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1
Evers, di Stefan, and e. Carlo Lisotto. "Algoritmo del trattamento dell’emicrania." European Neurological Review 8, no. 2 (2013): 149. http://dx.doi.org/10.17925/enr.2013.08.02.149a.
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Nel corso di un simposio satellite tenutosi nel corso del XXI Congresso Mondiale di Neurologia 2013 è stata presentata la terza edizione della Classificazione Internazionale delle Cefalee, con una descrizione sintetica delle variazioni apportate rispetto alla precedente edizione, che riflettono l’importanza della diagnosi basata sulla fenomenologia piuttosto che sull’eziologia dei disturbi. Per questo motivo è stato creato un algoritmo di trattamento per l’emicrania, mirato a valutare il percorso corretto e a rafforzare il messaggio che i triptani rappresentano l’opzione terapeutica più efficace. Nel corso del simposio sono state inoltre discusse le nuove linee guida sui parametri di efficacia utilizzati negli studi clinici, sottolineando l’importanza della protratta scomparsa del dolore senza recidiva, un parametro di grande rilevanza per i pazienti. Gli studi incrossoverdi preferenza del paziente rappresentano un reale confronto intra-individuale tra diversi triptani e consentono di valutareendpointsmultipli definiti dalla preferenza del paziente invece che dallo sperimentatore. Negli studi clinici frovatriptan ha mostrato una tollerabilità favorevole e un effetto protratto nel tempo, con un tasso di recidive inferiore a quello riportato con gli altri triptani. Questi risultati sono stati ottenuti dai diversi studi di preferenza condotti in Italia e in altri paesi europei.
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Marcus, Steven C., Anand R. Shewale, Stephen D. Silberstein, Richard B. Lipton, William B. Young, Hema N. Viswanathan, and Jalpa A. Doshi. "Comparison of healthcare resource utilization and costs among patients with migraine with potentially adequate and insufficient triptan response." Cephalalgia 40, no. 7 (March 29, 2020): 639–49. http://dx.doi.org/10.1177/0333102420915167.
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Background Triptans are the most commonly prescribed acute treatments for migraine; however, not all triptan users experience adequate response. Information on real-world resource use and costs associated with triptan insufficient response are limited. Methods A retrospective claims analysis using US commercial health plan data between 2012 and 2015 assessed healthcare resource use and costs in adults with a migraine diagnosis newly initiating triptans. Patients who either did not refill triptans but used other non-triptan medications or refilled triptans but also filled non-triptan medications over a 24-month follow-up period were designated as potential triptan insufficient responders. Patients who continued filling only triptans (i.e. triptan-only continuers) were designated as potential adequate responders. All-cause and migraine-related resource use and total (medical and pharmacy) costs over months 1–12 and months 13–24 were compared between triptan-only continuers and potential triptan insufficient responders. Results Among 10,509 new triptan users, 4371 (41%) were triptan-only continuers, 3102 (30%) were potential triptan insufficient responders, and 3036 (29%) did not refill their index triptan or fill non-triptan medications over 24 months’ follow-up. Opioids were the most commonly used non-triptan treatment (68%) among potential triptan insufficient responders over 24 months of follow-up. Adjusted mean all-cause and migraine-related total costs were $5449 and $2905 higher, respectively, among potential triptan insufficient responders versus triptan-only continuers over the first 12 months. Conclusions In a US commercial health plan, almost one-third of new triptan users were potential triptan insufficient responders and the majority filled opioid prescriptions. Potential triptan insufficient responder patients had significantly higher all-cause and migraine-related healthcare utilization and costs than triptan-only continuers.
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Panconesi, A., E. Pavone, M. Franchini, N. Mennuti, ML Bartolozzi, L. Guidi, and R. Banfi. "Triptans: Low utilization and high turnover in the general population." Cephalalgia 30, no. 5 (October 1, 2009): 576–81. http://dx.doi.org/10.1111/j.1468-2982.2009.02001.x.
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Studies performed in selected populations have shown a poor utilization of triptans for migraine. Our study was aimed at establishing patterns of triptans utilization in a large community using the pharmaceutical prescriptions database of two consecutive years in a regional Health Authority in Italy. About 0.5% of the population observed received triptans prescriptions in a year, but > 50% of the cases received only one prescription. On the other hand, 46% of triptan users did not receive a triptan prescription in the following year (past users): in 80% of cases, patients received only 1–2 triptan packages. The evaluation of the discontinued triptan type has shown percentages varying between 30 and 70%. The percentage of triptan users who received a triptan prescription for the first time in the successive year of study (new users) was 52%. These findings together highlight a high turnover in triptans utilization. Less than 15% of subjects received more than one triptan product in the 2 years. In conclusion, we observed a low percentage of triptan users and a low rate of utilization, associated with a high percentage of discontinuation and new utilization (high turnover), without any substantial increase in triptans utilization during the years. All these data probably do not support optimal satisfaction with triptan therapy.
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Lipton, Richard B., Steven C. Marcus, Anand R. Shewale, David W. Dodick, Hema N. Viswanathan, and Jalpa A. Doshi. "Acute treatment patterns in patients with migraine newly initiating a triptan." Cephalalgia 40, no. 5 (March 5, 2020): 437–47. http://dx.doi.org/10.1177/0333102420905307.
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Background Triptans are the most commonly used acute treatment for migraine. This study evaluated real-world treatment patterns following an initial triptan prescription to understand refill rates and use of non-triptan medications for the acute treatment of migraine. Methods Commercially-insured adult patients over 18 years of age with a triptan prescription between 1/1/2013 to 31/12/2013 were identified from the Optum Clinformatics™ Data Mart database, with date of the first triptan fill designated as index date. Inclusion was limited to those with no fills for a triptan in the 12 months prior to index date (i.e. new users or initiators of triptans) and continuous enrollment in the 12 months pre- and 24 months post-index date. Fills for index triptan, non-index triptan, and other acute treatments for migraine were assessed for up to 24 months post-index. Results Among 10,509 patients, 50.8% did not refill the initial triptan within 12 months and 43.6% did not refill within 24 months. In the 12 months post-index, 90.5% of patients used only one type of triptan, 8.4% used two different triptans, and 1.0% used three or more triptans. Among patients with and without a triptan refill, use of opioids (39% vs. 42%), non-steroidal anti-inflammatory drugs (22% vs. 22%), and butalbital-containing products (9% vs. 10%) were similar. Conclusion More than half of those who newly initiated a triptan did not refill their initial prescription, and less than 1 in 10 used two or more triptans within 12 months. High rates of non-triptan acute medication use were found over 12 and 24 months of follow-up, most commonly opioids.
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Lipton, Richard B., Andrew Blumenfeld, Christopher M. Jensen, Robert Croop, Alexandra Thiry, Gilbert L’Italien, Beth A. Morris, Vladimir Coric, and Peter J. Goadsby. "Efficacy of rimegepant for the acute treatment of migraine based on triptan treatment experience: Pooled results from three phase 3 randomized clinical trials." Cephalalgia 43, no. 2 (February 2023): 033310242211416. http://dx.doi.org/10.1177/03331024221141686.
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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 ( p ≤ 0.013), except for freedom from the most bothersome symptom in the triptan-naïve group ( p = 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
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Davidsson, Olafur B., Isa A. Olofsson, Lisette JA Kogelman, Michael Asger Andersen, Klaus Rostgaard, Henrik Hjalgrim, Jes Olesen, and Thomas Folkmann Hansen. "Twenty-five years of triptans – a nationwide population study." Cephalalgia 41, no. 8 (February 14, 2021): 894–904. http://dx.doi.org/10.1177/0333102421991809.
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Background The efficacy of triptans as the main acute treatment strategy for migraine headache at the population-wide level needs to be understood to inform clinical decision-making. We summarise key trends in triptan use using more than 25 years of Danish nationwide data. Methods We conducted a nationwide register-based cohort study based on all Danish residents with access to public healthcare between 1 January 1994 and 31 October 2019 and summarise informative trends of all purchases of triptans in Denmark in the same period. Complete purchase records of Sumatriptan, Naratriptan, Zolmitriptan, Rizatriptan, Almotriptan, Eletriptan, and Frovatriptan were used. Findings Over a 25-year period, triptan use increased from 345 to 945 defined daily doses (DDD) per 1000 inhabitants per year and the yearly prevalence of triptan use increased from 5.17 to 14.57 per 1000 inhabitants. Between 2014 and 2019, 12.3% of the Danish migraine population purchased a triptan. Following their initial purchase, 43% of patients had not repurchased triptans within 5 years. At most, 10% of patients indicating triptan discontinuation tried more than one triptan. The prevalence of triptan overuse, defined as having purchased at least 20 DDDs of triptans per month for 3 consecutive months, increased in parallel with the prevalence of triptan use, prevalent in 56 of every 1000 triptan users every year between 2014 and 2019. Interpretation In a cohort with access to free clinical consultations and low medication costs, we observed low rates of triptan adherence, likely due to disappointing efficacy and/or unpleasant side effects rather than economic considerations. Triptan success continues to be hindered by poor implementation of clinical guidelines and high rates of treatment discontinuance.
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Katić, Božena J., Srini Rajagopalan, Tony W. Ho, Ya-Ting Chen, and X. Henry Hu. "Triptan persistency among newly initiated users in a pharmacy claims database." Cephalalgia 31, no. 4 (October 11, 2010): 488–500. http://dx.doi.org/10.1177/0333102410383058.
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Objective Our study was conducted to describe prescription refill patterns among patients newly treated with triptans. Background Although triptans are efficacious in treating migraine headache, the persistency of triptan use among newly initiated users has not been well described. Methods From a US pharmacy claims database, we identified patients receiving new triptan monotherapy prescriptions from 2001 to 2005. Prescription refill information was gathered for two years for each patient. Persistency was defined as sustained refills of the index triptan prescription, regardless of duration between refills. Results Of 40,892 patients receiving a new triptan prescription, 53.8% (N=22031) did not persistently refill their index triptan. Of these, 25.5% discontinued prescription migraine therapy, 7.4% switched to a different triptan, and 67.1% switched to a non-triptan migraine medication at the time of their first refill. Only 46.2% of patients received at least one persistent refill. Conclusions Migraine patients were more likely to discontinue their triptan after their index prescription than at any other time in their prescription refill history. The majority of patients did not persistently refill triptans, but filled prescriptions for non-specific migraine therapies such as opioids and non-steroidal anti-inflammatory drugs. Reasons for triptan discontinuation warrant further investigation.
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Lucas, C., J.-P. Auray, A.-F. Gaudin, J.-F. Dartigues, G. Duru, P. Henry, M. Lantéri-Minet, A. Pradalier, G. Chazot, and A. El Hasnaoui. "Use and Misuse of Triptans in France: Data from the Grim2000 Population Survey." Cephalalgia 24, no. 3 (March 2004): 197–205. http://dx.doi.org/10.1111/j.1468-2982.2003.00651.x.
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The extent and nature of triptan use for headache relief has been evaluated in a large epidemiological survey in the French general population. Over 25 000 individuals were screened for headache and for triptan use. Of this sample, 290 triptan users were identified from whom extensive data on headache characteristics and healthcare resource consumption were obtained. The use of triptans is relatively infrequent, 0.2% in the general population, with only 7.5% of migraine sufferers using these drugs. The majority of triptan users were female (80%) and presented headache characteristics typical of migraine (80%). The remaining 20% of subjects were thus using triptans for headache types in which the utility of these drugs has not been demonstrated. Among migraineurs, triptan consumers reported more frequent and severe headaches than non-consumers, and reported a higher incidence of nausea and vomiting. The principal determinant of triptan prescription was consultation with a general practitioner (GP), which may itself have been triggered by the severity of the headaches. GPs, rather than specialists, are the primary prescribers of triptans in France.
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Ng-Mak, Daisy S., Ya-Ting Chen, Tony W. Ho, Bianca Stanford, and Montse Roset. "Results of a 2-year retrospective cohort study of newly prescribed triptan users in European nationwide practice databases." Cephalalgia 32, no. 12 (July 24, 2012): 875–87. http://dx.doi.org/10.1177/0333102412449929.
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Objective: This study was conducted to characterize prescription refill patterns for triptans among European patients with new prescriptions of triptans. Background: Persistency with prescriptions of triptan monotherapy for migraine headache among newly prescribed users in European primary-care practices has not been well described. Methods: Using electronic medical databases in the UK ( N = 3618), France ( N = 2051) and Germany ( N = 954), we conducted a retrospective cohort analysis to identify refill patterns over 2 years among migraineurs receiving new prescriptions of triptan monotherapy in 2006. Results: Of all patients, >33% of migraineurs with new triptan prescriptions received ≥1 refill of their index triptan prescriptions (UK, 44.3%; France, 34.2%; Germany, 37.7%). More than 50% never received index-triptan refill prescriptions (UK, 55.7%; France, 65.8%; Germany, 63.3%). Small proportions of patients (<7.0%) switched to alternative triptans, and even fewer switched to different prescription-medication classes (UK and Germany, 2.3%; France, 4.0%). More than 48% of patients received no further prescriptions for migraine after index prescriptions (UK, 48.5%; France, 54.9%; Germany, 54.7%). After the second year, >83.0% of patients in each country had no further prescriptions for migraine medications, <14.0% remained persistent with index prescriptions, <4.0% switched to other triptans, and <3.0% switched to alternative medication classes. Conclusions: In migraine patients who received new prescriptions of triptan monotherapy from their primary-care physicians, poor triptan prescription refill frequency was observed in Europe. Although consistent with potential clinical challenges in migraine management, our findings should be interpreted with caution given certain inherent limitations associated with the database study design. Further research is warranted to confirm our findings and to identify reasons for, or predictors of, triptan discontinuation.
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Pavone, E., R. Banfi, M. Vaiani, and A. Panconesi. "Patterns of Triptans Use: A Study Based on the Records of a Community Pharmaceutical Department." Cephalalgia 27, no. 9 (September 2007): 1000–1004. http://dx.doi.org/10.1111/j.1468-2982.2007.01401.x.
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Studies performed in selected populations show that the use of triptans for migraine is low. Our study was aimed at establishing patterns of triptan utilization in a large community using the drug prescription database of a regional Health Authority in Italy. In a population of 224 065 residents, 0.55% received at least one prescription of triptans in 1 year: 77.9% were female and 22.1% male. Oral dosage forms accounted for 94% of prescriptions. About 60% of patients received a single prescription (containing one or two packages) of one triptan in 1 year. Age distribution showed that 7% of patients were aged >65 years. They received 14% of packages, prevalently sumatriptan and zolmitriptan (the two triptans with the longest commercialization in Italy); 5.7% of patients received 40% of packages. Moreover, 3.2% of triptans users received >120 dosage units in the year in the form of tablets (>10 single doses/month), and were potential triptan abusers. Our data indicate suboptimal treatment of migraine patients and also incorrect treatment of some patients (potential triptans abusers, the elderly).
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Tauqeer, Fatima, Mollie Wood, Sarah Hjorth, Angela Lupattelli, and Hedvig Nordeng. "Perinatal use of triptans and other drugs for migraine—A nationwide drug utilization study." PLOS ONE 16, no. 8 (August 23, 2021): e0256214. http://dx.doi.org/10.1371/journal.pone.0256214.
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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.
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Ferrari, Anna, Luca Spaccapelo, and Emilio Sternieri. "Pharmacoepidemiology of triptans in a headache centre." Cephalalgia 30, no. 7 (March 17, 2010): 847–54. http://dx.doi.org/10.1177/0333102409357956.
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Aims: The aims of this survey were: (i) to examine the pharmacoepidemiology of triptans in a headache centre; (ii) to compare the characteristics of patients who continued to take triptans with those of patients who had discontinued them. Methods: We enrolled all migraine patients according to ICHD-II criteria, ensuring they were over 18 years of age, consecutively examined during a follow-up visit at the Headache Centre of the University Hospital of Modena from October 2008 to March 2009. Only patients who had used or were using a triptan were included. A specific questionnaire about the use and tolerability of triptans was created for the study and administered to every patient. Results: On the whole, 343 patients (migraine without aura: 72%; chronic migraine: 26%; migraine with aura: 2%; mean age 40.4 ± 10 years) had used or were using triptans. Most patients (72%) continued to use triptans, above all for their efficacy. The minority (28%) discontinuing them were younger and suffered from less severe migraine; 59% of them had discontinued triptans because of adverse effects. Indeed, 92% of these patients versus 57% of patients who were currently using triptans reported adverse effects ( p < .0001, Fisher’s exact test). The number of patients reporting adverse effects significantly decreased with age ( r = −0.230, p < .005, simple linear regression analysis). The triptan discontinued by the highest percentage of patients (84%) was subcutaneous 6 mg sumatriptan. Significantly more patients reported adverse effects with subcutaneous 6 mg (89%) and tablet 100 mg sumatriptan (67%) than with any other triptan. Conclusions: The increase of the tolerability of triptans with age could partly explain why younger patients suffering from less severe migraine tend to discontinue triptans more than older patients suffering from more severe migraine. In the latter, the efficacy and better tolerability (but not necessarily safety) of triptans could foster the overuse of these medications.
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Pascual, J. "Almotriptan in Triptan-Naïve Patients: New Evidence of Benefits." Cephalalgia 28, no. 2_suppl (September 2008): 14–20. http://dx.doi.org/10.1111/j.1468-2982.2008.01686.x.
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Although triptans represent the standard of care for migraine that is severe, disabling and/or suboptimally responsive to migraine non-specific analgesia, they are often underused in clinical practice. Simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) may provide effective treatment in some patients, but it is an inadequate response to these drugs that drives the therapeutic progression to triptans at the end of the traditional ‘step-care’ approach. However, there are several disadvantages to this approach. It may cause patients to lose confidence in their physician during this hierarchical ‘trial-and-error’ search for optimal treatment when prescribed medications are ineffective, leading them to cease consulting before triptans are tried. It may also result in a protracted time interval of suboptimal treatment, with unnecessary suffering in patients who are triptan candidates. The alternative approach of ‘stratified care’, in which medication is prescribed according to the severity of symptoms, enables triptans to be used earlier in the treatment plan, especially when triptan candidates are given a choice between simple analgesic/NSAID and triptan medication from the start. This raises the question about the efficacy of triptans in triptan-naïve (TN) patients. A recent exploratory post-hoc analysis compared the effect of almotriptan 12.5 mg in TN patients ( n = 342) with that in triptan-experienced patients ( n = 237). Almotriptan was effective in both cohorts with a consistent trend in favour of the efficacy of almotriptan in TN patients, notably for sustained pain freedom (SPF) and SPF plus no adverse events. Moreover, both headache recurrence at 24 h and the use of rescue medication was lower in the TN patients, whereas tolerability was equally good in both cohorts. These findings indicate that TN patients can expect excellent symptom control when they progress from non-specific analgesia to treatment with almotriptan and support the earlier use of triptans in line with the stratified care paradigm.
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Viana, Michele, Armando A. Genazzani, Salvatore Terrazzino, Giuseppe Nappi, and Peter J. Goadsby. "Triptan nonresponders: Do they exist and who are they?" Cephalalgia 33, no. 11 (April 5, 2013): 891–96. http://dx.doi.org/10.1177/0333102413480756.
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Background: Triptans represent the best treatment option for most migraine attacks, although this is not as well studied as it might be in controlled trials. Their efficacy and tolerability vary, both between agents, and from patient to patient, with about 30%–40% of patients not responding adequately to therapy. As yet unexplained, the failure of one triptan does not predict failure with another, and therefore triptan nonresponders cannot be defined as individuals who have failed a single triptan. Five clinical studies provide evidence that switching from a triptan that is ineffective to a second one can result in effective treatment in a proportion of patients. Systematic studies investigating whether there are patients who do not respond to all triptans in all formulations are lacking. Methods: Here we discuss the importance of identifying triptan nonresponders, the literature supporting their existence, and the issues to be resolved to design trials to investigate this. Conclusion: So far, no scientific data about the presence of a triptan nonresponder population are available. We propose a pragmatic study design to assess the existence of this subpopulation, recognizing the complexity of the question and the likelihood that more than one issue is at play in nonresponders.
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Spielmann, Kevin, Angela Kayser, Evelin Beck, Reinhard Meister, and Christof Schaefer. "Pregnancy outcome after anti-migraine triptan use: A prospective observational cohort study." Cephalalgia 38, no. 6 (July 31, 2017): 1081–92. http://dx.doi.org/10.1177/0333102417724152.
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Objective The objective of our study is to assess the impact of triptan exposure on pregnancy outcome. Methods We performed a prospective observational cohort study with 432 pregnant women exposed to triptans and enrolled by the German Embryotox system. Pregnancy outcomes were compared with a migraine and a non-migraine comparison cohort. Primary objectives were major birth defects and spontaneous abortion; secondary endpoints were preterm delivery, birth weight, pregnancy complications and the rate of electively terminated pregnancies. Results Compared to a non-migraine cohort the rates of major birth defects (ORadj 0.84; 95% CI 0.4–1.9), spontaneous abortions (ORadj 1.20; 95% CI 0.9–1.7), preterm delivery (ORadj 1.01; 95% CI 0.7–1.5), and preeclampsia (ORadj 1.33; 95% CI 0.7–2.5) were not increased in triptan-exposed pregnancies. Conclusions Our findings support the evidence that triptans are not major teratogens. When compellingly needed during pregnancy, sumatriptan as the best studied triptan appears an acceptable treatment option. A detailed fetal ultrasound should be offered in cases of first trimester exposure to less well-studied triptans. Trial registration number in German Clinical Trials Register: DRKS00007660
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Braunstein, David, Anne Donnet, Vincent Pradel, Vincent Sciortino, Véronique Allaria-Lapierre, Michel Lantéri-Minet, and Joëlle Micallef. "Triptans use and overuse: A pharmacoepidemiology study from the French health insurance system database covering 4.1 million people." Cephalalgia 35, no. 13 (February 9, 2015): 1172–80. http://dx.doi.org/10.1177/0333102415570497.
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Introduction The objective of this study was to estimate and to characterize the actual patterns of triptan use and overuse in France using a drug reimbursement database. Methods We included all people covered by the French General Health Insurance System (GHIS) from the Provence-Alpes-Côte-d’Azur (PACA) and Corsica administrative areas who had at least one dispensed dose of triptans between May 2010 and December 2011. All dispensed doses of triptans, migraine prophylactic treatment and psychotropic medications were extracted from the GHIS database. Triptan overuse was defined as triptan use >20 defined daily doses (DDD) per month on a regular basis for more than three consecutive months. Risk of overuse was assessed using logistic regression adjusted for gender and age. Results We included 99,540 patients who had at least one prescription of a triptan over the 20 months of the study. Among them, 2243 patients (2.3%) were identified as overusers and received 20.2% of the total DDD prescribed. Twelve percent of overusers and 6.9% of non-overusers were aged more than 65 years (OR: 1.81). Overusers did not have a greater number of prescribers and pharmacists than non-overusers. They were more frequently prescribed a prophylactic medication for migraine treatment (56.8% vs 35.9%, OR: 2.36), benzodiazepines (69.9% vs 54.7%, OR: 1.93) and antidepressants (49.4% vs 30.2%, OR: 2.33). Conclusions This work suggests that triptan overuse may be due to insufficient prescriber awareness of appropriate prescribing. The off-label prescription of triptans among the elderly necessitates investigating their cardiovascular risk profile in this sub-group.
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Xia, Ying, Christina ML Kelton, Patricia R. Wigle, Pamela C. Heaton, and Jeff J. Guo. "Twenty years of triptans in the United States Medicaid programs: Utilization and reimbursement trends from 1993 to 2013." Cephalalgia 36, no. 14 (September 30, 2016): 1305–15. http://dx.doi.org/10.1177/0333102416629237.
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Objective After sumatriptan was approved by the Food and Drug Administration in 1992, triptans became first-line anti-migraine therapies. Rapidly rising triptan expenditures, however, led payers, including Medicaid, to implement cost-containment policies. We describe triptan utilization and reimbursement trends in Medicaid. Methods Using national summary files for outpatient drug utilization, utilization and expenditure data from 1993 to 2013 were extracted and summed for all triptan national drug codes reimbursed by Medicaid. Data were collected separately for tablets, injections and sprays. Results The number of triptan prescriptions increased from 87,348 in 1993 to 0.9 million in 2004; fell to 0.4 million in 2009; rose to 1 million in 2011; and rose 1.2 million in 2013. In 2013, Medicaid spent $96.8 million on triptans: 74.4%, 18.4% and 7.2% for tablets, injections and sprays, respectively. Average reimbursement per prescription was $54 for tablets, $351 for injections and $235 for sprays in 2013. From 1993 to 2013, sumatriptan was the most widely prescribed among the triptans. Conclusions The substantial increase in triptan prescriptions from 2009 to 2011, without being convincingly explained by either rising migraine prevalence or rising Medicaid enrollment, is suggestive of reduced access to these medications prior to 2009. Cost-containment policies may have inadvertently prevented Medicaid migraineurs from obtaining appropriate pharmacotherapy. Prior presentations An earlier version of this paper was presented as a poster at the Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research, Philadelphia, PA, May 2015, where it received a finalist award.
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A, Farshid, and Lakshmi Csr. "FORMULATION OF NANOPARTICLES OF ANTI-MIGRAINE DRUGS TRIPTANS BY COACERVATION METHOD." Asian Journal of Pharmaceutical and Clinical Research 10, no. 11 (November 1, 2017): 122. http://dx.doi.org/10.22159/ajpcr.2017.v10i11.20302.
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Objective: Triptans are effective medicines used to treat migraine and certain other headaches. This study has been conducted to prepared nanoparticles (NPs) of triptans by coacervation technique using a different drug to polymer ratios and evaluated.Methods: Polymers such as albumin and gelatin and cross-linking agent were used at different levels to prepare triptan NPs with high entrapment efficiency (EE) and low particle size (PS). Completion of the reaction was confirmed by infrared spectra. NPs were evaluated for shape and surface morphology, polydispersity index, zeta potential, EE, and PS distribution.Results: Among all the formulation, AA5 formulation of triptan-loaded albumin NPs (ANPs) has small PS and high EE.Conclusion: In this study, we have found that the ANPs in the presence of 4% glutaraldehyde as a cross-linking agent could be used as a delivery vehicle of triptans.
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Cortelli, Pietro, Gianni Allais, and Chiara Benedetto. "Overview of Triptans in the Treatment of Acute Migraine." European Neurological Review 12, no. 02 (2017): 71. http://dx.doi.org/10.17925/enr.2017.12.02.71.
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The advent of triptans for effective relief of migraine represented a therapeutic breakthrough. Triptans are serotonin (5-hydroxytryptamine, or 5-HT) agonists with high affinity for 5-HT1B and 5-HT1D receptors. There are, at present, seven commonly used triptans: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. Some controversy still surrounds the mode of action of this class. When first studied, it was thought that triptans provided relief from migraine through cranial vasoconstriction, probably via action at postsynaptic 5-HT1B receptors on the smooth-muscle cells of blood vessels. More recently, however, triptans have also been demonstrated to block release of vasoactive peptides from the perivascular trigeminal neurons owing to their action at presynaptic 5-HT1D receptors on the nerve terminal. Triptans may also facilitate descending pain inhibitory systems. However, it is not certain whether or not the activation of vascular 5-HT1B receptors is essential for relieving migraine. Many drug characteristics need to be taken into account when selecting the best triptan for an individual patient. Clinical characteristics of the migraine attack and the patient’s lifestyle and medical history are also important. Despite their biochemical similarity, triptans have distinct pharmacokinetic and pharmacodynamic profiles. Frovatriptan and naratriptan, for example, have a longer half-life and therefore a delayed onset of action and prolonged duration compared with the other triptans, which are fast acting, with a rapid dose-dependent efficacy and higher risk of adverse events and migraine recurrence. Migraine recurrence is affected by the pharmacological and pharmacokinetic properties of the triptan but is unrelated to initial clinical efficacy. Triptans with a longer half-life and largest 5-HT1B receptor affinity have the lowest rates of headache recurrence.
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Lipton, RB, ME Bigal, and PJ Goadsby. "Double-Blind Clinical Trials of Oral Triptans Vs Other Classes of Acute Migraine Medication — A Review." Cephalalgia 24, no. 5 (May 2004): 321–32. http://dx.doi.org/10.1111/j.1468-2982.2003.00690.x.
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Although the migraine clinical trials literature is enormous, we identified only nine published double-blind studies which compare an oral triptan with a non-triptan acute treatment. Of the nine comparative trials that met inclusion criteria for this review, six compared sumatriptan with other drugs, zolmitriptan was studied in two trials and eletriptan in one trial. In seven of the nine studies reviewed herein, differences between active treatments on the primary endpoints were not dramatic. Experience in clinical practice suggests that, for many patients, oral triptans are superior to non-specific acute treatments, creating a discrepancy between clinical trials results and clinical practice experience. Four possible explanations for the disparities between clinical trials and clinical practice are likely: (i) statistically significant differences may not have emerged because the studies lack adequate statistical power; (ii) patients treated with triptans in clinical practice may be relatively more responsive to triptans and relatively less responsive to other agents than those who participate in clinical trials (patient selection); (iii) headache response at 2 h, as measured in clinical trials, may not fully capture the benefits of triptans relative to other therapies, as assessed in clinical practice; (iv) waiting until pain is moderate or severe, as required in clinical trials, may disadvantage triptans relative to comparators.
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Knievel, Kerry, Andrew S. Buchanan, Louise Lombard, Simin Baygani, Joel Raskin, John H. Krege, Li Shen Loo, Mika Komori, and Joshua Tobin. "Lasmiditan for the acute treatment of migraine: Subgroup analyses by prior response to triptans." Cephalalgia 40, no. 1 (November 19, 2019): 19–27. http://dx.doi.org/10.1177/0333102419889350.
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Background Lasmiditan demonstrated superiority to placebo in the acute treatment of migraine in adults with moderate/severe migraine disability in two similarly designed Phase 3 trials, SAMURAI and SPARTAN. Post-hoc integrated analyses evaluated the efficacy of lasmiditan in patients who reported a good or insufficient response to triptans and in those who were triptan naïve. Methods Subgroups of patients reporting an overall response of “good” or “poor/none” to the most recent use of a triptan at baseline (defined as good or insufficient responders, respectively) and a triptan-naïve subpopulation were derived from combined study participants randomized to receive lasmiditan 50 mg (SPARTAN only), 100 mg or 200 mg, or placebo, as the first dose. Outcomes including headache pain-freedom, most bothersome symptom-freedom, and headache pain relief 2 hours post-first dose of lasmiditan were compared with placebo. Treatment-by-subgroup analyses additionally investigated whether therapeutic benefit varied according to prior triptan response (good or insufficient). Results Regardless of triptan response, lasmiditan showed higher efficacy than placebo (most comparisons were statistically significant). Treatment-by-subgroup analyses found that the benefit over placebo of lasmiditan did not vary significantly between patients with a good response and those with an insufficient response to triptans. Lasmiditan also showed higher efficacy than placebo in triptan-naïve patients. Conclusions Lasmiditan demonstrated comparable efficacy in patients who reported a good or insufficient response to prior triptan use. Lasmiditan also showed efficacy in those who were triptan naïve. Lasmiditan may be a useful therapeutic option for patients with migraine. Trial Registration SAMURAI (NCT02439320); SPARTAN (NCT02605174).
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Reuter, Uwe, John H. Krege, Louise Lombard, Elisa Gomez Valderas, Judith Krikke-Workel, Grazia Dell-Agnello, Sherie A. Dowsett, and Dawn C. Buse. "Lasmiditan efficacy in the acute treatment of migraine was independent of prior response to triptans: Findings from the CENTURION study." Cephalalgia 42, no. 1 (October 13, 2021): 20–30. http://dx.doi.org/10.1177/03331024211048507.
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Background A significant proportion of triptan users exhibit an insufficient response or inadequate tolerability to a triptan, and some may develop a contraindication. Lasmiditan, a selective 5-HT1F receptor agonist, may be an option for these individuals. We assessed lasmiditan efficacy in a subgroup of patients in CENTURION (Phase 3 migraine consistency study) who exhibited an insufficient response to triptans, including a subgroup with insufficient response due to efficacy only. Methods Patients were randomized to lasmiditan 200 mg for four attacks, lasmiditan 100 mg for four attacks, or placebo for three and lasmiditan 50 mg for one attack. Triptan insufficient responders were pre-defined as patients with insufficient efficacy or tolerability, or who developed a contraindication. Results In triptan insufficient responders, lasmiditan was superior to placebo ( p < 0.05) for pain freedom beginning at 1 h (both doses); pain relief beginning at 0.5 (200 mg) or 1 h (100 mg); migraine-related disability freedom, much/very much better on the Patient Global Impression of Change, and most bothersome symptom freedom at 2 h; sustained pain freedom; and need for rescue medication. Lasmiditan showed benefit for consistency of effect across attacks for 2-h pain freedom and pain relief. Findings were similar in triptan responders and triptan naïve patients and when the triptan insufficient response definition was based on efficacy only. Conclusions Lasmiditan was efficacious across multiple clinically relevant endpoints in the acute treatment of migraine independent of prior response to triptans. Trial Registration: CENTURION (NCT03670810); SAMURAI (NCT02439320); SPARTAN (NCT02605174)
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Reuter, Uwe, John H. Krege, Louise Lombard, Elisa Gomez Valderas, Judith Krikke-Workel, Grazia Dell-Agnello, Sherie A. Dowsett, and Dawn C. Buse. "Lasmiditan efficacy in the acute treatment of migraine was independent of prior response to triptans: Findings from the CENTURION study." Cephalalgia 42, no. 1 (October 13, 2021): 20–30. http://dx.doi.org/10.1177/03331024211048507.
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Background A significant proportion of triptan users exhibit an insufficient response or inadequate tolerability to a triptan, and some may develop a contraindication. Lasmiditan, a selective 5-HT1F receptor agonist, may be an option for these individuals. We assessed lasmiditan efficacy in a subgroup of patients in CENTURION (Phase 3 migraine consistency study) who exhibited an insufficient response to triptans, including a subgroup with insufficient response due to efficacy only. Methods Patients were randomized to lasmiditan 200 mg for four attacks, lasmiditan 100 mg for four attacks, or placebo for three and lasmiditan 50 mg for one attack. Triptan insufficient responders were pre-defined as patients with insufficient efficacy or tolerability, or who developed a contraindication. Results In triptan insufficient responders, lasmiditan was superior to placebo ( p < 0.05) for pain freedom beginning at 1 h (both doses); pain relief beginning at 0.5 (200 mg) or 1 h (100 mg); migraine-related disability freedom, much/very much better on the Patient Global Impression of Change, and most bothersome symptom freedom at 2 h; sustained pain freedom; and need for rescue medication. Lasmiditan showed benefit for consistency of effect across attacks for 2-h pain freedom and pain relief. Findings were similar in triptan responders and triptan naïve patients and when the triptan insufficient response definition was based on efficacy only. Conclusions Lasmiditan was efficacious across multiple clinically relevant endpoints in the acute treatment of migraine independent of prior response to triptans. Trial Registration: CENTURION (NCT03670810); SAMURAI (NCT02439320); SPARTAN (NCT02605174)
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Bigal, Marcelo E., Abouch V. Krymchantowski, and Tony Ho. "Migraine in the triptan era: progresses achieved, lessons learned and future developments." Arquivos de Neuro-Psiquiatria 67, no. 2b (June 2009): 559–69. http://dx.doi.org/10.1590/s0004-282x2009000300040.
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Triptans, serotonin 5-HT1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine. This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. Herein we first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We then review the class of the triptans - mechanism of action and clinical evidence. We close by briefly discussing the class of CGRP receptor antagonists, which is currently being developed for the acute treatment of migraine.
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Frese, A., A. Gantenbein, M. Marziniak, IW Husstedt, PJ Goadsby, and S. Evers. "Triptans in Orgasmic Headache." Cephalalgia 26, no. 12 (December 2006): 1458–61. http://dx.doi.org/10.1111/j.1468-2982.2006.01224.x.
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Orgasmic headache (headache associated with sexual activity type 2 according to the International Headache Society classification) is a sudden severe headache which occurs at orgasm. Experiences with triptan therapy are described. Two out of four patients with severe headache continuing for >2 h had a positive response to acute triptan therapy. Two out of three patients using triptans as short-term prophylaxis reported a reliable response on several occasions. Trip- tans might be a treatment option to shorten orgasmic headache attacks after the diagnosis is clear and, particularly, subarachnoid haemorrhage has been excluded. In patients who chose to predict their sexual activity, short-term prophylaxis with oral triptans 30 min before sexual activity might be a therapeutic option in those not responsive to or not tolerating indomethacin.
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Da Cas, Roberto, Anna Nigro, Salvatore Terrazzino, Grazia Sances, Michele Viana, Cristina Tassorelli, Giuseppe Nappi, et al. "Triptan use in Italy: Insights from administrative databases." Cephalalgia 35, no. 7 (September 22, 2014): 619–26. http://dx.doi.org/10.1177/0333102414550419.
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Introduction In this drug utilization study, we aimed at assessing the pattern of triptan use in Italy by means of the drug prescription databases of two local health authorities, accounting for approximately 1 million citizens. Methods The study population included all residents aged 18 to 84 years in the Vercelli province (about 175,000 inhabitants) and in the Umbria region (about 885,000 inhabitants), who had at least one dispensation for triptans in 2012. A frequent user, who might be at risk of medication-overuse headache (MOH), was defined as a patient being dispensed at least 10 defined daily doses (DDD) of triptans every month for at least three consecutive months. Results Triptans were used by 0.7%–1% of the population. While most patients were dispensed fewer than 60 DDDs per year, about 10% of all triptan users were classified as frequent users. In both areas, patients below the age of 29 were less likely to be frequent users while the 40- to 49-year-old population was the most affected, with no sex difference. About two-thirds of frequent users persisted in this behavior for an additional three-month period in the following six months. Conclusions Our data indicate that approximately 10% of all triptan users in the Italian population are potentially at risk for MOH. An approach based on drug prescription databases could be useful to identify patients at risk for MOH.
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Meiyanti, Meiyanti. "The role of triptans in the management of migraine." Universa Medicina 28, no. 1 (February 26, 2016): 49–58. http://dx.doi.org/10.18051/univmed.2009.v28.49-58.
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Migraine is one of the most prevalent disorders seen in clinical practice today and also a major cause of disability in the workplace. The prevalence of migraine is highest during the years of peak productivity, ie, between the ages of 25 and 55 years. The triptans are a group of selective 5-hydroxtriptamine (HT)1 serotonin receptor agonists that activate the 5-HT1B/1D receptor and possibly also the 5-HT1A dan 5-HT1F receptors. To date 7 subclasses of serotonin receptors have been identified, namely subclasses 5-HT1 to 5-HT7. Triptan causes cranial vasoconstriction, inhibits peripheral trigeminal activity and the trigeminal afferents. With its triple action, triptans can control acute attacks of migraine. Triptan is contraindicated in patients with previous ischemic or coronary artery disease, cerebral or peripheral vascular disease and other cardiovascular disorders. Triptans should be given immediately after an acute attack of migraine. The triptans are useful in the management of an acute migraine, but are not indicated for preventive therapy of migraine. Several new advances in migraine management have been made in regard to the recognition of the disease, the pathogenesis of migraine, and the phenomenon of central sensitization. More treatment options become available to patients and prescribers, the impact of such therapy on worker productivity will become more important in determining the value of such interventions.
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Bigal, Marcelo E., Carlos A. Bordini, Ana L. Antoniazzi, and José G. Speciali. "The triptan formulations: a critical evaluation." Arquivos de Neuro-Psiquiatria 61, no. 2A (June 2003): 313–20. http://dx.doi.org/10.1590/s0004-282x2003000200032.
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The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Different triptans are available in different strengths and formulations including oral tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections. In Europe, sumatriptan is also available as a suppository. Specific differences among the triptans exist as evidenced by different pharmacological profiles includingT½, Tmax, Cmax, AUC, metabolism, drug-drug interaction profiles, amongst other parameters. How or whether these differences translate to clinical efficacy and tolerability differences is not well differentiated. Clinical distinctions among these agents are subtle and proper choice of triptan requires attention to the specific characteristics of each individual patient, knowledge of patient preference, accurate history of the efficacy of previous acute care medications as well as individual features of the drug being considered. Delivery systems may play an important role in the onset of action of triptans. The selection of an acute antimigraine drug for a patient depends upon the stratification of the patient's migraine attack by peak intensity, time to peak intensity, level of associated symptoms such as nausea and vomiting, time to associated symptoms, comorbid diseases, and concomitant treatments that might cause drug-drug interactions. The clinician has in his armamentarium an ever-expanding variety of medications, available in multiple formulations and dosages, with good safety and tolerability profiles. Continued clinical use will yield familiarity with the various triptans, and it should become possible for the interested physician to match individual patient needs with the specific characteristics of a triptan to optimize therapeutic benefit.
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Dodick, DW. "Triptans and Chest Symptoms: The Role of Pulmonary Vasoconstriction." Cephalalgia 24, no. 4 (April 2004): 298–304. http://dx.doi.org/10.1111/j.1468-2982.2004.00675.x.
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Triptans are effective and well tolerated in the treatment of acute migraine. Chest symptoms are a common adverse effect unrelated to coronary vasoconstriction in most patients. Although the aetiology of chest symptoms remains to be fully defined, pulmonary vasoconstriction is a possible underlying mechanism. Preclinical studies of isolated human blood vessels were used to identify the cerebral selectivity of triptans and ascertain if selectivity vs the pulmonary vasculature predicts a lower rate of chest symptoms. Controlled clinical trials and post-marketing surveillance studies were reviewed to document the incidence of chest symptoms after triptan therapy. In clinical trials, the incidence of chest symptoms at usual therapeutic doses ranged from 1 to 4% depending on the triptan and study design, whereas in post-marketing surveillance studies, up to 41% of patients specifically asked about chest symptoms reported them. A comparative clinical trial showed that almotriptan was associated with lower incidence of chest symptoms than sumatriptan (0.3 vs 2.2%). The intrinsic activity of almotriptan, a second-generation triptan, on human pulmonary arteries and veins was lower than that of sumatriptan. Pre-clinical studies of isolated pulmonary blood vessels may predict the clinical likelihood of chest symptoms; however, additional comparisons are needed.
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Dodick, David W., Anand S. Shewale, Richard B. Lipton, Seth J. Baum, Steven C. Marcus, Stephen D. Silberstein, Jelena M. Pavlovic, et al. "Migraine Patients With Cardiovascular Disease and Contraindications: An Analysis of Real-World Claims Data." Journal of Primary Care & Community Health 11 (January 2020): 215013272096368. http://dx.doi.org/10.1177/2150132720963680.
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Introduction: Triptans, the most commonly prescribed acute treatments for migraine attacks are, per FDA labeling, contraindicated in cardiovascular (CV) disease patients and have warnings and precautions for those with CV risk factors. Methods: Headache specialists, cardiologists, and health economics and outcomes researchers convened to identify diagnostic codes for: (1) CV diseases contraindicating triptans based on FDA labeling; (2) conditions comprising “other significant underlying CV disease”; and (3) CV risk factors included as warnings and precautions for triptans. A retrospective, cross-sectional analysis of commercially insured adult US migraine patients in the 2017 Optum® Clinformatics® Data Mart (CDM) and the 2017 IBM® Watson Health MarketScan® Commercial Claims database was used to estimate the proportion of migraine patients with CV contraindications and warnings and precautions to triptans. Results: Of the 56,662 migraine patients analyzed from Optum CDM, 13.5% had ≥1 CV disease as specified in triptan labeling and an additional 8.5% had ≥1 “other CV disease” judged by the panel to constitute a “significant underlying CV disease” (total: 22.0% migraine patients). Of 176 724 migraine patients analyzed from MarketScan, 12.2% had ≥1 CV disease as specified in the labeling and an additional 8.0% had ≥1 “other significant underlying CV disease” (total: 20.2% of migraine patients). An additional 25.4% and 25.1% of migraine patients had ≥2 CV risk factors in Optum CDM and MarketScan. In total, 47.4% and 45.3% of migraine patients in both databases had a CV disease specified as a contraindication, an “other CV disease” endorsed as significant, or ≥2 CV risk factors identified as warnings and precautions to triptans. Conclusions: Analyses of more than 230,000 people with migraine showed that ≥20% of commercially insured US migraine patients have a CV condition that specifically contraindicates triptan treatment, and an additional 25% have ≥2 CV risk factors identified as warnings and precautions to triptans.
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Gawel, Marek J., Irene Worthington, and Anne Maggisano. "Progress in Clinical Neurosciences A Systematic Review of the Use of Triptans in Acute Migraine." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 28, no. 1 (February 2001): 30–41. http://dx.doi.org/10.1017/s0317167100052525.
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ABSTRACT:Objective:A systematic review of the literature was undertaken, to consolidate evidence concerning the efficacy and safety of triptans currently available in Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide guidelines for selection of a triptan.Methods:Data from published, randomized, placebo-controlled trials were pooled and a combined number needed to treat (NNT) and number needed to harm (NNH) was generated for each triptan. Direct comparative trials of triptans were also examined.Results:The lowest NNTfor headache response/pain-free at one/two hours is observed with subcutaneous sumatriptan. Among the oral formulations, the lowest NNT is observed with rizatriptan and the highest NENT with naratriptan. The lowest NNH is observed with subcutaneous sumatriptan.Conclusions:Triptans are relatively safe and effective medications for acute migraine attacks. However, differences among them are relatively small. Considerations in selecting a triptan include individual patient response/tolerance, characteristics of the attacks, relief of associated symptoms, consistency of response, headache recurrence, delivery systems and patient preference.
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Dahlöf, CGH. "Infrequent or Non-Response to Oral Sumatriptan does not Predict Response to Other Triptans—Review of Four Trials." Cephalalgia 26, no. 2 (February 2006): 98–106. http://dx.doi.org/10.1111/j.1468-2982.2005.01010.x.
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A migraineur can claim to be an infrequent responder (‘non-responder’) to an oral triptan independent of which triptan he or she is presently using. Four trials of an alternative triptan (zolmitriptan/rizatriptan; eletriptan; naratriptan; almotriptan) in patients with a history of infrequent response to oral sumatriptan were compared and contrasted in terms of study design, patient characteristics, and efficacy and tolerability of the triptan under investigation. Unfortunately, none of the reported studies used an appropriate parallel design, which would have had the non-responding triptan (oral sumatriptan) in one arm and without encapsulation. While the four trials differed in terms of study design (open-label vs. placebo-controlled), definition of sumatriptan ‘non-responder’ (retrospective vs. prospective) and pain intensity at baseline (30% severe to 70% severe), all four demonstrated that lack of response to sumatriptan did not predict lack of response to an alternative triptan. Changing triptans resulted in 2-h pain-relief rates of 25–81% in patients with a history of poor response to sumatriptan. It can be concluded that migraine patients who respond infrequently to sumatriptan should be switched to a different triptan, as lack of response to one triptan does not predict likelihood of responsiveness to another. A review of the available evidence suggests that almotriptan may be one of the most appropriate choices for an alternative triptan.
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Smelt, Antonia FH, Willem JJ Assendelft, Christel E. van Dijk, and Jeanet W. Blom. "Triptan use after starting prophylactic migraine treatment: A retrospective cohort study in a primary care population." Cephalalgia 34, no. 11 (February 12, 2014): 927–32. http://dx.doi.org/10.1177/0333102414521511.
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Background Clinical trials on the prophylactic effect of propranolol and metoprolol for migraine show that starting this medication leads to a decrease in the use of attack medication of 0.9–8.9 doses per month. However, studies in daily practice are lacking. Methods We compared the number of triptans prescribed in the six months before and the six months after the start of propranolol/metoprolol in a Dutch national representative primary care cohort. Results Of the 168 triptan-using patients who started with propranolol or metoprolol, the number of triptans prescribed before starting was 4.6 doses per month. The number of triptans prescribed six months before compared with six months after starting propranolol/metoprolol decreased with 1.0 dose per month (Wilcoxon rank test; p = 0.000). Conclusion In this primary care population, although the number of triptans prescribed decreased after starting propranolol or metoprolol, the decrease is relatively small compared to data from clinical trials.
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Thorlund, Kristian, Edward J. Mills, Ping Wu, Elodie Ramos, Anjan Chatterjee, Eric Druyts, and Peter J. Goadsby. "Comparative efficacy of triptans for the abortive treatment of migraine: A multiple treatment comparison meta-analysis." Cephalalgia 34, no. 4 (October 9, 2013): 258–67. http://dx.doi.org/10.1177/0333102413508661.
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Background Migraine is the most common neurological condition in developed countries. The abortive treatment of migraine attacks is important both for quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D receptor agonists, effectively relieve the pain, disability, and associated symptoms of migraine while improving health-related quality of life. Although a number of direct head-to-head triptan comparisons have been made, data for all possible permutations are not available, and unlikely to ever be so, although in clinical practice such information would be useful. Objective We aimed to determine the relative efficacy of all available triptans to abort migraine headache among patients with previous adequate response to migraine treatments. Methods We included only double-blinded randomized clinical trials comparing triptans to either placebo or another triptan. Our primary outcomes were pain-free response at two hours and 24-hour sustained pain-free response, and our secondary outcomes were headache response at two hours and 24-hour sustained headache response. We used Bayesian multiple treatment comparison meta-analyses of seven triptans used in adult patients to abort migraine attacks. We applied a random-effects analysis with meta-regression adjusting for dose. Results are reported as odds ratios with 95% credible intervals. Results We included data from 74 randomized clinical trials. All triptans were significantly superior to placebo for all outcomes, with the exception of naratriptan for 24-hour sustained pain-free response. Eletriptan consistently yielded the highest treatment effect estimates. For the two-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, almotriptan, naratriptan, and frovatriptan for at least one of the two outcomes. Rizatriptan yielded the second highest treatment effects followed by zolmitriptan. For the 24-hour endpoints, eletriptan was statistically significantly superior to sumatriptan, rizatriptan, almotriptan, and naratriptan for at least one of the two outcomes. Frovatriptan data were not available at that endpoint. Further, the probability that eletriptan is the most likely of all triptans to produce a favorable outcome was 68% for pain-free response at two hours, and 54% for 24-hour sustained pain-free response. Conclusion Triptans appear to offer differing treatment effects. In the populations studied eletriptan was most likely to produce pain-free responses that were sustained.
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Dekker, F., NJ Wiendels, V. de Valk, C. van der Vliet, A. Knuistingh Neven, WJJ Assendelft, and MD Ferrari. "Triptan overuse in the Dutch general population: A nationwide pharmaco-epidemiology database analysis in 6.7 million people." Cephalalgia 31, no. 8 (May 18, 2011): 943–52. http://dx.doi.org/10.1177/0333102411408626.
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Introduction: A population-based observational study was used to assess the prevalence, demographics, risk factors, and costs of triptan overuse, defined as more than 30 (International Headache Society criteria) or 54 (stringent criteria) defined daily doses per 3 months. Methods: Analysis of the Dutch Health Care Insurance Board Database for 2005, which included prescriptions for 6.7 million people (46% of the total Dutch population). Results: Triptans were used by 85,172 (1.3%) people; of these, 8,844 (10.4%; 95% CI 10.2–10.6) were overusers by International Headache Society and 2,787 (3.3%; 95% CI 3.2–3.4) were overusers by stringent criteria. The triptan-specific odds ratios for the rate of International Headache Society overuse compared with sumatriptan were: 0.26 (95% CI 0.19–0.36) for frovatriptan; 0.34 (95% CI 0.32–0.37) for rizatriptan; 0.76 95% CI 0.68–0.85) for naratriptan; 0.86 (95% CI 0.72–1.02) for eletriptan; 0.97 (95% CI 0.88–1.06) for zolmitriptan; and 1.49 (95% CI 1.31–1.72) for almotriptan. Costs for overuse were 29.7 million euros; for the International Headache Society criteria this was 46% of total costs and for stringent criteria it was 23%. Discussion: In the Dutch general population, 1.3% used a triptan in 2005, of which 10.3% were overusers and accounted for half of the total costs of triptans. Users of frovatriptan, rizatriptan and naratriptan had a lower level of overuse.
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Roberto, Giuseppe, Carlo Piccinni, Roberto D’Alessandro, and Elisabetta Poluzzi. "Triptans and serious adverse vascular events: Data mining of the FDA Adverse Event Reporting System database." Cephalalgia 34, no. 1 (August 6, 2013): 5–13. http://dx.doi.org/10.1177/0333102413499649.
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Aim The aim of this article is to investigate the vascular safety profile of triptans through an analysis of the United States Food and Drug Administration Adverse Event Reporting System (FDA_AERS) database with a special focus on serious and unexpected adverse events. Methods A case/non-case analysis was performed on the reports entered in the FDA_AERS from 2004 to 2010: Cases were reports with at least one event included in the MedDRA system organ classes ‘Cardiac disorder’ or ‘Vascular disorders’, whereas non-cases were all the remaining reports. Co-reported cardiovascular drugs were used as a proxy of cardiovascular risk and the adjusted reporting odds ratio (adj.ROR) with 95% confidence intervals (95% CI) was calculated. Disproportionality signals were defined as adj.ROR value >1. Adverse events were considered unexpected if not mentioned on the relevant label. Results Among 2,131,688 reports, 7808 concerned triptans. Cases were 2593 among triptans and 665,940 for all other drugs. Unexpected disproportionality signals were found in the following high-level terms of the MedDRA hierarchy: ‘Cerebrovascular and spinal necrosis and vascular insufficiency’ (103 triptan cases), ‘Aneurysms and dissections non-site specific’ (15), ‘Pregnancy-associated hypertension’ (10), ‘Reproductive system necrosis and vascular insufficiency’ (3). Discussion Our analysis revealed three main groups of unexpected associations between triptans and serious vascular events: ischaemic cerebrovascular events, aneurysms and artery dissections, and pregnancy-related vascular events. A case-by-case assessment is needed to confirm or disprove their plausibility and large-scale analytical studies should be planned for risk rate estimation. In the meantime, clinicians should pay special attention to migraine diagnosis and vascular risk assessment before prescribing a triptan, also promptly reporting any unexpected event to pharmacovigilance systems.
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Millson, D., M. Frischer, P. Croft, and PJ Goadsby. "Are Triptans with Enhanced Lipophilicity Used for the Acute Treatment of Migraine Associated with an Increased Consulting Rate for Depressive Illness?" Cephalalgia 20, no. 8 (October 2000): 732–37. http://dx.doi.org/10.1111/j.1468-2982.2000.00111.x.
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Sumatriptan, the first marketed triptan, acts predominantly as a peripheral 5-HT1B/1D agonist. Recently launched (naratriptan and zolmitriptan) triptans with enhanced lipophilicity (TEL) may theoretically reduce central 5-HT levels, potentially exacerbating depressive illness. The aim of this study was to compare depressive illness patient consulting rates (PCR) between the newer triptans and sumatriptan treated patients. Migraine-diagnosed patients were identified from the West Midlands General Practice Research Database (GPRD). Univariate and logistic regression analyses were used to determine the relationship between age, sex, migraine duration, prior depression, prior and current triptan medication and the current PCR for depression. Of a total patient database of 642 000 patients 21 331 (3.3%) had a diagnosis of migraine. From 1993 to 1997, sumatriptan-treated migraineurs had significantly higher depression PCRs (22.3%) compared with non-triptan users (19.3%), a difference of 6.4% (95% confidence interval (CI) 4.6–8.4%, P < 0.001). In the year (April 1997 to March 1998) following the launch of the TELs, depression PCRs were significantly higher among patients using these compounds compared with sumatriptan-treated patients (5.1%, CI 1.8–12.0%, P < 0.05). However, after taking account of prior depression (odds ratio (OR) 6.45, 95% CI 3.63–11.43), TELs were not significantly associated with depression (OR 0.27, 95% CI 0.03–2.13). Furthermore, rates of newly diagnosed depression after treatment were similar in the two triptan groups (sumatriptan 4.2%; TELs 3.9%). Although, the TELs are being prescribed to patients with higher pre-existing rates of depression, they are not associated with subsequently increased consulting for depressive illness compared with patients taking sumatriptan. This study highlights the potential to use GPRD to test targeted hypotheses exploring pharmacovigilance issues for patients using new medicines.
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Dodick, DW, and V. Martin. "Triptans and CNS Side-Effects." Cephalalgia 24, no. 6 (June 2004): 417–24. http://dx.doi.org/10.1111/j.1468-2982.2004.00694.x.
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Triptans are the treatment of choice for acute migraine. While seemingly a homogenous group of drugs, results from a meta-analysis reveal significant differences in efficacy and tolerability among oral triptans. The incidence of drug-related central nervous system (CNS) side-effects with some triptans is as high as 15% and may be associated with functional impairment and reduced productivity. The occurrence of adverse events associated with triptans in general, and CNS side-effects in particular, may lead to a delay in initiating or even avoidance of an otherwise effective treatment. Potential explanations for differences among triptans in the incidence of CNS side-effects may relate to pharmacological and pharmacokinetic differences, including receptor binding, lipophilicity, and the presence of active metabolites. Of the triptans reviewed, at clinically relevant doses, almotriptan 12.5 mg, naratriptan 2.5 mg and sumatriptan 50 mg had the lowest incidence of CNS side-effects, while eletriptan 40 and 80 mg, rizatriptan 10 mg and zolmitriptan 2.5 and 5 mg had the highest incidence. The most likely explanations for the differences in CNS side-effects among triptans are the presence of active metabolites and high lipophilicity of the parent compound and active metabolites. Eletriptan, rizatriptan and zolmitriptan have active metabolites, while lipophilicity is lowest for almotriptan and sumatriptan. If CNS sideeffects are a clinically relevant concern in the individual patient, use of a triptan with a low incidence of CNS side-effects may offer the potential for earlier initiation of treatment and more effective outcomes.
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Ferrari, MD, PJ Goadsby, KI Roon, and RB Lipton. "Triptans (Serotonin, 5-HT1B/1D Agonists) in Migraine: Detailed Results and Methods of A Meta-Analysis of 53 Trials." Cephalalgia 22, no. 8 (October 2002): 633–58. http://dx.doi.org/10.1046/j.1468-2982.2002.00404.x.
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The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the ‘raw patient data’ of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24 089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h postdose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.
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Ramsberg, J., and M. Henriksson. "The Cost-Effectiveness of Oral Triptan Therapy in Sweden." Cephalalgia 27, no. 1 (January 2007): 54–62. http://dx.doi.org/10.1111/j.1468-2982.2007.01243.x.
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The literature suggests that triptans are cost effective compared with older types of migraine treatment. However, which of the triptans that is most cost effective has not been established. We compared the costs and effects of triptan treatment from a Swedish societal perspective, using evidence from the literature. A probabilistic cost-effectiveness model was constructed to investigate the costs and effects of treating a single attack in a typical migraine patient. The end-point used in the base-case analysis was sustained pain free without any adverse events (SNAE). We searched the scientific literature for meta-analyses reporting the efficacy of oral triptans. All treatments except rizatriptan 10 mg and eletriptan 40 mg were dominated. The incremental cost per SNAE of rizatriptan 10 mg compared with eletriptan 40 mg was approximately €100. There was substantial uncertainty concerning the results, but probabilistic analysis showed that rizatriptan 10 mg and eletriptan 40 mg had the highest probability of being cost-effective.
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Kudrow, David, Sagar Munjal, Leah Bensimon, Tasneem Lokhandwala, Binglin Yue, Anna D’Souza Coutinho, and Stephen D. Silberstein. "Treatment patterns of patients diagnosed with major headache disorders: A retrospective claims analysis." Cephalalgia Reports 3 (January 1, 2020): 251581632091399. http://dx.doi.org/10.1177/2515816320913992.
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Objective: To describe patient characteristics, treatment patterns, and health care costs among patients diagnosed with major headache disorders overall and by type (tension-type headache [TTH], migraine, cluster headache [CH], or >1 primary headache type), and secondarily to evaluate drug treatment patterns among triptan initiators with a major headache diagnosis. Methods: Using US claims data from January 2012 through December 2017, we identified adults with evidence of a major headache disorder: TTH, migraine, or CH; the first diagnosis date was deemed the index date. To evaluate triptan use specifically, patients who initiated triptans were identified; the first triptan claim date was deemed the index date. Patient characteristics, treatment patterns (concomitant treatments, adherence, number of fills), and annual health care costs data were obtained. Results: Of the 418,779 patients diagnosed with major headache disorders, the following 4 cohorts were created: TTH (8%), migraine (87%), CH (1%), and >1 primary headache type (4%). The majority used analgesic (54–73%) and psychotropic (57–81%) drugs, primarily opioids (36–53%). Headache-related costs accounted for one-fifth of all-cause costs. Of the 229,946 patients who initiated triptans, the following 7 study cohorts were analyzed: sumatriptan (68%), rizatriptan (21%), eletriptan (5%), zolmitriptan (3%), naratriptan (2%), frovatriptan (1%), and almotriptan (<1%). The major concomitant analgesic medication classes were opioids (41%) and nonsteroidal anti-inflammatory drugs (34%). Conclusion: The primary headache disorder treatment paradigm is complex, with significant variability. Predominant concomitant use of opioids and switching to opioids is of concern, necessitating solutions to minimize opioid use. Switching to non-oral/fast-acting or targeted preventive therapies should be considered.
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Tfelt-Hansen, P. "Maximum Effect of Triptans in Migraine? A Comment." Cephalalgia 28, no. 7 (July 2008): 767–68. http://dx.doi.org/10.1111/j.1468-2982.2007.01415.x.
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The efficacy of triptans in the treatment of migraine was recently contested. How high is then the maximum effect of a triptan? After subcutaneous naratriptan 10 mg a 88% pain-free response was observed. This result was obtained despite the fact that more half of the patients had a migraine duration of > 4 h. These results indicate that subcutaneous naratriptan in a high dose can overcome central sensitization that occurs in migraine attacks.
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Schneider-Ziebe, Anissa, and Uwe May. "The treatment of migraine patients with triptans – is there a need for further Rx-to-OTC switches?" Gesundheitsökonomie & Qualitätsmanagement 25, no. 01 (February 13, 2019): 15–23. http://dx.doi.org/10.1055/a-0836-2852.
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Abstract Objective The disease migraine affects a large share of the German population and is linked to a high economic potential in terms of direct and indirect sickness costs. Triptans are the recommended treatment in the case of an acute migraine attack. Both, the disease and its appropriate treatment are of interest in the context of self-medication and Rx-to-OTC switch efforts. Therefore, a survey was carried out with the intention to collect data among migraine patients regarding the use of analgesics in general and of triptans specifically. This data can be the basis for further health economic considerations. Methods By an online survey among 206 migraine patients, different data regarding patients suffering from migraine, the frequency and sort of symptoms and the use of analgesics in general as well as triptans specifically was collected and analysed. A special focus was on symptoms affecting patients’ productivity, their use of triptans and their satisfaction with the current supply situation with triptans. Results The survey revealed among other findings that most patients suffer from symptoms which limit their productivity or their ability to work and make an immediate treatment necessary. Most patients know well about their disease and feel able to treat themselves in the context of self-medication once they are diagnosed by a physician. In this context a demand for further triptans available without a prescription could be identified. This is specifically, because patients respond differently to various triptans. Therefore, a larger variety of prescription free triptans would increase the number of patients with access to OTC triptans significantly. Conclusion Most survey respondents know well about their disease and the appropriate treatment and feel able to treat themselves within the scope of self-medication. Nevertheless, they mostly respond to one triptan only. In the case of an acute migraine attack an immediate treatment is required, ideal is an intake of triptans as soon as first symptoms occur. In this context pharmacies play an important role as fast and low-threshold access point to medications. Because only a limited number of patients responds to the already prescription free available triptans, there is a demand for further Rx-to-OTC switches of triptans among migraine patients which should be considered in further switch efforts in Germany.
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Jelinski, SE, WJ Becker, SN Christie, R. Giammarco, GF Mackie, MJ Gawel, AG Eloff, and JE Magnusson. "Clinical Features and Pharmacological Treatment of Migraine Patients Referred to Headache Specialists in Canada." Cephalalgia 26, no. 5 (May 2006): 578–88. http://dx.doi.org/10.1111/j.1468-2982.2005.01077.x.
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We set out to examine selected clinical characteristics of migraine patients referred to neurologists specializing in headache in Canada, and to document their pharmacological therapy both before and after consultation with the neurologist. Demographic, clinical and pharmacotherapy data were collected at the time of consultation for 606 patients referred to five headache clinics and who were given a migraine diagnosis by the neurologist. Data were analysed as part of the Canadian Headache Outpatient Registry and Database (CHORD) Project. The mean age of the migraine patients was 39.7 years; and 82.5% were female. The majority of patients suffered severe impact from their headaches. Prior to consultation, 48.7% were taking a triptan; after consultation, 97.2% were on a triptan. Before consultation, 30.9% were on a prophylactic drug; after consultation, 70.4% were. 20.8% of patients were medication overusers. Of these medication overusers, 42.4% were overusing an opiate, usually in combination with other analgesics; 21.6% were overusing a triptan. Medication changes made by the neurologists at consultation included a large increase in the use of both triptans and prophylactic medications. Medication overuse, particularly opiate overuse, remains a significant problem in patients with migraine in Canada.
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Láinez, MJA. "Clinical Benefits of Early Triptan Therapy for Migraine." Cephalalgia 24, no. 2_suppl (November 2004): 24–30. http://dx.doi.org/10.1111/j.1468-2982.2004.00895.x.
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The introduction of the triptans brought advances in achieving complete and sustained pain resolution in migraine patients, compared with non-migraine-specific treatments. However, sustained pain-free rates for triptans recorded in many clinical trials are still relatively low. This may be due to study participants being treated late into the attack, when pain is already moderate or severe. Studies with almotriptan have shown that efficacy is enhanced when treatment is given early in a migraine attack while pain is still mild, compared with later administration when pain intensity is greater. Developments in our understanding of migraine pathophysiology provide a rationale for this phenomenon, with improved efficacy seen when abortive treatment is administered before central sensitization develops. A limited window of therapeutic opportunity exists early in an attack to improve the outcome of triptan treatment. Early intervention is recommended to avoid the significant pain and disability commonly associated with moderate or severe migraine.
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Lampi, C., G. Huber, S. Haas, E. Rittberger, and HC Diener. "Difference in Triptan Effect in Patients With Migraine and Early Allodynia." Cephalalgia 28, no. 10 (October 2008): 1031–38. http://dx.doi.org/10.1111/j.1468-2982.2008.01642.x.
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The aim of this study was to determine whether in migraine patients with and without aura early treatment with various triptans leads to differences in pain reduction after 1 h and in modulating cutaneous allodynia. Thirty-six patients with early manifestation of a clinically recognizable allodynia of the face and non-responders to earlier treatment with sumatriptan 100 mg were included. Patients were randomized to six triptan treatment groups. Significant pain reduction was seen only in the group receiving zolmitriptan nasal spray 5 mg with a mean visual analogue scale (VAS) score of 3.8 (S.D. 1.2) at baseline and 2.4 (S.D. 1.3; P = 0.015) at 1 h after using the triptan and was thus a predictor of a VAS score 3 within 1 h. The study results indicate that migraine headache intensity can be reduced within 1 h by using zolmitriptan 5 mg nasal spray in spite of the presence of early cutaneous allodynia.
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Terzioglu, Nalan, and Hans-Dieter Höltje. "Receptor-Based 3D QSAR Analysis of Serotonin 5-HT1D Receptor Agonists." Collection of Czechoslovak Chemical Communications 70, no. 9 (2005): 1482–92. http://dx.doi.org/10.1135/cccc20051482.
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A three-dimensional quantitative structure-activity relationship study (3D QSAR) has been successfully applied to explain the binding affinities for the serotonin 5-HT1D receptor of a triptan series. The paper describes the development of a receptor-based 3D QSAR model of some known agonists and recently developed triptans on the 5-HT1D serotonergic receptor, showing a significant correlation between predicted and experimentally measured binding affinity (pIC50). The pIC50 values of these agonists are in the range from 5.40 to 9.50. The ligand alignment obtained from dynamic simulations was taken as basis for a 3D QSAR analysis applying the GRID/GOLPE program. 3D QSAR analysis of the ligands resulted in a model of high quality (r2 = 0.9895, q2LOO = 0.7854). This is an excellent result and proves both the validity of the proposed pharmacophore and the predictive quality of the 3D QSAR model for the triptan series of serotonin 5-HT1D receptor agonists.
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Hoffmann, Olaf, Nikolas Keilwerth, Margarethe Bastholm Bille, Uwe Reuter, Klemens Angstwurm, Ralf R. Schumann, Ulrich Dirnagl, and Joerg R. Weber. "Triptans Reduce the Inflammatory Response in Bacterial Meningitis." Journal of Cerebral Blood Flow & Metabolism 22, no. 8 (August 2002): 988–96. http://dx.doi.org/10.1097/00004647-200208000-00010.
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Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans. These effects were partially reversed by a specific 5HT1D as well as by a specific 5HT1B receptor antagonist. Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan. In line with these findings, patients with bacterial meningitis had significantly elevated CGRP levels in the cerebrospinal fluid. In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment. The findings suggest that, besides mediating meningeal nociception, meningeal nerve fibers contribute to the inflammatory cascade in the early phase of bacterial meningitis. Adjunctive treatment with triptans may open a new therapeutic approach in the acute phase of bacterial meningitis.
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Roberto, G., E. Raschi, C. Piccinni, V. Conti, L. Vignatelli, R. D’Alessandro, F. De Ponti, and E. Poluzzi. "Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: Systematic review of observational studies." Cephalalgia 35, no. 2 (September 22, 2014): 118–31. http://dx.doi.org/10.1177/0333102414550416.
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Background Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. Aim The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. Methods We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. Results From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18–4.41; I2 = 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52–1.43; I2 = 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64–1.26), and the second one suggested an increased risk of 2.51 (1.10–5.71). In this case, because of the high degree of heterogeneity, results were not pooled. Conclusions To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.
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Gendolla, A. "Early Treatment in Migraine: How Strong is the Current Evidence?" Cephalalgia 28, no. 2_suppl (September 2008): 28–35. http://dx.doi.org/10.1111/j.1468-2982.2008.01688.x.
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Over the last 10 years, triptans (serotonin 5-HT1B/1D receptor agonists) have proved to be efficacious in treating migraine pain. However, recent evidence suggests that patients are still not receiving optimal pain management, particularly in clinical trials, where triptan treatment is generally not initiated until pain has reached moderate intensity. Pathophysiological evidence indicates that if treatment is initiated at an early stage, while pain is still mild and before the onset of central sensitization, outcomes for patients may be improved. In addition, a small number of clinical trials have been reported in which triptans were taken early (within 1 h of pain onset) or while pain was still mild; although constraints of trial design and data analysis limit definite conclusions, overall the results suggest that this early/mild approach results in more rapid and sustained pain relief. New studies are therefore needed to clarify the clinical benefits of early treatment, whilst taking into account potential risks, such as medication overuse. Ultimately, migraine treatment strategies require optimization in order to meet patient expectations and to reduce the current burden of migraine-associated disability.