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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 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 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 -
Therapeutic Drug Monitoring Feb 2008The triptans are a class of tryptamine-based drugs indicated for in the treatment of migraine headaches. The triptans act as serotonin (5-hydroxytriptamine) (5-HT)... (Review)
Review
The triptans are a class of tryptamine-based drugs indicated for in the treatment of migraine headaches. The triptans act as serotonin (5-hydroxytriptamine) (5-HT) agonists by binding to various serotonin receptors, causing vasoconstriction and neuronal inhibition to alleviate migraines. There are 7 types of triptans currently available on the U.S. market: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. The objective of this study was to examine the use and effects of triptans in pregnancy. Although three of the triptans have pregnancy registries maintained by the manufacturer, triptan use in pregnancy has not been extensively studied. Information on the use of sumatriptan during pregnancy is relatively more abundant, because it has been on the market longer than the other triptans and may also have a higher percentage of the market share. There are no data to suggest teratogenicity for any of the triptans, although preterm birth rates appear to be elevated.
Topics: Animals; Female; Humans; Migraine Disorders; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Serotonin Receptor Agonists; Tryptamines
PubMed: 18223456
DOI: 10.1097/FTD.0b013e318162c89b -
Neurotherapeutics : the Journal of the... Apr 2010
Topics: Headache; Humans; Neuropeptides; Nitric Oxide Synthase; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists
PubMed: 20430312
DOI: 10.1016/j.nurt.2010.03.007 -
The Cochrane Database of Systematic... Jul 2013This is an updated version of the original Cochrane review published in Issue 4, 2010 (Law 2010). Cluster headache is an uncommon,severely painful, and disabling... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 4, 2010 (Law 2010). Cluster headache is an uncommon,severely painful, and disabling condition, with rapid onset. Validated treatment options are limited; first-line therapy includes inhaled oxygen. Other therapies such as intranasal lignocaine and ergotamine are not as commonly used and are less well studied. Triptans are successfully used to treat migraine attacks and they may also be useful for cluster headache.
OBJECTIVES
To assess the efficacy and tolerability of the triptan class of drugs compared to placebo and other active interventions in the acute treatment of episodic and chronic cluster headache in adult patients.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, ClinicalTrials.gov, and reference lists for studies from inception to 22 January 2010 for the original review, and from 2009 to 4 April 2013 for this update.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled studies of triptans for acute treatment of cluster headache episodes.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted data. Numbers of participants with different levels of pain relief,requiring rescue medication, and experiencing adverse events and headache-associated symptoms in treatment and control groups were used to calculate relative risk and numbers needed to treat for benefit (NNT) and harm (NNH).
MAIN RESULTS
New searches in 2013 did not identify any relevant new studies.All six included studies used a single dose of triptan to treat an attack of moderate to severe pain intensity. Subcutaneous sumatriptan was given to 131 participants at a 6 mg dose, and 88 at a 12 mg dose. Oral or intranasal zolmitriptan was given to 231 participants ata 5 mg dose, and 223 at a 10 mg dose. Placebo was given to 326 participants.Triptans were more effective than placebo for headache relief and pain-free responses. By 15 minutes after treatment with subcutaneous sumatriptan 6 mg, 48% of participants were pain-free and 75% had no pain or mild pain (17% and 32% respectively with placebo).NNTs for subcutaneous sumatriptan 6 mg were 3.3 (95% CI 2.4 to 5.0) and 2.4 (1.9 to 3.2) respectively. Intranasal zolmitriptan 10mg was of less benefit, with 12% of participants pain-free and 28% with no or mild pain (3% and 7% respectively with placebo).NNTs for intranasal zolmitriptan 10 mg were 11 (6.4 to 49) and 4.9 (3.3 to 9.2) respectively.
AUTHORS' CONCLUSIONS
Based on limited data, subcutaneous sumatriptan 6 mg was superior to intranasal zolmitriptan 5 mg or 10 mg for rapid (15 minute)responses, which are important in this condition. Oral routes of administration are not appropriate.
Topics: Cluster Headache; Humans; Oxazolidinones; Randomized Controlled Trials as Topic; Serotonin Receptor Agonists; Sumatriptan; Tryptamines
PubMed: 24353996
DOI: 10.1002/14651858.CD008042.pub3 -
Neurotherapeutics : the Journal of the... Apr 2018Migraine is a common neurological disease characterised by the presence of attacks of unilateral, severe head pain accompanied by other symptoms. Although it has been... (Review)
Review
Migraine is a common neurological disease characterised by the presence of attacks of unilateral, severe head pain accompanied by other symptoms. Although it has been classified as the sixth most disabling disorder, the available therapeutic options to treat this condition have not progressed accordingly. The advance in the development of 5-HT receptor agonists for migraine, including 5-HT and 5-HT receptor agonists, has meant a major step forward towards the progression of a better treatment for migraine. Triptans have a limited efficacy, and their effect on vasoconstriction makes them unsafe for patients with cardiovascular and/or cerebrovascular diseases. Therefore, novel effective antimigraine treatments without cardiovascular effects are required, such as selective 5-HT receptor agonists (ditans). Lasmiditan has much higher affinity for the 5-HT receptor than for the vasoconstrictor 5-HT receptor. This has been confirmed in preclinical studies performed to date, where lasmiditan showed no effect on vasoconstriction, and in clinical trials, where healthy individuals and patients did not report cardiac events due to treatment with lasmiditan, although it should be confirmed in larger cohorts. Lasmiditan crosses the blood-brain barrier and may act both centrally and peripherally on 5-HT receptors expressed on trigeminal neurons. It is a well-tolerated compound that does not induce major adverse events. Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk. This review will focus on the characterisation of 5-HT receptor agonists and their effects as migraine therapies.
Topics: Animals; Benzamides; Clinical Trials as Topic; Humans; Migraine Disorders; Piperidines; Pyridines; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin 5-HT1 Receptor Agonists; Treatment Outcome; Tryptamines; Vasoconstriction; Receptor, Serotonin, 5-HT1F
PubMed: 29488143
DOI: 10.1007/s13311-018-0615-6 -
PloS One 2021To characterize nationwide utilization patterns of migraine pharmacotherapy before, during, and after pregnancy in women with triptan use.
OBJECTIVE
To characterize nationwide utilization patterns of migraine pharmacotherapy before, during, and after pregnancy in women with triptan use.
METHODS
Population-based data were obtained by linking the Medical Birth Registry of Norway and the Norwegian Prescription Database from 2006 to 2017. We included 22,940 pregnancies among 19,669 women with at least one filled triptan prescription, a proxy for migraine, in the year before pregnancy or during pregnancy. The population was classified into four groups: i) continuers; ii) discontinuers; iii) initiators, and vi) post-partum re-initiators. Participant characteristics and prescription fills for other drugs such as analgesics, antinauseants, and preventive drugs among the groups were examined, along with an array of triptan utilization parameters.
RESULTS
In total, 20.0% of the women were classified as triptan continuers, 54.1% as discontinuers, 8.0% as initiators, and 17.6% as re-initiators. Extended use of triptans (≥15 daily drug doses/month) occurred among 6.9% of the continuers in the first trimester. The top 10% of triptan continuers and initiators accounted for 41% (95% CI: 39.2% - 42.5%) and 33% (95% CI: 30.3% - 35.8%) of the triptan volume, respectively. Triptan continuers and initiators had similar patterns of acute co-medication during pregnancy, but use of preventive drugs was more common among the continuers before, during, and after pregnancy.
CONCLUSION
Among women using triptans before and during pregnancy, one in four continued triptan treatment during pregnancy, and extended triptan use was relatively low. Triptan discontinuation during and in the year after pregnancy was common. Use of other acute migraine treatments was higher among both continuers and initiators of triptans. Women using preventive migraine treatment were most commonly triptan continuers and re-initiators after pregnancy. Prescribing to and counseling of women with migraine should be tailored to the condition severity and their information needs to promote optimal migraine management in pregnancy.
Topics: Adult; Analgesics; Drug Utilization; Female; Humans; Migraine Disorders; Norway; Pharmaceutical Preparations; Pregnancy; Pregnancy Complications; Serotonin 5-HT1 Receptor Agonists; Tryptamines
PubMed: 34424941
DOI: 10.1371/journal.pone.0256214