Rizatriptan vs Placebo for Attacks of Vestibular Migraine: A Randomized Clinical Trial.

Abstract

Importance Vestibular migraine has no established treatments. Objective To test the efficacy of rizatriptan for treating vestibular migraine attacks. Design, Setting, and Participants This double-blind, randomized clinical trial of rizatriptan vs placebo was conducted from December 2014 through July 2020 (data analyses in 2021 and sensitivity analyses in 2022 and 2024) at 2 tertiary neurotologic centers. Adults with vestibular migraine were included. Intervention All participants underwent prospective observation to confirm diagnosis and illness activity and were then randomized in a 2:1 ratio to receive rizatriptan 10 mg or placebo to treat up to 3 vestibular migraine attacks per participant. Main Outcomes and Measures Participants rated symptoms as absent, mild, moderate, or severe at scheduled intervals. Primary outcomes were the percentage of attacks with reductions in vertigo and unsteadiness/dizziness from moderate or severe to absent or mild at 1 hour. Secondary outcomes were the percentage of attacks with complete resolution of vestibular symptoms at 1 hour; reductions in headache and associated symptoms at 1 hour; use of rescue medications after 1 hour; reductions in vestibular, headache, and associated symptoms at 24 hours without rescue medications; treatment satisfaction and quality of life at 48 hours; and rates of serious adverse effects and discontinuation due to adverse effects. Results Of 222 total participants (mean [SD] age, 42.3 [11.7] years; 70.7% were women), 134 (60.4%) with active illness treated 307 attacks. Efficacy was tested using 240 attacks with vestibular symptoms rated as moderate or severe when participants took study drug. At 1 hour, rizatriptan did not differ from placebo for reducing vertigo (73/151 [48.3%] vs 50/88 [56.8%] attacks; odds ratio [OR], 0.71 [95% CI, 0.42-1.21]), unsteadiness/dizziness (29/151 [19.2%] vs 11/89 [12.4%] attacks; OR, 1.69 [95% CI, 0.80-3.57]), or any secondary outcomes. Similar percentages of participants in rizatriptan and placebo groups (26.4% for both groups) added rescue remedies after 1 hour. At 24 hours, rizatriptan had medium effects over placebo for unsteadiness/dizziness (OR, 2.65) and motion sensitivity (OR, 3.58). Post hoc analyses of all treated attacks found a medium effect favoring rizatriptan for headache and photophobia or phonophobia at 24 hours. Treatment satisfaction was equivocal. Quality of life was mixed. No participants experienced serious adverse effects or discontinued treatment for adverse effects. Conclusions and Relevance In this study, rizatriptan was ineffective at 1 hour for treating vestibular migraine attacks and had limited benefit on symptoms at 24 hours. Findings do not support using rizatriptan for vestibular migraine attacks. Trial Registration ClinicalTrials.gov Identifier: NCT02447991.