Oral Triptans Research Articles

Intranasal zolmitriptan for the treatment of acute migraine.

To review the pharmacokinetics, efficacy, tolerability, and patient acceptance of zolmitriptan nasal spray (NS). Gastroparesis may delay or diminish the absorption of oral triptans, and nausea or vomiting may do the same and/or make it difficult to take a tablet. Some migraineurs require or prefer faster relief than oral medications provide. Injectable triptans provide the fastest drug delivery into the bloodstream, but many patients are reluctant to use them. Nasal sprays may address some of the problems with tablets and injectables while still providing rapid absorption of drug. Non-systematic review. Significant levels of zolmitriptan NS are detectable in plasma within 2-5 minutes, and the rapid absorption is due to early uptake through the nasal mucosa. In 2 randomized trials, users of zolmitriptan NS were significantly more likely than placebo recipients to be pain-free at 15 minutes post-dose, the first time point measured, and about half of patients had sustained response at 24 hours. Studies in which patients could treat a migraine of any severity have documented significant headache response or relief with zolmitriptan NS at 10 minutes. In one trial, the rate of total symptom relief was significantly better with the NS than with placebo from 30 minutes post-dose. The most common side effect of zolmitriptan NS is unusual taste. Patient satisfaction studies indicate that zolmitriptan NS is appreciated for its speed of onset, ease of use, reliability, and overall efficacy. Zolmitriptan NS provides onset of headache relief within 10 minutes for some patients and quickly abolishes some of the major migraine symptoms. Good candidates are migraineurs whose episodes rapidly escalate to moderate-to-severe pain and those who have morning migraine, have a quick time to vomiting, or have failed oral triptans.

Comparative cost-effectiveness analysis of oral triptan therapy for migraine in four European countries

To assess the differences in the cost-effectiveness of oral triptan therapy for migraines among European countries. A cost-effectiveness analysis of triptan therapy for migraine was conducted from a health-care payer perspective in four European countries (France, Italy, Spain and the UK). The study included those orally administered triptans available in all of these countries (almotriptan, brand-name sumatriptan, generic sumatriptan, zolmitriptan), and it was performed using a decision-tree model that incorporated costs of the drugs and probabilities associated with the possible events and outcomes. Average cost-effectiveness ratios were calculated in two different scenarios. The average cost-effectiveness ratio showed wide variations across the different countries, these differences being up to 131 % (almotriptan), 77 % (brand-name sumatriptan), 153 % (generic sumatriptan) and 77 % (zolmitriptan). Generic sumatriptan was the most cost-effective drug analysed in the studied countries. Caution must be taken when trying to transfer conclusions of pharmacoeconomics studies on migraines even in neighbouring countries. This cross-country variability is a concern for decision-makers and also for the elaboration of international recommendations and clinical practice guidelines.

A Cross‐Sectional Survey to Assess the Migraineur's Medication Decision‐Making Beliefs: Determining When a Migraine Is Triptan‐Worthy

To investigate the factors that influence a migraineur's beliefs regarding oral triptans for the acute treatment of migraines and to provide further insight into patients' decision-making process when faced with migraine. A multicenter, cross-sectional, observational study of subjects currently prescribed an oral triptan medication for the acute treatment of migraine headaches. Subjects were recruited from 6 headache clinics and one primary care practice in the United States. Enrolled subjects completed a questionnaire that could be completed either at the site as part of the visit or at home. The questionnaire comprised 27 questions assessing demographic characteristics, migraine history, migraine frequency and severity, and general beliefs about migraine treatments. The study population was stratified into 2 cohorts (Early Treatment and Delayed Treatment) based on how they typically use their oral triptan to treat a typical migraine. A total 506 subjects were enrolled in the study, of which 502 were stratified into the Early Treatment cohort (41.2%) and Delayed Treatment cohort (58.8%). Demographic and clinical characteristics were generally similar between the 2 cohorts. In terms of general treatment patterns, there were notable differences between the Delayed and Early Treatment cohorts, with the Delayed Treatment cohort significantly more likely to take an over-the-counter (OTC) or non-triptan medication first (P ≤ .001) and only take a triptan if the OTC or non-triptan medication did not work (P ≤ .001). Furthermore, 55% of the Delayed Treatment cohort delayed taking a triptan to be certain that the headache was a migraine (vs 32% of the Early Treatment cohort; P ≤ .001). When asked to specify the reasons for delaying treatment with a triptan, the Delayed Treatment cohort had, in general, greater concerns about using their oral triptan in comparison with the Early Treatment cohort. In particular, respondents were primarily concerned with running out of their triptan medication with 35% of the Delayed Treatment cohort expressing this concern compared with 22% of the Early Treatment cohort (P ≤ .001). Statistically significant differences were also noted for concerns about taking medications (P ≤ .001), side effects (P ≤ .05), expense (P ≤ .01), and taking prescription medications (P ≤ .001). Results build upon previously published studies and suggest that patient beliefs directly influence how migraineurs manage their migraines and have implications for patient outcomes. Such insights should be used to facilitate physician-patient communication and reinforce the need for patient-centered care to improve patient outcomes.

Oral Triptans and Nausea: Treatment Considerations in Migraine

The objective of this paper is to review evidence showing that migraine patients who are nauseated before using oral triptans tend to have a poor treatment response, as well as to establish a framework for further investigation of the association between response to oral medications and pretreatment nausea among migraineurs. SYNTHESIS AND CONCLUSION: In patients with migraine, pretreatment nausea predicts a poor response to oral triptans. This finding may be inherent in the oral route of delivery of medication, as pretreatment nausea is associated with gastric stasis, which can impair absorption of oral medications and reduce therapeutic efficacy. In addition, oral triptans contribute to the development of nausea among migraine patients who are nausea free before they treat, perhaps because oral tablet use triggers or exacerbates nausea in the same manner as eating or drinking among patients who are nauseated or vulnerable to nausea. Importantly, these observations are derived from a small evidence base and post-hoc analyses or, in the case of treatment-emergent nausea, adverse event reports. Further assessment of the relationships between nausea and oral triptans is necessary before drawing firm conclusions. Should these observations be validated, the use of oral triptans in migraine attacks with nausea or in patients prone to nausea should be reevaluated. Novel routes of administration for triptans allow patients to receive the benefits of migraine-specific therapy even when oral therapy is suboptimal.

Why Triptan Treatment Can Fail: Focus on Gastrointestinal Manifestations of Migraine

Results of randomized, double-blind, controlled studies establish the efficacy of triptans in the acute treatment of migraine, but triptan benefits demonstrated in clinical trials have not consistently been realized in clinical practice. This paper explores the contribution of gastrointestinal manifestations of migraine--namely nausea (with or without vomiting) and gastroparesis--to triptan treatment failure. Migraine-related nausea and vomiting and migraine-associated gastroparesis appear to be prevalent and highly impactful and have been characterized as being among the greatest challenges affecting migraine care today. These gastrointestinal signs and symptoms have not been satisfactorily taken into account in the management of migraine, which is dominated by the use of oral therapies. Oral triptans are not the optimal therapy in the presence of migraine-related nausea because nausea predicts poor response to oral triptans and because nausea can cause patients to delay oral treatment, which can further compromise therapeutic efficacy. Oral triptans are not the optimal therapy in the presence of migraine-associated gastroparesis because these agents rely on gastric motility and gastrointestinal absorption and may be ineffective or slowly or inconsistently effective in the presence of gastroparesis. Health care providers need to work with their patients to address the still-all-too-frequent problem of treatment failure in migraine. First, health care providers need to have greater appreciation of the importance of nausea, vomiting, and gastroparesis as factors affecting migraine prognosis and treatment success. Second, health care providers need to systematically assess migraine patients for gastrointestinal signs and symptoms. Finally, patients and health care providers need to be willing to practice customized migraine care, in which patients tailor the treatment and formulation to the characteristics and context of the individual migraine episode.

Unilateral nasal pain with migraine features

Migraine attacks exclusively felt in the face are very rare, the pain involving the territories supplied by the second and third branches of the trigeminal nerve. Two patients suffering from heminasal pain attacks accompanied with typical migrainous features and responsive to oral or intranasal triptans - but not to intranasal lidocaine or oxymetazoline. In one patient, the attacks could be precipitated upon slight touching on the tip of the nose, in the other attacks were preceded by the nasal sensation typically heralding sneezing. Migraine pain mostly develops within the innervation territory of the first branch of the trigeminal nerve, which includes the nose. Therefore, episodes of unilateral nasal pain with migrainous features could be considered a migraine with unusual topography (nasal migraine). Painful nasal attacks occasionally preceded by stimulation of trigeminal afferents in the nose, could be conceived of as migraine-tic syndrome.

Therapeutic applications for subcutaneous triptans in the acute treatment of migraine

Background:The features of migraine attacks and the contexts in which migraine attacks occur vary from attack to attack and from patient to patient. Current treatment strategies, which are dominated by the use of oral forms of migraine medication, do not address this patient-to-patient and attack-to-attack heterogeneity. While current therapies, and, in particular, oral triptan tablets can be effective for many types of migraine attacks that a patient can experience, they may not be the optimum treatment for every migraine in every patient.Scope:This clinical review of subcutaneous sumatriptan discusses its characteristics, efficacy, and tolerability and considers its place in clinical practice. The review focuses particularly on several specific clinical settings in which subcutaneous sumatriptan might be a more appropriate therapeutic choice than the oral triptan tablet.Findings:Of the triptan formulations, subcutaneous sumatriptan is the most rapidly absorbed and demonstrates a favorable pharmacokinetic profile. Data from randomized, double-blind, clinical trials and studies of patients’ perceptions and preferences suggest that subcutaneous sumatriptan can be particularly useful to help restore normal work functioning, for migraine attacks that cannot be treated early in their course, for migraine attacks associated with gastrointestinal symptoms, such as nausea or vomiting, and for difficult-to-treat migraines, including early-morning migraine and menstrual migraine. The majority of patients (9 in 10) trying subcutaneous sumatriptan indicated that they will use it again. Patients not fully satisfied with previous triptan therapy reported enhanced satisfaction with, and confidence in, treatment after trying subcutaneous sumatriptan.Conclusions:By virtue of their availability as multiple compounds and in multiple formulations including oral, intranasal, and injectable forms, triptans can be used to customize migraine therapy to the individual patient and the individual migraine attack. Due to its route of delivery and favorable pharmacokinetic profile, subcutaneous triptans may represent an attractive alternative for specific clinical settings. Subcutaneous sumatriptan can play a key role in maximizing likelihood of pain-free response and rapid return to normal daily activities and, as such, should be considered an important part of the treatment armamentarium for migraine.

Efficacy endpoints in migraine clinical trials: the importance of assessing freedom from pain

Many efficacy endpoints have been used in clinical trials of acute migraine pharmacotherapy. Headache response or headache relief (i.e., moderate/severe pain reduced to mild/no pain) at a single, specified time-point, traditionally the primary endpoint, and headache recurrence (i.e., return of pain after initial postdose relief) are inadequate. Headache relief does not provide information about pain-free response and counts a partial response as a treatment success. Headache recurrence can reflect sustained efficacy but is confounded by initial response to treatment, because ineffective drugs have low recurrence rates. The International Headache Society (IHS) guidelines state that 2 hour pain-free response and sustained pain-free response (i.e., freedom from pain with no recurrence or use of rescue or study medication 2-24 hours postdose) provide the most clinically relevant information about the efficacy of migraine pharmacotherapy. The pain-free criterion counts partial responses as failures and thus is a more rigorous test of therapeutic benefit than headache relief, and the two endpoints together incorporate the main treatment attributes that determine patient satisfaction. As an example, consider needle-free subcutaneous sumatriptan and oral triptan tablets. An open-label study of needle-free subcutaneous sumatriptan by Cady and colleagues found that 2 hour pain-free response and sustained pain-free response were 64% and 42% respectively. For oral triptan tablets, the 2001 metaanalysis by Ferrari and colleagues reported 2 hour pain-free response rates ranging from 23% to 38% and sustained pain-free response rates ranging from 11% to 26%. The measures of pain-free response 2 hours postdose and sustained pain-free response can differentiate among treatments and be used to guide therapeutic choices.

Oral Triptans in the Preventive Management of Cluster Headache

Cluster headache is a rare primary neurovascular headache and a severe pain condition with unilateral headache over 15-180 minutes and concomitant unilateral autonomic symptoms. The detailed pathophysiology of the condition is still unclear. Only a few evidence-based therapeutic options for acute therapy and the preventive management of the disease are available. Triptans, in particular sumatriptan 6mg subcutaneously, are highly effective for acute treatment. This review focuses on the potential use of oral triptans in the prophylaxis of cluster headache.

Transdermal Sumatriptan for Acute Treatment of Migraineurs With Baseline Nausea

To evaluate the efficacy and safety of transdermal sumatriptan in migraine patients who have baseline nausea. Migraine-associated nausea and vomiting can limit the effectiveness of acute treatment with oral agents by causing delays, avoidance, or incomplete absorption of medication due to post-dose vomiting. In a multicenter, randomized, double-blind, placebo-controlled study in adult (aged 18-66 years) migraineurs, 530 patients were randomized to receive transdermal sumatriptan or a placebo patch and remained in the study until they had treated a single moderate to severe migraine attack or had gone 2 months without treatment. At baseline (before applying the study patch), patients recorded headache pain intensity and the presence or absence of migraine-associated symptoms, including nausea. The use of analgesic or anti-emetic rescue medications within 2 hours of patch activation was prohibited. Post-hoc analyses were conducted to assess the proportion of patients with nausea at baseline who experienced headache relief and who were free from nausea, photophobia, and phonophobia at 1 and 2 hours post-activation. A total of 454 patients were included in the intent-to-treat population for efficacy analyses. Baseline demographic and migraine headache characteristics were generally similar between the treatment groups. In the overall study population, transdermal sumatriptan was significantly superior to placebo at 1 hour post-activation for pain relief (29% vs 19%, respectively; P < .0135) and freedom from nausea (71% vs 58%, respectively; P < .05) and at 2 hours post-activation for freedom from pain (18% vs 9%, respectively; P < .009), pain relief (53% vs 29%, respectively; P < .0001), freedom from nausea (84% vs 63% respectively; P < .001), freedom from photophobia (51% vs 36%, respectively; P < .0028), freedom from phonophobia (55% vs 39%, respectively; P < .0002); and freedom from migraine (16% vs 8%, respectively; P < .0135). In the post-hoc analysis, transdermal sumatriptan was markedly superior to placebo for pain relief and freedom from pain, nausea, photo-, and phonophobia at 1 and 2 hours post-activation. Transdermal sumatriptan is superior to oral triptans for migraine patients whose baseline nausea causes them to delay or avoid acute treatment.

Examining the Interrelationship of Migraine Onset, Duration, and Time to Treatment

The objective of this study is to investigate migraines, both longitudinally and cross-sectionally, to understand the impact that time of treatment has on migraine duration and the patients' return to daily functioning. Several studies have explored the relationship between migraine treatment and its impact on migraine duration; however, the interrelationship of migraine onset and impact of treatment timing on migraine resolution is not completely understood. Five hundred and nine migraineurs completed 1 online baseline survey and a diary survey after each of their next 3 migraines. All subjects were 18 or older and were employed full time. Migraine episodes treated within 1 hour were significantly shorter on average than those treated after 1 hour (9.1 hours vs 12.3 hours) (P < .05). Over-the-counter medication was the most frequently reported first-line treatment (44%) followed by an oral triptan (30%), another prescription medication (14%), and combination therapy (4%). Rescue treatment was reported in 57% of attacks. The majority of over-the-counter (69%) and another prescription (55%) treated attacks required rescue whereas only 39% of first-line triptan attacks required rescue. Treating migraines early with an oral triptan-containing therapy appears to be a very effective method for reducing migraine duration and preventing the need for additional medication. Our findings also suggest that physicians should spend more time educating patients how to identify migraines early. Understanding the relationship between these key factors will provide insight into appropriate treatment and management of migraines, and more importantly, equip patients with the tools necessary to improve their outcomes and overall impact on functioning.

Sponsorship-Related Outcome Selection Bias in Published Economic Studies of Triptans

Economic studies funded by the pharmaceutical industry are more likely to report favorable results and recommendations for the sponsor's product than are studies funded by nonindustry establishments. To determine whether clinical outcome data obtained from the same meta-analyses are used differently in various economic studies of oral triptans and whether there is an association between the study sponsorship and the choice of clinical outcome measure. Economic studies of triptans were identified by updating a previously published systematic review. Twelve studies that used the same meta-analyses as the source of clinical outcome data were identified. Two independent reviewers extracted the essential data from the identified studies. In the 12 appraised studies, 9 alternative measures of effectiveness were derived from the same meta-analyses. Eleven studies were industry-related, and in these the selected clinical outcome consistently favored the sponsor's product. Also the reported results suggested that the sponsor's product was more cost-effective than the competitors' products. The cost-effectiveness of triptans is dependent on both the definition of clinical effectiveness and the treatment-related costs. Only bias related to the selection of the clinical outcome measure has been taken into account in this review. The results of published economic studies of triptans are conflicting and biased. There is a tendency to select clinical outcome measures that support the sponsor's product. This leads to concern about the possible poor applicability of these results in decision making.

Sumatriptan needle-free subcutaneous (Sumavel® DosePro™) approved for the acute treatment of migraine, with or without aura, and cluster headaches

Sumatriptan subcutaneous administration is the fastest and most effective of the triptans for relief of acute migraine headache. This occurs even when the patient has already developed symptoms related to central sensitization, a key parameter in determining the effectiveness of these agents. In patients whose migraine attacks have historically failed to respond to oral triptans, this route of administration has also proven to be more consistent and effective. Until recently this method of drug delivery was dependent upon a needle for administration. A new method of delivery for this agent, Sumavel® DosePro™, eliminates the needle and disposal issues coupled with an improved ease of use of drug delivery and acceptable tolerability for patients in clinical trials.

Optimal balance of efficacy and tolerability of oral triptans and telcagepant: a review and a clinical comment

Dose–response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant. The upper part of the efficacy curve of the triptans is generally flat, the so-called ceiling effect; and none of the oral triptans, even in high doses, are as effective as subcutaneous sumatriptan, In contrast, AEs increases with increasing dose without a ceiling effect. The optimal dose for the triptans is mainly determined by tolerability. Telcagepant has an excellent tolerability and can be used in migraine patients with cardiovascular co-morbidity. Based on the literature the triptans and telcagepant are rated in a table for efficacy and tolerability.

Experience with onabotulinumtoxinA (BOTOX) in chronic refractory migraine: focus on severe attacks

The objective of this study is to analyse our experience in the treatment of refractory chronic migraine (CM) with onabotulinumtoxinA (BTA) and specifically in its effects over disabling attacks. Patients with CM and inadequate response or intolerance to oral preventatives were treated with pericranial injections of 100 U of TBA every 3 months. The dose was increased up to 200 U in case of no response. The patients kept a headache diary. In addition, we specifically asked on the effect of BTA on the frequency of disabling attacks, consumption of triptans and visits to Emergency for the treatment of severe attacks. This series comprises a total of 35 patients (3 males), aged 24–68 years. All except three met IHS criteria for analgesic overuse. The number of sessions with BTA ranged from 2 to 15 (median 4) and nine (26%) responded (reduction of >50% in headache days). However, the frequency of severe attacks was reduced to an average of 46%. Oral triptan consumption (29 patients) was reduced by 50% (from an average of 22 to 11 tablets/month). Those six patients who used subcutaneous sumatriptan reduced its consumption to a mean of 69% (from 4.5 to 1.5 injections per month). Emergency visits went from an average of 3 to 0.4 per trimester (−83%). Six patients complained of mild adverse events, transient local cervical pain being the most common. Although our data must be taken with caution as this is an open trial, in clinical practice treatment of refractory CM with BTA reduces the frequency of disabling attacks, the consumption of triptans and the need of visits to Emergency, which makes this treatment a profitable option both clinically and pharmacoeconomically.

“Mixing Triptans”: Patient Satisfaction

Although some patients may prefer using an oral triptan other than sumatriptan and injectable sumatriptan to treat an attack of persistent migraine, administration of 2 different triptans within a 24-hour period currently is contradicted. We sought to determine patient satisfaction with an acute migraine treatment regimen wherein patients were permitted to administer an oral triptan other than sumatriptan and injectable sumatriptan within 24 hours of one another We evaluated a consecutive series of migraine patients who either had tried and failed oral sumatriptan or were using another oral triptan and were satisfied with it. We advised subjects that they could administer their oral triptan and injectable sumatriptan within a single 24-hour period (but not within 2 hours of one another); we termed such treatment "mixing triptans." We asked all subjects to keep detailed written headache diaries for the 6-month treatment period, and at the 6-month end-of-study visit we asked subjects who had treated at least 3 migraine attacks by mixing triptans to rate their satisfaction with that treatment according to a 5-point Likert scale. Of the 200 subjects enrolled, 132 (66%) used an oral triptan other than sumatriptan and injectable sumatriptan within a 24-hour period on at least 3 occasions. At their final follow-up visits, 117 (89%) of the 132 reported themselves "very satisfied" or "satisfied" with this specific treatment regimen. No serious adverse events were recorded. The option of sequentially using an oral triptan other than sumatriptan and injectable sumatriptan to treat a given attack of migraine appears to correlate with a high rate of patient satisfaction. While in our subject population this treatment regimen was well tolerated, our study results do not suffice to establish the safety of "mixing triptans."

Membership Survey: Use of Oral Triptans and Injectable Sumatriptan Within the Same 24‐Hour Period

Membership Survey: Use of Oral Triptans and Injectable Sumatriptan Within the Same 24-Hour Period John F. Rothrock MD, John F. Rothrock MD Editor-in-Chief, HeadacheSearch for more papers by this author John F. Rothrock MD, John F. Rothrock MD Editor-in-Chief, HeadacheSearch for more papers by this author First published: 03 January 2011 https://doi.org/10.1111/j.1526-4610.2010.01811.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume51, Issue1January 2011Pages 141-141 RelatedInformation

The Use of Triptans for Pediatric Migraines

Migraine headaches frequently occur in the pediatric population, with a prevalence of 3% in children 2-7 years of age, 4-11% in children 7-11 years of age, and 8-23% in children 11 years of age and older. Migraine without aura is more than twice as common as migraine with aura in children. Headaches are the third leading cause of emergency room referrals and rank in the top five health problems of children. The 2004 American Academy of Neurology's treatment parameter for migraine in children and adolescents recommended that nasal sumatriptan be considered for acute treatment; however, data were lacking to make a decision regarding the available oral triptans at that time. The more recently released European guidelines discuss three different triptans for use in children but no specific triptan was recommended. Currently, six of the seven available triptans have been studied for efficacy and safety in the pediatric population; however, only a few well controlled clinical studies have been conducted. Sumatriptan has the most available data on outcomes in general, with nasal sumatriptan showing the most positive results. Nasal sumatriptan is approved in children older than 12 years of age in Europe. Oral sumatriptan does not show any clinical benefit versus placebo in children. Rizatriptan and zolmitriptan have conflicting efficacy and safety data, with most studies favoring the use of oral rizatriptan and nasal zolmitriptan. Almotriptan is the first triptan to obtain a US FDA indication in adolescents with migraines lasting 4 or more hours. This approval was based upon two studies, one large clinical trial and one very small, open-label, pilot study. At this time, there are insufficient data to recommend naratriptan and eletriptan for first- or second-line use in pediatric patients with migraines. There are currently no efficacy data for frovatriptan in pediatric patients, which limits its use in this population. Adverse effects of triptans and pharmacokinetic data in children and adolescents are similar to those in adults. The triptan class should be considered as an acute treatment option for children and adolescents with migraines, although their use is mostly 'off-label'. Of the available triptans, there are more positive efficacy data for sumatriptan and zolmitriptan nasal sprays, and rizatriptan and almotriptan tablets than for the other triptans.

Placebo response in migraine

Sir I am currently in the process of revising the Guidelines for Drug Trials in Migraine of The International Headache Society. While browsing the literature for information on the placebo response in migraine randomised clinical trials (RCTs), I read with interest the extensive meta-analysis on this subject published by Macedo et al. in the European Journal of Clinical Pharmacology [1]. There is, however, one fundamental misunderstanding in this article, namely, the definition of headache relief. These authors state that headache relief is a 50% reduction in pain [1]. The RCTs used the standard that all migraine sufferers should have moderate or severe headache pain before drug administration and that headache relief, as defined by Glaxo [2], was a decrease in headache pain from moderate (2) or severe (3) to none (0) or mild (1) at 1 h (subcutaneous sumatriptan) or 2 h (oral and intranasal triptans) post-drug administration. Therefore, successful headache relief could be assessed as 3–0, 3–1, 2–0, or 2–1. The placebo response depends on many factors, such as study design, route of administration, and cultural elements (for example, Europe vs. North America [1]. In addition, an important determinant factor could also be whether the patients are treated as in-patients in headache clinics or whether they self-administer at home. In one crossover RCT in which a subcutaneous autoinjector with sumatriptan 6 mg was used to treat migraine, patients were recruited from general practice and treated migraine attacks at home. Headache relief was 61 and 6% at 60 min after the administration of the active drug and placebo, respectively [3]. The therapeutic gain (TG) was 55% (95% confidence interval 44–65%). Thus, the result obtained with the placebo was extremely low, but the TG was similar to the TG of 49 [1] and 51% [4] reported in meta-analyses. Finally, there is an increasing tendency to use pain free at 2 h as the primary efficacy measure in RCTs on acute treatment migraine [5], and pain free is what the migraine patients want to be [6].

Antimigraine Efficacy of Telcagepant Based on Patient's Historical Triptan Response

To evaluate whether the same or different patients respond to triptans and telcagepant. Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans. It is currently unknown whether migraine patients who cannot be adequately helped with triptans might benefit from treatment with telcagepant. Post-hoc analysis of data from a randomized, controlled trial of telcagepant (150 mg, 300 mg) zolmitriptan 5 mg, or placebo for a moderate/severe migraine. Responder rates were analyzed according to patients' self-reported historical triptan response (HTR): (1) good HTR (N = 660): response in 75-100% of attacks; (2) intermediate HTR (N = 248): response in 25-74% of attacks; (3) poor HTR/no use (N = 407): response in < 25% of attacks, or patient did not take triptans. A limitation of the analysis is that the last subgroup comprised mainly (91%) patients who reported that they did not take triptans, but it was not known whether these patients were triptan-naïve or had previously used triptans and stopped taking them. For zolmitriptan, 2-hour pain relief rates were higher in the good HTR subgroup (116/162, 72%) than in the intermediate (29/62, 47%) and poor/no use (44/111, 40%) HTR subgroups. The 2-hour pain relief rates were similar across HTR subgroups for telcagepant 150 mg (48-58%), 300 mg (52-58%), and placebo (26-31%). In the poor/no use HTR subgroup, more patients receiving telcagepant 300 mg (56/98, 57.1%) had 2-hour pain relief than those receiving zolmitriptan (44/111, 39.6%; odds ratio = 2.11 [95% CI: 1.20,3.71], P = .009); the percentage for telcagepant 150 mg (57/119, 47.9%) was not significantly different from zolmitriptan (odds ratio = 1.41 [95% CI: 0.82, 2.40], P = .211). This suggests that different patients may respond to triptans or telcagepant 300 mg. Caution should be exercised in interpreting the results because of the post-hoc nature of the analysis (clinical trial registry: NCT00442936).