Repeated Doses of Combined Oral Lysine Acetylsalicylate and Metoclopramide in the Acute Treatment of Migraine

The combination of lysine acetylsalicylate and metoclopramide is effective in the treatment of migraine attacks. It was unknown whether repeated doses could improve efficacy.
The aim of this open trial was to evaluate the effects of a second, and eventually a third dose of lysine acetylsalicylate and metoclopramide when a first dose of the treatment was ineffective. Patients were asked to take a second dose 2 hours after a first dose when they thought that the first dose was ineffective. They were allowed to take a third dose or their rescue medication 2 hours after the second dose when they judged that the treatment remained ineffective.
Two hundred ninety-two patients were included in the study; 262 of the 292 patients treated 517 attacks.
Headache relief (reduction in headache severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks after a third dose.
Complete headache relief without recurrence and without use of a rescue medication was reported in 37% of the total attacks.
The patients judged their treatment as good or excellent in 78% of attacks treated with one dose, in 41% of those treated with two doses, and in 19% of those treated with three doses.
Tolerance, as judged by the patients, was considered good in 92% of treated attacks. Minor side effects occurred in 6% of attacks after a first dose, in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in 2% after unspecified delay, and in 14% overall.
In conclusion, the efficacy of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks can be improved by repeated doses. It is well tolerated.     

Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study

Two-hundred-and-seventy-eight patients with acute migraine attacks with or without aura were treated in 17 centers with 1.8 g lysine acetylsalicylate i.v. (Aspisol®;=1 g acetylsalicylic acid), 6 mg sumatriptan s.c. or placebo using a double-blind, double-dummy, randomized, multicenter parallel group study design. Two-hundred-and-seventy-five of them fulfilled the criteria for efficacy analysis, corresponding to 119 patients treated with lysine acetylsalicylate (L-ASA), 114 with sumatriptan and 42 with placebo injections. Both treatments were highly effective compared to placebo ( p <0.0001) in decreasing headache from severe or moderate to mild or none (verbal rating scale, VRS, placebo=23.8%). Sumatriptan showed a significantly ( p =0.001) better response (91.2%) compared to L-ASA (response 73.9%). Of the patients in the L-ASA-group, 43.7% were pain-free after 2 h; 76.3% after sumatriptan and 14.3%, after placebo. It took patients on average 12.6 (L-ASA), 8.2 (sumatriptan), and 19.4 h (placebo) to be able to work again. There was no significant difference between treatment groups in recurrence of headache in responders within 24 h (18.2% L-ASA, 23.1%, sumatriptan, 20% placebo). Accompanying symptoms (nausea, vomiting, photophobia, phonophohia, and visual disturbances) improved with both verum treatments to a similar extent. L-ASA was significantly better tolerated than sumatriptan (adverse events L-ASA 7.6%, sumatriptan 37.8%). In conclusion, subcutaneous sumatriptan and lysine acetvlsalicylate i.v. are effective treatments for patients suffering from migraine attacks. Sumatriptan is more effective, but resulted in more adverse events.     

Treatment of migraine attacks with a long-acting somatostatin analogue (octreotide, SMS 201–995)

Long-acting somatostatin analogue (SMS 201–995) inhibits serotonin, bradykinin, prostaglandins, substance P, and vasoactive intestinal peptide, which may be involved in migraine. We therefore decided to test the efficacy of SMS 201–995 in relieving the pain of acute migraine attacks. Headache relief was defined as a reduction in severity from grade 3 or 2 (severe or moderate) to 1 or 0 (mild or none). Patients experiencing migraine attacks were evaluated clinically. A double-blind parallel group trial was performed in which patients randomly received either a subcutaneous injection of placebo (saline) or SMS 201–995 (100 μg). SMS 201–995 was significantly more effective than placebo in reducing headache grade at 2 h (1.5 0.6 vs 2.2 0.7; p < 0.01), 4 h (1.6 ± 0.6 vs 2.1 ± 0.8; p < 0.05) and 6 h (0.8 ± 0.9 vs 2.1 ± 0.8; p < 0.001) after the initiation of treatment. By 6 h, apparent headache relief (reduction in severity from grade 3 or 2 to 1 or 0) was experienced in 76.5% of SMS 201–995 treated patients and 25% of the placebo-treated group. Headache relief was significantly better in patients taking SMS 201–995 ( p < 0.02). Furthermore, none of the patients became pain-free (headache grade 0) on placebo, while significantly more patients (47%) were pain-free on SMS 201–995 at 6 h ( p < 0.01). Headache improvement started significantly earlier in those patients treated with SMS 201–995 than with placebo. SMS 201–995 significantly improves the pain of migraine attacks, 2 h after the beginning of treatment. Additionally, we observed no side effects of SMS 201–995. We therefore conclude that a single dose of 100 μg given subcutaneously is an effective and well-tolerated agent for the treatment of migraine attacks.     

Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute migraine attacks: a double-blind, placebo-controlled parallel group multicenter study

The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute migraine attacks as an alternative to parenteral application of lysine acetylsalicylate or triptans was investigated, using a multi-center, randomized, double-blind, placebo controlled study design. Migraine diagnosis was made according to the International Headache Society Classification. Sixty patients were included in three headache outpatient centers (Neurology Departments of the Universities of Regensburg, Münster and München). In the acute migraine attack patients were treated intravenously with either 1000mg paracetamol (acetaminophen) or placebo. The primary end point was pain-free after 2h. Secondary efficacy criteria were pain-free after 24h or pain relief after 2hours and after 24hours. With regard to the efficacy criteria, 37% of patients reported pain relief or painfree after two hours, 12 patients after treatment with acetaminophen and 10 patients after treatment with placebo. Out of these, 3 patients in the acetaminophen and 4 patients in the placebo group were painfree. After 24hours 86% of the patients reported pain relief: 24 treated with acetaminophen and 27 treated with placebo. The results indicate, that 1000mg intravenous acetaminophen is not superior to placebo in treating severe acute migraine attacks.     

Sumatriptan in Acute Migraine Using a Novel Cartridge System Self-Injector

SYNOPSIS
This double-blind. randomized, placebo-controlled, parallel-group, multicenter study assessed the efficacy, acceptability, safety, and tolerability of subcutaneous sumatriptan 6 mg administered using a novel cartridge system self-injector for the acute treatment of migraine.
Eighty-six patients treated one migraine attack at home with sumatriptan or placebo. A second identical injection was available after 1 hour for inadequate relief or if the headache recurred. Rescue medication was available I hour later. The primary end point was headache relief (improvement in headache from moderate or severe to mild or no pain) within 60 minutes of the first injection. Secondary end points included the acceptability of the self-injector, requirement for and efficacy of a second dose, relief of nonheadache symptoms, use of rescue medication, and adverse events.
Significantly more patients taking sumatriptan than placebo reported headache relief I hour after the first injection (88% vs 11%, P <0.001). The device was well accepted by patients; about 90% found it easy to use and wanted to take further medication using it. Significantly fewer patients taking sumatriptan than placebo required a second injection (33% vs 92%, P <0.001) or rescue medication after the second injection (35% vs 67% P <0.05). Significantly more patients taking sumatriptan than placebo reported headache relief after the second injection (83% vs 32%, P <0.01), and resolution of non-headache migraine symptoms (54% vs 23%, P <0.01). Sumatriptan was generally well tolerated.
Subcutaneous sumatriptan 6 mg self-administered using the novel self-injector is an effective, well accepted, and well tolerated acute treatment of migraine.     

Oral sumatriptan: effect of a second dose, and incidence and treatment of headache recurrences

Oral sumatriptan in a dose of 100 mg aborts about 60% of migraine attacks within 2 h, but the headache may recur within 24 h. We investigated: (i) the incidence of headache recurrence after oral sumatriptan, (ii) whether a second tablet of sumatriptan at 2 h increases initial efficacy and/or (iii) prevents headache recurrence and (iv) whether a further tablet of sumatriptan treats headache recurrence. In a randomized, parallel-group clinical trial, 1246 patients treated one to three migraine attacks (with or without aura) with 100 mg oral sumatriptan. Two hours later they all took a double-blind randomized second tablet of sumatriptan (group I) or placebo (group II). Patients who initially improved, but then experienced headache recurrence took a further double-blind randomized tablet of sumatriptan or placebo. Proportions of patients who improved from moderate/severe headache to mild/none were similar in groups I and II at 2 h (55 vs 56%) and 4 h (80 vs 77%). Incidences of headache recurrence (moderate/severe-any grade of headache) and median times to headache recurrence were also similar: 22-32% at 16 h in group I and 25-33% at 16.5 h in group II. Sumatriptan was superior to placebo in treating headache recurrence: 74 vs 49% ( p = 0.017) in group I and 70 vs 30% ( p = 0.0001) in group II. Thus, one-fourth of patients experience headache recurrence at about 16 h after successful treatment of a migraine attack with 100 mg oral sumatriptan. A second tablet of sumatriptan at 2 h does not increase initial efficacy and neither prevents nor delays headache recurrence. A further tablet of sumatriptan is, however, highly effective in treating headache recurrence. All dose regimens were well tolerated.     

Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials

Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n = 2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for the acute treatment of a migraine attack. Migraine was diagnosed according to International Headache Society criteria. Headache severity, associated migraine symptoms and functional disability were measured immediately before dosing and at 0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache after an initial response) was also recorded. In addition to conventional pain relief (reduction of moderate or severe headache to mild or none) and pain free measures, the analysis looked at the elimination of associated migraine symptoms and disability in patients who had symptoms or disability at baseline. Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability. The benefit was maintained over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18% for placebo (P < 0.001). Rizatriptan 10 mg was also more effective than rizatriptan 5 mg, with a significant superiority at 2 h on all measures except for elimination of nausea. The benefit was maintained over 24 h; 38% of patients on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg (P = 0.001).     

The Relative Efficacy of Phenothiazines for the Treatment of Acute Migraine: A Meta-Analysis

Objective and Background.— Ranges of agents are used in the emergency departments to treat migraine headache. Some experts suggest that phenothiazines are among the most effective; clinical trials have been small with varied results. We performed a systematic review and meta-analysis to determine the relative effectiveness of phenothiazines compared with placebo and other active agents for the treatment of acute migraine.
Methods.— We searched MEDLINE, EMBASE, CINAHL, Cochrane database, and international clinical trial registers for randomized controlled trials comparing parenteral phenothiazines with placebo or another active parenteral agent for treatment of acute migraine in adults. The primary outcome was relief of headache, and secondary outcome was clinical success. Analysis was for phenothiazines vs placebo, pooled other active agents, and metoclopramide for each outcome. Odds ratios (ORs) were calculated and pooled by using a random effects model (RevMan v5).
Results.— Thirteen trials were appropriate and had available data. Phenothiazines were compared with placebo in 5 trials and to another active agent in 10 (metoclopramide 4). Phenothiazine was more effective than placebo for headache relief (OR 15.02, 95% confidence interval [CI] 7.57-29.82) and clinical success (OR 8.92, 95% CI 4.08-19.51). Phenothiazines were more effective than other agents combined (OR 2.04, 95% CI 1.25-3.31) and the metoclopramide subgroup (OR 2.25, 95% CI 1.29-3.92) for clinical success, but no differences were found for headache relief. The clinical success rate of phenothiazines was 78% (95% CI 74-82).
Conclusion.— Phenothiazines are more effective than placebo for the treatment of migraine headache and have higher rates of clinical success than other agents against which they have been compared.     

Rofecoxib in the acute treatment of migraine: a randomized controlled clinical trial

OBJECTIVE: To investigate the efficacy, tolerability, and safety of rofecoxib and ibuprofen for acute migraine treatment. BACKGROUND: Rofecoxib was effective and well tolerated in a previous study of treatment of a single migraine attack. We sought to replicate these findings for a single attack and also study the clinical profile of rofecoxib in the acute treatment of multiple migraine attacks. Ibuprofen was included as a reference nonselective NSAID. METHODS: Adult migraineurs (n = 783) treated one migraine attack with either rofecoxib (25 or 50 mg), ibuprofen 400 mg, or placebo in a randomized, double-blind study. Patients could elect to enroll in a 3-month double-blind extension phase. RESULTS: In the single-attack phase, headache relief at 2 hours postdose was reported by 59.4%, 62.2%, and 57.7% of patients who took rofecoxib 25 mg, rofecoxib 50 mg, and ibuprofen 400 mg, respectively, versus 30.5% for placebo (all P < .001 vs placebo). The active drugs were statistically superior to placebo on a variety of additional measures. In the extension phase, the mean percentage of patients' attacks with headache relief at 2 hours postdose was 61.8% for rofecoxib 25 mg, 65.4% for rofecoxib 50 mg, and 59.3% for ibuprofen 400 mg. The mean percentage of patients' attacks with 24-hour sustained headache relief was greater for rofecoxib 50 mg (52.0%) than for rofecoxib 25 mg (47.8%, P < .050) or ibuprofen (39.0%, P < .010). In the single-attack phase, the adverse event rate was higher for rofecoxib 50 mg (37.8%) than placebo (27.8%, P < .050); rates were similar to placebo for rofecoxib 25 mg (32.0%, n.s.) and ibuprofen 400 mg (28.1%, n.s.). In the extension phase, treatment groups had similar adverse event rates. CONCLUSIONS: Rofecoxib 25 and 50 mg and ibuprofen 400 mg were effective and generally well tolerated in the acute treatment of migraine.     

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.     

Managing migraine headaches experienced by patients who self–report with menstrually related migraine: a prospective, placebo–controlled study with oral sumatriptan

The objective was to evaluate the efficacy and tolerability of oral sumatriptan (100 mg) in patients who self–reported with menstrually related migraine. A prospective, multicentre, randomised, double–blind, placebocontrolled, two–group crossover study was carried out in 20 UK primary and secondary care surgeries. Of 115 patients with a self–reported history of menstrually related migraine that entered the study, 93 patients completed it. Patients treated all migraine attacks for 2 months with sumatriptan (100 mg) and for 2 months with placebo. The primary endpoint was the proportion of patients reporting headache relief at 4 hours for the first treated attack. Only 11% of patients fulfilled the protocol definition of menstrually related migraine. Patients reported a variable pattern of migraine attacks occurring inside and outside the menstrual window. For the first attack, significantly more patients receiving sumatriptan than placebo reported headache relief for attacks occurring inside (67% vs. 33%, p=0.007) and outside (79% vs. 31%, p<0.001) the menstrual period. Sumatriptan was generally well tolerated. Oral sumatriptan (100 mg) is an effective and well tolerated acute treatment for patients who report menstrually related migraine.     

A randomized double-blind placebo-controlled crossover study of subcutaneous sumatriptan in general practice

Objective. To evaluate the therapeutic response to sumatriptan in the acute migraine attack. Material and methods. Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included in the study. The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo for the first attack and the alternative medication, i.e. placebo or sumatriptan, for the second attack (crossover). Following treatment, a neurology resident interviewed and examined the patients, Results. When sumatriptan was compared to placebo, significantly more of the 209 evaluable patients reported headache relief at I h (56% vs 8%, p < 0.001) and 2 h (62% vs 15%, p < 0.001) after the first injection. Resolution of nausea, photophobia, and phonophobia was significantly more common in patients on sumatriptan than in those on placebo ( p < 0.001 for all comparisons). The adverse events were usually transient and of mild or moderate severity; however, three patients withdrew due to adverse events. Ninety-five percent of patients evaluated by a neurology resident met the IHS criteria for migraine. Conclusion. In general practice, sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine.     

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan and ibuprofen in the treatment of migraine attacks

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently used in clinical trials in the acute treatment of migraine attacks. Recently the efficacy of a new high buffered formulation of 1000 mg effervescent ASA without metoclopramide compared to placebo has been shown. To further confirm the efficacy of this new formulation in comparison with a triptan and a nonsteroidal anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind, randomized trial with 312 patients was conducted in Germany, Italy and Spain. Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg), ibuprofen (400 mg) and placebo. The percentage of patients with reduction in headache severity from moderate or severe to mild or no pain (primary endpoint) was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for placebo. All active treatments were superior to placebo (P < 0.0001), whereas active treatments were not statistically different. The number of patients who were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA and sumatriptan was statistically significant (P = 0.025). With respect to other secondary efficacy criteria and accompanying symptoms no statistically significant differences between ASA and ibuprofen or sumatriptan were found. Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg ibuprofen in the treatment of migraine attacks regarding headache relief from moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan was most effective.     

Eletriptan for the treatment of migraine in patients with previous poor response or tolerance to oral sumatriptan

To determine the tolerability and efficacy of eletriptan in patients who had discontinued oral sumatriptan due to lack of efficacy or intolerable adverse events (AEs) during previous clinical treatment (not a controlled trial). Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel group, placebo-controlled multicentre study, patients with and without aura (n = 446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n = 171) or placebo (n = 87) for treatment of up to three migraine attacks. Two-hour headache response, based on first-dose, first-attack data, was 59% for eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was rapid, with 1-h headache response rates significantly superior for E40 and E80 vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly superior to placebo, based on first-dose, first-attack data, for 2-h pain-free response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated significant consistency of response, with headache relief rates at 2 h on at least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs were mild to moderate in severity and dose related. The most commonly reported AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce an effective response in patients who had previously discontinued treatment with sumatriptan due to lack of efficacy or side-effects.     

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.     

A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic™ M) in the treatment of migraine

(Headache 2011;51:1078‐1086) Background.— Therapeutic needs of migraineurs vary considerably from patient to patient and even attack to attack. Some attacks require high‐end therapy, while other attacks have treatment needs that are less immediate. While triptans are considered the “gold standard” of migraine therapy, they do have limitations and many patients are seeking other therapeutic alternatives. In 2005, an open‐label study of feverfew/ginger suggested efficacy for attacks of migraine treated early during the mild headache phase of the attack. Methods/Materials.— In this multi‐center pilot study, 60 patients treated 221 attacks of migraine with sublingual feverfew/ginger or placebo. All subjects met International Headache Society criteria for migraine with or without aura, experiencing 2‐6 attacks of migraine per month within the previous 3 months. Subjects had <15 headache days per month and were not experiencing medication overuse headache. Inclusion required that subjects were able to identify a period of mild headache in at least 75% of attacks. Subjects were required to be able to distinguish migraine from non‐migraine headache. Subjects were randomized 3:1 to receive either sublingual feverfew/ginger or a matching placebo and were instructed but not required to treat with study medication at the earliest recognition of migraine. Results.— Sixty subjects treated 208 evaluable attacks of migraine over a 1‐month period; 45 subjects treated 163 attacks with sublingual feverfew/ginger and 15 subjects treated 58 attacks with a sublingual placebo preparation. Evaluable diaries were completed for 151 attacks of migraine in the population using feverfew/ginger and 57 attacks for those attacks treated with placebo. At 2 hours, 32% of subjects receiving active medication and 16% of subjects receiving placebo were pain‐free (P = .02). At 2 hours, 63% of subjects receiving feverfew/ginger found pain relief (pain‐free or mild headache) vs 39% for placebo (P = .002). Pain level differences on a 4‐point pain scale for those receiving feverfew/ginger vs placebo were ?0.24 vs ?0.04 respectively (P = .006). Feverfew/ginger was generally well tolerated with oral numbness and nausea being the most frequently occurring adverse event. Conclusion.— Sublingual feverfew/ginger appears safe and effective as a first‐line abortive treatment for a population of migraineurs who frequently experience mild headache prior to the onset of moderate to severe headache.     

Pilot study of MK-462 in migraine

MK-462 is a potent, selective 5HT_1D receptor agonist which may be useful in treating acute migraine. We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg ( n = 8) and 40 mg ( n =36) vs placebo ( n =21), administered to 65 male and post-menopausal female migraine patients aged 22–51 with moderate or severe migraine headache. Headache severity and functional disability were measured at 0.5, 1, 1.5, and 2 h post-dose. The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point. The 40 mg dose was well tolerated and was significantly ( p <0.05) superior to placebo at the 1.5 and 2 h time points (with 27/36 or 75% obtaining relief at 2 h compared to 7/21 or 33% for placebo). Adverse events occurred in 50% of patients on 20 mg MK-462, 72% of those on 40 mg MK-462, and in 52% of placebo-treated subjects. The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (10 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%). Based on these preliminary results, MK-462 appears worthy of continued study for the treatment of acute migraine.     

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.     

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.