Treatment of Acute Migraine Attack With Diclofenac Sodium: A Double-Blind Study

The efficacy of diclofenac sodium, a potent prostaglandin inhibitor, in patients with acute migraine attacks in a double-blind placebo-controlled study involving 86 migraine patients. Forty-six patients with acute migraine attacks were treated with intramuscular injection of 75 mg diclofenac sodium, and another group of forty patients with intramuscular injection of paracetamol. Partial or complete relief of pain and other symptoms of acute migraine attack was achieved within 10 minutes after treatment in the diclofenac sodium group and within 32 minutes in the paracetamol group. Complete relief of attack was achieved within 30 minutes after diclofenac sodium in 40 patients (88%) compared to 7 patients (17.5%) of the paracetamol group (P less than 0.001). Five of the patients treated with diclofenac sodium needed a second injection for complete relief of pain during the 2-to-4 hour follow-up period. Side effects were rare and minimal. In conclusion, diclofenac sodium administered intramuscularly is a very effective drug in treating acute migraine attacks.     

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 oral zolmitriptan in menstrually associated migraine: a randomized, prospective, parallel-group, double-blind, placebo-controlled study

BACKGROUND: Approximately 60% of female migraineurs report experiencing migraine in association with menstruation, while 7% to 25% experience attacks almost exclusively with menstruation. OBJECTIVE: To examine the efficacy and tolerability of oral zolmitriptan in the acute treatment of menstrually associated migraine. In this study, menstrually associated migraine was defined as migraine that consistently occurred from 72 hours before to 5 days after onset of menses. Methods.-Participants were women with regular menstrual cycles, aged 18 to 55 years, who had experienced migraine with at least two thirds of prior menstrual cycles. Subjects were randomized to treat one attack per menstrual cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity based: mild migraines were treated with half of a 2.5-mg zolmitriptan tablet, moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines were treated with 5 mg (two 2.5-mg tablets) of zolmitriptan, or placebo. RESULTS: Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and 251 were assigned placebo. Twelve hundred thirty-two attacks were treated, and a 2-hour headache response was achieved in 48% of zolmitriptan-treated attacks as compared with 27% of placebo-assigned attacks (P <.0001). Zolmitriptan was superior to placebo in achieving a headache response as early as 30 minutes (18% versus 14%, P=.03) and at 1 hour (33% versus 23%, P <.001). Drug-related adverse events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects receiving placebo. CONCLUSION: Oral zolmitriptan exhibits efficacy and good tolerability in the treatment of menstrually associated migraine. Improvement over placebo was observed as early as 30 minutes following treatment.     

Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study

In a randomized double-blind study, 120 patients with moderate to strong pain after surgical removal of wisdom teeth were given the following in single oral doses: 100-mg enteric-coated diclofenac tablets; 1 g acetaminophen (INN, paracetamol); 1 g acetaminophen plus 60 mg codeine; 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen; or 100-mg enteric-coated diclofenac tablets plus 1 g acetaminophen plus 60 mg codeine. Patients recorded pain intensity and pain relief for 8 hours. Upside assay sensitivity was confirmed because acetaminophen plus codeine was superior to acetaminophen. Diclofenac plus acetaminophen with and without codeine had superior analgesic effect compared with diclofenac, acetaminophen, or acetaminophen plus codeine. Addition of 60 mg codeine increased the degree of side effects. These results support the clinical practice of combining diclofenac with acetaminophen for acute pain. Of clinical importance are superior and prolonged analgesia and fewer side effects after enteric-coated diclofenac tablets plus acetaminophen compared with acetaminophen plus codeine.     

Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets

BACKGROUND: The gastric stasis that commonly accompanies migraine headache may impair absorption of conventional oral tablets in the stomach. A fast-disintegrating/rapid-release formulation of sumatriptan has been developed to enhance tablet disintegration and drug dispersion and potentially improve absorption. OBJECTIVE: Two studies were conducted comparing the time to onset of relief from moderate or severe migraine pain with the fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100 mg and placebo. METHODS: These were 2 identically designed randomized, double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was taken on an outpatient basis to treat a single moderate or severe migraine attack. Using a personal digital assistant, patients recorded the time of dosing and the time at which pain severity reached none or mild (ie, pain relief) or none (ie, pain free) in real time so that the time to onset of relief could be measured as a continuous variable. Onset of relief was defined as the earliest time point at which a statistically significant difference in pain relief compared with placebo was achieved and maintained through 2 hours after dosing. Before dosing and at pre-determined time points after dosing, patients also provided an assessment of migraine pain as none, mild, moderate, or severe. At a clinic visit within 1 week after treatment of the migraine attack, patients were queried about adverse events. For each adverse event, investigators recorded whether study medication was considered the cause. Data analyses were undertaken for each study individually and, in post hoc analyses of the primary and key secondary end points, on pooled data from both studies. RESULTS: The 2 studies comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan 100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8 years across treatment groups, and most patients were female (83%-87%) and white (92%-93%). In the analysis of pooled data, sumatriptan tablets provided significantly more effective pain relief compared with placebo as early as 20 minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing with the 50-mg dose (P < or = 0.05). Similar results were observed for the individual studies: in study 1, sumatriptan tablets were significantly more effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). The cumulative percentages of patients with a pain-free response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15% for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the individual studies, significantly more patients receiving either sumatriptan dose were migraine free 2 hours after dosing and had sustained pain relief and a sustained pain-free response over 24 hours compared with placebo (P < or = 0.001, both sumatriptan doses vs placebo). The only drug-related adverse events reported in >2% of patients in any treatment group in either study were nausea (both studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia (study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo). CONCLUSIONS: In these studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation were effective for the acute treatment of moderate to severe migraine pain, were generally well tolerated, and achieved an onset of pain relief as early as 20 minutes for 100 mg and as early as 30 minutes for 50 mg.     

Diclofenac sodium in ureteral colic: a double-blind comparison trial with placebo

A randomized prospective double blind study of the analgesic effect of 75 mg intramuscular diclofenac sodium (Voltaren), a potent prostaglandin synthetase inhibitor, versus placebo (saline solution) was carried out in 131 consecutive patients with acute ureteral colic. Diclofenac provided complete relief of pain 25 minutes after the injection in 59% of the cases, while placebo provided relief in 29% (p less than 0.01). Forty patients in the placebo group and seventeen patients in the diclofenac group needed an open injection of 75 mg diclofenac intramuscularly after 25 minutes due to persistent pain. Fifty-four of the fifty-seven patients treated with an open injection of diclofenac achieved complete relief of pain after 30 minutes. There were no side-effects of the treatment.     

Efficacy, tolerability, and patient satisfaction with 50- and 100-mg sumatriptan tablets in those initially dissatisfied with the efficacy of 50-mg sumatriptan tablets

BACKGROUND: Both 50- and 100-mg sumatriptan tablets are effective and well tolerated in the acute treatment of migraine. However, given a choice between the 2 doses, many patients in clinical practice and clinical studies prefer the 100-mg dose. OBJECTIVE: This study was designed to assess whether patients initially dissatisfied with the efficacy of 50-mg sumatriptan tablets would be satisfied with 100-mg sumatriptan tablets. METHODS: In phase 1 of the study, triptan-naive patients with migraine (International Headache Society diagnosis) received open-label treatment of 3 migraine attacks with 50-mg sumatriptan tablets. At the end of phase 1, those who were dissatisfied with the efficacy but satisfied with the tolerability of 50-mg sumatriptan tablets entered phase 2 and were randomized in a double-blind, parallel-group fashion to receive either 50- or 100-mg sumatriptan tablets for the treatment of 3 attacks. Patients who were satisfied with the efficacy or dissatisfied with the tolerability of the 50-mg tablets in phase 1 were given the option of continuing open-label treatment with 50-mg sumatriptan tablets in phase 2. The primary end point was the percentage of patients satisfied with medication at the end of phase 2 double-blind treatment. Patient satisfaction with specific medication attributes was assessed using the Patient Perception of Migraine Questionnaire. RESULTS: Seven hundred twenty-two patients were enrolled in phase 1 of the study (the intent-to-treat population), 609 of whom had evaluable satisfaction data at the end of open-label treatment. Three hundred twenty-six (54%) of these patients were satisfied with 50-mg sumatriptan tablets, whereas 283 (46%) were not satisfied. Among those who were dissatisfied, lack of efficacy was cited as the sole reason for dissatisfaction by 242 (86%). Two hundred thirty-one of those who were dissatisfied with efficacy only and wished to continue the study were randomized to double-blind treatment with either 50-mg sumatriptan tablets (n = 123; 82% female, 18% male; mean age, 37.6 years) or 100-mg sumatriptan tablets (n = 108; 86% female, 14% male; mean age, 36.0 years). The remaining 310 patients elected to continue open-label treatment with 50-mg sumatriptan tablets. At the end of double-blind treatment, 64 of 101 patients (63%) in the 100-mg group indicated that they were satisfied with treatment, compared with 55 of 113 (49%) in the 50-mg group (P = 0.031). Across the 3 attacks treated in the double-blind phase. headache relief 2 hours postdose was reported by 47% to 53% of patients in the 50-mg group and 45% to 60% of patients in the 100-mg group. The overall incidence of patients reporting > or =1 adverse event was 19% (23/123) in the 50-mg group and 22% (24/108) in the 100-mg group. CONCLUSIONS: For most patients, 50 mg is the appropriate starting dose of sumatriptan tablets. In patients who experience inadequate relief with 50 mg, increasing the dose to 100 mg is an appropriate therapeutic option.     

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.     

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

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

Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg

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

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.     

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.     

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies

OBJECTIVE: To examine the short- and long-term efficacy and tolerability of rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were conducted in patients aged 12 to 17 years. The first study was a randomized, double-blind, placebo-controlled, single-attack study followed by a randomized, 1-year, open-label extension. The second study was a randomized, 1-year, open-label study. In the single-attack study, patients treated a moderate or severe migraine headache and up to two recurrences with rizatriptan 5-mg tablets (n = 234) or placebo (n = 242). Patients were instructed to use the study medication only on nonschool days. Headache severity, associated symptoms, and functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial dose. In the 1-year studies, patients treated up to 6 migraine attacks per month with rizatriptan 5-mg tablets (n = 273), rizatriptan 5-mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was assessed by the patient at 2 hours after the initial dose. In all studies, the primary efficacy measure was pain relief at 2 hours post dose. RESULTS: In the single-attack study, the proportion of patients with pain relief at 2 hours was not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients than expected (about 30%) treated their migraine attacks on the weekend. Among these patients, the proportion with pain relief at 2 hours was significantly higher in the rizatriptan group than in the placebo group (74% vs. 58%, P = 0.022). In the multiple-attack studies, pain relief at 2 hours was achieved in significantly more attacks treated with rizatriptan 5-mg tablet (77%) or with rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was well tolerated in both the studies, with an adverse event profile not significantly different from that of placebo or standard care. CONCLUSIONS: Rizatriptan 5 mg was not more effective than placebo in the treatment of a single migraine attack in adolescents, but appeared to be more effective than standard care for treating multiple attacks occurring over 1 year in these patients. Rizatriptan 5 mg was well tolerated in adolescents during short-term and long-term use.     

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute treatment of migraine--results from phase 1 of the REALIZE Study

OBJECTIVES: The objective of phase 1 (reported here) of this two-phase study was to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to provide relief from all migraine symptoms, in a controlled setting, designed to replicate clinical practice. BACKGROUND: Zolmitriptan nasal spray has been shown to be fast acting and highly effective in the treatment of migraine, as assessed using standard endpoints, such as headache response and pain-free rates. METHODS: In the double-blind first phase of the study, patients with migraine were randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single migraine attack. Attacks were treated according to patients' normal patterns of use, in order to closely reflect clinical practice; that is, no specific regimen was dictated in terms of time to treatment or at what level of pain intensity the headache should be treated. Patients could take a second dose of study medication or an agreed escape medication if adequate pain relief had not been achieved 2 hours after the first dose. The primary efficacy endpoint was total symptom relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the first dose. Secondary efficacy endpoints included headache response, pain-free status and sustained pain-free status, and ability to perform normal activities. RESULTS: The intention-to-treat population comprised 461 zolmitriptan nasal spray recipients and 451 placebo recipients. The total symptom relief rate 1 hour post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the groups was significant from 30 minutes post-dose. Treatment with zolmitriptan nasal spray, compared with placebo, also produced a higher headache response rate from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray was also significantly superior to placebo in terms of sustained pain-free status and patients' ability to perform normal activities. Zolmitriptan nasal spray was well tolerated. CONCLUSIONS: These findings confirm the efficacy demonstrated by zolmitriptan nasal spray in previous clinical trials.     

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.     

Diclofenac epolamine is effective in the treatment of acute migraine attacks. A randomized, crossover, double blind, placebo-controlled, clinical study

Hydrosoluble diclofenac epolamine (DHEP) represents an interesting approach to acute migraine attacks, where gastrointestinal motility and drug absorption are often reduced. Its efficacy was investigated in a randomized, crossover, double-blind trial on 155 patients who treated four consecutive mild-to-moderate migraine attacks, either with DHEP (65-mg sachet) or placebo. If pain was not relieved within 1 h, a second dose was given. The total number of treated attacks was 481. A pain-free condition was achieved within 2 h in 45.8% and 25.1% of attacks treated, respectively, with DHEP or placebo (P < 0.0001), with a therapeutic gain of 20.7%. Time to attack resolution, light and noise sensitivity and impact on working ability were significantly reduced by DHEP compared with placebo. Moreover, significantly fewer patients required a second drug dose or a rescue medication when treated with DHEP than with placebo. No adverse reaction was recorded. In conclusion, DHEP was effective and safe for pain relief in patients with an acute mild-to-moderate migraine attack.     

A double-blind, dose comparison study of topiramate for prophylaxis of basilar-type migraine in children: a pilot study

BACKGROUND: Basilar-type migraine (BM) is the most common migraine "variant," representing 3-19% of migraine in children.BMis characterized by attacks of dizziness, vertigo, visual disturbances, ataxia, and/or diplopia, followed by migraine headache. OBJECTIVE: The objective of this study is to assess the efficacy and safety of topiramate for prophylaxis of BM in children and adolescents (6-18 years). DESIGN: Outpatient, double-blind, parallel-group, dose comparison study with 2 phases: prerandomization (screening/washout and 4-week prospective baseline) and 12-week double blind (titration and maintenance). METHODS: Following consent and assent, subjects with BMs, as defined by the International Classification of Headache Disorders (second edition), and > or =4 migraines/month were randomized to receive either 25 mg per day or 100 mg per day of topiramate in a 1 : 1 ratio. RESULTS: Fourteen children (4 boys, 10 girls) completed the double-blind phase (7 in the 25-mg group and 7 in the 100-mg group). During the prospective baseline, the mean headache frequency of the combined group "all migraines" per month was 4.5/month (25 mg) and 4.8/month (100 mg). Average duration of migraine was 5.5 hours (25 mg) and 5.0 hours (100 mg) and average mean pain (5-point faces scale) was 3.3 for both (25 mg 100 mg). The reduction in median monthly migraine rate during the double-blind treatment phase relative to baseline was 2.9 (64.4%) and 3.6 (75.0%) for the 25-mg and 100-mg topiramate-treated groups, respectively (P < .001). The reduction in median monthly BM rate during the double-blind treatment phase relative to baseline was 2.5 (74.24%) and 2.3 (82.8%) for the 25-mg and 100-mg topiramate-treated groups, respectively. The overall reduction in BM attacks reduced from 2.84/month to 0.59/month (79.2%; P < .0042). Overall, 86% of patients responded with a greater than 50% reduction in migraine frequency (100%, 25 mg and 71%, 100 mg). Mean reduction in migraine duration was 18 minutes (25 mg) and 89 minutes (100 mg). There was no significant difference in migraine severity between the 2 groups. Parent Global Assessment was "very much" or "much improved" in 6 of 7 (25 mg) and 3 of 7 (100 mg) patients. Migraine disability as measured by PedMidas reduced from moderate to no disability (P < .001). There were no serious adverse events. CONCLUSIONS: Preventive therapy with topiramate resulted in reducing the overall migraine frequency and the frequency of attacks of BM at both 25 mg and 100 mg doses relative to the historical baseline and prospective baseline periods. The 2 treatment groups resulted in comparable outcomes.     

Pharmacokinetics of rizatriptan tablets during and between migraine attacks

Gastric stasis during migraine attacks results in delayed absorption of several orally administered antimigraine agents. This study, as part of a larger trial, was conducted to examine the pharmacokinetics of rizatriptan tablets during and between migraine attacks. Participating patients met IHS criteria for migraine with or without aura, and suffered between one and eight migraines per month for the previous 6 months. In part 1 of the study, 21 patients were randomized to receive a single 5-mg tablet of rizatriptan or placebo in the migraine-free state. In part 2, the same patients were treated during migraine with rizatriptan 5-mg tablets (n=18) or placebo (n=3). Blood samples were obtained before dosing and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours after dosing. The plasma concentration profile (ie, AUC_(0-∞), C_max, T_max) of rizatriptan 5-mg tablets administered during and between migraine attacks were comparable. The median T_max for rizatriptan between and during attacks was 1 hour, indicating rapid absorption even during a migraine attack. Rizatriptan 5 mg was well tolerated and 67% of the patients experienced headache relief 2 hours postdose.     

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.     

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.