Triptan Medications Research Articles

Telcagepant provides new hope for people with migraine

The triptan drugs provide effective migraine relief for many people. Nevertheless, a substantial number of migraine-affected individuals are unresponsive to triptans, and such therapy can also lead to an array of adverse effects. A new class of antimigraine drugs, currently undergoing clinical trials, could offer hope to those for whom triptan medication is unsuitable.

Applying the benefits of the AwM Study in the clinic

The Act when Mild (AwM) Study has illustrated the benefits to migraineurs of taking triptan medication when their migraine pain is still mild and within 1 h of the onset of symptoms. Yet many patients wait until the attack has fully developed before taking their medication, with potentially inferior outcomes. In order to reproduce the benefits of early intervention using the AwM paradigm in daily practice, a number of key barriers need to be addressed at both the physician and patient level. Notable physician-related barriers to be overcome, particularly at the primary care level, include accuracy of an early diagnosis of migraine in newly presenting patients, communication skills that generate a therapeutic engagement with migraine patients and enhance patient confidence, the application of knowledge about up-to-date strategies to optimize treatment outcomes, and the setting of achievable goals to avoid unrealistic expectations. Patient-related obstacles that need to be identified and overcome encompass patient attitude, expectations, and behaviour. Migraine patients may be reluctant to consult their physician, and, of those who do, many stop consulting because they perceive that physicians can do little to improve their situation. For this reason, migraine patients need to be counselled about the most appropriate medication for their level of symptoms. Moreover, patients need to be confident before they will adhere routinely to the advice they receive, and high in the priority of advice is the use of medication, particularly triptans, at the first sign of a migraine attack, rather than waiting until their attack has progressed to moderate or severe intensity. Patients who adhere to this advice are likely to experience a notable reduction in the pain, disability and time lost that they would otherwise suffer. The beneficial effects of early triptan intervention illustrated in the AwM Study can therefore be best reproduced in the clinic if the correct advice given to patients is not only accepted and applied by them, but also followed up by their physician.

Almotriptan in Triptan-Naïve Patients: New Evidence of Benefits

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.

The Serotonin Syndrome, Triptans, and the Potential for Drug–Drug Interactions

The serotonin syndrome is an acute adverse reaction to medications that enhance serotonergic activity. The severity of cases ranges from mild to fatal. Recently, the U.S. Food and Drug Administration issued an alert that the risk of developing serotonin syndrome may be increased by the concomitant administration of triptan medications with certain other medications. However, a review of published data does not allow an accurate assessment of such risks related to triptans. We conclude that it is currently unclear whether administration of triptans with other serotonergic medications increases the risk of serotonin syndrome.

Sumatriptan 6 mg subcutaneous as an effective migraine treatment in patients with cutaneous allodynia who historically fail to respond to oral triptans

The objective of the study was to assess the efficacy of 6 mg subcutaneous (SC) sumatriptan to treat migraine and the relationship between response of migraine and cutaneous allodynia in a population of migraine patients who historically failed to respond to oral triptan medications. This was an openlabel study consisting of patients with migraines who historically failed to respond to oral triptan medications. Forty-three patients were asked to treat three migraine attacks with 6 mg SC sumatriptan. The primary efficacy endpoint was the percentage of patients achieving relief of headache at 2 h. Ninetyone percent of the patients responded to a single dose of SC sumatriptan 6 mg. Fifty percent of all patients were pain-free by 2 h and over 30% had a 24-h sustained pain-free response. When administered within 90 min from the onset of migraine (i.e., during the developing phase of cutaneous allodynia), SC 6 mg sumatriptan proved to be effective despite the occurrence of allodynia in a group of patients, who historically had failed to respond to oral triptan medications. These findings suggest that the window of opportunity to treat allodynic patients with injectable triptans may be longer (up to 2 h) than with oral triptans (up to 1 h).

Headache and cerebral venous air embolism

A 47-year-old man with migraine without aura presented with bilateral throbbing sudden onset headache resistant to usual triptan medication. He had dental implants revised 3 days earlier. General and neurologic examinations were normal. Brain CT showed cerebral venous …

Which triptan for which patient?

The triptans were developed for the acute treatment of a migraine attack and have revolutionised the treatment of this disorder since their introduction in the early 1990s. Although their mechanisms of actions are similar and based on the stimulation of specific serotonin (5-hydroxytryptamine) receptors including peripheral 1B and central and peripheral 1D subtypes, each triptan has its own distinctive pK properties that result in different profiles of efficacy and tolerability. Triptans work by decreasing neurogenic inflammation peripherally in the meninges, vasoconstriction of meningeal vessels and by modulating secondary-order neurons in the brain stem. Studies of patient attitudes towards their acute care regimens reveal that they are often unhappy with some aspect of their treatment-usually the speed of action, degree of efficacy, presence of adverse events and the need for additional doses due to frequent and/or rapid recurrence. The majority of patients, when asked in a clinical trial performed at tertiary care headache centres, are willing to try another triptan. The aim of this article is to review the pK and clinical characteristics of these acute care, migraine-specific triptan medications and discuss how their individual characteristics lead to their preferred choice in various clinical scenarios. The pK and clinical efficacy data presented are taken from older published studies in which triptans were compared to placebo or each other, but the patients were asked to wait till the headache reached moderate or severe intensity prior to taking study medication. New studies have looked at early treatment paradigms and result in better efficacy data, but are difficult to compare due to different endpoints.

Assessment of clinical, service, and cost outcomes of a conversion program of sumatriptan to rizatriptan ODT in primary care patients with migraine headaches.

Managed care organizations can increase the value of drug therapy by negotiating discounts on drug acquisition costs with pharmaceutical manufacturers and promoting use of preferred drugs, including the conversion of patients to preferred medications. This investigation was designed to assess conversion success, migraine drug utilizations, and patient satisfaction with a clinical pharmacist-managed conversion program from sumatriptan to rizatriptan ODT, both formulary drugs. This was a retrospective cohort study conducted in a managed care organization for patients aged 18 years or older who had picked up at least one outpatient prescription for any sumatriptan dosage form at the pharmacy between January 2002 and June 2002. Patients. pharmacy and medical data were reviewed to assess eligibility (e.g., no history of rizatriptan failure) for conversion from sumatriptan to rizatriptan orally disintegrating tablet (ODT). There was no copayment difference for members for rizatriptan ODT versus sumatriptan. A questionnaire was developed to assess 2 domains: (1) patient satisfaction with the medication conversion process and (2) preference for rizatriptan ODT or sumatriptan. A random sample of 315 patients who initiated conversion to rizatriptan ODT was surveyed. Electronic pharmacy claims were reviewed to determine the number of patients who were successfully converted from sumatriptan to rizatriptan ODT. Pharmacy expenditures and total health care utilization and expenditures in the 180 days prior to (baseline) and after the conversion (followup) to rizatriptan ODT were compared for the cohorts of subjects who were successfully converted and those patients who were not successfully converted. Therapeutic conversion from sumatriptan to rizatriptan ODT was attempted in 457 patients; 214 (47%) were successfully converted. The only difference between the 2 cohorts at baseline for the 6 months prior to attempted conversion was a higher mean number of sumatriptan doses per patient per month (PPPM) in the 243 failed conversions (mean 3.5, SD 2.9) compared with the 214 successful conversions (mean 2.8, SD 2.8, P =0.003). The median triptan doses increased by 1.0 PPPM in both cohorts (P =0.882), from 2.0 to 3.0 doses PPPM in the group of successful conversions and from 2.7 to 4.0 in the group of unsuccessful conversions. The survey response rate was 55% for both successful and for unsuccessful conversions. More than 90% of the patients in both cohorts were satisfied with the level of care provided by the clinical pharmacy staff during medication conversion, and there was no difference between the 2 cohorts in patient satisfaction (P=0.761). Rizatriptan ODT was preferred by 68.0% and 8.5% of successful and failed conversion subjects, respectively (P <0.001). Using representative group purchase prices, triptan expenditures for successful conversion subjects were reduced by a median of -2 dollars (6 %) PPPM while triptan expenditures for unsuccessful conversions increased by a median of 8 dollars (P <0.001). There were no differences for either cohort in median PPPM changes in migraine-related office visits (0.0 median change in office visits, P =0.748) or office-visit costs (0 dollars median change, P =0.861) for preconversion versus postconversion attempts Regression modeling identified that lower total counts of sumatriptan doses filled during baseline period was an independent predictor of successful conversion to rizatriptan ODT (P <0.001). There was an average of 3.5 triptan medication fills per patient for successful conversion during the 6-month follow-up period, with 78% of these subjects filling at least 2 prescriptions for rizatriptan ODT during this period. This conversion program for sumatriptan to rizatriptan ODT was successful in converting almost half of primary care patients to the preferred product despite the absence of a copayment incentive for members to agree to the conversion. There were no measurable medical or economic consequences of the conversion, and patient satisfaction with the quality of care was maintained. Future efforts are likely to have a higher success rate if focused on converting patients with less-severe migraine headaches, as measured by the need for baseline rescue medication, since lower acuity was the only independent predictor of successful conversion in this conversion program for 2 triptan drugs.

Frovatriptan: clinical review and future directions

Triptan medications are selective serotonin receptor (5-HT1B/D) agonists approved for the treatment of acute migraine attacks. Among the currently available triptans, frovatriptan is unique with a long half-life (~26 h), metabolism by multiple pathways and a low side-effect profile. Clinical trial data demonstrates efficacy for frovatriptan across multiple doses, with the 2.5 mg dose selected for lower side effects. Frovatriptan is approved for use in the conventional treatment of an ongoing migraine attack, as are the other currently available triptan medications. The long half-life of frovatriptan has led to the initiation of studies of frovatriptan for the short-term prevention of menstrually related migraine attacks, during which patients are often difficult to treat. This newly investigated treatment approach for patients with predictable menstrually related migraine may, in the future, lead to treatment paradigms that benefit those patients with migraine attacks that are difficult to manage.

Successful Treatment of Status Migrainosus After Electroconvulsive Therapy With Dihydroergotamine

We describe a case of status migrainosus precipitated by electroconvulsive therapy (ECT) that was refractory to treatment with triptan medications but which resolved with dihydroergotamine (DHE). We briefly review some of the receptor pharmacology possibly related to this observation.

Development and Testing of the Japanese Version of the Migraine-Specific Quality of Life Instrument

We developed and tested a version of the migraine-specific quality of life (MSQOL) instrument for use in Japan. The MSQOL was translated into Japanese, evaluated by physicians and nurses who has experienced migraine headaches, 'backtranslated', approved by the author of the original version, and tested in 70 out-patients with migraine. There were no ceiling or floor effects. All three subscales were found to be internally consistent: alpha > or = 0.76. The patients' scores were similar to those reported in the user's manual, with the exception of a difference of about 11 points on the Avoidance Behaviors subscale. Some correlations between MSQOL scores and SF-36 scores were statistically significant, although none exceeded 0.52. Linear associations between some measures of symptoms and some MSQOL scales were statistically significant, but those associations were consistent neither for the two kinds of symptom reports (severity and frequency) nor across all MSQOL subscales. Low MSQOL scores in early 1999 correlated with more return visits for medication and with greater amounts of triptan (anti-migraine) medication in 2001 and 2002. Overall, we interpret these results as indicating that, while they cannot be used as substitutes for reports of symptoms, scores on the Japanese version of the MSQOL can be used to assess the impact of migraine headaches on patients' lives.

Prophylaxis of menstrual migraine with triptans: problems and possibilities.

Menstruation is a prominent, predictable attack trigger for many women with migraine. If abortive therapy of menstrual attacks is ineffective, prophylactic therapy is used to prevent attacks or render them shorter and less resistant to acute therapy. Interest is increasing in the use of triptan medications for the prophylaxis of menstrual migraine, and clinical trials to evaluate this approach are underway. Potential problems with triptan prophylaxis of menstrual migraine that deserve attention include the lack of consensus on the definition of menstrual migraine and the difficulty in making a reliable diagnosis of the disorder. Unconvincing demonstrations of efficacy and unresolved cost and safety concerns should temper enthusiasm for their use in this manner. Further studies, using a consistent definition of menstrual association and employing diary validation of the diagnosis, are needed to determine the efficacy of the triptans in women who consistently experience migraine attacks associated with menstruation. Triptans would have to show compelling advantages over other therapy to be a plausible prophylactic treatment for menstrual migraine.

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Keeping Up with Neurology on the Web

Depression scores following migraine treatment in patients attending a specialized center for headache and neurology.

To determine the changes in clinical characteristics and depression levels among patients following treatment for migraine. Epidemiologic studies have provided consistent evidence regarding an association between migraine and depression. In Puerto Rico, however, migraine has not yet been systematically investigated. A chart review of 144 Puerto Rican patients who presented with migraine, diagnosed according to the International Headache Society criteria, and depression over a 2-year period was performed. The level of depression, before and after migraine treatment, was evaluated using the Zung Self-rating Depression Scale. The mean age of patients was 37.0 +/- 14.4 years; 77.1% were women. More than half (52.8%) reported severe headache and 56.9% reported a monthly frequency of five attacks or more. Nearly 9% were using antidepressant therapy and 8% were under psychiatric treatment. The mean Zung index score at baseline was 50.6 +/- 10.9. Following treatment with triptans, the intensity and frequency of migraine and the Zung index score decreased significantly (P<.00001). A trend for a greater reduction in Zung index scores among patients receiving triptan medications for more than a year was demonstrated (P =.07). These results indicate that migraine treatment with triptans appears to be effective in decreasing the headache frequency and intensity, and depression levels, independent of antidepressant medication use or psychiatric treatment.

Migraine treatment outcomes with rizatriptan in triptan-naive patients: a naturalistic study

Background: The 5-hydroxytryptamine 1B/1D agonists, or triptans, are the newest class of drugs to become available for the acute treatment of migraine. The class currently includes sumatriptan, zolmitriptan, naratriptan, and rizatriptan. The efficacy of rizatriptan in the acute treatment of migraine has been established against placebo and other oral triptans in controlled comparative trials. Objective: The US Migraine Assessment Protocol (USMAP) collected data on the use of rizatriptan in a naturalistic setting reflecting clinical practice. This paper presents results for patients enrolled in the USMAP study who had never taken a triptan before the study. Methods: At enrollment, 216 patients completed a questionnaire describing their responses to their current nontriptan medications. They were then given specially packaged samples of 4 standard 10-mg rizatriptan tablets and 4 orally disintegrating 10-mg rizatriptan tablets (wafers) and were asked to take a different formulation for each of their next 2 attacks, the sequence to be at their discretion. Within ∼24 hours after taking rizatriptan, patients were to call a toll-free number to report their responses to rizatriptan using an interactive voice-response system. Results: Within 2 hours after initial dosing of rizatriptan, significantly more patients taking either the rizatriptan tablet or the rizatriptan wafer reported onset of pain relief, had become largely symptom free, and were able to resume usual activities compared with their baseline responses to nontriptans ( P < 0.05). In addition, compared with their baseline responses to nontriptans, significantly more patients taking either rizatriptan formulation had mild or no pain 2 hours after dosing ( P < 0.05). More than twice as many patients taking the rizatriptan tablets or wafers were either somewhat or very satisfied with the medication compared with their satisfaction with nontriptans ( P < 0.05). Conclusions: In the naturalistic setting of this study, migraineurs who had not previously taken a triptan medication reported more rapid relief of pain, more effective pain relief, and more rapid resumption of normal activities when taking rizatriptan tablets or wafers than when taking a nontriptan medication. Patients dissatisfied with their current non-triptan migraine therapy may benefit from treatment with rizatriptan.

Menstrual Migraine.

Slightly less than half of women with migraine report that menstruation is an important trigger of headache episodes. However, it is rare that menstruation is the only trigger for a patient and its importance as a trigger may be over- emphasized. Accurate diagnosis requires a prospectively kept diary of information showing a consistent and mechanistically valid temporal correlation between migraine attacks and menstrual periods. Abnormal central nervous system response to normal fluctuations in hormones is the likely underlying cause of menstrual migraine. Patients with menstrual migraine do not generally have hormonal abnormalities. Currently available abortive therapy works well for menstrual-related migraine attacks. For the small subset of women for whom this is not the case, and whose menstrual periods and associated headaches are predictable, pre-emptive treatment of the expected headache with scheduled perimenstrual use of a number of agents can be helpful. A hormonal trigger for migraine headache does not mean that treatment must also be hormonal in nature. Choice of therapy depends on the frequency of menstrual migraine, predictability of menstrual periods, patient preference, and cost. For the small group of women with refractory menstrual migraine, hormonal therapy can be tried, with the understanding that the quality of evidence for these interventions is low and their risk to benefit ratios not established. The perimenstrual use of triptan medications is currently being investigated for the treatment of menstrual migraine. Preliminary results are inconclusive, and until further evidence regarding the efficacy, safety, practicality, and cost effectiveness of this approach is available, their routine use in this manner for menstrual migraine is not recommended.