Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study

OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, versus placebo for early intervention while head pain was mild in patients with disabling migraine. METHODS: A post hoc analysis was performed in a subgroup of patients from a large, randomized, placebo-controlled study of patients with disabling headache who treated while pain was mild. Pain-free response 2 and 4 hours postdose, headache recurrence, and safety were examined. Significance tests were performed only for the first-treated attacks. RESULTS: Twenty-six patients with disabling headache treated 46 mild and 166 moderate or severe headaches. For the first-treated headaches while pain was mild, pain-free rates were significantly higher for sumatriptan than placebo 4 hours postdose (78% versus 0%, P =.02), but not 2 hours postdose (52% versus 0%, P =.22). Across all headaches treated while pain was mild, pain-free responses were higher for sumatriptan than placebo 4 hours (85% versus 17%) and 2 hours (50% versus 0%) postdose compared with placebo. When the same patients treated headaches while pain was moderate or severe, pain-free rates were lower than that reported for treatment during mild pain. There was a trend toward lower headache recurrence in headaches treated while pain was mild compared with moderate or severe pain (13% versus 18%). No drug-related adverse events were reported in the headaches treated while pain was mild. CONCLUSIONS: Patients with disabling migraine may benefit from early intervention with sumatriptan, 50 mg, while pain is mild.     

Efficacy of sumatriptan nasal spray in recurrent migrainous headache: an open prospective study

OBJECTIVE: To evaluate the effectiveness of sumatriptan 20 mg via nasal spray and 100-mg tablets in treating migrainous headache in patients without a concomitant migraine diagnosis. METHODS: We prospectively investigated the efficacy of sumatriptan 20 mg via nasal spray and 100-mg tablets in patients with a history of at least 5 moderate to severe headache attacks lasting 2 to 72 hours that consistently did not meet the International Headache Society (IHS) criteria for migraine or episodic tension-type headache. RESULTS: Nineteen headache attacks classifiable as migrainous disorder without aura (IHS 1.7) were evaluated in 13 patients using 20-mg sumatriptan nasal spray within a 10-week period. A 2-point decrease in headache severity on a four-point scale was achieved in 74% (95% confidence interval [CI], 50% to 89%) of the attacks within 2 hours. The pain-free incidence (a reduction in headache severity from moderate or severe to none) was 37% (95% CI, 17% to 63%) after 2 hours. Ten patients completed the second part of the study, taking oral sumatriptan for 14 migrainous attacks: a 2-point decrease in headache severity was achieved in 38% (95% CI, 13% to 71%) of the attacks within 2 hours and in 77% (95% CI, 48% to 92%) within 4 hours. CONCLUSION: This is the first prospective study to show that intranasal or oral sumatriptan may be effective in patients experiencing moderate to severe headache attacks which consistently do not fulfill the IHS criteria for migraine or episodic tension-type headache.     

Sumatriptan nasal spray and cognitive function during migraine: results of an open-label study

OBJECTIVE: To examine measures of cognitive function during acute migraine, before and after treatment with sumatriptan nasal spray, 20 mg. BACKGROUND: Migraineurs frequently report symptoms of cognitive impairment during migraine. The efficacy of sumatriptan for treatment of migraine-related cognitive impairment is undocumented. METHODS: This open-label, single-attack study of 28 subjects used the Headache Care Center-Automated Neuropsychological Assessment Metrics, a computerized neuropsychological assessment battery, to measure cognitive function under three patient conditions: migraine-free, untreated migraine, and following sumatriptan (primary outcome). Headache response and pain-free response, percent effectiveness, and clinical disability were measured. RESULTS: Cognitive function (simple reaction time, sustained attention/concentration, working memory, visual-spatial processing) and alertness/fatigue were adversely affected during migraine compared with migraine-free performance (P<.05), and rapidly restored following sumatriptan nasal spray, 20 mg (P<.05). Headache and pain-free response were 86% and 68%, respectively, at 135 minutes postdose. Changes in migraine pain severity, clinical disability, and percent effectiveness following treatment with sumatriptan nasal spray, 20 mg, were significantly correlated with cognitive function measures across all subtests (P<.001). CONCLUSIONS: Sumatriptan nasal spray, 20 mg, restored migraine-related cognitive function and clinical disability.     

Efficacy and Tolerability of Subcutaneous Sumatriptan for Acute Migraine: A Comparison Between Ethnic Groups

OBJECTIVE: To evaluate efficacy and tolerability of subcutaneous sumatriptan 6 mg versus placebo for acute migraine between ethnic groups. BACKGROUND: Patients in previous sumatriptan studies have been predominantly Caucasian and the effects of sumatriptan between different ethnic groups are unknown. METHODS: This was a multicenter, 3-phase, 12-attack study. Phases I and III (inclinic) were randomized, double-blind, placebo-controlled, crossover designs. Phase II (outpatient) was a single-blind design. Sumatriptan was compared to placebo across 2 groups (non-Caucasian and Caucasian) and individual ethnic subgroups (black, Hispanic, and others). Headache response, pain-free response, associated symptoms, and clinical disability were assessed. Tolerability assessments included the incidence of adverse events, physical examinations, vital signs, electrocardiograms, and clinical laboratory data. RESULTS: Two hundred patients treated at least one migraine attack (150 non-Caucasians: 46 blacks, 68 Hispanics, 36 others). Two hours postdose, significantly more inclinic sumatriptan-treated patients reported headache response (non-Caucasians, 81% versus 37% placebo; Caucasians, 87% versus 19% placebo; P<.001) and mild or no clinical disability, compared with placebo (non-Caucasians, 87% versus 50% placebo; Caucasians, 90% versus 38% placebo; P<.001). Blacks (80%), Hispanics (83%), and others (74%) reported similar patterns of headache response at 2 hours. Similar results were reported during the outpatient phase. The incidence of adverse events following sumatriptan during the inclinic phase was similar between ethnic groups (non-Caucasian, 75%; Caucasian, 79%) and higher than placebo (non-Caucasian, 51%; Caucasian, 31%). Overall, adverse events in the outpatient phase of the study were lower than in the inclinic phase. CONCLUSION: Sumatriptan injection is effective and well tolerated in non-Caucasians and Caucasians for the treatment of acute migraine attacks. Only minor differences in efficacy or tolerability were observed between blacks, Hispanics, and others.     

Valdecoxib for treatment of a single, acute, moderate to severe migraine headache

OBJECTIVE: To evaluate the analgesic efficacy and safety of a single 20- or 40-mg dose of valdecoxib compared with placebo in treatment of a single, acute, moderate or severe migraine headache, with or without aura. BACKGROUND: Valdecoxib, an oral COX-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis and treatment of primary dysmenorrhea. This study assessed the optimal dose of valdecoxib for treatment of a single, acute, moderate to severe migraine headache. METHODS: This was a double-blind, randomized, placebo- and active-controlled, multicenter, single-dose (primary end point) and multiple-dose (secondary end point), 56-day study of valdecoxib in the treatment of a single, acute, moderate or severe migraine headache, with or without aura. Migraine headaches were diagnosed according to International Headache Society (IHS) criteria. The primary efficacy end point was headache response (defined as reduction of headache pain intensity from moderate or severe to mild or none) at 2 hours postdose. Patients assessed their headache pain intensity and presence or absence of migraine-associated nausea, vomiting, phonophobia, and photophobia at intervals from 0 to 24 hours postdose. Sumatriptan 50 mg (encapsulated, in standard method, to maintain blinding) was included as a positive control for assay sensitivity. No statistical comparisons were performed between active treatment arms (valdecoxib 20 mg, valdecoxib 40 mg, and sumatriptan 50 mg). Adverse events and safety parameters were monitored throughout the study. RESULTS: In the intent-to-treat population of 570 patients (135 valdecoxib 20 mg, 151 valdecoxib 40 mg, 143 sumatriptan, and 141 placebo), no significant differences in baseline demographics among treatment groups were observed. The headache response rate with valdecoxib 40 mg and sumatriptan 50 mg was significantly greater than that with placebo at all time points from 2 to 24 hours postdose. With valdecoxib 20 mg, headache response rate was significantly greater than placebo from 2 to 4 hours. Significantly fewer patients treated with valdecoxib 40 mg, compared with placebo, experienced nausea, vomiting, and phonophobia at 2 hours postdose. CONCLUSIONS: A single 40-mg dose of valdecoxib is effective and well tolerated in treatment of migraine headache pain and associated symptoms.     

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-na?ve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.     

Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg

OBJECTIVE: To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan 100 mg. Background.-Eletriptan 80 mg has demonstrated significantly greater efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies. Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100 mg in one previous trial. METHODS: Two thousand one hundred thirteen patients with a diagnosis of migraine according to International Headache Society criteria were randomized using a double-blind, double-dummy, parallel-group design, and treated for a single migraine attack with either eletriptan 40 mg, sumatriptan 100 mg, or placebo. The primary endpoint was 2-hour headache response. Secondary endpoints included headache response rates at 1 hour, pain-free rates, absence of associated symptoms, functional response at 1 and 2 hours, and sustained headache response. RESULTS: Headache response rates at 2 hours postdose were significantly higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (59%; P <.001) and placebo (26%; P <.0001). Eletriptan 40 mg consistently showed significant (P <.01) efficacy over sumatriptan 100 mg across secondary clinical outcomes, including 1-hour headache response; 2-hour pain-free response; absence of nausea, photophobia, and phonophobia; functional improvement; use of rescue medication; treatment acceptability; and sustained headache response (P <.05). Overall, treatment-related adverse events were low, nausea being the only adverse event with an incidence of 2% or higher (4.9% with eletriptan, 4.2% sumatriptan, 2.8% placebo). CONCLUSION: This trial confirmed that eletriptan 40 mg offers superior efficacy in treating migraine pain and associated symptoms and in restoring patient functioning when compared with sumatriptan 100 mg.     

Efficacy of a fixed combination of indomethacin,prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter,randomized, crossover trial

OBJECTIVE: To compare the efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine suppositories with sumatriptan suppositories in the treatment of 2 consecutive migraine attacks of moderate or severe intensity in a multicenter, randomized, crossover study. BACKGROUND: A fixed combination of indomethacin, prochlorperazine, and caffeine is the most commonly used drug for the acute treatment of migraine in Italy. No studies have been published comparing the efficacy of this combination with sumatriptan, the most widely prescribed of the triptans. METHODS: One hundred twelve patients with migraine with or without aura according to the diagnostic criteria of the International Headache Society were randomized to treat 2 migraine attacks with a fixed combination of indomethacin, prochlorperazine, and caffeine and 2 migraine attacks with sumatriptan. Both drugs were rectally administered in a single dose for each attack. Patients were asked to take study medication as soon as possible at the onset of a headache. RESULTS: Of the 112 patients, 88 were compliant to the protocol. More attacks became pain-free at 2 hours postdose (primary end point) on the combination than on sumatriptan (49% versus 34%; P<.01), while there was no difference in the relief of headache at 2 hours postdose (71% versus 65%). The combination was statistically superior to sumatriptan in the time to a pain-free response (a higher percentage of attacks became pain-free from 0.5 hours postdose to 5 hours postdose), in alleviation of nausea, and in a sustained pain-free response (pain-free at 2 hours postdose with no use of rescue medication or relapses within 48 hours). Moreover, a significant consistent response was achieved for the combination compared with sumatriptan across (higher percentage of patients pain-free at 2 hours postdose in the first, second, third, and fourth treated attack) and within patients (pain-free in 2 of 2 treated attacks in 35% of patients taking the combination and 20% of patients on sumatriptan). Both drugs were well-tolerated. CONCLUSIONS: This study, analyzed according to the more recent guidelines for controlled trials in migraine, showed that a fixed combination of indomethacin, prochlorperazine, and caffeine is significantly more effective than sumatriptan in the acute treatment of migraine attacks. It is notable that the combination is less expensive than sumatriptan per unit dose.     

Responsiveness of non-IHS migraine and tension-type headache to sumatriptan

In a long-term efficacy and satiety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as. non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT₁ receptors that spans a range of clinical presentations.     

Sumatriptan in migraine with unilateral cranial autonomic symptoms: an open study

OBJECTIVE: To investigate the response to sumatriptan in migraineurs with unilateral cranial autonomic symptoms such as lacrimation, eye redness, eyelid edema, nasal congestion, and rhinorrhea. BACKGROUND: Given the potential large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal autonomic reflex in such patients, the presence of unilateral cranial autonomic symptoms may predict a positive response to sumatriptan. METHODS: Seventy-two consecutive migraineurs with unilateral cranial autonomic symptoms were given sumatriptan 50-mg tablets to treat 1 migraine attack and were asked to record their clinical response to the drug at different time points. End points were pain-relief and pain-free response at 1 and 2 hours. RESULTS: Pain relief was reported by 47 patients (65.3%) at 1 hour and by 59 (81.9%) at 2 hours. Pain-free response was reported by 22 patients (30.6%) at 1 hour and by 44 (61.1%) at 2 hours. Responsiveness to sumatriptan did not correlate with the type or number of unilateral cranial autonomic symptoms, demographic characteristics, prophylactic treatments, use of contraceptives, or concomitant tension-type headache. CONCLUSIONS: Migraineurs with unilateral cranial autonomic symptoms seem to respond to sumatriptan better than other migraineurs. The presence of unilateral cranial autonomic symptoms may predict a positive response to the triptans.     

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a double-blind, randomized trial

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor response to sumatriptan therapy for acute migraine attacks has been documented in the literature, but few controlled trials have investigated the efficacy of an alternative triptan in this subgroup of patients. METHODS: Patients with an International Headache Society diagnosis of migraine who self-described as experiencing at least two unsatisfactory responses to sumatriptan treated their first migraine attack with open-label sumatriptan 50 mg. Patients who did not achieve 2-hour pain relief (improvement of headache from moderate/severe to mild/no headache) were then randomized to treat their second attack with almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief with sumatriptan and were randomized to treatment of their second attack with almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at baseline. Two-hour pain-relief rates were significantly higher with almotriptan compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005) and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack, 7.1% of patients in the almotriptan group experienced adverse events compared to 5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an effective and well-tolerated alternative for patients who respond poorly to sumatriptan 50 mg. A poor response to one triptan does not predict a poor response to other agents in that class.     

Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials

OBJECTIVE: This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. BACKGROUND: Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. METHODS: Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. RESULTS: In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). CONCLUSIONS: Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.     

The Relationship of Locus of Control and PsychosociaI-Behavioral Response in Chronic Headache

It has been suggested that patients' perceptions of the impact chronic headache has on their lives as well as perceived control of their headaches may be associated with the intensity, duration, and exacerbation of pain they experience. The present study examined associations among International Headache Society (IHS) diagnostic category, pain characteristics such as severity and duration, perceived impact and control of headaches, and adaptive response. Two hundred twenty-five patients with migraine, tension-type, or combined migraine and tension-type headache served as subjects. General activity level was related to IHS diagnosis, with migraine headache patients reporting that they are more active than tension-type headache patients (F(2, 196) = 5.69, P < .01). Headache locus of control was not significantly related to IHS diagnosis, however external headache locus of control was significantly related to headache intensity (r = .32, P < .001, r = .25, P < .001), as well as to patients' perceptions of the extent to which pain interfered with various domains of their lives (r = .33, P < .001, r = .28, P < .001), and adaptive response (F(6, 402) = 4.68, P < .001). It appeared that perceived control over headaches and perceived impact of headaches were not related to IHS diagnostic category and were not strongly related to each other, but were related to headache severity.     

Efficacy and Safety of Sumatriptan Tablets (25 mg, 50 mg, and 100 mg) in the Acute Treatment of Migraine: Defining the Optimum Doses of Oral Sumatriptan

That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N=1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior ( P <0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior ( P <0.05) to sumatiptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.     

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.     

Clarification of developing and established clinical allodynia and pain-free outcomes

OBJECTIVE: The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief questionnaire. BACKGROUND: Using quantitative sensory testing (QST) recent studies demonstrate that the presence of cutaneous allodynia, a clinical manifestation of central sensitization, can be detrimental to the success of migraine therapy with sumatriptan. QST is costly and requires much time, therefore it is not feasible to use in clinical practice. METHODS: In this prospective study, migraineurs completed a questionnaire about their skin sensitivity during migraine. Each migraineur treated 2 migraine headaches with sumatriptan (100 mg): 1 headache at the earliest sign of migraine pain (mild, within 1 hour of onset) and 1 headache at least 4 hours after the onset of pain while moderate or severe. RESULTS: Thirty-six migraine headaches were evaluated in 18 migraineurs. A total of 44% of the headaches were not associated with allodynia at any time. Irrespective of allodynic status, headaches were more likely to become pain-free with early versus late treatment (2 hours; 78% vs. 33%, respectively). Headaches were equally likely to become pain-free when allodynia was reported before treatment but not 2 and 4 hours after treatment (2 hours; 67 vs. 63%, respectively, 4 hours 80 vs. 81%, respectively). However, no headaches were pain-free when allodynia was reported at 2 and 4 hours after treatment. CONCLUSIONS: Headaches without allodynia were aborted when treated early or late, and headaches with allodynia were aborted only when allodynia was not present after treatment. These findings suggest that different mechanisms account for allodynia before and after treatment; a developing phase in which central sensitization depends on incoming pain signals from the peripheral nociceptors and an established phase in which the sensitization becomes independent of the pain signals that come from the dura.     

Sumatriptan and naproxen sodium for the acute treatment of migraine

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine. BACKGROUND: The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute (abortive) and preventive treatment. This suggests that multi-mechanism therapy, which acts on multiple target sites, may confer improved efficacy and symptom relief for patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n = 972) treated a single moderate or severe migraine attack with placebo, naproxen sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets were encapsulated in order to achieve blinding of the study. RESULTS: In the sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain relief response (primary endpoint), which was significantly more effective than sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P < .001). Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response (P < .001). The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), and versus placebo (38%; P= .08). The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and types of adverse events reported did not differ between treatment groups, with dizziness and somnolence being the most common. CONCLUSIONS: This is among the first prospective studies to demonstrate that multi-mechanism acute therapy for migraine, combining a triptan and an analgesic, is well tolerated and offers improved clinical benefits over monotherapy with these selected standard antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg resulted in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium 500 mg for the acute treatment of migraine. Because encapsulation of the sumatriptan for blinding purposes may have altered its pharmacokinetic profile and thereby decreased the efficacy responses, additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine. This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy.     

Almotriptan improves response rates when treatment is within 1 hour of migraine onset

BACKGROUND: Results from open-label trials with almotriptan and sumatriptan have shown higher response rates when treatment was initiated early after acute migraine onset. OBJECTIVE: To investigate the temporal component of early intervention by measuring 2-hour pain-free and sustained pain-free responses to almotriptan and sumatriptan when the study drug was taken within 1 hour of onset of moderate to severe pain. METHODS: This was a post hoc analysis from a double-blind, randomized, placebo-controlled trial of almotriptan and sumatriptan. Men and women, 18 to 65 years of age, who met International Headache Society criteria for migraine with or without aura were eligible. Patients were randomized to receive a single oral dose of almotriptan 12.5 or 25 mg, sumatriptan 100 mg, or placebo at the onset of a severe or moderate migraine attack. For this post hoc analysis, the almotriptan 25-mg dose was excluded because 12.5 mg is the recommended dose. The primary efficacy assessment was sustained pain-free, defined as pain-free at 2 hours postdose with no recurrence from 2 to 24 hours and no use of rescue medication. Only patients who took study medication within 1 hour of migraine onset were included in the analysis. RESULTS: Of the 475 patients involved in the original study, 253 (53.3%) initiated treatment within the 0- to 1-hour interval. For these patients, 2-hour pain-free rates were 37.9% for almotriptan 12.5 mg (P=.016 versus placebo), 35.7% for sumatriptan 100 mg (P=.028 versus placebo), and 18.9% for placebo. Only almotriptan was significantly higher than placebo on the sustained pain-free rate-34.7% (P=.022 versus placebo); the sustained pain-free rate for sumatriptan was 29.6% and for placebo, 17.0%. CONCLUSION: Initiation of treatment with almotriptan 12.5 mg within the first hour after acute migraine onset resulted in a significantly higher sustained pain-free response compared with placebo. There was no significant difference in sustained pain-free rates between sumatriptan and placebo. These results are consistent with those from a previous open-label trial, and suggest that early intervention with almotriptan can improve clinical outcome.