Comparison of Cinnarizine/Dimenhydrinate Fixed Combination with the Respective Monotherapies for Vertigo of Various Origins: A Randomized, Double-Blind, Active-Controlled, Multicentre Study

Background and Objective : Vertigo may arise from dysfunction in the peripheral and/or the central vestibular system. Simultaneous activity of a medication at both sites will serve to improve the efficacy of antivertigo treatment. The aim of this study was to compare the efficacy and tolerability of a fixed combination of the peripherally acting cinnarizine (20 mg) plus the centrally acting dimenhydrinate (40 mg) with those of equally dosed monotherapies in the treatment of vertigo of various origins. Methods : This prospective, randomized, double-blind, active-controlled, multicentre study included patients who assessed at least one vertigo symptom as being of at least medium intensity (≥2) on a 5-point visual analogue scale (VAS; ranging from 0 = not present to 4 = very strong) and who had pathological vestibulospinal movement patterns and/or nystagmus reactions. Patients were randomly assigned to receive either cinnarizine 20 mg/dimenhydrinate 40 mg as a fixed combination, cinnarizine 20 mg as monotherapy or dimenhydrinate 40 mg as monotherapy, each three times daily for 4 weeks. Patients were examined at baseline (t 0 ), and after 1 week (t 1w ) and 4 weeks (t 4w ) of treatment. The primary efficacy endpoint was the decrease in mean vertigo score (MVS) at t 4w , which was calculated by averaging the total score for 12 individual vertigo symptoms, each assessed using the 5-point VAS. Results : The study included 182 patients, of whom 177 were evaluable for efficacy. The mean ± SD reduction in MVS after 4 weeks of treatment with the fixed combination (−1.44 ± 0.56) was significantly greater than the reductions with each of the active treatments alone (cinnarizine −1.04 ± 0.53; dimenhydrinate −1.06 ± 0.56; p = 0.0001, both comparisons). Cinnarizine 20mg/dimenhydrinate 40 mg as a fixed combination was associated with a significantly higher responder rate (78% of patients with MVS ≤0.5 at t 4w ) than the monotherapies. The odds ratios for MVS ≤0.5 at t 4w in the cinnarizine or dimenhydrinate groups versus the fixed combination group were 0.345 and 0.214, respectively. The fixed combination reduced concomitant vegetative symptoms significantly more effectively than cinnarizine at both t 1w (p < 0.05) and t 4w (p