Rizatriptan wafer–sublingual vs. placebo at the onset of acute migraine

Rizatriptan wafer is a 5HT_1B/1D agonist for use in the acute treatment of migraine. It is a freeze-fried formulation, approved for oral administration, which dissolves on the tongue and is swallowed with saliva. In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a randomized, double-blind, placebo-controlled, out-patient study involving 39 migraineurs. Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo. At 1 h, 50% of the patients receiving rizatriptan wafer and 50% of the patients receiving placebo experienced significant relief. Implications and potential reasons for a high placebo response are discussed.     

Rizatriptan combined with rofecoxib vs. rizatriptan for the acute treatment of migraine: an open label pilot study

Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. As with any other acute treatment for migraine, headache recurrence may occur in up to one-third of responders. Combination with non-steroidal anti-inflammatory drugs (NSAIDs) seems to reduce the incidence of headache recurrence in clinical practice. Rofecoxib is a member of a new class of NSAIDs, which selectively inhibits the COX-2 enzyme and therefore is associated with a lower risk of gastrointestinal side-effects; the drug has a long plasma half-life (17 h). This open label study compared rizatriptan with rizatriptan plus rofecoxib in the acute treatment of migraine. Fifty-six triptan naive patients from a tertiary centre (37 women and 19 men, ages 16-55 years, mean 35 years) with International Headache Society migraine were randomized into two groups. They were instructed to treat three consecutive moderate or severe attacks with either 10 mg rizatriptan (group 1: 18 women and 10 men) or with 10 mg rizatriptan plus 25 mg rofecoxib (group 2: 19 women and 9 men). The presence of headache and nausea at 1, 2 and 4 h, and of side-effects, use of rescue medication and recurrence were compared. Fifty-four patients completed the study. Group 1 treated 76 attacks and group 2 treated 81 attacks. Absence of headache at 1 h was seen in 19 attacks (25%) in group 1 and in 34 attacks (42%) in group 2 (P=0.082); at 2 h absence of headache was seen in 60% of group 1 attacks and in 76% of group 2 attacks (P=0.115). At 4 h, 75% of group 1 attacks and 88% of group 2 attacks were pain free (P=0.122). With regard to nausea, of those who had nausea at baseline, 31% and 49% of attacks in groups 1 and 2, respectively, were nausea free at 1 h (P=0.091), 75% and 79% at 2 h (P=0.736) and 82% and 91% (P=0.479) at 4 h. Recurrence, based on all attacks of those patients who achieved pain free at 4 h, was observed in 53% of group 1 and 20% of group 2 attacks (P<0.001). Sustained pain-free rates (for the 4-h time point) were 45.6% of group 1 and 78.9% of group 2 attacks. There were no significant differences with regard to rescue medication consumption after 4 h and side-effects in both groups. There was a non-significant trend for the combination group to have a higher response rate. The group treated with rizatriptan and rofecoxib had a lower recurrence rate than the group treated with rizatriptan. This study demonstrated that combining a fast acting triptan such as rizatriptan with rofecoxib reduced headache recurrence rates, was well tolerated and may be more effective than the use of rizatriptan alone. Double-blind, placebo-controlled studies are necessary to confirm these observations.     

Double-blind study of naproxen vs placebo in the treatment of acute migraine attacks

Naproxen was compared with placebo in a double-blind, crossover trial in classic and common migraine. The trial was terminated at a fixed date; 37 patients had entered, 5 of whom were excluded. Naproxen was given as 750 mg at the first symptom of the attack, a total of 1250 mg per 24 h was allowed. Patients were followed for six attacks or three months in each phase, whichever came first. The severity of the headache was significantly less with naproxen in the first 2 h of the attack (p = 0.047), whereas there was no difference when the whole attack was considered. Significantly more patients preferred naproxen (p = 0.042). Side effects occurred in five patients, causing withdrawal of one patient while on naproxen.     

Rizatriptan for treatment of acute migraine in patients taking topiramate for migraine prophylaxis

Objective.— To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Background.— There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication. Methods.— This was a worldwide, randomized, placebo‐controlled, double‐blind, multiple‐attack study in adults with a >1‐year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing ≥2 moderate/severe attacks per month. Participants treated 3 moderate/severe attacks in crossover fashion (2 with rizatriptan 10‐mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2‐hour pain relief. Results.— Two‐hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P < .001). Response rates also favored rizatriptan for sustained pain relief from 2‐24 hours (32.6% vs 11.1%, P < .001), 2‐hour pain freedom (36.0% vs 6.5%, P < .001), normal functional ability at 2 hours (42.2% vs 12.7%, P < .001), and overall treatment satisfaction at 24 hours (60.8% vs 33.6%, P < .001). Few participants reported adverse experiences (16 [15.8%] with rizatriptan, 3 [3.2%] with placebo); none were serious. Conclusion.— Rizatriptan 10‐mg ODT was superior to placebo at all pain end points for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Rizatriptan was generally well tolerated in this population. These results are comparable with those from clinical trials in patients not using prophylaxis, suggesting that the use of topiramate does not affect the efficacy or tolerability of rizatriptan for acute migraine treatment.     

Rizatriptan in the treatment of migraine

Rizatriptan is a selective 5-hydroxytriptamine1B/1D receptor agonist that was launched in 1998 for the acute treatment of migraine in adults. Based on data from 6 large clinical trials in patients > or =18 years of age in whom migraine was diagnosed according to International Headache Society criteria, the marketed 10-mg and 5-mg oral doses of rizatriptan are effective in relieving headache pain and associated migraine symptoms. The 10-mg dose is more effective than the 5-mg dose. At 2 hours after dosing, up to 77% of patients taking rizatriptan 10 mg had pain relief compared with 37% of those taking placebo, up to 44% were completely pain free compared with 7% of those taking placebo, and up to 77% were free of nausea compared with 58% of those taking placebo (P < 0.05 for all 3 comparisons). Both doses of rizatriptan are generally well tolerated. In placebo-controlled studies involving treatment of a single migraine attack, the most common side effects (incidence > or =2%) occurred in <10% of patients, typically were transitory (2 to 3 hours), and were mild or moderate. Rizatriptan is an effective and well-tolerated acute treatment for migraine.     

Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study

Gastroparesis frequently happens during migraine attacks, postponing the onset of action of orally administered drugs. Furthermore, triptans seem to work better in the earlier phases of the migraine attacks. Therefore, associating a gastrokinetic drug with a triptan may translate into better efficacy and higher consistency of response. Trimebutine is an opioid derivative with exclusive action on receptors of the Meissner and Auerbach plexus throughout the digestive tube. It has no absorption or central penetration. Herein we contrast the combination of rizatriptan plus trimebutine with rizatriptan alone in the acute treatment of migraine. Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order. We collected information on the severity of the attack, as well as presence of nausea and photophobia at the time of drug intake, and after 1, 2 and 4 h. Recurrence and adverse events were also contrasted. Sixty-four attacks were treated with each drug regimen. At 1 h postdose, 30 (46.8%) of 64 attacks treated with the combination resolved completely, vs. eight (12.5%) of the rizatriptan-treated attacks, a difference of 34% (P < 0.01). At 2 h postdose, 47 (73.4%) attacks treated with the combination vs. 20 (31.2%) of those treated with rizatriptan alone resolved completely, a difference of 42% (95% confidence interval 26, 58, P < 0.001). Regarding nausea and photophobia, the combination was also associated with significantly better response. Recurrence was similar among the two drug regimens, as well as adverse events. The combination rizatriptan and trimebutine is more effective than rizatriptan alone. The combination does not increase adverse events or recurrence of pain.     

Ergotamine vs. metoclopramide vs. their combination in acute migraine attacks

The effect of ergotamine tartrate was compared with that of the antiemetic agent metoclopramide and with those of two combinations in a double-blind trial of 24 adult female patients with migraine. The following combinations of the drugs were used in oral administration in a total of 176 acute migraine attacks: (a) Ergotamine 1 mg, (b) Metoclopramide 20 mg, (c) Ergotamine 1 mg + metoclopramide 20 mg, (d) Ergotamine 2 mg + metoclopramide 20 mg. The duration of attacks was significantly shorter on both of the combinations compared with the single drugs. The intensity of the pain was somewhat weaker and the appearance of nausea and vomiting somewhat but not significantly less during the combination treatments. In their overall opinion the patients favored the 2 mg + 20 mg combination significantly more than the others. Both ergotamine and metoclopramide are efficient in acute migraine attacks. Their combination seems to enhance the therapeutic response in some respects.     

Treatment of acute migraine attack: naproxen and placebo compared

A double-blind, cross-over, randomized study of acute migraine attack compared treatment results of naproxen with that of placebo. Each treatment period continued for either three months or six migraine attacks, whichever occurred first. The initial dose of naproxen was 750 mg, with additional 250-500 mg doses taken if and when required, to a maximum of five 250 mg tablets within a period of 24 h in each migraine attack. Forty-one patients were enrolled in the study; they had all experienced at least two but not more than eight migraine attacks a month during the preceding year. Thirty-two patients completed the two treatment periods. Naproxen was statistically significantly superior to placebo in reducing the severity of head pain, nausea, and photophobia; in shortening the duration of head pain, nausea, vomiting, photophobia, and lightheadedness; in diminishing the frequency of vomiting; and in decreasing the need for escape medication. Both patient and physician treatment preferences significantly favoured naproxen. Nine side effects were experienced by seven patients while receiving placebo and seven by five patients during naproxen treatment. Mild gastrointestinal discomfort was the main complaint. Only one patient withdrew from treatment because of a side effect, which occurred while receiving placebo.     

Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine

This was a randomized, double-blind study designed to evaluate the comparative efficacy and tolerability of the 40-mg dose of eletriptan and the 2.5-mg dose of naratriptan. Patients (n = 548) meeting International Headache Society (IHS) criteria for migraine were randomized to treat a single migraine attack with either eletriptan 40 mg, naratriptan 2.5 mg, or placebo. Headache response rates at 2 h and 4 h, respectively, were 56% and 80% for eletriptan, 42% and 67% for naratriptan (P < 0.01 for both time-points vs. eletriptan), and 31% and 44% for placebo (P < 0.0001 vs. both active drugs at both time-points). Eletriptan also showed a significantly greater pain-free response at 2 h (35% vs. 18%; P < 0.001) as well as lower use of rescue medication (15% vs. 27%; P < 0.01) and higher sustained headache response at 24 h (38%) compared with naratriptan (27%; P < 0.05) and placebo (19%; P < 0.01). Both eletriptan and naratriptan were well tolerated. The results confirm previous meta-analyses that have suggested the superiority of eletriptan vs. naratriptan in the acute treatment of migraine.     

Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group

Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.     

Rizatriptan RPD for severe migraine in the emergency department--a multicenter study

Many patients with severe migraine come to the Emergency Department (ED) due to failure of different drug regimens to stop their headache. We treated 98 patients with severe migraine who were seen in three different EDs. We used rizatriptan RPD wafers 10 mg and observed the patients for 2 h. We found that at 2 h, 92.9% (91/98) of the patients had pain relief, and 73.5% were pain free. The mean time to pain relief was 26.9 +/- 29.6 min with a median of 15 min, and the time to pain free was 70.2 +/- 47.3 min with a median of 75 min. Eighty-five percent of the patients were free of associated symptoms, such as nausea and vomiting, at 2 h with a mean time to symptom free of 55 +/- 47.5 min and a median of 45 min. Rizatriptan was reported to be much better than other drugs by 74.4% of the patients. Side effects were minor and transient. Recurrence of migraine occurred part of the day in 17.1% of the patients and all day or almost all day in 8.6% of the patients only. The results were consistent in all three EDs. We conclude that rizatriptan RPD is very effective and reliable as a first-line therapy for acute migraine in the ED. It dissolves immediately in the mouth without the inconvenience of an injection. It works fast and has few side effects and low headache recurrence.     

A double-blind study of ibuprofen versus placebo in the treatment of acute migraine attacks

The efficacy of ibuprofen, a non-steroidal anti-inflammatory drug, was assessed in the acute treatment of migraine. Twenty-five patients completed a double-blind placebo-controlled multicrossover trial. The initial dose of ibuprofen was 1200 mg. Six migraine attacks were randomly treated in each patient, three with ibuprofen and three with placebo. The results indicated a statistically significant reduction in the duration of the migraine attacks and also a statistically significant reduction in the severity of headache and nausea in the ibuprofen-treated attacks. The use of additional medication was significantly reduced in the ibuprofen-treated attacks (25.6% vs 57.5%). No serious side effects were reported. Ibuprofen is valuable in the treatment of acute migraine attacks.     

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized,double-blind,placebo-controlled study

OBJECTIVE: To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs. METHODS: Randomized, double-blind, placebo-controlled study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or placebo (n = 147) for a moderate or severe headache and for up to two recurrences. Headache severity, presence or absence of associated symptoms, and functional disability were assessed over a 4-hour postdose period, and any adverse events were recorded. The primary efficacy measure was pain-free status at 2 hours postdose. RESULTS: Rizatriptan 5 mg was well tolerated. The most commonly reported adverse events (all with incidence of 5% or less) among patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue, nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32% for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients with pain relief (reduction of predose pain intensity to mild or none) at 2 hours was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults. Compared with placebo, rizatriptan significantly improved functional disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the weekend placebo response rate was similar to that seen in adults. CONCLUSIONS: Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack.