News
Article
Author(s):
A recent study revealed that rizatriptan was ineffective for treating vestibular migraine attacks, showing limited symptom relief compared with placebo.
Jeffrey P. Staab, MD
A recently published study showed that treatment with rizatriptan at 10 mg doses was ineffective at treating vestibular migraine attacks, with limited benefits on symptoms observed shortly after attacks and up to 24 hours.1
Coming into the study, eligible patients were aged 18 to 65 with a primary diagnosis of ICVD/ICHD-3 vestibular migraine with untreated attacks exceeding 2 hours to avoid confounds from natural resolution of shorter attacks. Following an observation phase, the double-blind, randomized trial included 134 patients with active illness who were randomly assigned 2:1 to either rizatriptan 10 mg or placebo to treat up to 3 vestibular migraine attacks per person. Overall, 307 attacks were recorded, 240 of which were used for the efficacy analysis, rated as moderate or severe when participants took the study drug.
Led by Jeffrey P. Staab, MD, a professor and chair of the department of psychiatry and psychology at Mayo Clinic, priori analyses showed that 90.2% (277 of 307) of treated attacks manifested moderate or severe vestibular symptoms and headache by the 1 hour mark, considered the primary end point. This inferred that 9.8% of attacks occurred without noticeable cephalalgia. Overall, there were no significant differences between the treated and placebo groups on any of the primary or secondary outcomes; however, there was a medium effect for complete relief of unsteadiness or dizziness favoring rizatriptan at 1 hour (OR, 3.79; 95% CI, 0.51-28.4), albeit with low rates of remission and a wide confidence interval.
Additional data from the priori analyses showed that rizatriptan was superior to placebo with medium effects for unsteadiness or dizziness and motion sensitivity at 24 hours. The 2 groups failed to differentiate themselves for other symptoms; however, there was a medium effect favoring rizatriptan for photophobia or phonophobia (OR, 2.77; 95% CI, 1.00-7.77).
Testing the priori hypotheses were completed in 2021, while the post-hoc analyses were added in 2022 and 2024. Here, investigators identified 4 key nonrandom effects: (1) 67 attacks were excluded from 1-hour outcomes due to mild symptoms or early rescue treatment; (2) baseline vertigo severity differed between groups, with more attacks qualified by dizziness than vertigo; (3) 80 attacks were excluded from 24-hour outcomes due to rescue treatment use after 1 hour; and (4) 29.9% of participants withdrew before treating 3 attacks, mainly due to reduced attack frequency. Sensitivity analyses adjusted for baseline symptom severity, included all 307 attacks in regression models, and used data imputation for early withdrawals.
In the post-hoc analyses, more attacks met analysis criteria based on unsteadiness/dizziness (96.2%) than vertigo (59.4%), which randomization did not account for. As a result, more attacks in the rizatriptan group had moderate/severe vertigo at baseline (64.6% vs 50.6%; P < .03), while the placebo group had more attacks with absent/mild vertigo. Similar, though nonsignificant, baseline imbalances were seen for headache and nausea.
Additional post-hoc data revealed that the proportion of attacks with absent or mild vertigo increased more in the rizatriptan group (35.4% to 48.3%) than in the placebo group (49.4% to 56.8%), though the difference was not significant. Investigators confirmed the original negative findings even after adjusting for baseline severity and imputing missing data. Overall, no meaningful symptom improvements were seen in either group during the first hour across all 307 attacks.
Excluding 80 attacks with rescue remedy use reduced power for a priori 24-hour outcomes. To address this, post hoc analyses using all treated attacks and continuous symptom severity measures found modest benefits of rizatriptan over placebo, with medium effect sizes for headache (–0.33), photophobia/phonophobia (–0.35), unsteadiness/dizziness (–0.48), and motion sensitivity (–0.49).
Post hoc analyses showed higher rates of mild or moderate fatigue and sleepiness with rizatriptan compared to placebo—known side effects of the drug. No significant differences were found between groups for other adverse effects, including neurologic, chest, abdominal symptoms, fever, or anxiety (0.3%–8.6%; all P > .05). Treatment responses were inconsistent across participants from the first to third attack.
Keep your finger on the pulse of neurology—subscribe to NeurologyLive for expert interviews, new data, and breakthrough treatment updates.