Double-blind comparison of an acetaminophen 400 mg-codeine 25 mg combination versus aspirin 1000 mg and placebo in acute migraine attack

The purpose of this study was to compare the efficacy and tolerance of a single dose of the acetaminophen 400 mg-codeine 25 mg combination (ACC) aspirin 1000 mg (A) and a placebo (P) for the treatment of acute migraine attack. The study design was randomized, multicentre, double-blind and double dummy with cross-over on three periods. Of the 198 patients who had three attacks 29.8%, 52.3% and 49.7% had recorded the complete or almost complete disappearance of the pain at 2 h after P, A and ACC respectively. When compared with the placebo, the difference was significant for the A and ACC. When complete disappearance of pain at 2 h was used as a criterion, no significant difference was observed. These results enabled the sensitivity of the evaluation criteria suggested for clinical trials of migraine attack to be discussed.     

Flunarizine (10 and 20 mg) i.v. versus placebo in the treatment of acute migraine attacks: a multi-centre double-blind study

In a multi-centre, randomized double-blind study, the effect and tolerance of 10 and 20 mg flunarizine i.v. versus placebo was tested on 102 migraineurs with acute migraine attacks with and/or without aura. Thirty-seven patients received 10 mg flunarizine, 32 received 20 mg and 33 received placebo. The groups were comparable. Response to treatment was defined as pain reduction of at least 50% within 60 min on a visual analogue scale after i.v. drug administration. This effect was noted on 59.4% with 20 mg flunarizine, on 24.3% with 10 mg flunarizine and on 30.3% with placebo. The tolerance of flunarizine i.v. was similar to placebo. Blood pressure and pulse rate were not affected by flunarizine. All in all, 20 mg flunarizine i.v. appeared to be a suitable alternative for treatment of acute migraine attacks.     

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

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

Comparison of propranolol LA 80 mg and propranolol LA 160 mg in migraine prophylaxis: a placebo controlled study

Thirty patients with severe classical and common migraine participated in a double-blind placebo-con-trolled cross-over study of migraine prophylaxis with propranolol LA (long-acting) 80 mg once daily, or propranolol LA 160 mg once daily or placebo. Each treatment was given for two months. There were no significant differences between the three treatment periods in headache frequency, headache severity, nausea frequency or severity. There was a non-significant trend for reduced duration of headache with the two doses of propranolol. The possible reasons for this negative effect are discussed. The safety of propranolol and its lack of serious side effects were demonstrated.     

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

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

Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine. Rizatriptan-Zolmitriptan Study Group

The efficacy and tolerability of rizatriptan (MAXALT) and zolmitriptan (ZOMIG) were compared in a randomized, double-blind, double-dummy, stratified (on prior use of rizatriptan and/or zolmitriptan), placebo-controlled, single attack study in 766 patients. Rizatriptan tended to provide freedom from pain sooner than zolmitriptan (hazard ratio 1.26, P = 0.075), acting within 60 min following dosing. More patients were pain free at 2 h on rizatriptan than on zolmitriptan (43.2% vs. 35.6%, P=0.041), while headache relief at 2 h was similar (70.5% vs. 66.8%). At 2 h, fewer patients on rizatriptan had symptoms of photophobia (35.6% vs. 43.5%, P = 0.029) and nausea (25.2% vs. 32.5%, P=0.046), and more patients on rizatriptan had normal function (45.4% vs. 37.0%, P=0.025) than zolmitriptan. Headache recurred in 28% of patients taking rizatriptan, 29% taking zolmitriptan and 26% taking placebo. Both active treatments were effective compared to placebo and were well tolerated. The most common side-effects with rizatriptan were asthenia/fatigue, somnolence and dizziness, while the most common side-effects with zolmitriptan were asthenia/fatigue and dizziness.     

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

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

A double-blind comparison of granisetron and placebo for the treatment of acute migraine in the emergency department

Three hundred and ninety-seven patients who presented to the emergency department were screened for a randomized, double-blind, placebo-controlled study of iv granisetron (40 micrograms/kg or 80 micrograms/kg) in acute migraine. Twenty-eight patients fulfilled the stringent eligibility criteria and completed the study. Rescue medication was required 2 h post-infusion in 8 of 10 patients receiving granisetron 40 micrograms/kg, 5 of 10 patients receiving granisetron 80 micrograms/kg, and 6 of 8 patients receiving placebo. Significant improvement (p less than 0.05) in headache pain (on a visual analogue scale and categorical scale) was observed in the 80-micrograms/kg group. Headache pain evaluated with the Hunter headache scale indicated improvement for the sensory and affective components of headache pain in both granisetron groups. Except for more nausea at 30 min in the placebo group, no significant differences were noted between treatments. All three treatments were well tolerated. Granisetron may be effective for acute migraine headache; however, further studies with increased patient numbers are required.     

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.     

A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine

OBJECTIVE: Evaluate the long-term tolerability of almotriptan 12.5 mg for the treatment of acute migraine attacks occurring over a 6-month period. BACKGROUND: Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular selectivity for meningeal arteries and has demonstrated efficacy for the treatment of acute migraine in short-term controlled trials. METHODS: This was a 6-month open-label study. Adults (18 years of age or older) were required to have a diagnosis of acute migraine with or without aura (according to the diagnostic criteria of the International Headache Society), a history of at least 1 year of moderate-to-severe migraine pain with at least two and a maximum of six migraines per month, and at least 24 hours of freedom from head pain between attacks. Patients were instructed to take a single 12.5-mg dose of almotriptan at the onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape medication could be taken; if relapse occurred in less than 24 hours, a second 12.5-mg dose could be taken. Tolerability was assessed from the nature and incidence of all adverse events, and efficacy was assessed according to the end point of pain relief 2 hours following almotriptan administration. RESULTS: Of 585 patients treated, 582 were included in the intent-to-treat population. The most frequent drug-related adverse events were nausea (3.1%) and dizziness (2.4%). No serious drug-related adverse events were reported, and no deaths occurred. Adverse events led to discontinuation of treatment in 36 patients (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six percent of patients achieved pain relief at 2 hours for all attacks treated, and 49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and pain-free rates were higher among those with moderate baseline pain. CONCLUSIONS: When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and effective for the long-term treatment of acute migraine.     

Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized,double blind,placebo controlled study

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of migraines in Brazil. Some investigators have found it to be a highly effective medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a randomized, placebo controlled, double blind study to assess the effect of dipyrone on the pain and symptoms associated with migraine without aura or with aura and the adverse effect profile of this medication. METHODS: For the migraine without aura group, 44 patients were assigned at random to receive 1 g intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline. For the migraine with aura group, 30 patients received both dipyrone or placebo. We used seven parameters of analgesic evaluation and an analog scale to assess nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is an effective drug for the relief of acute migraine pain and associated symptoms.     

Early migraine intervention with sumatriptan 100 mg in patients with a history of nonresponse to sumatriptan 50 mg: an open-label, prospective study of multiple attacks

Background

Early treatment with sumatriptan tablets (50 and 100 mg) has been shown to be effective in retrospective and prospective study designs. Despite the efficacy of sumatriptan 50 mg and early intervention, however, some patients continue not to respond completely to this dose. New evidence with a scientific basis for early intervention suggests that some patients may need to treat early to prevent the establishment of central sensitization. Also, patients cite complete pain relief as the most important attribute of a migraine medication.

Objective

The primary objective of this study was to determine the 2-hour efficacy of sumatriptan 100 mg in achieving complete pain relief in patients with a history of nonresponse to sumatriptan 50 mg in an early-intervention treatment paradigm. Secondary end points included complete pain relief at 4 hours, consistency of complete relief in at least 2 of 3 attacks, sustained complete relief over 24 hours, satisfaction with the 100-mg dose, and relief of associated symptoms.

Methods

This open-label, prospective study was conducted at the Wesley Headache Clinic (Memphis, Tennessee). Male and female patients between the ages of 18 and 65 years who fulfilled International Headache Society classification criteria for migraine, and who had a documented history of nonresponse to sumatriptan 50 mg at 2 hours after dosing when treating in the early, mild-pain phase in at least 2 of 3 migraine attacks were eligible for the study. Patients were instructed to receive one 100-mg sumatriptan tablet at the earliest sign of pain, while still mild, in 3 subsequent migraine attacks. After each treated attack, patients were to record a detailed diary entry.

Results

Twenty patients (17 women, 3 men; mean age, 44 years) treated all 3 migraines during the early, mild-pain phase and completed the study. Of the 60 attacks treated, 48 (80%) were pain free at 2 hours, 56 (93%) were pain free at 4 hours, and 45 (75%) were pain free at 2 hours and continued to be pain free at 24 hours (sustained pain-free response). Sumatriptan 100 mg was well tolerated; none of the patients reported any adverse events.

Conclusions

In this study of migraineurs with a history of nonresponse to sumatriptan 50 mg at 2 hours after dosing in the early, mild-pain phase of migraine, increasing the dose of sumatriptan from 50 mg to 100 mg in the early-intervention paradigm, in most attacks complete pain relief was achieved for up to 24 hours. Because patients have indicated that becoming pain free was their therapeutic goal, based on the results of this study, physicians may want to consider increasing the dose of sumatriptan to 100 mg at the first sign of pain if the patient has consistently not responded to sumatriptan 50 mg in the early-intervention model.     

Sumatriptan (50 and 100 mg) in repeated migraine attacks: a patient preference study

Oral sumatriptan in 100-mg tablets is an effective and well tolerated treatment for the acute migraine attack. Since the launch of that dose, further studies have suggested good efficacy also for lower doses. This Italian multicentre study aimed at evaluating patient preference between the 50- and 100-mg does for acute treatment of migraine. Data on efficacy and safety are provided as secondary end points of this trial. The study design is on open basis: the patients treated their first 3 migraine attacks with 50 mg sumatriptan and then were able to choose whether to increase the dose to 100 mg or to continue with the initial treatment for the next 3 attacks. Two hundred one patients treated at least 3 attacks and 182 treated 6 attacks: 68% of the patients, after the third attack, preferred to continue with 50-mg sumatriptan tablets, while 32% preferred to switch to the 100-mg dose. In the first 3 attacks treated with 50 mg, 60% of patients improved at 2 hours and 72% at 4 hours after the first dose. In the set of patients that preferred to use 100 mg for the second block of 3 attacks (32%), the improvement at 2 and 4 hours after the dose was respectively 34% and 48%. Minor adverse events were reported by 15% of the patients. We conclude that less than one-third of patients treated with sumatriptan needs the 100-mg dose. Received: 29 October 1999 / Accepted in revised form: 27 January 2000     

Effectiveness of oral diclofenac in the acute treatment of common migraine attacks: a double-blind study versus placebo

In a multicentre double-blind cross-over trial, oral diclofenac at a dose of 50 mg to 100 mg was compared to placebo in the acute treatment of migraine attacks. A hundred and seven patients suffering from migraine without aura were included, and 91 were analysed for efficacy; they had to treat four successive attacks--two with diclofenac and two with placebo. Diclofenac was significantly more effective than placebo (p less than 0.05) on the main judgement parameter, which was the number of attacks aborted within 2 h of drug intake, as well as on the following secondary parameters: the necessity for an escape medication and the evaluation of global efficacy. Diclofenac was well tolerated. This trial demonstrates the efficacy of diclofenac in the acute treatment of migraine attacks. It confirms the good clinical relevance of the main judgement parameter chosen, which is the one recommended by the International Headache Society, but appears to be a severe one in terms of successes.     

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.     

Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in migraine without aura: a randomized, double-blind, crossover study

OBJECTIVE: A phase II, randomized, double-blind, crossover study was designed to evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs during migraine attacks. BACKGROUND: Diclofenac has been demonstrated to be an effective migraine treatment in several placebo-controlled studies. A rapidly absorbed softgel of diclofenac has been shown to be effective in the rapid relief of acute pain, and may have advantages in migraine treatment. In addition, caffeine has consistently been shown to increase both the efficacy and speed of onset of concurrently administered analgesics. The ability of caffeine to both enhance and accelerate analgesic effects has been documented with a variety of different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine). METHODS: The 3-period crossover study was designed to compare diclofenac softgel 100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute treatment of migraine. Subjects treated one moderate or severe attack with each study medication. The primary efficacy parameter was the percentage of subjects with headache relief at 60 minutes as defined by a reduction of headache severity from moderate or severe at baseline to absent or mild compared with placebo. Though the sample size estimate required that 72 subjects treat 3 separate attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39 treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus caffeine group. Differences were statistically significant for the diclofenac softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel, and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This result is highly statistically significant (chi22= 11.56, P=.003). Both the diclofenac plus caffeine (P <.03) and diclofenac only (P <.03) groups were significantly different from the placebo group in terms of the visual analog scale score at 60 minutes. CONCLUSIONS: The major finding of the present study is that diclofenac softgel plus caffeine produces statistically significant benefits relative to placebo at 60 minutes. Diclofenac softgel alone did not differ significantly from placebo, perhaps due to limits in sample size. Nonsignificant trends support the analgesic adjuvant benefit of caffeine when added to diclofenac softgels.     

Crossover Comparison of Rizatriptan 5 mg and 10 mg Versus Sumatriptan 25 mg and 50 mg in Migraine

Rizatriptan is a selective 5-HT_1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.     

Sumatriptan injection is superior to placebo in the acute treatment of migraine with regard to both efficacy and general well-being

The efficacy of subcutaneous injection of sumatriptan in the acute treatment of migraine was assessed in a double-blind, randomized, placebo-controlled cross-over study of 27 migraine patients. In addition, the patients were asked to give information about their well-being and subjective symptoms by means of a self-administered standardized questionnaire. A total of 22 migraine sufferers received a subcutaneous (sc) injection of 8 mg of sumatriptan and 24 received placebo. Of these patients, 19 received both treatments and thus completed the study. The primary efficacy end-point was a reduction in headache severity from severe or moderate to mild or no headache at 30, 60, 90 and 120 min. An effective response to treatment was achieved within 30 min in 63% and within 60 min in 84% of patients when treated with 8 mg sumatriptan sc, compared with 11% for placebo (p less than 0.001). Sumatriptan also provided significant relief from nausea and photophobia as compared with placebo. The proportion of patients that needed rescue medication after 120 min was significantly lower (p less than 0.001) with active treatment when compared with placebo. Sumatriptan was well tolerated and the majority of adverse events were mild and transient. The most frequent symptoms were those of malaise/fatigue or numbness. No changes in blood pressure or ECG readings were observed during the treatment. Compared with placebo, subcutaneous 8 mg sumatriptan also caused a substantial improvement in general well-being as revealed by the Minor Symptoms Evaluation Profile-acute (MSEP-acute) questionnaire.(ABSTRACT TRUNCATED AT 250 WORDS)