Stephen O'Quinn

Sumatriptan for the Range of Headaches in Migraine Sufferers: Results of the Spectrum Study

Background.—Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension‐type as defined by the International Headache Society (IHS).

Effect of early intervention with sumatriptan on migraine pain: Retrospective analyses of data from three clinical trials

OBJECTIVE This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. BACKGROUND Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. METHODS Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. RESULTS In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). CONCLUSIONS Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.

Treatment of Mild Headache in Disabled Migraine Sufferers: Results of the Spectrum Study

Objective.—To evaluate the effectiveness of sumatriptan, 50‐mg tablets, versus placebo for early intervention while head pain was mild in patients with disabling migraine.

Naratriptan as Short‐Term Prophylaxis of Menstrually Associated Migraine: A Randomized, Double‐Blind, Placebo‐Controlled Study

Objective.—To determine the efficacy of naratriptan 1‐mg and 2.5‐mg tablets twice daily compared with placebo as short‐term prophylaxis of menstrually associated migraine.

Effectiveness of Sumatriptan in Reducing Productivity Loss Due to Migraine: Results of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

OBJECTIVE To determine the effect of sumatriptan on migraine-related workplace productivity loss. PATIENTS AND METHODS In this randomized, double-blind, placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of sumatriptan or matching placebo to treat a moderate or severe migraine within the first 4 hours of a minimum of an 8-hour work shift. Outcome measures included productivity loss and number of patients returning to normal work performance 2 hours after injection and across the work shift, time to return to normal work performance, and time to headache relief. RESULTS A total of 206 patients underwent screening, 140 (safety population) of whom returned for clinic treatment. Of these 140 patients, 119 received migraine treatment in the workplace (intent-to-treat population), 116 of whom comprised the study population. Of these 116 patients, 76 self-administered sumatriptan, and 40 self-administered placebo. Sumatriptan treatment tended to reduce median productivity loss 2 hours after injection compared with placebo (25.2 vs 29.9 minutes, respectively; P = .14). Significant reductions in productivity loss were obtained across the work shift after sumatriptan treatment compared with placebo (36.8 vs 72.6 minutes, respectively; P = .001). Significantly more sumatriptan-treated patients vs placebo-treated patients experienced shorter return to normal work performance at 2 hours (53/76 [70%] vs 12/40 [30%], respectively) and across the work shift (64/76 [84%] vs 23/40 [58%], respectively; P < .001). Significantly more sumatriptan-treated patients experienced headache relief 1 hour after injection compared with placebo-treated patients (48/76 [63%] vs 13/40 [33%], respectively; P = .004). CONCLUSION Across an 8-hour work shift, sumatriptan was superior to placebo in reducing productivity loss due to migraine.

Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan.

Objectives.—To determine whether 347 patients would respond to a 50‐mg oral dose of sumatriptan, even though they considered themselves poor responders to this acute therapy for migraine, and to investigate whether oral naratriptan can be an effective acute therapy for migraine in the subset of patients who did not respond to sumatriptan under double‐blind, well‐controlled conditions.

Sumatriptan Nasal Spray and Cognitive Function During Migraine: Results of an Open‐Label Study

Objective.—To examine measures of cognitive function during acute migraine, before and after treatment with sumatriptan nasal spray, 20 mg.

Effects of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine☆

BACKGROUND Some comparative trials of selective serotonin 1B/ID-agonists in migraine have reported -15% lower efficacy for sumatriptan tablets than that reported in placebo-controlled trials. OBJECTIVE This study was designed to test the hypothesis that the encapsulation methods used to mask active drug may delay absorption of sumatriptan from dosing to 2 hours after dosing (the traditional end point in clinical trials of migraine treatment), an effect that may be enhanced by migraine-associated gastric stasis. METHODS Two randomized, open-label, 2-way crossover trials were conducted to evaluate the absorption and bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome protocol SUM40268). Absorption was assessed by calculating the area under the plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and maximum plasma concentration. Data for the AUC from time zero to infinity and maximum plasma concentration were used to assess standard bioequivalence, which is considered to occur when the 90% CIs for the geometric mean treatment ratios (test/reference) fall between 0.8 and 1.25. RESULTS Study 1 included 26 healthy subjects (73% men, 27% women; mean age, 39.1 years), and study 2 included 30 patients with migraine (67% women, 33% men; mean age, 42.7 years). Sumatriptan absorption was delayed with the encapsulated tablet compared with the conventional tablet 0 to 2 hours after dosing, particularly during a migraine. AUC2 values with encapsulated sumatriptan compared with the conventional tablet were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI, 0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was demonstrated in both healthy volunteers and patients experiencing a migraine. CONCLUSIONS Encapsulation delayed absorption of sumatriptan 0 to 2 hours after dosing, particularly during a migraine. This delay in absorption of the encapsulated form may account for the lower efficacy of sumatriptan in some comparative studies.

Low Migraine Headache Recurrence With Naratriptan: Clinical Parameters Related to Recurrence

Objective.–To evaluate clinical parameters that may affect the incidence of headache recurrence or the time to headache recurrence, or both, in migraineurs treated with naratriptan, 2.5‐mg tablets.

Economic implications of early treatment of migraine with sumatriptan tablets

BACKGROUND Early treatment of migraine with sumatriptan 50 mg and 100 mg, while pain is mild, has been reported to enhance pain-free response 2 hours and 4 hours postdose and sustained pain-free response 2 to 24 hours postdose compared with treatment when pain has become moderate to severe. Early treatment with sumatriptan 50 mg and 100 mg also resulted in less redosing, which translated to a reduction in the mean number of doses used per migraine episode. OBJECTIVE We examined the economic implications of early treatment with sumatriptan 50 mg and 100 mg while pain is mild versus treatment when pain has become moderate to severe. METHODS Using data from retrospective analyses of a dose-ranging clinical trial of sumatriptan (protocol S2CM09) involving 1003 patients, we estimated the mean cost per treatment success for a hypothetical population of 1000 migraine patients who received treatment with sumatriptan 50-mg or 100-mg tablets early while pain was mild versus treatment when pain had become moderate to severe. RESULTS With a conservative estimate of migraine frequency of 1.5 episodes per month, the total cost of early migraine treatment with sumatriptan 50 mg and 100 mg was reduced by