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Headache 2015Although triptans are widely used in the acute management of migraine, there is uncertainty around the comparative efficacy of triptans among each other and vs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although triptans are widely used in the acute management of migraine, there is uncertainty around the comparative efficacy of triptans among each other and vs non-triptan migraine treatments. We conducted systematic reviews and network meta-analyses to compare the relative efficacy of triptans (alone or in combination with other drugs) for acute treatment of migraines compared with other triptan agents, non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA), acetaminophen, ergots, opioids, or anti-emetics.
METHODS
The Cochrane Library, MEDLINE, and EMBASE were searched for randomized controlled trials that compared triptans (alone or in combination with other drugs) with placebo-controlled or active migraine treatments. Study selection, data extraction, and quality assessment were completed independently by multiple reviewers. Outcome data were combined and analyzed using a Bayesian network meta-analysis. For each outcome, odds ratios, relative risks, and absolute probability of response were calculated.
RESULTS
A total of 133 randomized controlled trials met the inclusion criteria. Standard dose triptans relieved headaches within 2 hours in 42 to 76% of patients, and 2-hour sustained freedom from pain was achieved for 18 to 50% of patients. Standard dose triptans provided sustained headache relief at 24 hours in 29 to 50% of patients, and sustained freedom from pain in 18 to 33% of patients. Use of rescue medications ranged from 20 to 34%. For 2-hour headache relief, standard dose triptan achieved better outcomes (42 to 76% response) than ergots (38%); equal or better outcomes than NSAIDs, ASA, and acetaminophen (46 to 52%); and equal or slightly worse outcomes than combination therapy (62 to 80%). Among individual triptans, sumatriptan subcutaneous injection, rizatriptan ODT, zolmitriptan ODT, and eletriptan tablets were associated with the most favorable outcomes.
INTERPRETATION/CONCLUSIONS
Triptans are effective for migraine relief. Standard dose triptans are associated with better outcomes than ergots, and most triptans are associated with equal or better outcomes compared with NSAIDs, ASA, and acetaminophen. Use of triptans in combination with ASA or acetaminophen, or using alternative modes of administration such as injectables, may be associated with slightly better outcomes than standard dose triptan tablets.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Administration Schedule; Humans; Migraine Disorders; Oxazolidinones; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists; Treatment Outcome; Tryptamines
PubMed: 26178694
DOI: 10.1111/head.12601 -
Expert Opinion on Pharmacotherapy Mar 2017Recent triptan development has focused on new administration methods and formulations, triptan combination therapies, treatment in menstrually related migraines, and... (Review)
Review
Recent triptan development has focused on new administration methods and formulations, triptan combination therapies, treatment in menstrually related migraines, and novel serotonin receptor subtype agonists (5HTf). Areas covered: Clinical triptan research related to migraine was reviewed, analyzing EMBASE and PUBMED data bases from 01/01/2011 to 06/29/2016, with a focus on clinical trials of class 1 or 2 level of evidence. There have been advances in drug combination therapies, as well as administration devices that aid in ease of use, increase efficacy, and decrease adverse reactions. Some new agents and devices have similar or less efficacy compared to previous generic triptan formulations. New agents have action at the 5HTf receptor subtype, and avoid vascular side effects of classic 5Ht1b/d agonists, however adverse reactions may limit their clinic use. Long half-life triptans, frovatriptan and naratriptan, do appear to have good benefit in menstral related migraine. Expert opinion: Recent advances in triptan development can offer some advantages to migraine therapy and patient preferences, but have a much higher cost compared to individual generic triptan agents. In the coming years, triptan advances with high efficacy, limiting ADRs and cost are welcomed, in this regard the 5HT1b/d triptans are already well established.
Topics: Carbazoles; Humans; Migraine Disorders; Piperidines; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Tryptamines
PubMed: 28129702
DOI: 10.1080/14656566.2017.1288721 -
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 -
The American Journal of Medicine Jan 2018Headache, an almost universal human experience, is one of the most common complaints encountered in medicine and neurology. Described and categorized since antiquity,... (Review)
Review
Headache, an almost universal human experience, is one of the most common complaints encountered in medicine and neurology. Described and categorized since antiquity, with the first classification by Aretaeus of Cappadocia, other classifications followed. The evaluation of this condition may be straightforward or challenging, and, though often benign, headache may prove to be an ominous symptom. This review discusses the current diagnosis and classification of headache disorders and principles of management, with a focus on migraine, tension-type headache, trigeminal autonomic cephalgias, and various types of daily headache.
Topics: Analgesics; Headache; Headache Disorders; Humans; Serotonin 5-HT1 Receptor Agonists
PubMed: 28939471
DOI: 10.1016/j.amjmed.2017.09.005 -
Current Clinical Pharmacology 2017Migraine is a recurrent, disabling, complex and highly prevalent neurological disorder. The mystery behind the cause of migraine is continuously evolving, according to... (Review)
Review
Migraine is a recurrent, disabling, complex and highly prevalent neurological disorder. The mystery behind the cause of migraine is continuously evolving, according to the scientific understanding of the disease. This growing understanding helps to identify novel therapeutic targets for the management of migraine to treat the ailing migraineurs. The role of serotonin (5HT) in migraine is recognized to be the cornerstone for the currently available therapeutic options namely ergot alkaloids and triptans. The role of mediators such as Calcitonin Gene-Related Peptide (CGRP), nitric oxide and excitatory neurotransmitter glutamate, has been realized and ignited the development of drugs targeting these factors. Lasmiditan, known as a Neurally Active Anti- Migraine Agent (NAAMA) is a specific 5HT1F agonist, developed as a new group named as 'ditans'. The drug was designed and developed to meet the unmet needs of currently available medications to circumvent the vascular adverse effects. Having a group of drugs with a nonvascular mechanism of action, devoid of unwanted effects with a different spectrum of indication and contraindications, is the need of the hour to expand the armamentarium available to tackle acute migraine attack.
Topics: Animals; Benzamides; Drug Design; Humans; Migraine Disorders; Molecular Structure; Piperidines; Pyridines; Receptors, Serotonin; Serotonin; Serotonin 5-HT1 Receptor Agonists; Signal Transduction; Structure-Activity Relationship; Treatment Outcome; Receptor, Serotonin, 5-HT1F
PubMed: 28425871
DOI: 10.2174/1574884712666170419155048 -
Drugs of Today (Barcelona, Spain : 1998) Jul 2019Depression is a neuropsychiatric disorder that affects more than 350 million people all over the world. There are psychological and pharmacological treatments for... (Review)
Review
Depression is a neuropsychiatric disorder that affects more than 350 million people all over the world. There are psychological and pharmacological treatments for depression which mainly focus on monoaminergic neurotransmission theory. The main concern regarding available antidepressants is the lag period and other side effects, such as sexual dysfunction. Gepirone is a drug of the azapirone group which is a 5-HT1A receptor agonist belonging to the buspirone family. Gepirone is under clinical development and has been shown to be more effective than selective serotonin reuptake inhibitors (SSRIs), as this drug treats the psychiatric disorders without causing sexual dysfunction, which limits the use of SSRIs. It possesses greater selectivity for the 5-HT1A receptor than SSRIs. Clinical studies have shown that gepirone has differential action at pre- and postsynaptic 5-HT1A receptors. Gepirone extended-release tablets (gepirone ER, Travivo) showed promising effects in adult outpatients for the treatment of major depressive disorder (MDD) in a double-blind, randomized, placebo-controlled clinical study. Gepirone also showed an antianxiety effect in a placebo-controlled trial in generalized anxiety disorder. Absorption of gepirone is increased when administered with food as there is no substantial change in Cmax and half-life but it significantly increases AUC and mean residence time. Gepirone undergoes first-pass metabolism and its major metabolites are 1- (2-pyrimidinyl)-piperazine (1-PP) and 3-OH-gepirone, both of which are pharmacologically active. In addition to its better efficacy, gepirone is well tolerated and the major adverse effects observed have been nausea, dizziness and lightheadedness. Evidence from preclinical and clinical studies revealed that gepirone could be a breakthrough therapeutic agent in the treatment of anxiety and MDD.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Pyrimidines; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists
PubMed: 31347611
DOI: 10.1358/dot.2019.55.7.2958474 -
Pain May 2005
Review
Topics: Animals; Brain; Humans; Migraine Disorders; Receptors, Serotonin, 5-HT1; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Sumatriptan
PubMed: 15836963
DOI: 10.1016/j.pain.2005.03.008 -
Headache May 2022To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years.
OBJECTIVE
To gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years.
BACKGROUND
Beyond the age of 50 years, migraine is still common-yet the incidence of vascular disorders increases. Triptans, medications for treating migraine attacks, are vasoconstrictive drugs and contraindicated in persons with vascular disorders.
METHODS
Based on a nationwide insurance database from 2011, we compared the prescription of vascular drugs (identified by Anatomical Therapeutic Chemical codes), vascular diagnoses and hospitalizations, between triptan users greater than 50 years and a matched control group.
RESULTS
Of the 3,116,000 persons over 50 years, 13,833 (0.44%) had at least one triptan prescription; 11,202 (81%) were women. Thirty percent of the triptan users (13,833/47,336 persons) were over 50 years. Of those over 50 years, 6832 (49.4%) had at least one vascular drug and 870 (6.3%) had at least one inpatient vascular diagnosis; 15.7% (2166 of 13,833 users) overused triptans. We compared triptan-users to 41,400 nonusers, using a 1:3 match. In triptan-users, prescriptions of cardiac therapies and beta blockers were significantly more common (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.24-1.47 and OR = 1.19, 95% CI = 1.14-1.25, respectively); whereas prescriptions of calcium channel blockers and renin/angiotensin inhibitors were significantly less common (OR = 0.82, 95% CI = 0.76-0.88 and OR = 0.75, 95% CI = 0.72-0.79, respectively). The prescriptions of antihypertensive, diuretic, and antilipidemic drugs as well as platelet inhibitors and direct thrombin inhibitors did not differ in users and nonusers. Triptan users had significantly more hospital stays (OR = 1.39, 95% CI = 1.33-1.45); however, the number of days spent in the hospital and more importantly the frequency of inpatient vascular diagnoses did not differ statistically significantly between the two groups.
CONCLUSION
In persons over 50 years of age, a prescription of triptans is common. Vascular comorbidity is comparable in users and nonusers of triptans showing that triptans are prescribed despite vascular comorbidity and suggesting that triptan use does not increase vascular risk in patients with migraine over the age of 50 years. Nevertheless, regular evaluation for contraindications against triptans and for vascular risk factors is recommended in this age group.
Topics: Cohort Studies; Comorbidity; Female; Humans; Insurance; Male; Middle Aged; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Tryptamines
PubMed: 35593784
DOI: 10.1111/head.14304 -
The Journal of Headache and Pain Jun 2011Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and... (Review)
Review
Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant. The upper part of the efficacy curve of the triptans is generally flat, the so-called ceiling effect; and none of the oral triptans, even in high doses, are as effective as subcutaneous sumatriptan, In contrast, AEs increases with increasing dose without a ceiling effect. The optimal dose for the triptans is mainly determined by tolerability. Telcagepant has an excellent tolerability and can be used in migraine patients with cardiovascular co-morbidity. Based on the literature the triptans and telcagepant are rated in a table for efficacy and tolerability.
Topics: Azepines; Calcitonin Gene-Related Peptide Receptor Antagonists; Humans; Imidazoles; Migraine Disorders; Serotonin 5-HT1 Receptor Agonists; Tryptamines
PubMed: 21350792
DOI: 10.1007/s10194-011-0309-5 -
Handbook of Clinical Neurology 2024The advent of the triptans revolutionized acute migraine treatment. The older migraine-specific drugs, the ergot alkaloids (ergotamine and dihydroergotamine), also... (Review)
Review
The advent of the triptans revolutionized acute migraine treatment. The older migraine-specific drugs, the ergot alkaloids (ergotamine and dihydroergotamine), also relieve migraine attacks through agonism at the 5-HT and 5-HT receptors, but the triptans have much greater specificity for these receptors. Unlike the ergot alkaloids, the triptans do not activate many other receptor types, and therefore are much better tolerated. This reduction in side effects greatly enhanced their clinical utility as it allowed a far greater proportion of patients to take a full therapeutic dose. As a result, the clinical use of ergotamine is minimal today, although dihydroergotamine still has a significant clinical role. There is extensive evidence that the seven triptans available today, sumatriptan, zolmitriptan, rizatriptan, eletriptan, naratriptan, almotriptan, and frovatriptan, are effective in the acute treatment of migraine. Available formulations include oral tablets, orally dissolving tablets, subcutaneous injections, nasal sprays, and in some countries, rectal suppositories. For optimal benefit, therapy needs to be individualized for a given patient both regarding the triptan chosen and the formulation. This chapter discusses the ergot alkaloids and the triptans, including mechanism of action, evidence for efficacy, clinical use, and adverse effects.
Topics: Humans; Dihydroergotamine; Ergotamine; Migraine Disorders; Serotonin; Tryptamines; Serotonin 5-HT1 Receptor Agonists
PubMed: 38307644
DOI: 10.1016/B978-0-12-823357-3.00008-2