Adjunctive use of ezogabine/retigabine with either traditional sodium channel blocking antiepileptic drugs (AEDs) or AEDs with other mechanisms of action: Evaluation of efficacy and tolerability.

Integrated data from three double-blind, randomized, placebo-controlled trials were analyzed to evaluate the efficacy and tolerability of ezogabine (EZG; US adopted name)/retigabine (RTG; international non-proprietary name) when used in combination with ≥1 sodium channel blocking antiepileptic drug (AED), ≥1 non-sodium channel blocking AED, or ≥1 AED from both the sodium channel and non-sodium channel mechanistic groups. Efficacy and tolerability appeared to be similar across all three groups of patients.

Relief of menstrual symptoms and migraine with a single-tablet formulation of sumatriptan and naproxen sodium.

BACKGROUND: Dysmenorrhea and menstrual migraine may share a common pathogenic pathway. Both appear to be mediated, in part, by an excess of prostaglandin production that occurs during menstruation. METHODS: Data were pooled from two replicate randomized controlled trials of 621 adult menstrual migraineurs with dysmenorrhea who treated migraine with sumatriptan-naproxen or placebo. Along with headache symptoms, nonpain menstrual symptoms (bloating, fatigue, and irritability) and menstrual pain symptoms (abdominal and back pain) were recorded at the time periods of 30 minutes and 1, 2, 4, and 4-24 hours. Relief of menstrual symptoms was compared using a Cochran-Mantel-Haenszel test. Logistic regression was used to determine the odds of a headache response with increasing numbers of moderate to severe dymenorrheic symptoms. RESULTS: Sumatriptan-naproxen was superior to placebo for relief of tiredness, irritability, and abdominal pain at the time periods of 2, 4, and 4-24 hours (p≤0.023); back pain at the time periods of 4 and 4-24 hours (p≤0.023); and bloating at 4-24 hours endpoint (p=0.01). The odds ratios (ORs) of attaining migraine pain freedom for 2 hours and for sustained 2-24 hours decreased as moderate to severe dysmenorrhea symptoms increased with sumatriptan-naproxen versus placebo. CONCLUSIONS: Treatment with sumatriptan-naproxen may provide relief of menstrual symptoms and migraine in female migraineurs with dysmenorrhea. The presence of moderate to severe dysmenorrhea symptoms is associated with decreased response rates for menstrual migraine, suggesting that the co-occurrence of these disorders may negatively impact the results of migraine-abortive therapy.

Sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura: a randomized study.

OBJECTIVE: Probable migraine is a common, disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine. This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura. METHODS: Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( N = 222 intent-to-treat (ITT)) or placebo ( N = 221 ITT/complete case analysis (a) ) in this randomized, double-blind, parallel-group study. RESULTS: Sumatriptan/naproxen sodium was more effective than placebo with respect to the co-primary efficacy endpoints two-hour pain-free response (29% sumatriptan/naproxen sodium vs 11% placebo, P < 0.001) and two- to 24-hour sustained pain-free response (24% sumatriptan/naproxen sodium vs 9% placebo, P < 0.001). Sumatriptan/naproxen sodium was significantly more effective than placebo with respect to the secondary efficacy endpoints of pain-free response four hours postdose ( P < 0.001), pain-free response maintained one to two hours postdose ( P = 0.034) and two to four hours postdose ( P < 0.001), headache relief four hours postdose ( P < 0.001), headache relief maintained two to four hours postdose ( P = 0.015), sustained headache relief two through 24 hours postdose ( P = 0.002), and rescue medication use ( P < 0.001); but not productivity scores. The most common adverse events were dizziness (4% sumatriptan/naproxen sodium,<1% placebo), dry mouth (2% sumatriptan/naproxen sodium, <1% placebo), and nausea (2% sumatriptan/naproxen sodium, <1% placebo). CONCLUSION: Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function.

Long-term evaluation of sumatriptan and naproxen sodium for the acute treatment of migraine in adolescents.

OBJECTIVES: To evaluate the long-term safety, tolerability, effectiveness, impact on quality of life, and medication satisfaction of sumatriptan/naproxen sodium in the acute treatment of migraine headache in adolescents. METHODS: This 12-month, multicenter, open-label, safety study was conducted in adolescents (aged 12-17 years) with an average of 2-8 migraines/month typically lasting >2 hours untreated for >6 months prior to initiation. Subjects were instructed to treat migraines as early as possible and were allowed to rescue 2 hours post dose with a single dose of a naproxen-containing product, over-the-counter pain reliever, or anti-emetics. Subjects were advised not to take a second tablet of sumatriptan/naproxen sodium without at least a 24-hour headache-free period. Safety evaluations included adverse events, laboratory tests, and vital signs and electrocardiogram evaluation. Other evaluations included freedom from pain, quality of life, and medication satisfaction. RESULTS: Of the 656 subjects enrolled, 622 (95%) treated at least 1 migraine with sumatriptan/naproxen sodium, of which 435 (70%) and 363 (58%) completed 6 and 12 months of the study, respectively. Overall, there were 12,927 exposures to sumatriptan/naproxen sodium: on average 2.5 tablets were taken per month per subject. The most common treatment-related adverse events were nausea (7%), dizziness (3%), muscle tightness (3%), and chest discomfort (3%). There were no deaths; 4 subjects had 5 serious adverse events (suicide attempt, hemolytic anemia and syncope, suicidal ideation, spontaneous abortion) unrelated to sumatriptan/naproxen sodium and resolved without sequelae. Seven percent of subjects discontinued participation in the study because of an adverse event; 5% of subjects discontinued due to lack of efficacy. Overall, 42% of the migraine attacks were pain-free within 2 hours of treatment with sumatriptan/naproxen sodium, subjects reported improvements from baseline in 2 of 3 quality of life domains over time, and were generally satisfied with the efficacy and overall treatment at the end of the study. CONCLUSION: In adolescent migraineurs, after up to 12 months and over 12,000 exposures to sumatriptan/naproxen sodium, there were no new or clinically significant findings in the safety parameters, including the frequency and nature of adverse events, as compared to the individual components or to the adverse event profile in adults. In addition, sumatriptan/naproxen sodium provided freedom from pain over time, improvements in quality of life and medication satisfaction.

Sumatriptan-naproxen sodium for menstrual migraine and dysmenorrhea: satisfaction, productivity, and functional disability outcomes.

OBJECTIVE: To evaluate the impact of a sumatriptan/naproxen sodium combination tablet on patient satisfaction, productivity, and functional disability in menstrual migraine treated during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea. BACKGROUND: Menstrual migraineurs with dysmenorrhea represent a unique patient population not previously studied. When health outcomes end points are analyzed alongside traditional efficacy end points in migraine studies, a more comprehensive and robust understanding of the many factors that may influence patients' choice of and adherence to pharmacological treatments for migraine is observed. METHODS: In 2 replicate, multicenter, randomized, double-blind, placebo-controlled trials, participants with menstrual migraine and dysmenorrhea treated a single menstrual migraine attack with a single fixed-dose tablet of sumatriptan 85 mg formulated with RT Technology™ and naproxen sodium 500 mg (sumatriptan-naproxen sodium) or placebo. RESULTS: Participants randomized to sumatriptan-naproxen sodium were significantly more satisfied than those randomized to placebo at 24 hours post dose, as demonstrated by higher satisfaction subscale scores for efficacy (P < .001 for both studies), functionality (P = .003 for study 1; P < .001 for study 2), and ease of use (P = .027 for study 1; P = .011 for study 2). There was little bothersomeness of side effects associated with either treatment. Use of sumatriptan-naproxen sodium was also associated with lower reported "lost-time equivalents" in work and leisure time (pooled analysis, P = .003) and lower rates of functional disability (P = .05, study 1; P < .001, study 2) compared with placebo. CONCLUSION: A fixed-dose combination tablet containing sumatriptan and naproxen sodium significantly improved patient satisfaction, productivity, and restoration of normal functioning in menstrual migraineurs with dysmenorrhea.

Pharmacokinetics and tolerability of sumatriptan after single-dose administration of a fixed-dose combination tablet of sumatriptan/naproxen sodium 85/500 mg followed two hours later by subcutaneous sumatriptan 4- or 6-mg injection: a randomized, open-label, three-period crossover study in healthy volunteers.

BACKGROUND: Rescue medication options that are consistent with the product labeling for sumatriptan/naproxen sodium (S/N) and that have been permitted in >or=1 clinical trial include the use of a second tablet of S/N, sumatriptan tablets (to a total daily dose of 200 mg), and naproxen sodium tablets (within the maximum limits recommended in the labeling). Sumatriptan subcutaneous (SC) injection might be especially useful as rescue medication mostly because of its rapid onset of activity. OBJECTIVE: The aim of this study was to assess the pharmacokinetics and tolerability of sumatriptan SC used as rescue medication after the administration of oral S/N for the treatment of migraine. METHODS: This randomized, open-label, 3-period crossover study compared the exposure to sumatriptan (Cmax and AUC to 14 hours after the administration of the second dose [AUC(0-14)]) between 3 treatment regimens: an initial dose of S/N 85/500 mg followed 2 hours later by sumatriptan 4 or 6 mg SC (S/N + S4 and S/N + S6, respectively) (test), or sumatriptan 100 mg PO (2 tablets administered 2 hours apart) (S100 + S100) (reference). Healthy adults aged 18 to 55 years were randomly assigned to receive all 3 regimens in a randomized sequence. On day 1 of each treatment period, continuous cardiovascular monitoring (ECG telemetry), serial 12-lead ECG, and serial blood pressure (BP) measurements were conducted 1 hour before to 10 hours after the administration of the first dose. Blood samples for pharmacokinetic assessment were collected up to 14 hours after the administration of the first dose. Adverse events (AEs) were monitored from the time of consent until study completion. Participants returned to the clinic for pharmacokinetic blood sampling (for S/N + S4 and S/N + S6) and for tolerability assessment at 24, 48, and 72 hours after S/N administration. RESULTS: A total of 30 healthy adults were randomized. Five withdrew prematurely (3, withdrawn consent; 1, AE; and 1, protocol deviation). Half of the subjects were men, the mean age was 27.8 years, and the mean weight was 79.3 kg (range, 54.6-100.8 kg). With S/N + S4, sumatriptan Cmax and AUC(0-14) did not exceed those with S100 + S100. Sumatriptan Cmax was 1.26-fold higher with S/N + S6 than with S100 + S100. Sumatriptan AUC(0-14) with S/N + S6 was not significantly greater than that with S100 + S100. Differences in serial BP measurements between the SC and S100 + S100 regimens were not statistically significant. The numbers of subjects in whom any AE was reported were 10 (37%) with S/N + S4, 14 (54%) with S/N + S6, and 13 (48%) with S100 + S100. CONCLUSIONS: Sumatriptan 4 and 6 mg SC administered 2 hours after an S/N tablet yielded sumatriptan exposure that did not exceed that of S100 + S100. Cmax with the S/N + S6 regimen was 1.26-fold higher than reference values. Both regimens were reasonably well tolerated. Randomized controlled trials are needed to test the efficacy and tolerability of these SC regimens. ClinicalTrials.gov identifier: NCT00875784.

Distinct pharmacokinetic profile and safety of a fixed-dose tablet of sumatriptan and naproxen sodium for the acute treatment of migraine.

OBJECTIVE: To describe the pharmacokinetic and safety profiles of sumatriptan 85 mg formulated with RT Technology (RT) and naproxen sodium 500 mg in a fixed-dose combination tablet (sumatriptan/naproxen sodium) that targets both serotonergic dysmodulation and inflammation in migraine. METHODS: Six open-label, crossover studies were conducted in healthy volunteers (Studies 1, 2, 3, 4, 5) or patients with migraine (Study 6). RESULTS: Consistently across studies, naproxen administered as a component of sumatriptan/naproxen sodium demonstrated a delayed-release profile similar to that of an enteric-coated product. Naproxen from the combination tablet showed a delayed time to peak plasma concentration and lower peak plasma concentration while exposures (area under the plasma concentration-time curve) were similar. The peak plasma concentration for naproxen was approximately 36% lower and the time to peak plasma concentration approximately 4 hours later when naproxen was administered as sumatriptan/naproxen sodium compared with a single naproxen sodium 550 mg tablet. Sumatriptan peak plasma concentration and area under the plasma concentration-time curve after administration of sumatriptan/naproxen sodium (containing sumatriptan 85 mg) were comparable to those after administration of a commercially available sumatriptan 100 mg (RT) tablet. Sumatriptan time to peak plasma concentration occurred, on average, 30 minutes earlier with sumatriptan/naproxen sodium compared with sumatriptan 100 mg (RT). No clinically significant differences between sumatriptan/naproxen sodium and sumatriptan tablets 100 mg (RT) were identified with respect to electrocardiograms, blood pressure, or heart rate. In addition, food had no significant effect on the bioavailability of naproxen or sumatriptan after administration of sumatriptan/naproxen sodium but slightly delayed the time to peak plasma concentration of sumatriptan by approximately 40 minutes. The pharmacokinetics of sumatriptan and naproxen did not differ according to whether sumatriptan/naproxen sodium was administered during a migraine attack or a migraine-free period. The pharmacokinetics of 2 sumatriptan/naproxen sodium tablets administered 2 hours apart were consistent with the pharmacokinetic predictions from a single dose of the combination tablet. The adverse-event profile of the sumatriptan/naproxen sodium combination tablet did not appear to differ from that of the individual components of the same or similar dosage strengths administered alone or in combination. In addition, the incidence of adverse events with 2 sumatriptan/naproxen sodium tablets administered 2 hours apart was lower than that with the single dose. CONCLUSION: The combination tablet of sumatriptan/naproxen sodium has unique pharmacokinetic properties. The rapid absorption of sumatriptan with the delayed-release properties of naproxen sodium from sumatriptan/naproxen sodium might contribute to its therapeutic advantage over monotherapy with either component. No clinically meaningful effects of food, administration during a migraine attack, or administration of a second tablet (2 hours after initial dose) on the pharmacokinetics or safety of sumatriptan/naproxen sodium were observed.

Combination treatment for menstrual migraine and dysmenorrhea using sumatriptan-naproxen: two randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan-naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea. METHODS: Two replicate randomized, multicenter, double-blind, placebo-controlled, trials of adults with menstrual migraine and dysmenorrhea were conducted. Participants treated their menstrual migraine attack during the mild pain phase (within 1 hour of onset) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation (sumatriptan-naproxen) or placebo. The primary endpoint was 2-hour pain-free response. RESULTS: Sumatriptan-naproxen was statistically superior to placebo in both studies (n=311, Study 1; n=310, Study 2) for 2-hour and, 2- to 24-hour sustained pain-free response, use of headache and menstrual rescue medications, and several nonpain menstrual symptom categories. Two-hour pain-free rates were Study 1, 42% compared with 23%, and Study 2, 52% compared with 22%, P<.001. Two- to 24-hour sustained pain-free rates were Study 1, 29% compared with 18%, P=.022; Study 2, 38% compared with 10%, P<.001. Headache and menstrual medication rates were Study 1, 37% compared with 53%, P=.005; Study 2, 31% compared with 69%, P<.001. Women treated with sumatriptan-naproxen continued to be pain free through 48 hours compared with placebo: Study 1, 26% compared with 17%, P=.040; Study 2, 28% compared with 8%, P<.001. No serious adverse events were reported in either study; nausea and dizziness were the most frequently reported adverse events. CONCLUSION: Sumatriptan-naproxen provided an effective pain-free response at 2 hours, which was maintained up to 48 hours in menstrual migraineurs with dysmenorrhea. Sumatriptan-naproxen was well-tolerated and resulted in decreased rescue medication use and relief of nonpainful menstrual symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00329459 and NCT00329355 LEVEL OF EVIDENCE: I.

Revisiting the efficacy of sumatriptan therapy during the aura phase of migraine.

OBJECTIVE: To reexamine the efficacy of terminating migraine headache by administration of sumatriptan during the visual-aura phase of the attack. Background.- Although the antimigraine action of triptans is most effective soon after onset of the headache, treatment during the aura phase has been found to be ineffective. METHODS: Nineteen subjects having migraine with aura were studied using a 4-way crossover, open-label design. Each patient was asked to treat 8 consecutive attacks with 100 mg of sumatriptan RT: 3 attacks treated at a timing of the patient's discretion (baseline); 1 attack treated 4 hours after onset of pain (late); 2 attacks treated within 1 hour of onset of pain (early); 2 attacks treated during the aura phase - before the onset of pain (aura). Pain level and cutaneous allodynia were reported by the patients at the onset of pain, at the time of treatment, and 2 and 24 hours after treatment. RESULTS: Sumatriptan treatment during the aura preempted the development of headache in 34/38 (89%) attacks. The same patients were rendered pain-free in 30/38 (79%) of attacks treated within 1 hour of pain onset, and in 4/19 (21%) of attacks treated 4 hours after the onset of pain. The incidence of allodynia at the time of treatment was 2/38 (5%) in attacks treated during aura, 8/38 (21%) in attacks treated early, and 14/19 (74%) in attacks treated late. CONCLUSION: Considering the discrepancy between the present and previous clinical studies, it is worthwhile revisiting the efficacy of preemptive triptan therapy during the aura phase of migraine attacks, using larger-scale, 3-way, crossover, placebo-controlled studies.

Fixed-dose Sumatriptan/Naproxen Sodium Compared with each Monotherapy Utilizing the Novel Composite Endpoint of Sustained Pain-free/no Adverse Events.

A novel composite endpoint, sustained pain-free/no adverse events, was recently proposed as a more rigorous means of capturing in a single measure the attributes of migraine pharmacotherapy that patients consider most important: rapid and sustained pain-free response with no side-effects. Using pooled data from two replicate randomized, double-blind, parallel-group, placebo-controlled studies, this post hoc analysis compared the fixed-dose combination tablet sumatriptan/naproxen sodium (n = 726) with sumatriptan monotherapy (n = 723), naproxen sodium monotherapy (n = 720), and placebo (n = 742) with respect to sustained pain-free/no adverse events and closely related composite measures. Sustained pain-free/no adverse events was defined as having both a sustained pain-free response from 2 through 24 hours post-dose with no use of rescue medication and having no adverse events within up to 5 days after dosing with study medication. The percentage of patients with sustained pain-free/no adverse events was 16% with sumatriptan/naproxen sodium compared with 11%, 9% and 7% for sumatriptan, naproxen sodium and placebo, respectively (p<0.01 sumatriptan/naproxen sodium versus each other treatment). Sumatriptan/naproxen sodium was also significantly more effective than sumatriptan, naproxen sodium, and placebo for other composite endpoints including the percentages of patients with (1) sustained pain-free/no adverse events within 1 day; (2) sustained pain-free/no drug-related adverse events within up to 5 days; (3) sustained pain-free/no drug-related adverse events within 1 day; (4) sustained pain relief/no adverse events within up to 5 days; and (5) sustained pain relief/no adverse events within 1 day. The results demonstrate the superiority of sumatriptan/naproxen sodium to sumatriptan monotherapy, naproxen sodium monotherapy and placebo with respect to the rigorous and clinically relevant endpoint of sustained pain-free/no adverse events and reinforce the usefulness of utilizing this new composite endpoint.

Two double-blind, multicenter, randomized, placebo-controlled, single-dose studies of sumatriptan/naproxen sodium in the acute treatment of migraine: function, productivity, and satisfaction outcomes.

OBJECTIVE: To describe return to normal function, productivity, and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium, sumatriptan alone, naproxen sodium alone, or placebo. PATIENTS, DESIGN, AND SETTING: Patients in 2 identical, US, phase 3, randomized, double-blind, parallel-group, placebo-controlled, single-dose, multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium (85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation), sumatriptan, naproxen sodium, or placebo. MAIN OUTCOME MEASURES: Ability to function (not impaired, mildly impaired, severely impaired, or required bed rest) was collected in diary cards completed immediately prior to treatment, every 30 minutes for the first 2 hours, and hourly from 2 to 24 hours while awake. Patients completed the Productivity Assessment Questionnaire (PAQ) 24 hours after study drug administration. The Patient Perception of Migraine Questionnaire (PPMQ) was administered at screening and 24 hours post treatment to capture patient satisfaction. RESULTS: Compared with the other groups, the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing. They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies, and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications. CONCLUSIONS: Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly, and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups. Overall productivity loss was significantly reduced following use of sumatriptan/naproxen sodium.

Clarification of developing and established clinical allodynia and pain-free outcomes.

OBJECTIVE: The aim of this study was to determine whether clinical indicators of cutaneous allodynia predict the success of migraine therapy with sumatriptan using a brief questionnaire. BACKGROUND: Using quantitative sensory testing (QST) recent studies demonstrate that the presence of cutaneous allodynia, a clinical manifestation of central sensitization, can be detrimental to the success of migraine therapy with sumatriptan. QST is costly and requires much time, therefore it is not feasible to use in clinical practice. METHODS: In this prospective study, migraineurs completed a questionnaire about their skin sensitivity during migraine. Each migraineur treated 2 migraine headaches with sumatriptan (100 mg): 1 headache at the earliest sign of migraine pain (mild, within 1 hour of onset) and 1 headache at least 4 hours after the onset of pain while moderate or severe. RESULTS: Thirty-six migraine headaches were evaluated in 18 migraineurs. A total of 44% of the headaches were not associated with allodynia at any time. Irrespective of allodynic status, headaches were more likely to become pain-free with early versus late treatment (2 hours; 78% vs. 33%, respectively). Headaches were equally likely to become pain-free when allodynia was reported before treatment but not 2 and 4 hours after treatment (2 hours; 67 vs. 63%, respectively, 4 hours 80 vs. 81%, respectively). However, no headaches were pain-free when allodynia was reported at 2 and 4 hours after treatment. CONCLUSIONS: Headaches without allodynia were aborted when treated early or late, and headaches with allodynia were aborted only when allodynia was not present after treatment. These findings suggest that different mechanisms account for allodynia before and after treatment; a developing phase in which central sensitization depends on incoming pain signals from the peripheral nociceptors and an established phase in which the sensitization becomes independent of the pain signals that come from the dura.

Gastric stasis in migraine: more than just a paroxysmal abnormality during a migraine attack.

OBJECTIVE: The aim of this article is to evaluate gastric motility and emptying in the ictal and interictal period in migraine. BACKGROUND: Nausea is a predominant symptom of migraine and the basis of it is thought to be gastric stasis. Objective methods to establish this are however lacking. We utilized gastric scintigraphy studies to determine gastric motility in the ictal and interictal period of migraine. METHODS: Ten migraine subjects were compared to equal number of age and sex matched controls. Gastric scintigraphy using a standard meal was performed in all control subjects once and in all 10 migraine subjects in the interictal period and nine studies were performed in the ictal period migraine. RESULTS: The time to half emptying was delayed in migraine ictally (78%) and interictal period (80%) using normative data at this institution. Gastric stasis was less pronounced ictally (149.9 minutes) compared to interictal period (188.8 minutes). There was a significant delay compared to nonmigrainous controls (migraine 188.8 minutes vs normal controls 111.8 minutes; P < .05). These data were replicated in percentage of radioactive material remaining in the stomach at 2 hours. CONCLUSIONS: Contrary to previous belief, this study has demonstrated that migraineurs suffer from gastric stasis both during and outside an acute migraine attack. This may suggest that migraineurs may have an abnormal autonomic function compared to nonmigrainous controls. The potential role of this in pathophysiology of migraine is discussed and avenues for further investigations are explored.

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

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