Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

AIMS AND METHODS: In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets. RESULTS: Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated. CONCLUSION: The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.     

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.     

Pilot study evaluating preference for 3-mg versus 6-mg subcutaneous sumatriptan

BACKGROUND: Subcutaneous sumatriptan (6 mg) is undeniably an excellent treatment of migraine. However, some patients have avoided using 6 mg sumatriptan because of unpleasant or unwanted side effects. OBJECTIVE: To evaluate the efficacy of subcutaneous sumatriptan (3 mg) during a moderate or severe migraine attack. METHODS: Thirty subcutaneous sumatriptan-naive patients with a history of migraine with and without aura treated their next two moderate or severe migraines with either 3-mg or 6-mg sumatriptan injection. The primary endpoint was whether patients preferred the low-dose (3 mg) or the high-dose (6 mg) subcutaneous sumatriptan. Other objectives included percentage of patients pain free at 15 and 30 minutes, 1 and 2 hours; a pain-free response lasting between 2 and 24 hours, patient satisfaction, and acceptability of formulation. A new combination endpoint (efficacy and lack of significant side effects) was also evaluated. RESULTS: Eighty percent of patients preferred 3-mg over 6-mg subcutaneous sumatriptan. At 1 hour postdose 57% of patients were pain free with 3 mg and 53% with 6 mg. At 2 hours postdose 87% were pain free with 3 mg and 80% with 6 mg. A sustained pain-free response was obtained by 70 to 80% of patients. When combining a pain-free response at 2 hours and a sustained pain-free response at 24 hours with no significant side effects, more patients met the endpoint with 3 mg (63 to 67%) than with 6 mg (33 to 50%). CONCLUSIONS: Combining efficacy and tolerability endpoints may be clinically meaningful and reflective of real-world expectations. In some patients, a lower dose of sumatriptan injection may be beneficial.     

Early intervention in migraine with sumatriptan tablets 50 mg versus 100 mg: a pooled analysis of data from six clinical trials

BACKGROUND: In clinical trials evaluating sumatriptan in the treatment of moderate or severe migraine pain, the 50- and 100-mg doses have been comparably effective and well tolerated. OBJECTIVE: To assess the dose-efficacy relationship of sumatriptan tablets given early for mild pain, data from 6 randomized, double-blind, placebo-controlled, early-intervention studies of sumatriptan tablets 50 mg and 100 mg (5 of which have been published) were pooled for analysis. These constitute all the studies conducted to date of sumatriptan tablets prospectively given early for mild pain. METHODS: The primary efficacy end point in all the studies was the proportion of patients reporting a pain-free result (ie, mild, moderate, or severe pain reduced to none) 2 hours postdose. Other efficacy end points included the proportion of patients who were migraine free (ie, no pain and no associated symptoms of nausea, vomiting, photophobia, or phonophobia) 2 hours postdose; the proportion reporting worsening of pain (ie, moderate or severe pain) 2 hours postdose; and the proportion with a sustained pain-free result (ie, pain free from 2-24 hours postdose with no use of a second dose of study medication or of rescue medication). Tolerability was assessed by evaluating the incidence of individual adverse events. The investigators assessed each adverse event's relationship to study medication. RESULTS: The number of patients in the intent-to-treat population was 2297 (771 sumatriptan 50 mg, 759 sumatriptan 100 mg, 767 placebo). Patients' mean age ranged from 39.4 to 39.8 years across groups, and most patients were female (90%-92%) and white (89%-90%). A pain-free result 2 hours post dose was reported by significantly more patients who took either dose of sumatriptan tablets compared with placebo and by significantly more patients who took the 100-mg dose compared with the 50-mg dose (50 mg, 49%; 100 mg, 58%; placebo, 24%; P < 0.001, both sumatriptan doses vs placebo, and 100 mg vs 50 mg). A similar pattern was observed for migraine-free results 2 hours postdose (50 mg, 42%; 100 mg, 47%; placebo, 20%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg), worsening of pain 2 hours postdose (50 mg, 26%; 100 mg, 21%; placebo, 46%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg), and sustained pain-free results from 2 through 24 hours postdose (50 mg, 30%; 100 mg, 35%; placebo, 12%; P < 0.05, both sumatriptan doses vs placebo, and 100 mg vs 50 mg). Both doses of sumatriptan were well tolerated, and no dose-related trends in the incidence of individual drug-related adverse events were observed. CONCLUSIONS: In this analysis of pooled data from 6 clinical trials, sumatriptan tablets 50 mg and 100 mg administered early in a migraine attack while the pain was mild were well tolerated and significantly more effective than placebo. The 100-mg dose of sumatriptan was significantly more effective than the 50-mg dose.     

2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study

BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.     

The central analgesia induced by antimigraine drugs is independent from Gi proteins: superiority of a fixed combination of indomethacin, prochlorperazine and caffeine, compared to sumatriptan, in an in vivo model

A hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1 mg/kg, prochlorperazine 1 mg/kg and caffeine 3 mg/kg, s.c.) and sumatriptan (20 mg/kg, s.c.) exert their central antinociceptive action independently from the Gi proteins. In addition, the antinociceptive efficacy of Indoprocaf in this study was statistically superior to that of sumatriptan. This study also showed that the single active ingredients of Indoprocaf, indomethacin (1 mg/kg, s.c.), prochlorperazine (1 mg/kg, s.c.) and caffeine (3 mg/kg, s.c.), were able to exert their central antinociceptive action independently from the Gi proteins. However, Indoprocaf at analgesic doses was able to abolish almost completely the abdominal constrictions, with a statistically higher efficacy compared to the single active ingredients, showing an important synergic effect of Indoprocaf. This synergic effect was evident not only when Gi proteins activity was abolished by PTX, but also under control condition, when Gi proteins were active. This study suggests that the central antinociceptive action induced by antimigraine drugs is independent from Gi proteins.     

Indomethacin, alone and combined with prochlorperazine and caffeine, but not sumatriptan, abolishes peripheral and central sensitization in in vivo models of migraine.

Recently it has been proposed that the throbbing pain of migraine is mediated by sensitization of peripheral trigeminovascular neurons, and that cutaneous allodynia of migraine is mediated by sensitization of central trigeminovascular neurons, and, moreover, that the triptans are less effective in aborting a migraine attack if the central sensitization is already established. The combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) is a drug of well-established use in the acute treatment of migraine. The aim of this study was to investigate whether the 3 active principles of IndoProCaf, alone and combined, compared to sumatriptan, were able to abolish the peripheral sensitization induced by kainic acid and the central sensitization induced by N-methyl-D-aspartate (NMDA) in in vivo models of hyperalgesia. The study showed that indomethacin or IndoProCaf is able to abolish both the kainic acid-induced and the NMDA-induced hyperalgesia. If administered at different times, IndoProCaf was always effective in reversing the kainic acid-induced hyperalgesia. Sumatriptan was not able to reverse either the kainic acid-induced or the NMDA-induced hyperalgesia. The efficacy of indomethacin, alone and combined with prochlorperazine and caffeine, in abolishing peripheral and central sensitization in in vivo models of hyperalgesia is a further explanation of the clinical efficacy of IndoProCaf in the treatment of migraine. PERSPECTIVE: This study suggests that, although triptans were shown to be able to abort migraine attacks only if given before the establishment of cutaneous allodynia and central sensitization, IndoProCaf should be able to abort migraine attacks independently from the time of administration, because it is able to abolish an already established peripheral and central sensitization.     

Economic implications of early treatment of migraine with sumatriptan tablets

BACKGROUND: Early treatment of migraine with sumatriptan 50 mg and 100 mg, while pain is mild, has been reported to enhance pain-free response 2 hours and 4 hours postdose and sustained pain-free response 2 to 24 hours postdose compared with treatment when pain has become moderate to severe. Early treatment with sumatriptan 50 mg and 100 mg also resulted in less redosing, which translated to a reduction in the mean number of doses used per migraine episode. OBJECTIVE: We examined the economic implications of early treatment with sumatriptan 50 mg and 100 mg while pain is mild versus treatment when pain has become moderate to severe. METHODS: Using data from retrospective analyses of a dose-ranging clinical trial of sumatriptan (protocol S2CM09) involving 1003 patients, we estimated the mean cost per treatment success for a hypothetical population of 1000 migraine patients who received treatment with sumatriptan 50-mg or 100-mg tablets early while pain was mild versus treatment when pain had become moderate to severe. RESULTS: With a conservative estimate of migraine frequency of 1.5 episodes per month, the total cost of early migraine treatment with sumatriptan 50 mg and 100 mg was reduced by $31.68 and $20.16, respectively, per patient per year. The average cost per pain-free treatment success was reduced by 32% to 57% with sumatriptan 50 mg and 100 mg if migraines were treated while pain was mild in intensity versus when pain had become moderate to severe. CONCLUSIONS: Treatment of migraine with sumatriptan 50-mg and 100-mg tablets is effective regardless of whether pain is mild, moderate, or severe. However, initiating treatment while pain is mild may be more cost-effective than delaying treatment until pain has become moderate to severe.     

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.     

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.     

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.     

A comparison of preference for and efficacy of tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg), and zolmitriptan (2.5 mg) in the acute treatment of migraine

Abstract This randomized, multicenter, open-label, five-way crossover study was conducted to assess patients preference for tablet formulations of sumatriptan (50 mg and 100 mg), naratriptan (2.5 mg), rizatriptan (10 mg), and zolmitriptan (2.5 mg) in the acute treatment of migraine and to identify determinants of preference. Patients treated one mild, moderate, or severe migraine with each triptan. The results show that sumatriptan 100 mg was significantly preferred over the random preference rate of 20% (p<0.001) whereas sumatriptan 50 mg, naratriptan, rizatriptan, and zolmitriptan were not. Patients primary reason for preferring a medication was best relief of migraine pain, and the treatment that patients preferred corresponded to the medication that was most likely to confer for them a pain-free response 2 hours postdose. Across all patients, efficacy 2 hours postdose was comparable among triptans with the exception of naratriptan, which was slightly less effective than the other medications (pain-free response 2 hours postdose: 40% sumatriptan 100 mg, 37% sumatriptan 50 mg, 28% naratriptan 2.5 mg, 38% rizatriptan 10 mg, 36% zolmitriptan 2.5 mg). The medications were also similarly well-tolerated. These data demonstrate that information on patients medication preference supplements and does not duplicate data from traditional efficacy measures. Patient preference data are useful in tailoring migraine therapy to the needs of the individual patient.     

Sumatriptan/Naproxen sodium for migraine: efficacy, health related quality of life, and satisfaction outcomes

OBJECTIVE: To describe the pain relief, satisfaction, and health-related quality of life results of moderate or severe migraines treated with a sumatriptan/naproxen sodium combination tablet. METHODS: Sumatriptan and naproxen sodium as a single-dose formulation tablet was used to treat moderate to severe migraines over a 12-month period in a phase 3, open-label, multicenter study (n = 565) in patients with at least 6 months' history of migraine headaches. RESULTS: Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen sodium. Overall subjects treated 24,485 attacks; of these, 81% attacks achieved pain relief and 60% pain-free by 2 hours. At 3 months, the percentage of patients satisfied or very satisfied increased from baseline on all 8 Patient Perception of Migraine Questionnaire (PPMQ) items and remained high throughout the study. Mean Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores also increased by 13-15 points from baseline during this time and remained high. CONCLUSIONS: Sumatriptan/naproxen sodium provides consistent relief of migraine attacks over 12 months, resulting in improved patient satisfaction and migraine specific quality of life.     

Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in patients with infrequent attacks: a randomised, double-blind, placebo-controlled study

Most migraine patients with infrequent attacks are currently not treated with migrainespecific medication such as triptans. The response of these patients to triptans is unknown. The objective of this study was to investigate the efficacy and tolerability of sumatriptan 50 mg vs. placebo in migraine patents with infrequent migraine attacks when medication is taken during the mild phase of an attack. The study design was double-blind, placebocontrolled, parallel-group and randomised. Migraine patients were recruited by general practitioners and referred to one of 4 study centres. Additional patients were recruited by advertising. The patients were eligible for the study if they had between 6 and 12 migraine attacks with or without aura per year. The patients were instructed to take the medication during the mild phase of a single attack. The primary efficacy measure was the percentage of patients pain-free after 2 h. Fortysix percent of treated attacks were moderate or severe. In the intention-to-treat analysis, sumatriptan was superior (20/51 patients were pain-free) to placebo (8/47 patients pain-free) (p=0.03). Adverse events (AEs) occurred more frequently after sumatriptan (40%) than after placebo (13%) (p=0.003) and most AEs were mild or moderate. In this migraine population with infrequent attacks, sumatriptan was superior to placebo and was generally well tolerated.     

Almotriptan increases sustained pain-free outcomes in acute migraine: results from three controlled clinical trials

OBJECTIVE: Evaluate the effect of almotriptan on sustained pain-free outcome in patients with acute migraine. METHODS: Three randomized, double-blind, placebo-controlled trials of almotriptan for the treatment of acute migraine were examined. Two trials evaluated almotriptan 6.25 mg and 12.5 mg, and the third evaluated almotriptan 12.5 mg and sumatriptan 100 mg. Patients aged 18 to 65 years were instructed to take 1 dose of study medication at the onset of a moderate-to-severe migraine headache. A second dose was allowed for relapse. Sustained pain-free was defined as a decrease in pain severity from moderate or severe at baseline to no pain at 2 hours postdose and without relapse or the use of escape medication between 2 and 24 hours. RESULTS: A total of 1791 adult migraine sufferers were studied. The proportion of patients achieving a sustained pain-free state was significantly (P<.05) higher in the almotriptan 6.25-mg (21.7% to 22.5%) and 12.5-mg (24.6% to 27.6%) groups than in the placebo group (7.5% to 12.1%). The proportion of patients achieving a sustained pain-free state was comparable between almotriptan 12.5 mg (24.6%) and sumatriptan 100 mg (28.5%) and significantly (P<.05) greater than with placebo (12.1%). Among patients with severe baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.05) with almotriptan 12.5 mg (17.3% to 20.9%) than with placebo (3.1% to 3.2%). Among those with moderate baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.01) with almotriptan 12.5 mg (31.3% to 32.0%) than with placebo (10.2% to 16.1%). CONCLUSIONS: Almotriptan 12.5 mg is significantly better than placebo and comparable to sumatriptan 100 mg for achieving a sustained pain-free state.     

Sumatriptan is effective in the treatment of menstrual migraine: a review of prospective studies and retrospective analyses

Menstrual migraine may be debilitating, long-lasting, and refractory to treatment. Because the efficacy and tolerability of abortive and prophylactic treatment options for menstrual migraine have generally not been evaluated in controlled clinical trials, treatment choices are often made on the basis of personal experience and anecdotal reports. This article reviews evidence from retrospective analyses and prospective studies showing that sumatriptan injection and tablets are effective and well tolerated in menstrual migraine. (1) Sumatriptan injection 6 mg was as effective in the treatment of menstrual migraine attacks as it was for nonmenstrual attacks in a retrospective analysis of data from two randomized, double-blind, placebo-controlled, parallel-group trials (n = 1104). In the menstrual migraine group, 80% of women treated with sumatriptan injection 6 mg compared with 19% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (2) Sumatriptan injection 6 mg was effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, parallel-group, two-attack study (n = 226). Across the two attacks, 70-71% of patients treating menstrual migraine attacks with sumatriptan injection 6 mg compared with 22-24% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (3) Sumatriptan tablets 100 mg were effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, crossover study in women diagnosed with menstrual migraine (n = 115). For menstrual migraine attacks, headache relief 4 h postdose was reported by 67% of sumatriptan-treated patients compared with 33% of placebo-treated patients. Sumatriptan injection and tablets were generally well tolerated in these studies, in which adverse events were characteristic of those typically observed in sumatriptan acute migraine clinical trials. These data demonstrate that sumatriptan injection and tablets are effective and well tolerated in the treatment of menstrual migraine.     

Efficacy and tolerability of sumatriptan tablets in a fast-disintegrating, rapid-release formulation for the acute treatment of migraine: results of a multicenter, randomized, placebo-controlled study

BACKGROUND: Sumatriptan tablets have been developed in a fast-disintegrating, rapid-release formulation designed to facilitate tablet disintegration and drug dispersion and to potentially mitigate the effects of gastric stasis that can accompany migraine. OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of sumatriptan 50- and 100-mg tablets in a fast-disintegrating, rapid-release formulation compared with those of placebo in patients with migraine. METHODS: This clinical trial had a randomized, double-blind, placebo-controlled, parallel-group design. Exclusion criteria included >6 migraines monthly during either of the 2 months before screening; uncontrolled hypertension; suspected or confirmed cardiovascular or cerebrovascular disease; and ophthalmic, basilar, or hemiplegic migraine. Sumatriptan 50 and 100 mg and placebo were taken on an outpatient basis during the mild-pain phase of a single migraine attack. Patients recorded details of the treated migraine on a diary card and rated pain severity immediately before dosing and 30 minutes, 45 minutes, 1 hour, and 2 hours after dosing using a 4-point scale (from 0 = none to 3 = severe). The primary efficacy end point was the proportion of patients who were pain free 2 hours after dosing. Additional efficacy end points were the proportion of patients who were pain free at 30 minutes, 45 minutes, and 1 hour after dosing; the proportion who were migraine free through 2 hours after dosing; and the proportion with a sustained pain-free response. RESULTS: Patients' mean age ranged from 39.7 to 41.5 years across the 3 groups, and the majority were women (79.7%-85.9%) and white (98.7%-100%). One hundred thirty-seven patients received sumatriptan 50 mg, 142 sumatriptan 100 mg, and 153 placebo. In the intent-to-treat population (n = 432), 51.1% of patients who received sumatriptan 50 mg and 66.2% of patients who received sumatriptan 100 mg were pain free 2 hours after dosing, compared with 19.6% of the placebo group (P < 0.001, each sumatriptan dose vs placebo). In an exploratory analysis, the 2-hour pain-free rate with sumatriptan 100 mg was significantly better than that with sumatriptan 50 mg (P = 0.007). Significantly more patients who received sumatriptan 100 mg were pain free compared with placebo at 30 minutes (P < 0.01), 45 minutes (P < 0.001), and 1 hour after dosing (P < 0.001); similar pain-free results were observed in patients who received sumatriptan 50 mg at 45 minutes (P < 0.05) and 1 hour (P = 0.01). In the per-protocol population (n = 313), pain-free efficacy 2 hours after dosing was 52.7% with sumatriptan 50 mg and 74.8% with sumatriptan 100 mg, compared with 21.0% with placebo (P < 0.001, each sumatriptan dose vs placebo). These rates were greater than those in the overall study population, approximately 12.0% of whom treated moderate or severe pain. The only drug-related adverse events reported in >/=3% of patients in any treatment group were nausea and vomiting (<1%, 5%, and 2% in the sumatriptan 50 and 100 mg and placebo groups, respectively), chest symptoms (2%, 3%, and 0%), and malaise and fatigue (1%, 3%, and <1%). No serious adverse events were reported. CONCLUSIONS: In this study, sumatriptan tablets in a fast-disintegrating, rapid-release oral formulation provided pain-free efficacy in the acute treatment of migraine. Efficacy was maximized with the 100-mg dose compared with the 50-mg dose, and by treating early when pain was mild. In the intent-to-treat population, 51.1% of patients who received sumatriptan 50 mg and 66.2% of those who received sumatriptan 100 mg were pain free 2 hours after dosing. In the per-protocol population, 3 of 4 patients taking the 100-mg tablets for mild pain within 1 hour of its onset were pain free at 2 hours. Sumatriptan tablets were generally well tolerated.     

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.     

Efficacy and tolerability of sumatriptan injection for the treatment of morning migraine: two multicenter, prospective, randomized, double-blind, controlled studies in adults

OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of sumatriptan injection in the treatment of morning migraine. METHODS: In 2 multicenter (20 sites for study 1 and 25 sites for study 2), randomized, double-blind, controlled, parallel-group studies, male and female patients aged 18 to 65 years with migraine meeting International Headache Society criteria received SC sumatriptan succinate injection 6 mg or inactive vehicle (control) for the outpatient treatment of a single morning migraine, defined as migraine with moderate or severe pain on awakening. The primary end point was the percentage of patients who achieved pain-free relief (moderate or severe pain reduced to no pain) at 2 hours after treatment. Tolerability was assessed using spontaneous reporting or noted by a clinician during the studies, assessed at the return visit. RESULTS: The efficacy analysis included, in the succinate group, 145 patients in study 1, 148 in study 2; control, 152 in study 1, 139 in study 2. The mean (SD) ages in the sumatriptan group were 40.2 (9.7) and 38.8 (10.1) years in studies 1 and 2, respectively; control, 41.4 (10.4) and 39.3 (9.7) years. The majority of patients in the 2 studies were female (sumatriptan, 84% and 93% in studies 1 and 2, respectively; control, 82% and 81%) and white (sumatriptan, 83% and 81%; control, 78% and 89%). Two hours after treatment, 48% and 57% of patients treated with sumatriptan injection compared with 18% and 19% of control patients reported pain-free relief in studies 1 and 2, respectively (both, P < 0.001). Two hours after treatment, 72% and 77% of patients treated with sumatriptan injection reported headache relief (moderate or severe pain reduced to mild or no pain) compared with 32% and 41% of control patients (both, P < 0.001). Onset of efficacy versus control (the first time point with statistical significance of pain relief) was observed beginning 10 minutes postdose (P < 0.05 sumatriptan injection vs placebo across pooled studies). Mean time to efficacy in the sumatriptan group was 10 minutes (P < 0.05 vs controls). The most commonly reported adverse events were nausea (sumatriptan, 6% and 4%; control, 2% and 2%) and injection-site reaction (ie, burning or stinging at the injection site) (sumatriptan, 5 % and 5%; control, 2% and 1%). Injection-site reaction was also the only adverse event considered treatment related and reported in > or =5 % of all patients. CONCLUSION: The results of these 2 randomized, double-blind, controlled studies suggest that sumatriptan injection was effective and well tolerated in the acute treatment of morning migraine in these adults.     

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.