Dihydroergotamine Nasal Spray During Migraine Attacks: A Double-Blind Crossover Study with Placebo

Abstract

Ergot derivatives have been used in the treatment of migraine for more than 50 years. We have compared the efficacy of dihydroergotamine (DHE) nasal spray with that of placebo in patients with classic or common migraine attacks. The study was performed in accordance with a double-blind, crossover design. In this study a great placebo effect was observed with a dose of 1.36 mg/attack, and the overall efficacy was rated by the patients to be 41% and 52% for placebo and DHE, respectively.

Ergotamine and Dihydroergotamine: History, Pharmacology, and Efficacy

“…The difference between the lower dose of DHE (0.5 to 1 mg) and placebo was statistically significant, but the differences between the higher dose of DHE and placebo and between the 2 DHE doses, were not. The remaining 2 trials found similar differences in the overall proportion of patients using DHE and placebo who reported adverse events (20% versus 7% and 29% versus 11%, respectively), 93,94 though the difference was statistically significant only for Ziegler et al 94 …”

“…Four of the above comparisons with placebo provided effect size estimates suitable for meta‐analysis 90,92‐94 . We chose the effect size for the higher dose of DHE (1 to 4 mg) in the Paiva et al study, 90 because that dose was closer to the doses used in the other trials.…”

“…Adverse events reported in association with DHE were generally mild to moderate and were clearly related to the IN route of administration. Only 3 of the included placebo‐controlled trials reported data that permitted comparison of the overall proportion of patients reporting adverse events with DHE nasal spray and with placebo 89,93,94 . Krause and Bleicher 89 reported data only on those adverse events that were considered by the investigators to be drug related.…”

“…Four of the above comparisons with placebo provided effect size estimates suitable for metaanalysis. 90,[92][93][94] We chose the effect size for the higher dose of DHE (1 to 4 mg) in the Paiva et al study, 90 because that dose was closer to the doses used in the other trials. The effect size estimates from the 4 trials were not heterogeneous ( 2 ϭ 0.257, 3 df, P ϭ .46), and the estimate obtained by combining them was 0.34 (0.10 to 0.57), indicating a statistically significant effect in favor of DHE.…”

“…Only 3 of the included placebo-controlled trials reported data that permitted comparison of the overall proportion of patients reporting adverse events with DHE nasal spray and with placebo. 89,93,94 Krause and Bleicher 89 reported data only on those adverse events that were considered by the investigators to be drug related. Of 14 patients using a total DHE dose of 1 to 2 mg (2 to 4 sprays), only 1 (7%) reported any drug-related reactions, compared with 5 of 15 patients (33%) using a lower dose of DHE (0.5 to 1 mg, 2 to 4 sprays), and no patients using placebo.…”