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Multiple-Attack Efficacy and Tolerability of Sumatriptan Nasal Spray in the Treatment of Migraine
Seymour Diamond, MD;
Arthur Elkind, MD;
R. Terry Jackson, MD;
Robert Ryan, MD;
Sandy DeBussey;
Mahnaz Asgharnejad, PharmD
Arch Fam Med. 1998;7:234-240.
ABSTRACT
Objective Sumatriptan hemisulfate nasal spray may provide a useful therapeutic option for patients with migraine who find injectable medications inconvenient or uncomfortable and for patients whose migraine-associated nausea and vomiting preclude the use of oral medication. This study was the first US trial to evaluate the effects of sumatriptan nasal spray administered for multiple migraine attacks.
Design/Interventions Sumatriptan nasal spray (5, 10, or 20 mg) was administered via a 1-shot nasal applicator into either nostril for up to 3 migraine attacks occurring over 6 months in a randomized, double-blind, parallel-group, placebo-controlled study.
Setting Fifty-six outpatient clinical centers in the United States.
Patients A total of 1086 men and women diagnosed with migraine with or without aura per International Headache Society criteria.
Main Outcome Measures Percentage of patients with headache relief (moderate or severe predose pain reduced to mild or none); percentage of patients with no or mild (vs moderate or severe) clinical disability; percentage of patients with nausea, vomiting, photophobia, or phonophobia; adverse events; clinical laboratory test results.
Results Across attacks, headache relief in the 20-, 10-, and 5-mg drug and placebo groups was experienced 120 minutes postdose by 60%, 54%, 44%, and 32% of patients, respectively (P<.05 for each sumatriptan nasal spray group vs placebo, for the 10-mg vs 5-mg drug group, and for the 20-mg vs 5-mg drug group). Two thirds of the 20-mg patients treating 3 attacks experienced relief at 2 hours postdose for at least 2 of 3 attacks. Clinical disability scores at 120 minutes in the 20-, 10-, and 5-mg drug and placebo groups reflected no or mild impairment in 70%, 67%, 57%, and 50% of patients, respectively (P<.05 for the 10- or 20-mg drug group vs placebo group, and for the 20-mg vs 5-mg drug group). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. For all parameters, individual-attack efficacy rates did not differ from across-attack rates. The incidence of adverse events was not dose related. The most frequently reported adverse event in the active treatment groups was taste disturbance (bad, bitter, or unpleasant).
Conclusions Sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) is effective and well tolerated in the treatment of multiple migraine attacks. The 20-mg dose was associated with the highest efficacy rates across the greatest number of parameters.
INTRODUCTION
SUMATRIPTAN, a medication frequently prescribed by the general or family physician consulted for migraine, has been shown in clinical trials to be effective in the treatment of migraine headache, clinical disability, and associated symptoms such as nausea, photophobia, and phonophobia.1-11 Headache is alleviated in approximately 80% of patients within 2 hours of subcutaneous dosing1-4 and in approximately 70% of patients within 4 hours of oral dosing.5-10
These clinical results are substantiated and extended by data from studies documenting patients' perceptions of sumatriptan.11-12 For example, in a survey of 648 patients who had received subcutaneous sumatriptan in a clinical trial,11 sumatriptan was rated more favorably than aspirin, acetaminophen, or patients' usual medications with respect to effectiveness, speed of relief, and number of doses required to achieve relief. Patients cited sumatriptan as the medication they would be most likely to use again to treat migraine. In another survey of 351 migraineurs using injectable or oral sumatriptan on an outpatient basis,12 53% indicated that they had fewer absences from work since they had begun to use sumatriptan.
The results of these surveys,11-12 which demonstrate patients' overall satisfaction with sumatriptan therapy, also reveal that subcutaneous sumatriptan may not be the optimal dosage form for all patients. One fifth of subcutaneous sumatriptan users in the study of 351 migraineurs12 cited syringe phobia as a reason for their hesitation to use the subcutaneous form. Besides fear of injections, ease of use may be an impediment to the use of subcutaneous sumatriptan among some patients: it was rated significantly less favorably than aspirin or acetaminophen on the dimension of ease of use.11
Oral sumatriptan might be a viable treatment option for patients with reservations about using injectable medication; however, some patients' migraine-associated nausea and vomiting preclude the effective use of oral medication. The newly developed sumatriptan nasal spray may provide an ideal therapeutic option for migraine patients who seek rapid migraine relief but find injectable medications inconvenient or uncomfortable and for patients who experience migraine-associated nausea and vomiting. The results of early European studies13 in which sumatriptan hemisulfate nasal spray (1, 5, 10, 20, or 40 mg) was administered for a single migraine attack demonstrate that sumatriptan hemisulfate nasal spray (10, 20, or 40 mg) is consistently more effective than placebo at alleviating headache and migraine-associated symptoms, including nausea, photophobia, and phonophobia, and at reducing clinical disability. The most frequently occurring adverse event in these studies was unpleasant taste, which was reported more often in the sumatriptan nasal spray groups compared with the placebo group.
This double-blind, placebo-controlled, parallel-group study was the first U S trial to evaluate the effects of sumatriptan nasal spray administered for multiple migraine attacks. Migraineurs from 56 US clinical centers could use sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) or placebo to treat up to 3 migraine attacks.
PATIENTS AND METHODS
PATIENTS
Men or women (between 18 and 65 years of age) with a 1-year or longer history of migraine with or without aura diagnosed according to International Headache Society criteria14 were eligible for the study. Patients must have had 2 to 8 migraine attacks per month and not more than 15 days per month with headache during the 2 months prior to screening. Patients with Raynaud syndrome, Prinzmetal angina, ischemic heart disease, uncontrolled hypertension, or a history suggestive of cerebrovascular pathology were excluded. Women of childbearing potential not using adequate contraception, pregnant women, or breast-feeding women were excluded. All patients provided written, informed consent prior to the initiation of screening procedures.
PROCEDURES
The protocol was approved by an institutional review board for each of the 56 clinical centers located throughout the United States. Each patient self-administered sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) or placebo for up to 3 migraine attacks in this randomized, double-blind, parallel-group study. For any given patient, the same randomized dose was taken for all attacks. Sumatriptan nasal spray (5, 10, or 20 mg) was administered via a 1-shot nasal applicator into either nostril.
Standardized screening assessments, conducted by study site personnel during a migraine-free period, included medical and migraine histories, physical examinations, 12-lead electrocardiograms, and clinical laboratory tests (hematology, blood chemistry, and urinalysis). Patients meeting study eligibility criteria returned to the study site for a second visit, during which they were randomized to treatment groups. Patients were assigned to treatments based on a randomization schedule generated prior to the study. The randomization schedule assigned patients to receive sumatriptan hemisulfate nasal spray in 20-, 10-, or 5-mg doses or placebo in a 3:3:3:2 ratio.
After they were randomized to treatment, patients were issued study medication and instructed in the use of patient diaries. Patients were asked to use study medication to treat up to 3 moderate or severe migraine attacks on an outpatient basis over the next 6 months. The use of any rescue medication within 120 minutes after study drug administration, ergotamine-containing medications within 24 hours before or after study drug administration, oral or injectable sumatriptan within 24 hours before or 4 hours after study drug administration, or monoamine oxidase inhibitors at any time during the study was prohibited. Patients recorded use of study medication and any concomitant medication on diary cards, which were reviewed to ensure patients' compliance with the study protocol.
For each attack, immediately before and 15, 30, 45, 60, 90, and 120 minutes after dosing with the study drug, patients rated headache severity (0 indicated no pain; 1, mild pain; 2, moderate pain; 3, severe pain); clinical disability (0 indicated ability to work/function normally; 1, ability to work mildly impaired; 2, ability to work severely impaired; 3, required bed rest); and the presence or absence of nausea, vomiting, phonophobia, and photophobia. Patients also recorded the time to meaningful relief of migraine through 120 minutes postdose. Unlike headache relief, which was scored using a 4-point scale, patient-defined meaningful relief was a subjective interpretation measured with a stopwatch started at dosing and stopped at the time of meaningful relief.
Patients who experienced headache relief (defined as a reduction of moderate or severe pain at baseline to mild or no pain) 120 minutes after dosing, who did not use rescue medication, and who experienced recurrence (defined as a return or significant worsening of their headache within the next 22 hours), were eligible to take a second identical dose of study drug. Patients taking the second dose rated headache severity 60 and 120 minutes after this dose.
Adverse events were defined as any untoward medical occurrence, drug related or not, that occurred or worsened after administration of the study drug. Clinical laboratory tests and electrocardiograms were repeated as clinically indicated during the exit visit occurring at the end of the study period or on patient withdrawal, whichever occurred first.
DATA ANALYSIS
All analyses were carried out for all centers combined after the homogeneity of centers with respect to the association of treatment and response was confirmed. Efficacy parameters were analyzed for each attack and for all attacks combined. The primary efficacy end point was the percentage of patients experiencing headache relief, defined as a reduction in pain from moderate (2) or severe (3) to none (0) or mild (1) 60 minutes after the first administration of the study drug. Other efficacy measures included the percentage of patients with headache relief 15, 30, 45, 90, and 120 minutes postdose; with nausea, vomiting, photophobia, phonophobia 15, 30, 45, 90, and 120 minutes postdose; with no or mild clinical disability 15, 30, 45, 90, and 120 minutes postdose; with meaningful relief within 120 minutes postdose; and for those patients treating 3 attacks, with relief for at least 2 of 3 attacks. Between-group differences in headache relief rates (no pain or mild pain), clinical disability (normal or mildly impaired), presence or absence of nausea, vomiting, photophobia, and phonophobia, percentage of patients with meaningful relief, and percentage of patients experiencing relief for at least 2 of 3 attacks were tested using the van Elteren, Fisher exact, and Cochran-Mantel-Haenszel tests. Across-attack analyses were performed using a logistic model. Continuous variables (time to meaningful relief) were tested using nonparametric survival analysis techniques.
The percentage of patients taking a second dose of study medication to treat a recurrence and the percentage of patients experiencing relief after the second dose of study medication were examined. However, the data were not statistically analyzed because patients were not rerandomized prior to taking the second dose.
The primary safety measures were the incidence of adverse events and the results of clinical laboratory tests. The number of patients per treatment group experiencing adverse events and clinically significant changes from baseline clinical laboratory values was tabulated.
The significance level for all statistical tests was prospectively set at  <.05. Approximately 550 patients were required to achieve 80% power to detect significant between-group differences assuming success rates of 30% at 60 minutes postdose for the 5-mg, 30% for the 10-mg, and 45% for the 20-mg drug groups and 25% for the placebo group and a correlation of 0.5 or less for the efficacy response across 3 attacks.
RESULTS
PATIENT CHARACTERISTICS
A total of 1196 patients enrolled in this study. The number of patients treating 1, 2, and 3 attacks was 1086, 904, and 698, respectively. Data from all 1086 patients treating at least 1 attack were included in the demographic and safety tabulations and in across-attack efficacy analyses. The number of patients included in the by-attack analyses varied according to the number treating the relevant attack (Table 1).
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Table 1. Demographic and Patient Characteristics*
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Demographic characteristics were similar between groups (Table 1). Most of the patients were white, female, and approximately 40 years of age. More than two thirds of the patients in each group suffered from migraine without aura (Table 1). Across treatment groups, 37% to 43% of patients took migraine prophylaxis during the study period (Table 1). Amitriptyline hydrochloride, propranolol hydrochloride, and verapamil were the most frequently used prophylactic medications.
HEADACHE RELIEF
Across attacks, headache relief 60 minutes postdose was experienced by 42% of patients in the 20-mg drug group, 40% of patients in the 10-mg drug group, and 34% of patients in the 5-mg drug group compared with 25% of placebo-treated patients (P<.05 overall, each sumatriptan nasal spray group vs placebo, and the 20-mg or 10-mg drug group vs the 5-mg drug group; Figure 1). Across attacks, headache relief 120 minutes postdose was experienced by 60% of patients in the 20-mg drug group, 54% of patients in the 10-mg drug group, and 44% of patients in the 5-mg drug group compared with 32% of placebo-treated patients (P<.05 overall, for each sumatriptan nasal spray group vs placebo, for the 20-mg or 10-mg vs the 5-mg drug group; Figure 1). Relief rates 60 and 120 minutes postdose examined by individual attack were similar to relief rates for all attacks combined (Figure 1). The percentages of patients treating 3 attacks and experiencing relief at 120 minutes for at least 2 of 3 attacks in the 20-mg, 10-mg, and 5-mg drug groups and the placebo group were 67%, 59%, 46%, and 34%, respectively (P<.05 for each sumatriptan nasal spray group vs the placebo group, for the 20-mg vs 5-mg drug group). Onset of relief compared with placebo occurred as early as 30 minutes postdose.
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Figure 1. Percentage of patients with relief (no pain or mild pain) 60 or 120 minutes after dosing with sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) or placebo. Asterisk indicates P<.05 vs placebo; dagger, P<.05 vs 5 mg of sumatriptan hemisulfate nasal spray; and double dagger, P<.05 vs 10 mg of sumatriptan hemisulfate nasal spray.
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PATIENT-DEFINED MEANINGFUL RELIEF
Across attacks, onset of patient-defined meaningful relief occurred by 120 minutes postdose in 56% of the patients in the 20-mg drug group, 50% of patients in the 10-mg drug group, and 41% of patients in the 5-mg drug group compared with 31% in the placebo-treated group (P<.05 each sumatriptan nasal spray group vs placebo; the 20-mg vs 5-mg drug group). Data examined by individual attack (not shown) were similar to data for all attacks combined.
CLINICAL DISABILITY
Across attacks, predose clinical disability scores were 2 (severely impaired) or 3 (requiring bed rest) for 56% to 63% of patients in each group. Clinical disability scores were reduced to 0 (no impairment) or 1 (mild impairment) 60 minutes postdose in 61% of patients in the 20-mg drug group, 60% of patients in the 10-mg drug group, and 55% of patients in the 5-mg drug group compared with 54% in the placebo-treated group (P<.05 overall, for the 20-mg or 10-mg drug group vs the placebo group, for the 20-mg vs 5-mg drug group). Clinical disability scores were reduced to 0 or one 120 minutes postdose in 70% of patients in the 20-mg drug group, 67% of patients in the 10-mg drug group, and 57% of patients in the 5-mg drug group compared with 50% in the placebo-treated group (P<.05 overall, for the 20-mg and 10-mg drug groups vs the placebo group, and for the 20-mg vs 5-mg drug group; Figure 2). Clinical disability scores 60 and 120 minutes postdose examined by individual attack were similar to clinical disability scores for all attacks combined (Figure 2).
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Figure 2. Percentage of patients with no or mild clinical disability 60 or 120 minutes after dosing with sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) or placebo. Asterisk indicates P<.05 vs placebo; dagger, P<.05 vs 5 mg of sumatriptan hemisulfate nasal spray.
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OTHER MIGRAINE SYMPTOMS
Across attacks, the percentages of patients with predose nausea, vomiting, photophobia, and phonophobia were similar between groups (Table 2). The incidences of nausea and photophobia 120 minutes after dosing were significantly different (P<.05) in each sumatriptan nasal spray group compared with the placebo group; the incidence of phonophobia 120 minutes after dosing was significantly different (P<.05) in the 10-mg and 20-mg drug groups compared with the placebo group (Table 2). The incidences of phonophobia and photophobia 120 minutes after dosing were significantly different (P<.05) in the 20-mg drug group compared with the 5-mg drug group. The infrequent occurrence of vomiting at baseline precluded meaningful statistical comparisons. Data examined by individual attack (not shown) were similar to data examined for all attacks combined.
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Table 2. Percentage of Patients Across Attacks With Migraine Symptoms Predose (Pre) and 120 Minutes Postdose (Post)
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RELIEF OF RECURRENT HEADACHE
Across attacks, the percentages of patients experiencing headache relief 120 minutes postdose and using a second dose of study drug to treat a mild, moderate, or severe recurrent headache were 34% in each of the sumatriptan nasal spray groups and 39% in the placebo group. Relief of mild, moderate, or severe recurrent headache 60 or 120 minutes after the second dose of the study drug appeared to occur in a greater proportion of sumatriptan-treated patients compared with placebo-treated patients (Figure 3). However, these differences were not statistically tested due to the small number of patients using a second dose of the study drug to treat recurrent headache and because patients were not rerandomized prior to taking the second dose.
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Figure 3. Percentage of patients with relief (no or mild pain) 60 or 120 minutes after administration of sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) or placebo for a recurrent headache. The number of patients using study medication to treat a recurrent headache in the 20-mg, 10-mg, and 5-mg drug groups and the placebo group was 55, 49, 51, and 24, respectively, for attack 1; 57, 54, 36, and 25, respectively, for attack 2; and 34, 30, 24, and 15 for attack 3, respectively.
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SAFETY EVALUATIONS
Adverse events reported in more than 2% of patients in any treatment group across attacks are listed in (Table 3) according to the dose taken prior to the onset of the event. The most frequently occurring adverse event was unpleasant taste, reported by more patients in the sumatriptan groups than in the placebo groups. Chest tightness and tingling were not among the most common adverse events.
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Table 3. Patients Experiencing Adverse Events Across Attacks (by Dose at Event)*
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The incidence of these adverse events did not vary systematically with the dose of the study drug (Table 3) or with the number of attacks treated (data not shown).
Four patients withdrew from the study due to adverse events. The first patient, a 32-year-old woman, experienced increased migraine severity after administration of a single dose of placebo nasal spray. The second patient, a 38-year-old woman, experienced forgetfulness and mild vomiting after treating a migraine with a single 20-mg dose of sumatriptan hemisulfate nasal spray. The third patient, a 42-year-old woman, experienced mild nausea and vomiting and developed facial blotches after administration of a single 20-mg dose of sumatriptan hemisulfate nasal spray. The fourth patient, a 50-year-old woman with a history of depression, was hospitalized for acute depression 3 days after receiving 2 20-mg doses of sumatriptan hemisulfate nasal spray. All of the events were judged by the investigator as being possibly related to administration of the study drug with the exception of vomiting in the second patient, which was judged as unrelated.
No patient was withdrawn from the study due to a disturbance in clinical laboratory values. The incidence of abnormal laboratory test results of potential clinical significance was low and comparable among treatment groups: 5%, 4%, 3%, and 6% in the 20-mg, 10-mg, and 5-mg drug groups and placebo group, respectively.
COMMENT
The results of this study demonstrate that sumatriptan nasal spray administered for several migraine attacks maintains the high degree of efficacy and tolerability observed with single-attack treatment. Two thirds of the patients treating 3 attacks with the 20-mg dose of sumatriptan hemisulfate nasal spray compared with one third of the placebo-treated patients experienced relief for at least 2 of the 3 attacks. On any given attack, about two thirds of the patients in the 20-mg sumatriptan hemisulfate nasal spray group experienced relief of headache, photophobia, and phonophobia by 120 minutes postdose. Although each dose of sumatriptan nasal spray was significantly more effective than placebo at alleviating headache and associated migraine symptoms, the 20-mg drug dose was consistently associated with the highest efficacy rates. Further, for most efficacy parameters, the 20-mg dose was statistically significantly more effective at ameliorating migraine symptoms than the 5-mg drug dose.
Considered in the context of other dose-ranging data with sumatriptan hemisulfate nasal spray (1, 5, 10, 20, and 40 mg),13 the results of this study suggest that 20 mg may be the optimally effective dose for the acute treatment of migraine. The results of 2 European studies13 demonstrate that the 10-, 20-, and 40-mg drug doses of sumatriptan hemisulfate nasal spray are each more effective than placebo in alleviating migraine headache and associated symptoms, but that the 40-mg dose is not more effective than the 20-mg one. Across the 2 studies,13 the 20-mg dose was most consistently effective: headache relief rates 120 minutes after a 20-mg drug dose ranged from 74% to 78%. The slightly higher efficacy rates at the 20-mg drug dose in the European studies compared with the US study reported here may be attributed in part to cultural differences in the perception and reporting of pain.
Most patients experienced headache relief within 60 minutes of intranasal dosing in this study; higher relief rates were achieved 120 minutes postdose. The 120-minute efficacy rates with the 20-mg strength of sumatriptan hemisulfate nasal spray (about 70%) are similar to the 4-hour efficacy rates reported with the 100-mg dose of oral sumatriptan succinate 9-12 and slightly lower than the 120-minute efficacy rates reported with the 6-mg-strength subcutaneous dose of sumatriptan succinate1-4 (about 80%). These data suggest that subcutaneous sumatriptan may be associated with slightly higher maximal efficacy rates than sumatriptan nasal spray. Furthermore, they suggest that sumatriptan nasal spray compared with oral sumatriptan may be associated with a shorter time to peak efficacy. Any observed difference between the formulations in time to onset of relief may be attributable to differing absorption characteristics of the 20-mg dose of sumatriptan hemisulfate nasal spray, which has a single-dose time to maximum plasma concentration of approximately 1 hour,13 and the 100-mg dose of oral sumatriptan, which has a single-dose time to maximum plasma concentration of approximately 1.5 hours.15-16
About one third of the patients in each sumatriptan nasal spray group treated headache recurrence with a second dose of study drug between 2 and 24 hours after initial dosing. Headache recurrence, the mechanism of which has not been determined, has been observed with the oral and subcutaneous forms of sumatriptan1-2,17-19 as well as with other migraine medications.18-19 In this study, a second administration of sumatriptan nasal spray appeared to be effective in alleviating recurrent headache 120 minutes after the second dose, although the few patients treating recurrent headache precluded statistical analysis of the data. Oral sumatriptan, too, has been shown to be effective in the treatment of headache recurring after subcutaneous sumatriptan administration.17
In addition to being effective in the treatment of headache, sumatriptan nasal spray was well tolerated in this study. Taste disturbance was the only adverse event that occurred more frequently in all sumatriptan groups compared with the placebo group. Neither 2-dose, as opposed to single-dose, administration of sumatriptan nasal spray nor multiple-attack, as opposed to single-attack, administration increased the risk of experiencing an adverse event. The adverse event profile of sumatriptan nasal spray appears to be similar to the profile for sumatriptan tablets.5-8
Migraine and migraine symptoms such as nausea/vomiting, photophobia, and phonophobia were among the most frequently reported adverse events in this study. This finding may reflect the fact that adverse events were reported regardless of their suspected degree of relationship to administration of the study drug.
Considered together, the data from this study demonstrate the efficacy and tolerability of sumatriptan nasal spray in the treatment of headache and other symptoms of migraine. The data from this study extend earlier findings by demonstrating that efficacy and tolerability of sumatriptan nasal spray is consistently maintained across several attacks. Convenient and easy to administer, sumatriptan nasal spray may provide a therapeutic option for patients who seek rapid migraine relief but are resistant to using injectable medication. Not vulnerable to expulsion via vomiting, sumatriptan nasal spray may also be an effective treatment option for patients who cannot use oral medication to control their migraine.
AUTHOR INFORMATION
Accepted for publication April 25, 1997.
This study was funded by Glaxo Wellcome Inc, Research Triangle Park, NC.
Reprints: Seymour Diamond, MD, Diamond Headache Clinic, 467 W Deming Pl, Suite 500, Chicago, IL 60614.
From the Diamond Headache Clinic, Chicago, Ill (Dr Diamond); Elkind Headache Center, Mt Vernon, NY (Dr Elkind); Department of General Internal Medicine, University of Mississippi, Jackson (Dr Jackson); Ryan Headache Center, St Louis, Mo (Dr Ryan); and Glaxo Wellcome Inc, Research Triangle Park, NC (Ms DeBussey and Dr Asgharnejad).
REFERENCES
1. The Subcutaneous Sumatriptan International Study Group. Treatment of migraine attacks with sumatriptan. N Eng J Med. 1991;325:316-321.
WEB OF SCIENCE
| PUBMED
2. Cady RK, Wendt JK, Kirchner JF, Sargent JD, Rothrock JF, Skaggs H. Treatment of acute migraine with subcutaneous sumatriptan. JAMA. 1991;265:2831-2835.
FREE FULL TEXT
3. Schoenen J, Bulcke J, Caekebeke J, et al. Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study. Cephalalgia. 1994;14:55-63.
FREE FULL TEXT
4. The Sumatriptan Auto-Injector Study Group. Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device. Eur Neurol. 1991;31:323-331.
WEB OF SCIENCE
| PUBMED
5. The Oral Sumatriptan Dose-Defining Study Group. Sumatriptan: an oral dose-defining study. Eur Neurol. 1991;31:300-305.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
6. The Oral Sumatriptan International Multiple-Dose Study Group. Evaluation of a multiple-dose regimen of oral sumatriptan for the acute treatment of migraine. Eur Neurol. 1991;31:306-313.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
7. Nappi G, Sicuteri F, Byrne M, Roncolato M, Zerbini O. Oral sumatriptan compared with placebo in the acute treatment of migraine. J Neurol. 1994;241:138-144.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
8. Cutler N, Mushet GR, Davis R, Clements B, Whitcher L. Oral sumatriptan for the acute treatment of migraine: evaluation of three dosage strengths. Neurology. 1995;45(suppl 7):S5-S9.
9. Sargent J, Kirchner JR, Davis R, Kirkhart B. Oral sumatriptan is effective and well tolerated for the acute treatment of migraine: results of a multicenter study. Neurology. 1995;45(suppl 7):S10-S14.
10. Rederich G, Rapoport A, Cutler N, Hazelrigg R, Jamerson B. Oral sumatriptan for the long-term treatment of migraine: clinical findings. Neurology. 1995;45(suppl 7):S15-S20.
11. Luciani RJ, Osterhaus JT, Gutterman DL. Patient preferences for migraine therapy: Subcutaneous sumatriptan compared with other medications. J Fam Pract. 1995;41:147-152.
WEB OF SCIENCE
| PUBMED
12. Dahlof CGH. How does sumatriptan perform in clinical practice? Cephalalgia. 1995;15 Suppl 15:21-28.
13. Salonen R, Ashford E, Dahlof C, et al. Intranasal sumatriptan for the acute treatment of migraine. J Neurol. 1994;241:463-469.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
14. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia. 1988;8:1-96.
15. Dechant KL, Clissold FP. Sumatriptan: A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs. 1992;43:776-798.
WEB OF SCIENCE
| PUBMED
16. Fowler PA, Lacey LF, Thomas M, et al. The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan. Eur Neurol. 1991;31:291-294.
WEB OF SCIENCE
| PUBMED
17. Cady RK, Rubino J, Crummett D, Littlejohn T. Oral sumatriptan in the treatment of recurrent headache. Arch Fam Med. 1994; 3:766-772.
18. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group. A randomized, double-blind comparison of sumatriptan and cafergot in the acute treatment of migraine. Eur Neurol. 1991;31:314-322.
WEB OF SCIENCE
| PUBMED
19. The Oral Sumatriptan and Aspirin Plus Metoclopramide Comparative Study Group. A study to compare oral sumatriptan with oral aspirin plus oral metoclopramide in the acute treatment of migraine. Eur Neurol. 1992;32:177-184.
FULL TEXT
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WEB OF SCIENCE
| PUBMED
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