RESUMO
OBJECTIVE: This study was performed to evaluate the efficacy and safety of the combination of sumatriptan (50 mg) plus promethazine (SPr) (25 mg) compared with sumatriptan (50 mg) plus placebo in patients with migraine attacks. BACKGROUND: Migraine is a chronic, disabling disorder with an estimated worldwide prevalence of 10% in adults imposing substantial social and economic impact. Efficient treatment of migraine attacks could benefit patients by reducing their disability and the need for health care resources, and improving economic productivity. DESIGN AND METHODS: This was a multicenter, randomized, double-blind trial conducted at 5 university-affiliated research centers in Iran. Between January 2013 and April 2013, 350 individuals with a history of migraine were evaluated. Patients were diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria. The 242 patients meeting the eligibility criteria were randomly assigned to SPr group (n = 121) or the sumatriptan plus placebo (SP) group (n = 121). The study medications were taken on an outpatient basis during the moderate to severe phase of migraine attack. Patients recorded details of the treated migraine on a diary card and rated pain severity immediately before dosing and 30 minutes, 1 hour, 2 hours, and 4 hours after dosing using a 4-point scale (0 = none to 3 = severe). RESULTS: Of 242 patients randomized, 216 were included in the intention-to-treat efficacy analysis. In the SPr group, 39.6% of subjects experienced 2-hour headache-free response (primary outcome), which was significantly more effective than SP treatment (26.3%, odds ratio: 1.83, 95% confidence interval: 1.03-3.26, P = .038). Significantly more patients receiving SPr treatment (62.2%) had headache improvement compared with SP treatment (37.2%) at 2 hours (odds ratio: 2.77, 95% confidence interval: 1.60-4.81, P < .001). A similar pattern of between-group differences was observed for 4-hour headache-free response (P = .006) and headache improvement response (P = .003). The incidence of headache recurrence within 2-48 hours after treatment was lowest in the SPr group (15.0%) compared with SP group (26.6%, P = .041). The only significant drug-related adverse events reported in ≥15% of patients in any treatment group were somnolence (32.2% and 7% in the SPr and SP groups, respectively, P < .001), extrapyramidal symptoms (4.3% and 0%, P = .05), and nausea (1% and 8%, P = .03). CONCLUSION: This is the first prospective clinical trial to demonstrate that multimechanism therapy for migraine, combining a triptan and an antiemetic agent, is well tolerated and offers improved clinical benefits compared with monotherapy.
