Rizatriptan efficacy in ICHD-II pure menstrual migraine and menstrually related migraine

Objective.— To examine the efficacy of rizatriptan for the treatment of pure menstrual migraine (PMM). Background.— In 2004, the International Headache Society proposed new research criteria for menstrual migraine (International Classification of Headache Disorders [ICHD‐II]). Two subtypes were defined: PMM, in which attacks occur exclusively with menstruation, and menstrually related migraine (MRM), in which attacks may also occur at other times of the cycle. Methods.— The 2 protocols (MM1 and MM2) were identical randomized, double‐blind studies. Adult patients with ICHD‐II menstrual migraine were assigned to either rizatriptan 10‐mg tablet or placebo (2:1). Patients were to treat a single menstrual migraine attack of moderate or severe pain intensity. This prospectively planned substudy pooled data from patients with a diagnosis of PMM from both studies. The primary substudy endpoint was 2‐hour pain relief. Efficacy data were summarized for patients with a diagnosis of MRM. Results.— Of 707 (MM1: 357, MM2: 350) patients treated in the study, 146 patients (MM1: 81, MM2: 65) had a diagnosis of PMM. The percentage of patients reporting 2‐hour pain relief was significantly greater for rizatriptan than for placebo for both PMM (73% vs 50%, P = .006) and MRM subgroups (71% vs 52%, P < .001). Most other efficacy endpoints favored rizatriptan compared with placebo in patients with either PMM or MRM. Conclusion.— Rizatriptan 10 mg was superior to placebo for the treatment of PMM, as measured by 2‐hour pain relief. Rizatriptan was also effective for the treatment of MRM and for relief of migraine‐associated symptoms for both headache subtypes.     

Migraine Treatment With Rizatriptan and Almotriptan: A Crossover Study

Background.— Rizatriptan and almotriptan are effective and well-tolerated triptans that have not been compared directly. Objective.— To evaluate the effectiveness of rizatriptan 10 mg and almotriptan for the acute treatment of migraine, in a real-world setting. Methods.— Of a large, multicenter, open-label, crossover study, we conducted a substudy to contrast the effectiveness of rizatriptan 10 mg and almotriptan 12.5 mg for the acute treatment of 2 migraine attacks in a sequential, crossover manner. Time to outcome was assessed using stopwatches. Mean and median times to onset of pain relief (PR) and pain freedom (PF) for rizatriptan and almotriptan were compared. The effect of rizatriptan on times to onset of PR and PF, adjusting for potential confounding factors (treatment sequence, treatment order, and use of rescue medication), was computed via a Cox proportional hazard model. Results.— Out of the 146 patients taking almotriptan as their usual care medication, 79 used stopwatch for both attacks. Significantly more patients taking rizatriptan achieved onset of PR within 2 hours after dosing than those taking almotriptan (88.6% vs 73.4%, P = .007). A higher proportion of patients taking rizatriptan achieved PF within 2 hours after dosing than those taking almotriptan (55.7% vs 45.6%, P = .10). Times to onset of PR and PF were significantly shorter with those patients taking rizatriptan than with those taking almotriptan (median time to PR: 45 vs 60 minutes, P = .002; median time to PF: 100 vs 135 minutes, P = .004). The adjusted proportional hazard ratios (rizatriptan vs almotriptan) for times to onset of PR and PF were 1.51 (95% confidence interval 1.20 to 1.88) and 1.42 (95% confidence interval 1.15 to 1.76), respectively. More patients were very satisfied when treating their attacks with rizatriptan than with almotriptan. Rizatriptan was preferred by most patients. Conclusions.— Times to achieve PR and PF were significantly shorter for patients using rizatriptan, as compared with those using almotriptan.     

Elimination of migraine-associated nausea in patients treated with rizatriptan orally disintegrating tablet (ODT): a randomized, double-blind, placebo-controlled study

OBJECTIVE: To confirm the efficacy of rizatriptan 10 mg orally disintegrating tablet (ODT) for the elimination of migraine-associated nausea. BACKGROUND: Pooled studies of rizatriptan analyzing elimination of nausea as a secondary endpoint showed that 65% of rizatriptan patients reported elimination of nausea at 2 hours compared with 41% of patients taking placebo. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled single-attack trial enrolling adult patients with at least a 6-month history of migraine who typically experience migraine-associated nausea. Patients treated a moderate or severe migraine headache at the earliest sign of nausea with either rizatriptan 10 mg ODT or placebo (2 : 1). The primary endpoint was elimination of nausea at 2 hours postdose, and the secondary endpoint was pain relief at 2 hours postdose. RESULTS: Although not statistically significant, a greater percentage of patients had elimination of nausea at 2 hours with rizatriptan compared with placebo (70.3% vs 62.0%, P = .165, odds ratio [95% CI] = 1.45 [0.86, 2.46]). When patients were grouped by baseline headache severity, rizatriptan showed a greater advantage than placebo for patients with moderate pain (rizatriptan 72.8% vs placebo 57.4%), but no difference for patients with severe pain (rizatriptan 67.7% vs placebo 66.7%). There were significantly more patients who achieved 2-hour pain relief with rizatriptan (69.7% vs 54.3%, P = .012, odds ratio [95% CI] = 1.94 [1.16, 3.25]). CONCLUSION: Although the efficacy of rizatriptan 10 mg ODT for the elimination of migraine-associated nausea was comparable to that seen in previous rizatriptan trials, the higher-than-usual placebo response prevented a finding of a statistically significant difference. There was a sizable difference in placebo response between patients who treated moderate vs severe migraine. Rizatriptan was effective for 2-hour pain relief.     

Efficacy of Rizatriptan 10 mg administered early in a migraine attack

OBJECTIVE: To determine if administration of rizatriptan 10 mg is superior to placebo for the early treatment of acute migraine, while the pain is mild. BACKGROUND: Past studies have suggested that treatment outcomes can be improved if a triptan is administered early in the time course of a migraine attack. METHODS: Two randomized, parallel, placebo-controlled, double-blind studies. TAME (Treat A Migraine Early)1 was conducted at 46 centers in the United States; TAME2, at 48 centers in the United States. Totally, 1030 adult patients with at least a 6-month history of migraine were studied. Patients were instructed to treat within 1 hour of migraine onset, while pain was mild. Patients maintained a headache diary in which they rated their levels of pain and disability, and recorded other symptoms of migraine. Primary endpoints were pain freedom at 2 hours and sustained pain freedom at 24 hours post-dose. RESULTS: In TAME1, 57.3% versus 31.1% of patients reported pain freedom at 2 hours post-dose and 42.6% versus 23.2% reported 24-hour sustained pain freedom with rizatriptan versus placebo, respectively (P < .001 for both). In TAME2, 58.9% versus 31.1% of patients reported pain freedom at 2 hours post-dose and 48.0% versus 24.6% reported 24-hour sustained pain freedom with rizatriptan versus placebo, respectively (P < .001 for both). All other efficacy endpoints favored rizatriptan. Repeat doses of the medicine were not allowed; patients may have delayed treatment; non-migraine headaches may have been treated. CONCLUSIONS: Rizatriptan 10 mg was superior to placebo when treating migraine early, while pain is mild, as measured by pain freedom at 2 hours and 24-hour sustained pain freedom.     

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 (MAXALT) for the Acute Treatment of Migraine and Migraine Recurrence. A Placebo-Controlled, Outpatient Study

Rizatriptan is a novel 5-HT_1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo ( P <0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the l0-mg dose preferred as it is more effective with a faster onset of action.     

Oral Rizatriptan Versus Oral Sumatriptan: A Direct Comparative Study in the Acute Treatment of Migraine

Rizatriptan is a potent, oral, 5-HT_1B/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 ≤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.     

Characteristics of Menstrual vs Nonmenstrual Migraine: A Post Hoc,Within‐Woman Analysis of the Usual‐Care Phase of a Nonrandomized Menstrual Migraine Clinical Trial

Objective.— To compare, using a within‐woman analysis, the severity, duration, and relapse of menstrual vs nonmenstrual episodes of migraine during treatment with usual migraine therapy. Background.— Studies comparing the clinical characteristics of menstrual and nonmenstrual migraine attacks have yielded conflicting results, contributing to disagreement regarding whether menstrual migraine attacks are clinically more problematic than nonmenstrual migraine attacks. Methods.— Post hoc within‐woman analysis of the usual‐care phase (month 1) of a 2‐month, multicenter, prospective, open‐label study at 21 US medical practices (predominantly primary care). Participants were women ≥18 years of age with regular predictable menstrual cycles (28 ± 4 days) who self‐reported a ≥1‐year history of migraine attacks occurring between days ?2 and +3 (menses onset = day +1) and ≥8 such attacks within the previous 12 cycles. Migraine treatment episodes were categorized as menstrual (occurring on days ?2 to +3 of menses) or nonmenstrual (occurring on days +4 to ?3 of menses). Pain severity, functional impairment, duration, relapse in 24 hours, and use of rescue medication were compared. Sources of variability (within‐ or between‐patient) were determined using mathematical modeling. The http://www.clinicaltrial.gov code for trial is NCT00904098. Results.— Women (n = 153; intent to treat) reported 212 menstrual (59.2%) and 146 nonmenstrual (40.8%) migraine treatment episodes. Compared with nonmenstrual treatment episodes, menstrual episodes were more likely to cause impairment (unadjusted odds ratio, 1.65, 95% CI, 1.05‐2.60; P = .03), were longer (unadjusted hazard ratio 1.68; 95% CI, 1.31‐2.16; P < .001), and were more likely to relapse within 24 hours (unadjusted odds ratio, 2.66; 95% CI, 1.25‐5.68; P = .01). Within‐patient effects accounted for only 18‐33% of the total variance in these outcomes. Conclusions.— Post hoc, within‐woman analysis of migraine treatment episodes categorized based on International Headache Society criteria showed that menstrual treatment episodes were more impairing, longer lasting, and more likely to relapse than nonmenstrual treatment episodes in this selected population of women with frequent menstrual migraine. The current analysis indicates that most of the variability in these outcomes is due to differences between headache types and not within‐patient differences for a given type of headache, suggesting that menstrual episodes are potentially treatable. These findings underscore the differences between menstrual and nonmenstrual episodes of migraine and the need to offer effective migraine treatment to women. (Headache 2010;50:528‐538)     

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 10-mg ODT for Early Treatment of Migraine and Impact of Migraine Education on Treatment Response

Objective.— To examine the efficacy of rizatriptan 10-mg orally disintegrating tablet (ODT) for treating migraines of mild intensity soon after onset, with or without patient-specific migraine education.
Background.— Studies have shown rizatriptan tablet efficacy in early migraine treatment.
Methods.— In this randomized, placebo-controlled, double-blind, factorial design study, adults with a history of migraine were assigned to rizatriptan 10-mg ODT ± patient education (personalized summary of early migraine signs and symptoms) or placebo ± patient education in a 1 : 1 : 1 : 1 ratio. Patients were instructed to treat 1 attack at the earliest time they knew that their headache was a migraine, while pain was mild. During the next 24 hours, patients assessed pain severity, associated symptoms, functional disability, use of rescue medication, and treatment satisfaction. The primary endpoint was pain freedom at 2 hours; a key secondary endpoint was 24-hour sustained pain freedom.
Results.— Of 207 patients randomized to treatment, 188 (91%) treated a study migraine. Significantly more patients taking rizatriptan reported pain freedom at 2 hours compared with placebo (66.3% vs 28.1%, P  < .001). Similarly, significantly more patients taking rizatriptan reported 24-hour sustained pain freedom (52.2% vs 17.7%, P  < .001). A greater proportion of patients in the rizatriptan + education group reported pain freedom at 2 hours compared with those in the rizatriptan + no education group (71.7% vs 60.9%, P  = .430). Few adverse events were reported.
Conclusion.— Rizatriptan 10-mg ODT, when taken early, while headache pain is mild, was superior to placebo at providing pain freedom at 2 hours and 24-hour sustained pain freedom (NCT00516737).     

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.     

Efficacy and Safety of Rizatriptan Versus Standard Care During Long-term Treatment for Migraine

Rizatriptan is a novel, selective 5-HT_1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46 000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior ( P <0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.     

Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups

Rizatriptan is a novel, selective 5-HT1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46,000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior (P < 0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.     

Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group

Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.     

Efficacy of the Sustained-Release Hydromorphone in Neuropathic Pain Management: Pooled Analysis of Three Open-Label Studies

ABSTRACT

This pooled analysis was designed to determine whether the analgesic response to treatment with OROS® hydromorphone, as measured by the “pain on average” scale of the Brief Pain Inventory (BPI), was different in patients with neuropathic pain compared to those with nociceptive pain, after adjusting for differences in baseline characteristics. Three open-label studies on patients with neuropathic and nociceptive malignant and nonmalignant chronic pain were analyzed. A mixed model for repeated measures linear regression analysis was used to compare the effect of OROS® hydromorphone on patients with neuropathic and nociceptive pain, adjusting for potentially confounding factors. Data from patients with pure neuropathic pain and mixed pain were also compared. Safety and tolerability was assessed by recording the number of adverse events. The primary outcome was “pain on average” (BPI item 5) over time. Secondary outcomes were the effect of OROS® hydromorphone on other BPI items including “pain relief” and “interference with sleep.” Patients with neuropathic pain showed a similar response to treatment with OROS® hydromorphone to those patients with nociceptive pain. There was no statistically significant difference between the pain groups (difference between groups ?0.552 at visit 7; P = .060 for overall difference between groups). For some outcome variables, treatment was more effective for patients with neuropathic pain. The treatment was generally well tolerated. This pooled analysis shows that treatment with OROS® hydromorphone had similar efficacy for neuropathic and nociceptive pain.     

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.     

Rizatriptan 10-mg wafer versus usual nontriptan therapy for migraine: analysis of return to function and patient preference

BACKGROUND: More than half of patients with migraine suffer moderate to severe functional disability during migraine attacks. OBJECTIVE: To compare effects on functional disability at 2 hours after treating a migraine with rizatriptan 10-mg wafer versus usual nontriptan therapy for triptan-na?ve patients with migraine. DESIGN: Open-label, prospective, two-attack study conducted at 111 neurology clinics. METHODS: Adult patients with migraine treated two migraine attacks, the first with their usual nontriptan therapy (nonsteroidal anti-inflammatory drugs, 57%; analgesics, 27%; or ergot derivatives, 16%) and the second with rizatriptan 10-mg wafer. Patients recorded pain intensity and functional disability at the start, and functional disability at 2 hours, as well as the time of return to normal function. RESULTS: A total of 1353 patients, 76% of them female, completed the study and were considered evaluable. During first and second migraine attacks, 55% and 63% of patients, respectively, reported severe disability or requiring bed rest. At 2 hours after treatment, the likelihood of experiencing any disability was more than five times greater after usual nontriptan therapy than after rizatriptan (odds ratio, 5.68; 95% confidence interval (CI), 4.66 to 6.94; P < .001). Rizatriptan was twice as likely to return patients to normal function than usual nontriptan therapy after adjusting for confounding factors (adjusted hazard ratio, 2.08; 95% CI, 1.92 to 2.25; P < .001). Assessed over all time points up to 6 hours, the speed of return to normal function was 52% faster after rizatriptan therapy (P < .001). Significantly more patients preferred rizatriptan than usual nontriptan therapy (78.8% vs. 21.2%; P < .001). The most common reasons cited for preference for rizatriptan were faster relief of headache pain and faster return to normal function. CONCLUSIONS: Patients in this study were more likely to experience a return to normal function at 2 hours after receiving rizatriptan than after their usual nontriptan therapy for migraine. The results of this study, using patient-oriented, clinically relevant endpoints such as functional disability and preference, will help to guide practitioners in making recommendations for acute migraine treatment.