Triptans other than sumatriptan in child and adolescent migraine: literature review

Abortive drugs used for migraine in children and adolescents are usually the same as those used in adults. Only a few studies have assessed the efficacy of triptans other than sumatriptan in pediatric migraine. This systematic review describes the evidence concerning the efficacy and tolerability of these triptans. The PubMed research produced 481 results and only seven studies were randomized controlled trials. A total of 11 articles were reviewed. Zolmitriptan and rizatriptan were superior to placebo in most studies. Almotriptan demonstrated a high profile of tolerability. A single study of eletriptan demonstrated no statistical difference between this drug and placebo in terms of both efficacy and tolerability. All studies have reported a good triptan safety profile. The conflicting data regarding triptan efficacy are probably due to differences in populations, methodologies and efficacy measures among the different studies. Triptans are an important option in the symptomatic treatment of childhood and adolescent migraine.     

Treatment of hemiplegic migraine with triptans

The objective of this study was to investigate the efficacy, safety and tolerability of triptans in patients who suffer from familial or sporadic hemiplegic migraine. Seventy-six subjects had used triptans at least once as an abortive treatment. Average triptan response was 6.9 (SD ±3.1) and adverse event severity 4.9 (SD ±3.3) on a scale from 0 to 10 (no response or side effect 0, excellent response or unbearable side effects 10). None of the patients had an ischaemic stroke or a heart attack. One patient reported prolonged neurological symptoms, related to a single dose of rizatriptan, but there were no pathological findings in several MRI-scans. Triptans seem to be safe and effective treatment for most hemiplegic migraine patients.     

Acute migraine therapy: recent evidence from randomized comparative trials

(1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria.(2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved tolerability over sumatriptan.(3) Combination indomethacin/caffeine/prochlorperazine most likely has similar therapeutic efficacy to triptan therapy, with further research needed to complete understanding of any potential differences between these treatments.(4) Multi-targeted combination therapy with a triptan plus a non-steroidal anti-inflammatory (NSAID), such as sumatriptan/naproxen sodium, is more effective in acute migraine treatment than monotherapy with either agent alone.(5) It is unclear whether triptans offer clinically relevant benefits over aspirin or NSAIDs in migraine patients. Thus NSAIDs, particularly effervescent aspirin, should be considered the first-line treatment of migraine attacks.     

Almotriptan in the treatment of migraine

Almotriptan is an orally administered, highly selective serotonin 5-HT(1_B/1_D) receptor agonist that is effective in the acute treatment of moderate to severe migraine attacks. Since its introduction on to the market in 2001, several studies involving a large number of migraine patients have confirmed its efficacy and tolerability profile. Almotriptan, was found to be among the best-responding triptans in terms of pain relief and pain-free rate at 2 h. It has been reported that almotriptan has the best sustained pain-free (SPF) rate and the lowest adverse events (AEs) rate of all the triptans. When these clinical characteristics were combined to form the composite endpoint SPF and no AEs (SNAE), almotriptan emerged as the triptan with the best efficacy and tolerability profile. It also showed a good efficacy profile during the early treatment (within 1 h of onset) of migraine attacks characterized by moderate pain intensity. On the basis of these findings, almotriptan may be considered a therapeutic option for the acute treatment of migraine attacks.     

Integrating the triptans into clinical practice

The triptans (selective serotonin agonists) are becoming the first-line alternatives in the acute pharmacological treatment of migraine, at least for attacks of moderate-to-severe intensity. Although clinical trials demonstrate significant differences in efficacy between triptan tablets, they often appear similar in efficacy when used in clinical practice, particularly after dose adjustments. Most patients with migraine consider drugs that can be administered orally to be the most user-friendly. However, gastrointestinal absorption may be impaired during migraine attacks because gastric motility is inhibited, and there is a risk that nausea during the attack will culminate in vomiting. Furthermore, in addition to their antimigraine properties, triptans may prolong the gastric emptying time. For this reason the absorption of any triptan taken orally during the migraine attack will be erratic and treatment effects inconsistent. Despite these barriers to good efficacy and high reliability, the tablet is the most commonly used triptan formulation.     

Almotriptan: meeting today's needs in acute migraine treatment

Migraine is a common disorder associated with considerable individual and economic burden. Triptans are recommended for the treatment of migraine of any severity in patients who have failed to gain adequate relief with nonspecific medication; early transition to triptans avoids prolonged morbidity in patients failing to respond to nonspecific medications. There is evidence that early intervention therapy with oral formulations in migraine, soon after the onset of an attack and when pain is still mild, improves efficacy. Seven different triptans are currently marketed, with differing pharmacologic, efficacy and tolerability profiles. Almotriptan has many positive features, which include rigorously demonstrated efficacy in sumatriptan nonresponders, as early therapy and in menstrual migraine. In addition, almotriptan has a favorable pharmacologic profile with a lack of clinically relevant pharmacokinetic interventions with other drugs, adverse reactions rate similar to placebo, superior cost-effectiveness and excellent performance on composite clinical outcome measures that incorporate features of greatest importance to patients. Although effective in both triptan-naive and -experienced patients, and as both early and standard therapy, almotriptan shows greater efficacy in triptan-naive patients and as early treatment, and is consistently one of the preferred triptans in multiattribute decision-making analyses incorporating attributes of significance for patients and physicians. Therefore, almotriptan has many features that make it an ideal choice for a triptan-naive patient moving from nonspecific medication, a patient switching from another triptan owing to inefficacy or tolerability issues and patients being advised to take a triptan early in the course of a migraine attack.     

Triptans for treatment of acute pediatric migraine: a systematic literature review

The purpose of this article is to evaluate the effectiveness and safety of triptans for the treatment of acute migraine in children and adolescents. Randomized and open label trials of triptans in acute pediatric patients (ages 6-18 years) were identified by Medline (1966-2002) and PubMed (1991-2002). Additional reports were identified from the reference list of the retrieved studies. To study effectiveness, only randomized controlled trials were included, but open label studies were also included to study adverse effects. Pharmacokinetic studies of triptans in pediatric patients were also searched. Four randomized controlled trials were identified. One study reported oral sumatriptan, another oral rizatriptan, and two studies reported nasal spray sumatriptan. Rizatriptan is well tolerated but not clearly beneficial when used in adolescents. Effectiveness of nasal spray sumatriptan in acute pediatric migraine where other medications had failed was supported. Effectiveness of oral sumatriptan was not established. Adverse effects were minor for oral sumatriptan and rizatriptan and nasal sumatriptan. Pharmacokinetics of sumatriptan in pediatric patients has not been established. In conclusion, nasal spray sumatriptan should be considered in acute pediatric migraine in patients not experiencing adequate relief with other interventions.     

Meeting acute migraine treatment needs through novel treatment formulations

Migraineurs often do not use acute migraine-specific medications. Patient-reported satisfaction with triptans is modest. Patients are generally interested in obtaining more rapid and complete symptom relief. The role of trigeminal vascular activation may explain why some patients fail to respond to current treatment. Novel formulations of currently available acute migraine treatments have been developed, with improved clinical outcomes, response times, and pain-free rates. Currently available effective, novel, acute migraine therapies include needle-free injectable sumatriptan and effervescent diclofenac. Orally inhaled dihydroergotamine is a new treatment modality. These novel formulations may help patients achieve desirable outcomes, including faster and more complete relief, more consistent response, and improved drug tolerability.     

Acute treatment of migraine and the role of triptans

The use of triptans has improved the ability to treat migraine successfully compared with older treatments. Speed of relief, consistency of effect, and good tolerability have been the hallmarks of these agents. All of the currently available triptans have comparable efficacy and tolerability. Variables between the agents may lead to one agent or dose form being preferred over another in various clinical scenarios. The triptans that are forthcoming may improve on these options through enhanced efficacy rates, tolerability, and headache recurrence rates. There exist increasing options for migraine treatment that may further improve the clinical effects of the older and newer triptans through early treatment of migraine at the stages of mild migraine pain, or even during the prodromal phase of the attack. Additionally, recent work suggests that mini-prophylaxis of migraine at the menses is a highly successful treatment option with the triptans. In this age of managed care, providing cost-effective treatment of headache will take on increasing importance. Techniques such as stratification of acute treatments may enhance cost-effective care, whereas ready availability of the triptans may lead to significant improvements in utilization of parameters such as office visits, emergency room treatment, and even hospitalization.     

Treatment guidelines for acute migraine attacks

The Treatment Guideline Subcommittee of the Taiwan Headache Society evaluated the medications currently used for acute migraine attacks in Taiwan according to the principles of evidence-based medicine. We have assessed the quality of clinical trials, levels of evidence, and referred to other treatment guidelines proposed by Western countries and Japan. After several panel discussions, we merged opinions from the subcommittee members in order to propose a Taiwan consensus regarding the major roles, recommended levels, clinical efficacy, adverse events and cautions of clinical practice for these medications in treatment of acute migraine attacks. Acute medications currently available in Taiwan can be categorized into "migraine-specific" and "migraine-nonspecific" groups. Migraine-specific triptans and ergotamine, and migraine-nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs) have the best levels of evidence, and are recommended as the first-line medications for acute migraine attacks. The administration should follow the concept of "stratified care". For mild to moderate migraine attacks, oral NSAIDs are the first choice; with oral aspirin, combination analgesics, intravenous/intramuscular NSAIDs or ergotamine as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine are recommended and the suggestion is to administer them in the early stage of migraine attacks. NSAIDs can be used as alternatives. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either monotherapy. Parenteral steroid and fluid supply are the first choice in treatment of status migrainosus. Acetaminophen showed poor efficacy for moderate to severe migraine attacks but remains the first choice for children and pregnant women. Opiates are not recommended for acute migraine treatment at the present time because of serious adverse events. To prevent medication-overuse headache, the use of acute treatment should be limited to a maximum often days a month.     

Rizatriptan in migraine

The prevalence of migraine is high, affecting a significant proportion of the adult population during their most productive years of life and promoting impairment of their normal daily activities. Although guidelines for the acute treatment of migraine are available, outcome parameters are sometimes still below the expectations of both patients and physicians. Triptans represented an advance in clinical practice and have become the most well-studied class of medication for migraine. These agents present class I evidence for efficacy. However, they differ with regard to several of their clinical parameters, including onset of relief and consistency of response. Rizatriptan is a selective agonist of the 5-hydroxytryptophan(1B/1D )receptors, with proven superiority over placebo, ergotamine and selected oral triptans, demonstrating a good profile of safety and tolerability.     

A systematic review of the use of triptans in acute migraine

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 NNT for 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 NNT 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.     

Topiramate and triptans revert chronic migraine with medication overuse to episodic migraine

OBJECTIVE: This is a randomized, double-blind versus placebo study aimed at evaluating the efficacy of topiramate (TPM) in reducing the number of days with headache and the amount of acute medication taken monthly in patients with chronic migraine with medication overuse. We also studied the efficacy of single triptans available in Italy in interrupting headache crises during preventive treatment. METHODS: The studied sample was made up of 50 subjects: 30 patients were randomized for treatment with TPM, 100 mg/d, and 20 for placebo. Subjects treated with TPM were further randomized to evaluate, in double-blind versus placebo, the efficacy of single triptans available in Italy. The double-blind phase consisted of a titration phase (4 weeks) and of a maintenance phase (8 weeks). OUTCOME MEASURES: The reduction in the number of days with headache per 28 days and the reduction in the amount of acute medication taken per 28 days throughout the clinical trial in the TPM group were compared with those of the placebo group; the number of patients who were pain-free at 2 hours after the triptan intake and the headache recurrence rate in the 22 hours after the pain-free condition in the triptan group were compared with those of the placebo group. We also looked at tolerability profile. RESULTS: The group treated with TPM had a significant reduction in the number of days with headache (P < 0.0001 vs placebo) and in the mean amount of acute medication taken (P < 0.0001 vs placebo); all triptans were superior to placebo; there were no significant differences between different triptans; the analgesic effect of triptans increased throughout the trial. CONCLUSIONS: Topiramate proved to be well tolerated and effective in reverting chronic migraine with medication overuse to episodic migraine.     

Rational migraine management: optimising treatment with the triptans

In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have been approved for marketing in most countries of the world (naratriptan, rizatriptan and zolmitriptan). In addition, at least three others are in advanced stage of clinical development (almotriptan, eletriptan, and frovatriptan). This paper sets out to review the recent data with the aim of identifying: 1) What are the critical differences between the TELs and sumatriptan? 2) How do the currently licensed TELs compare? 3) Is it possible to provide a rational approach to migraine therapy based on objective differences in the clinical profile of these new drugs? Recent randomised controlled and comparator data were reviewed, including the independent FDA assessment of rizatriptan. Critical differences for the new TELs (naratriptan, rizatriptan and zolmitriptan) which may lead to more rational migraine management: Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5.0 mg) have demonstrated superior efficacy to sumatriptan 100 mg, and 25 and 50 mg respectively. Therefore, for first line use either rizatriptan or zolmitriptan would be appropriate for moderate and severe headache. Rizatriptan has a more rapid onset of action than sumatriptan 100 mg. Both rizatriptan and zolmitriptan have a more rapid onset of action than naratriptan. Therefore, for a rapid onset of action either rizatriptan or zolmitriptan would be appropriate. Naratriptan would appear to have a lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. However, 24-hour efficacy rates for zolmitriptan 2.5 mg were significantly greater than for sumatriptan 25 mg and 50 mg and were not significantly different from naratriptan. Therefore, for headaches of long duration and with a tendency to recur (e.g. menstrual headaches) either naratriptan or zolmitriptan would be appropriate. Naratriptan has lower reported adverse event rates comparable with placebo. This would support the use of naratriptan 2.5 mg in patients who have demonstrated poor tolerance to the "triptan type" adverse events.     

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.     

The use of multiattribute decision models in evaluating triptan treatment options in migraine

Background The physician treating patients with migraine is now able to choose from among seven triptans–almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. Objective To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method–TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)–can be applied to evaluate the currently available triptans. Methods In an example application, summary data from a recent meta–analysis of 53 published and unpublished placebo–controlled trials of the oral triptans were combined in TOPSIS models with computer–generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta–analysis, and uncertainty was assessed based on the confidence intervals from the meta–analysis. Results When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. Conclusion Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.     

Efficacy of parecoxib, sumatriptan, and rizatriptan in the treatment of acute migraine attacks

Triptans and analgetic nonsteroidal inflammatory drugs reduce acute pain syndromes in migraine. A further treatment option for an acute headache attack in patients with migraine may be the application of cyclooxygenase-2-specific inhibitors, as they have anti-inflammatory and analgesic properties. The objective of this pilot study was to investigate the effects of an oral fast-dissolving tablet of 10 mg of rizatriptan, an intravenous infusion of 40 mg of parecoxib, and a subcutaneous pen injection of sumatriptan (6 mg/0.5 mL) on pain relief in 3 cohorts of patients with episodic migraine. They were treated owing to the acute onset of a pain attack as a case of emergency. They were randomized to treatment with sumatriptan, rizatriptan, or parecoxib. The participants completed a visual analog scale for pain intensity at baseline before the drug administration and then after intervals of 20, 30, 60, and 120 minutes. Rizatriptan, parecoxib, and sumatriptan reduced pain symptoms. Twenty and 30 minutes after drug intake, rizatriptan was more efficacious than parecoxib and sumatriptan, and parecoxib was more effective than sumatriptan. Only a significant difference between rizatriptan and sumatriptan was found after 60 and 120 minutes. This trial demonstrates the effectiveness of a parecoxib infusion in the treatment of acute migraine and that the circumvention of the first pass effect of the liver by rizatriptan may be beneficial for fast pain relief.     

Profile of the antimigraine drug almotriptan

Triptans are the most relevant advance in the symptomatic treatment of migraine in the last decade. In this paper the basic properties as well as the efficacy and tolerability data of the last launched triptan, almotriptan, are reviewed. Almotriptan exhibits the highest bioavailability among triptans, this absorption being unaffected by sex, the presence of food in the stomach or by a migraine attack. At the recommended dose of 12.5 mg, almotriptan shows a rapid onset of effect, at 30 minutes, with efficacy parameters comparable to those of placebo. The potential advantages of almotriptan seem to be three: recurrence rate in the low range, lack of interactions with other drugs and a placebo-like tolerability profile, with a very low rate of chest symptoms. This balanced profile between efficacy and tolerability makes almotriptan 12.5 mg a good option for the symptomatic treatment of migraine.     

Defining response in migraine: which endpoints are important?

The primary endpoint traditionally measured in clinical trials of triptans for acute migraine therapy has been 2-hour pain relief, a decrease in pain intensity from moderate/severe to mild/none. Although harder to achieve, endpoints such as 2-hour pain free and the composite measure sustained pain free are now preferred as they better reflect what patients desire from medication, namely rapid onset of action, and complete and lasting relief of pain. A comprehensive meta-analysis has shown that oral triptans differ in their ability to achieve these endpoints, with almotriptan 12.5 mg, eletriptan 80 mg and rizatriptan 10 mg providing the highest likelihood of success. Although all triptans have simple and consistent pharmacokinetic features, they also have specific differences that may play a part in their differing clinical attributes. Incorporating tolerability to generate a more stringent endpoint, sustained pain free with no adverse events (SNAE), may provide an even better representation of patients' expectations. Comparison of SNAE rates using data from the meta-analysis of oral triptans indicates that almotriptan 12.5 mg has the best balance of high efficacy and good tolerability.