Elsevier

Clinical Therapeutics

Volume 29, Issue 1, January 2007, Pages 84-98
Clinical Therapeutics

Efficacy and tolerability of a fixed low-dose combination of cinnarizine and dimenhydrinate in the treatment of vertigo: A 4-week, randomized, double-blind, active- and placebo-controlled, parallel-group, outpatient study

https://doi.org/10.1016/j.clinthera.2007.01.010Get rights and content

Abstract

Background:

Most cases of vertigo are attributable to both peripheral and central vestibular disorders. Therefore, it would be of interest to determine whether a combination therapy having both peripheral and central actions would translate into more efficient symptom relief.

Objective:

This study was conducted to evaluate the efficacy and tolerability of a fixed low-dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg in the treatment of vertigo of central, peripheral, or combined central/peripheral origin.

Methods:

This was a prospective, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group, outpatient study in men and women (age >30 years) with central, peripheral, or combined central/peripheral vestibular vertigo. Patients who assessed ≥1 vertigo symptom as being of medium intensity (≥2) on a 5-point visual analog scale (from 0 = no symptoms to 4 = very severe symptoms) and who had abnormal vestibulospinal movement patterns on cramocorpography were eligible. Patients were randomly assigned to receive 1 tablet of the fixed combination of cinnarizine 20 mg + dimenhydrinate 40 mg, cinnarizine 50 mg, dimenhydrinate 100 mg, or placebo 3 times daily for 4 weeks. The primary efficacy end point was the decrease in mean vertigo score (MVS), which was composed of 12 individual vertigo symptoms, each assessed on the 5-point visual analog scale after 4 weeks of treatment.

Results:

The study enrolled 246 patients, of whom 239 were evaluable for efficacy. Approximately two thirds of the efficacy population were female and one third male. The mean age was 51.3 years, and the mean duration of vertigo was 2.6 years. The least squares mean (SD) change from baseline in MVS was significantly greater in the group receiving the fixed combination (1.37 [0.66]) than in any of the comparator groups (cinnarizine 50 mg: 0.87 [0.53]; dimenhydrinate 100 mg: 0.83 [0.66]; placebo: 0.76 [0.48]; all comparisons, P < 0.001). The differences were clinically relevant, based on the Mann-Whitney estimator. The incidence of vertigo-associated nausea was significantly reduced in the fixed-combination group relative to the comparator groups (P≤ 0.016). Thirty-four patients reported adverse events, 6 each in the fixed combination and placebo groups, 12 in the cinnarizine group, and 10 in the dimenhydrinate group. None of these adverse events were considered serious. After 4 weeks of treatment, the tolerability of treatment was rated as very good or good by 57 (96.6%) patients in the fixed-combination group; the values for cinnarizine, dimenhydrinate, and placebo were 54 (93.1%), 42 (72.4%), and 50 (87.7%), respectively.

Conclusions:

In this study, the fixed low-dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg was effective, clinically beneficial, and well tolerated in patients with vestibular vertigo of central and/or peripheral origin. It was significantly more effective in reducing the MVS compared with placebo and the routinely prescribed higher doses of cinnarizine (50 mg) and dimenhydrinate (100 mg).

References (38)

  • ScholtzA.W. et al.

    Treatment of vertigo due to acute unilateral vestibular loss with a fixed combination of cinnarizine and dimenhydrinate: A doubleblind, randomized, parallel-group clinical study

    Clin Ther

    (2004)
  • BrandtT.

    Vertigo. Its Multisensory Syndromes

    (1999)
  • LuxonL.M.

    Evaluation and management of the dizzy patient

    J Neurol Neurosurg Psychiatry

    (2004)
  • SchwarzD.W. et al.

    Physiology of the vestibular system

  • HamidM.A.

    Overview of clinical anatomy and physiology of the vestibular system

  • EdmeadsJ.

    Understanding dizziness. How to decipher this nonspecific symptom

    Postgrad Med

    (1990)
  • FroehlingD.A. et al.

    The rational clinical examination. Does this dizzy patient have a serious form of vertigo

    JAMA

    (1994)
  • HonrubiaV. et al.

    Quantitative evaluation of dizziness characteristics and impact on quality of life

    Am J Otol

    (1996)
  • KvetonJ.F.

    Symptoms of vestibular disease

  • SmithD.B.

    Dizziness: The history and physical examination

  • OosterveldW.J.

    Vertigo. Current concepts in management.

    Drugs

    (1985)
  • WackymP.A. et al.

    Pharmacotherapy of vestibular dysfunction

  • DarlingtonC.L. et al.

    Drug treatment for vertigo and dizziness

    N Z Med J

    (1998)
  • HainT.C. et al.

    Pharmacological treatment of vertigo

    CNS Drugs

    (2003)
  • FerminH. et al.

    The effect of dimenhydrinate upon the labyrinth (an experimental study)

    Acta Otolaryngol

    (1950)
  • GutnerL.B. et al.

    Action of dimenhydrinate (dramamine) and other drugs on vestibular function

    AMA Arch Otolaryngol

    (1951)
  • PhilipszoonA.J.

    Influence of cinnarizine on the labyrinth and on vertigo

    Clin Pharmacol Ther

    (1962)
  • GodfraindT. et al.

    Cinnarizine: A selective calcium entry blocker

    Drugs Today

    (1982)
  • TowseG.

    Cinnarizine—a labyrinthine sedative

    J Laryngol Otol

    (1980)
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