9%]) or ≥2 triptans (n = 325 [9.3%]), and 2272 (64.8%) had no history of insufficient response to triptans (current use = 595 [17.0%], naïve = 1677 [47.8%]). Rimegepant was effective on the co-primary endpoints in all subgroups ( ≤ 0.013), except for freedom from the most bothersome symptom in the triptan-naïve group ( = 0.06). No differences on co-primary endpoints were found in pairwise comparisons of rimegepant-treated participants.
CONCLUSIONS
Rimegepant was effective for the acute treatment of migraine in adults with a history of insufficient response to 1 or ≥2 triptans and in current triptan users. Efficacy on co-primary endpoints did not differ based on the number of insufficient triptan responses.Trial registration: Clinicaltrials.gov: NCT03235479, NCT03237845, NCT03461757.
Topics: Adult; Humans; Migraine Disorders; Piperidines; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists; Tryptamines; Clinical Trials, Phase III as Topic
PubMed: 36739511
DOI: 10.1177/03331024221141686 -
American Family Physician Jan 2022Cluster headache, the most common form of trigeminal autonomic cephalgia, is a rare primary headache disorder that affects less than 1% of the population. The mean age... (Review)
Review
Cluster headache, the most common form of trigeminal autonomic cephalgia, is a rare primary headache disorder that affects less than 1% of the population. The mean age of onset is 30 years, and it is two to three times more common in males. Cluster headache consists of attacks of severe unilateral pain located in the orbital, supraorbital, and/or temporal region that occur from every other day up to eight times per day and last from 15 to 180 minutes. The pain is associated with ipsilateral autonomic symptoms (most commonly lacrimation, conjunctival injection, nasal congestion or rhinorrhea, ptosis, edema of the eyelid, sweating of the forehead or face, and miosis) and a sense of agitation or restlessness. Attacks occur in clusters, called bouts, and are episodic or chronic. Common triggers include alcohol, nitroglycerin, food containing nitrates, and strong odors. Abortive treatments include triptans and oxygen; transitional treatments include steroids and suboccipital steroid injections; and prophylactic treatments include verapamil, lithium, melatonin, and topiramate. Newer treatments for cluster headache include galcanezumab, neurostimulation, and somatostatin receptor agonists.
Topics: Adult; Alcohol Drinking; Cluster Headache; Female; Humans; Male; Nitrates; Nitroglycerin; Oxygen; Pain; Physical Examination; Risk Factors; Steroids; Temporal Lobe; Time Factors; Tryptamines; Vagus Nerve Stimulation; Young Adult
PubMed: 35029932
DOI: No ID Found -
Advances in Experimental Medicine and... 2017Drugs targeting aquaporins have broad potential clinical applications, including cancer, obesity, edema, glaucoma, skin diseases and others. The astrocyte water channel... (Review)
Review
Drugs targeting aquaporins have broad potential clinical applications, including cancer, obesity, edema, glaucoma, skin diseases and others. The astrocyte water channel aquaporin-4 is a particularly compelling target because of its role of brain water movement, neuroexcitation and glia scarring, and because it is the target of pathogenic autoantibodies in the neuroinflammatory demyelinating disease neuromyelitis optica . There has been considerable interest in the identification of small molecule inhibitors of aquaporins, with various candidates emerging from testing of known ion transport inhibitors, as well as compound screening and computational chemistry. However, in general, the activity of reported aquaporin inhibitors has not been confirmed on retesting, which may be due to technical problems in water transport assays used in the original identification studies, and the challenges in modulating the activity of small, compact, pore-containing membrane proteins. We review here the state of the field of aquaporin-modulating small molecules and biologics, and the challenges and opportunities in moving forward.
Topics: Animals; Aquaporin 4; Biological Transport; Brain Edema; Gene Expression Regulation; Humans; Molecular Targeted Therapy; Neuromyelitis Optica; Osmolar Concentration; Osmotic Pressure; Protein Isoforms; Sumatriptan; Thiadiazoles; Triazoles; Tryptamines; Water
PubMed: 28258578
DOI: 10.1007/978-94-024-1057-0_16