A Systematic Review of Oral Triptans in Treatment of Migraine
Background. In the current literature, there is neither a reported systematic review comparing the efficacy of triptans at 30 minutes and 1 hour after the migraine treatment, nor data related to efficacy of new marketed triptans.
Objective. The main objective of this analysis was to compare the efficacy and tolerability of currently marketed oral, non-reencapsulated triptan formulations vs placebo in the treatment of moderate-to-severe migraine attacks.
Methods. A systematic review of double-blind, randomized clinical trials reporting data after a single migraine attack was conducted. Efficacy results are shown using relative risk ratios with 95% confidence intervals. A sensitivity analysis was also conducted.
Results. After reviewing 221 publications, 38 studies were included. All marketed triptans provided significant relief and/or absence of pain at 2 hours, and relief at 1 hour when compared with placebo. After 30 minutes, fast-dissolving sumatriptan 50 and 100 mg, sumatriptan 50 mg, and rizatriptan 10 mg showed significant relief when compared to placebo, whereas the fast-dissolving formulation of sumatriptan 100 mg was the only oral triptan that was superior to placebo in meeting the pain-free endpoint. On the other hand, fast-dissolving sumatriptan 50 and 100 mg and eletriptan 40 mg showed a lower rate of recurrence than placebo, whereas rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo. Adverse events associated with treatment with tablet formulations of sumatriptan and zolmitriptan were significantly more frequent than those of the placebo group.
The inclusion of trials with reencapsulated triptans in the analysis introduced minor specific changes in these results.
Conclusion. This analysis updates the comparative data available for the 7 currently marketed oral triptans and clearly demonstrates their efficacy when compared to placebo, even with stricter endpoints, such as efficacy at 30 minutes. No triptan exhibited better tolerability than placebo. Results are diverse, depending on the triptan, which probably is a reflection of heterogeneous pharmacokinetics.
Migraine is a disorder that affects approximately 15% of the population and adversely influences the quality of life of patients who suffer from it, mostly young or middle-aged women. Two pharmacological treatment options exist for migraine: preventive and symptomatic treatment. Symptomatic or acute treatment is necessary for all patients with migraine. The symptomatic treatment options include simple analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), ergotics, and serotonin 5-HT1B/1D receptor agonists (known as "triptans"). Except in children or in adult's mild attacks, the effectiveness of simple analgesics is very poor. On the other hand, because of efficacy and tolerability reasons, ergotics are not considered as the standard medication for migrainous patients. The symptomatic treatment of migraine lies, therefore, in the wise use of NSAIDs and triptans. In general, NSAIDs are indicated in mild-to-moderate attacks, whereas triptans are the medication of choice in the treatment of moderate-to-severe attacks and in those patients who do not respond to or do not tolerate NSAIDs.
There are 7 marketed triptans that, despite sharing the same action mechanism (agonism at serotonin 1B/1D receptors), are different in terms of pharmacodynamics and, particularly, in their pharmacokinetic characteristics. Thus, from a theoretical standpoint, the different triptans are expected to exhibit differences regarding their efficacy and tolerability profile. Comparisons among these compounds have generally been conducted by means of comparative trials with sumatriptan, the reference drug within this therapeutic group. Because it is practically impossible to compare all different triptans in the same clinical trial, various systematic reviews have been conducted, wherein data from controlled, randomized trials with these drugs have been analyzed and comparisons between the triptans made. These reviews are already more than 5 years old, since the authors closed their databases around the year 2000. In the past few years, results have been published for clinical trials performed with the most recently marketed triptan, frovatriptan. Furthermore, new oral formulations have been made available for some of the triptans. Finally, the potential effect of reencapsulation vs non-reencapsulation on the trial results, which has often been the subject of controversy, has not been specifically analyzed until now. At least theoretically, encapsulation could, for instance, affect early efficacy time points.
The main objective of this analysis is to compare the efficacy and tolerability of the marketed oral non-reencapsulated triptan formulations (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) vs placebo in the acute treatment of migraine attacks (severe and/or moderate). This comparison has been performed by a systematic review of double-blind randomized clinical trials (RCTs), which reported data after the first migraine attack. This comparison is the first including data collected in the first hour of the attack as well as data of new marketed triptans.
Abstract and Introduction
Abstract
Background. In the current literature, there is neither a reported systematic review comparing the efficacy of triptans at 30 minutes and 1 hour after the migraine treatment, nor data related to efficacy of new marketed triptans.
Objective. The main objective of this analysis was to compare the efficacy and tolerability of currently marketed oral, non-reencapsulated triptan formulations vs placebo in the treatment of moderate-to-severe migraine attacks.
Methods. A systematic review of double-blind, randomized clinical trials reporting data after a single migraine attack was conducted. Efficacy results are shown using relative risk ratios with 95% confidence intervals. A sensitivity analysis was also conducted.
Results. After reviewing 221 publications, 38 studies were included. All marketed triptans provided significant relief and/or absence of pain at 2 hours, and relief at 1 hour when compared with placebo. After 30 minutes, fast-dissolving sumatriptan 50 and 100 mg, sumatriptan 50 mg, and rizatriptan 10 mg showed significant relief when compared to placebo, whereas the fast-dissolving formulation of sumatriptan 100 mg was the only oral triptan that was superior to placebo in meeting the pain-free endpoint. On the other hand, fast-dissolving sumatriptan 50 and 100 mg and eletriptan 40 mg showed a lower rate of recurrence than placebo, whereas rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo. Adverse events associated with treatment with tablet formulations of sumatriptan and zolmitriptan were significantly more frequent than those of the placebo group.
The inclusion of trials with reencapsulated triptans in the analysis introduced minor specific changes in these results.
Conclusion. This analysis updates the comparative data available for the 7 currently marketed oral triptans and clearly demonstrates their efficacy when compared to placebo, even with stricter endpoints, such as efficacy at 30 minutes. No triptan exhibited better tolerability than placebo. Results are diverse, depending on the triptan, which probably is a reflection of heterogeneous pharmacokinetics.
Introduction
Migraine is a disorder that affects approximately 15% of the population and adversely influences the quality of life of patients who suffer from it, mostly young or middle-aged women. Two pharmacological treatment options exist for migraine: preventive and symptomatic treatment. Symptomatic or acute treatment is necessary for all patients with migraine. The symptomatic treatment options include simple analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), ergotics, and serotonin 5-HT1B/1D receptor agonists (known as "triptans"). Except in children or in adult's mild attacks, the effectiveness of simple analgesics is very poor. On the other hand, because of efficacy and tolerability reasons, ergotics are not considered as the standard medication for migrainous patients. The symptomatic treatment of migraine lies, therefore, in the wise use of NSAIDs and triptans. In general, NSAIDs are indicated in mild-to-moderate attacks, whereas triptans are the medication of choice in the treatment of moderate-to-severe attacks and in those patients who do not respond to or do not tolerate NSAIDs.
There are 7 marketed triptans that, despite sharing the same action mechanism (agonism at serotonin 1B/1D receptors), are different in terms of pharmacodynamics and, particularly, in their pharmacokinetic characteristics. Thus, from a theoretical standpoint, the different triptans are expected to exhibit differences regarding their efficacy and tolerability profile. Comparisons among these compounds have generally been conducted by means of comparative trials with sumatriptan, the reference drug within this therapeutic group. Because it is practically impossible to compare all different triptans in the same clinical trial, various systematic reviews have been conducted, wherein data from controlled, randomized trials with these drugs have been analyzed and comparisons between the triptans made. These reviews are already more than 5 years old, since the authors closed their databases around the year 2000. In the past few years, results have been published for clinical trials performed with the most recently marketed triptan, frovatriptan. Furthermore, new oral formulations have been made available for some of the triptans. Finally, the potential effect of reencapsulation vs non-reencapsulation on the trial results, which has often been the subject of controversy, has not been specifically analyzed until now. At least theoretically, encapsulation could, for instance, affect early efficacy time points.
The main objective of this analysis is to compare the efficacy and tolerability of the marketed oral non-reencapsulated triptan formulations (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) vs placebo in the acute treatment of migraine attacks (severe and/or moderate). This comparison has been performed by a systematic review of double-blind randomized clinical trials (RCTs), which reported data after the first migraine attack. This comparison is the first including data collected in the first hour of the attack as well as data of new marketed triptans.
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