Background and methods: In a multi-center, double-blind, placebo-controlled crossover study safety and efficacy of oral dihydroergotamine tartrate (DHE) 2 mg, paracetamol 1000 mg, and a fixed combination of these two agents was compared for the relief of migraine attacks. The effect of the four different treatments on severity and duration of migraine headache was assessed pretreatment and at one and two hours post-treatment in the patient diary (10 point numerical rating scale 0 = no pain, 9 = unbearable pain). Nausea, vomiting, photophobia, phonophobia, and adverse events were also recorded in the patient diary.
Results: For 288 patients (81% female, 19% male) of 474 enrolled the results of four consecutive migraine attacks could be evaluated; 186 patients were excluded from the analyses because of missing data or protocol violations. Compared with placebo, headache severity was significantly reduced after all three treatments at one and two hours and all three treatments resulted in statistically significant rapid relief of pain, proving a superior effect of the combination over the mono agents. Duration of headache was significantly shorter when the combination was taken and the number of patients having either no headache or a reduction of pain of more than 50% after one and two hours was bigger in the combination group. Eight adverse events were experienced in patients during placebo treatment, seven in patients during treatment with the fixed combination, five in patients during DHE treatment and two in patients during paracetamol treatment. All adverse events were transitory and none was serious.
Conclusion: The oral combination of 2 mg DHE and 1000 mg paracetamol is safe and effective in the treatment of acute migraine attacks and should be first choice of therapy in patients who do not respond to mild analgesics like paracetamol alone.