Introduction Of Triptans Research Articles

Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential.

Migraine is an important socioeconomic burden and is ranked the sixth cause of years of life lost because of disability in the general population and the third cause of years of life lost in people younger than 50 years. The cornerstone of pharmacological treatment is represented by the acute therapy. The serotonin (5-hydroxytryptamine [5-HT]) receptor subtype 1B/1D agonists, called triptans, are nowadays the first-line acute therapy for patients who experience moderate-to-severe migraine attacks. Unfortunately, a high percentage of patients are not satisfied with this acute treatment, either for lack of response or side effects. Moreover, their mechanism of action based on vasoconstriction makes them unsuitable for patients with previous cardio- and cerebrovascular diseases and for those with uncontrolled hypertension. Since the introduction of triptans, no other acute drug class has passed all developmental stages. The research for a new drug lacking vasoconstrictive effects led to the development of lasmiditan, a highly selective 5-HT1F receptor agonist with minimized interactions with other 5-HT receptor subtypes. Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA). Phase II and III trials had shown superiority compared to placebo and absence of typical triptan-associated adverse events (AEs). Most of the AEs were related to the central nervous system, depending on the high permeability through the blood–brain barrier and mild to moderate severity. The results of ongoing long-term Phase III trials will determine whether lasmiditan will become available in the market, and then active triptan comparator studies will assess patients’ preference. Future studies could then explore the safety during pregnancy and breastfeeding or the risk that overuse of lasmiditan leads to medication overuse headache.

Cost-Effectiveness Analysis of Early versus Non-Early Intervention in Acute Migraine Based on Evidence from the ‘Act when Mild’ Study

In spite of the important progress made in the abortive treatment of acute migraine episodes since the introduction of triptans, reduction of pain and associated symptoms is in many cases still not as effective nor as fast as would be desirable. Recent research pays more attention to the timing of the treatment, and taking triptans early in the course of an attack when pain is still mild has been found more efficacious than the usual strategy of waiting for the attack to develop to a higher pain intensity level. To investigate the cost effectiveness of early versus non-early intervention with almotriptan in acute migraine. An economic evaluation was conducted from the perspectives of French society and the French public health system based on patient-level data collected in the AwM (Act when Mild) study, a placebo-controlled trial that compared the response to early and non-early treatment of acute migraine with almotriptan. Incremental cost-effectiveness ratios (ICERs) were determined in terms of QALYs, migraine hours and productive time lost. Costs were expressed in Euros (year 2010 values). Bootstrapping was used to derive cost-effectiveness acceptability curves. Early treatment has shown to lead to shorter attack duration, less productive time lost, better quality of life, and is, with 92% probability, overall cost saving from a societal point of view. In terms of drug costs only, however, non-early treatment is less expensive. From the public health system perspective, the (bootstrap) mean ICER of early treatment amounts to €0.38 per migraine hour avoided, €1.29 per hour of productive time lost avoided, and €14,296 per QALY gained. Considering willingness-to-pay values of approximately €1 to avoid an hour of migraine, €10 to avoid the loss of a productive hour, or €30,000 to gain one QALY, the approximate probability that early treatment is cost effective is 90%, 90% and 70%, respectively. These results remain robust in different scenarios for the major elements of the economic evaluation. Compared with non-early treatment, a strategy of early treatment of acute migraine with almotriptan when pain is still mild is, with high probability, cost saving from the French societal perspective and can be considered cost effective from the public health system point of view.

Clinical Pharmacology of Current and Future Drugs for the Acute Treatment of Migraine: A Review and An Update

Migraine is a common disorder with a female prevalence of 17% and a male prevalence of 9%. Migraine is most often disabling and the patients need treatment of the attacks. The introduction of triptans has been a revolution for many migraine patients but only a minority of patients use these specific drugs. The pharmacokinetics and efficacy and tolerability of triptans are reviewed. The triptans can most likely with advantage be combined with NSAIDs and prokinetic drugs. Among future drugs, CGRP receptor antagonists are the most promising. These drugs have shown excellent tolerability with no more adverse events than placebo, but only one quarter of migraine patients have been pain-free after 2 hours in phase III studies. The development of current CGRP antagonists has been stopped.

New Agents for Acute Treatment of Migraine: CGRP Receptor Antagonists, iNOS Inhibitors

The treatment of migraine was advanced dramatically with the introduction of triptans in the early 1990s. Despite the substantial improvement in the quality of life that triptans have brought to many migraineurs, a substantial cohort of patients remain highly disabled by attacks and need new therapeutic approaches, which ideally should be quick-acting, have no vasoconstrictor activity, and have a longer duration of action and be better tolerated than current therapies. The calcitonin gene-related peptide (CGRP) receptor antagonists (gepants)-olcegepant (BIBN 4096 BS), telcagepant (MK-0974), MK3207, and BI 44370 TA-are effective in treating acute migraine. They have no vasoconstrictive properties, fewer adverse effects, and may act longer than triptans. Their development has been complicated by liver toxicity issues when used as preventives. Results from studies with BI 44370 TA do not support broad concern about a class effect, and further studies are ongoing in this respect. Many experimental studies and clinical trials suggest that nitric oxide may have a role in the pathophysiology of migraine. Therefore, the inhibition of nitric oxide synthase (NOS) for the acute or prophylactic treatment of migraine offered a feasible approach; as inducible NOS (iNOS) is involved in several pain states, such as inflammatory pain, it appeared to be an attractive target. However, despite high selectivity and potency, the iNOS inhibitor GW274150 was not effective for acute treatment or prophylaxis of migraine, suggesting that iNOS is very unlikely to be a promising target.

Current Understanding and Treatment of Headache Disorders

As general practitioners become increasingly adept at prescribing triptans and preventive treatment, neurologists are more likely to see patients who are refractory to standard therapies. The most pressing concern for physicians and patients is excluding secondary headache. Reversible cerebral vasoconstriction syndrome is increasingly recognized as an underdiagnosed cause of headache, and may present as a sudden-onset thunderclap headache. The past few years have brought exciting new advances in the understanding of migraine pathophysiology including new genes for migraine and discovery of a new pathway for light sensitivity. After almost 20 years since the introduction of triptans, calcitonin gene-related peptide antagonists now appear to be effective as acute migraine treatment for patients with poor response or contraindications to triptans. Finally, onabotulinumtoxin A has become only the 6th medication approved by the US Food and Drug Administration for migraine prevention and the first approved for chronic migraine. This article aims to highlight these exciting new topics in the treatment and understanding of headache disorders, which will help neurologists better treat and explain the disorders to their patients. Thunderclap headache is a neurologic emergency originally defined as a severe, sudden-onset headache; ruptured intracranial aneurysm had to be suspected and ruled out.1 In addition to subarachnoid hemorrhage, many other disorders, such as spontaneous CSF leak, cerebral venous thrombosis, pituitary apoplexy, sphenoid sinusitis, carotid or vertebral dissection, stroke, hypertensive emergency, third ventricle colloid cyst, and even an unruptured aneurysm, can present with thunderclap headache.2 Many patients with thunderclap headache have segmental cerebral vasoconstriction likely related to a disturbance in the control of vascular tone.3 Originally called Call-Fleming syndrome, it is now known as reversible cerebral vasoconstriction syndrome (RCVS).4 In almost all cases, cerebral vasoconstriction resolves within a few weeks. Angiography (conventional, MRI, or CT angiography) is crucial to make the diagnosis. …

Efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 100 mg: an evidence-based analysis

Acute migraine attacks have a strong impact on quality of life and require immediate therapeutic intervention to achieve rapid pain relief. The introduction of triptans into the market in 1993 has increased the therapeutic options in migraine patients considerably. The seven currently available triptans show many similar characteristics but there are also some clinically relevant pharmacological differences. Rizatriptan 10 mg has demonstrated, in a head-to-head study, higher response rates and a more rapid onset of action than sumatriptan 100 mg, together with a favorable tolerability profile. Meta-analyses of double-blind placebo-controlled studies confirmed the superior efficacy of rizatriptan. Owing to the limited efficacy of sumatriptan, a more effective triptan treatment is needed in the majority of patients with acute migraine attacks.

The Burden of Migraine in the United States: Current and Emerging Perspectives on Disease Management and Economic Analysis

Objectives Migraine is often perceived as a low-impact condition that imposes a limited burden to society and the health-care system. This study reviews the current understanding of the burden of migraine in the U.S., the history of economic understanding of migraine treatment and identifies emergent trends for future studies evaluating clinical and economic outcomes of migraine treatment. Methods This study traced the history of economic articles published on migraine by performing a literature search using PubMed MEDLINE database and ancestral searches of relevant articles. The intention was not to provide an exhaustive review of every article or adjudicate between studies with different findings. Results Migraine affects millions of individuals worldwide, generally during the most productive years of a person's life. Studies show that migraineurs are underdiagnosed, undertreated, and experience substantial decreases in functioning and productivity, which in turn translates into diminished quality of life for individuals, and financial burdens to both health-care systems and employers. Economic evaluations of migraine therapies have evolved with new clinical developments beginning with cognitive-behavioral therapy, introduction of triptans, concern over medication overuse, and emergence of migraine prophylaxis. Now recent clinical studies suggest that migraine may be a progressive disease with cardiovascular, cerebrovascular, and long-term neurologic effects. Conclusions Migraine imposes a substantial burden on patients, families, employers and societies. The economic standards by which migraine and treatment are evaluated have evolved in response to clinical developments. Emerging evidence suggests that migraine is a chronic and progressive disease. If confirmed, approaches to acute and prophylactic treatments and economic evaluations of migraine treatment may require major reconsideration.

Recent Advancements in Anti-Migraine Drug Research: Focus on Attempts to Decrease Neuronal Hyperexcitability

Migraine is a painful, sometimes debilitating disorder, which is frequently associated with various neurological symptoms. Its prevalence in the population is higher than that of any other neurological disorders, thus the burden of this disease on society is considerable. Although the introduction of triptans nearly two decades ago revolutionized the treatment of the disease there is still a huge unmet need regarding drugs with better properties. Formerly, migraine therapy primarily aimed at treating the pathological alterations of meningeal blood vessels that are thought to directly initiate a migraine headache attack. By now, it has been increasingly recognized by drug companies that abnormal neural function may be more important in the development of the disease and also in triggering an attack. Migraine is associated with an increased neuronal excitability and episodes of cortical spreading depression. Understanding the molecular mechanisms underlying the abnormal functioning of over-activated neuronal circuits may help to identify novel anti-migraine drug targets. Besides a general description of the pathophysiology and pharmacotherapy of migraine this review paper aims at discussing the possible drug targets through which migraine-related hyperexcitability and over-excitation can be attenuated. It will be shown how these new ideas appear in the recent patent literature.

Triptans vs Other Drugs for Acute Migraine. Are There Differences in Efficacy? A Comment

The introduction of triptans in migraine treatment was apparently a revolution. Comparative randomized clinical trials (RCTs) with triptan and other drugs do not give a clear-cut picture. Oral triptans are superior to oral ergotamine most likely because the bioavailability oral of ergotamine is extremely low (<1%). Compared with NSAIDs, in most cases aspirin, triptans were not superior and in several RCTs triptans caused more adverse events than aspirin plus metoclopramide. Guidelines for treatment of migraine should be evidence-based. It is suggested that based on current evidence, effervescent aspirin should be the first-line drug for the treatment of migraine. Aspirin is also much cheaper than the triptans.

Overview of treatment of acute migraine

AbstractAcute migraine is a major public health problem with a significant economic burden secondary to short‐term disability and absenteeism. Treatment of acute migraine is always challenging for primary care physicians and family practitioners, as there are no set universal guidelines for the treatment of acute migraine. In acute migraine treatment, nonsteroidal anti‐inflammatory drugs (NSAIDs), migraine‐specific medications, and adjunctive medications are used, depending on the severity of acute migraine attacks. Treatment of acute migraine has changed drastically since the introduction of the triptans. However, even after the introduction of triptans, nearly one‐half of migraine sufferers are still being treated with over‐the‐counter medications. In this literature review, we mention drugs that are being used in the treatment of acute migraine and their level of evidence recommended by the U.S. Headache Consortium. This article gives special emphasis to pharmacokinetics and clinical characteristics of all available triptans. Drug Dev Res 68:441–448, 2007. © 2008 Wiley‐Liss, Inc.

Non-oral formulations of triptans and their use in acute migraine

The introduction of triptans (5-HT (1B/1D) agonists) into clinical practice has expanded the therapeutic options for doctors treating migraine sufferers. The triptans are available in several different formulations such as conventional oral tablets, orally disintegrating wafers, subcutaneous injections, nasal sprays, and suppositories, which provide an excellent opportunity to tailor therapy to individual patients' needs. Although the oral formulations are the most popular with patients, they are not the most appropriate route of administration for drug delivery during the migraine attack. Due to gastrointestinal dysmotility, the intestinal absorption of any triptan administered orally may be impaired and treatment effects become inconsistent. For this reason, triptans preferably should be prescribed in a non-oral formulation (injection, nasal spray, or suppository). Parenteral administration of a triptan is more likely to provide relief of symptoms, even when it is used later in the course of the migraine attack.

Up to date on the use of triptans for child and adolescent migraine: state of the art

The introduction of triptans, in the early 1990s, has improved the therapy for acute migraine attack, offering a new quality of life for those patients who suffer from this disabling neurological disorder. Epidemiological data point out that about 10% of school–age children suffer from migraine, with a progressive increase in incidence and prevalence up to the threshold of adulthood. The increase in extent and prevalence of migraine from the years of growth stresses the importance of the application and adjustment of ad hoc therapeutic (either pharmacological or not) and diagnostic measures. Indeed, the peculiar neurobiological and psychological aspects which are typical of an “evolving” organism preclude the use, by simple “transposition” or “proportion”, of the knowledge acquired from adult–targeted studies. That requires the implementation of studies to analyze the specific responses of children and adolescents to the triptans. To date, the studies on such issues are absolutely insufficient to draw definitive conclusions and indications for the use of triptans for child and adolescent migraineurs.