Summary
The approach to drug treatment of vertigo is almost exclusively symptomatic. There are 3 major goals for drug treatment of vertigo. The first one is to eliminate the hallucination of motion. Drugs with vestibular ‘suppressant’ properties are used for this purpose. The major vestibular suppressants are anticholinergic and antihistamine drugs. The second goal is to reduce the accompanying neurovegetative and psychoaffective signs (nausea, vomiting, anxiety). Antidopaminergics are used for this purpose. The third goal is to enhance the process of ‘vestibular compensation’ to allow the brain to find a new sensory equilibrium in spite of the vestibular lesion. Until now, the pharmacological manipulation of vestibular compensation has been assessed in animals but not in humans with vestibular lesions. Vestibular suppressant drugs delay rather than enhance compensation. A variety of other drugs is also used in the treatment of vertigo, including benzodiazepines, histaminergic agents, sympathomimetics and calcium antagonists. Their mechanism of action is poorly understood.
The data base derived from clinical trials evaluating antivertigo medications is often questionable because of methodological limitations. This explains why habits of prescription are mainly empirical, and why striking differences can be noticed from one country to another. We can hope that new treatments may emerge from the present interest in receptor subclasses and neuromodulators of the vestibular system, and we must be ready to evaluate these potential new pharmacological agents with reliable clinical methods in humans.
Similar content being viewed by others
References
Oosterveld W. Vertigo: current concepts in management. Drugs 1985; 30: 275–83.
Courty E, Dordain G. Les antivertigineux. In: Dehen H, Dordain G, editors. Neuropharmacologie clinique. Paris: Doin, 1989: 257–73.
Matsuoka I, Ito J, Takahashi H, et al. Experimental vestibular pharmacology: a minireview with special reference to neuro-active substances and antivertigo drugs. Acta Otolaryngol Suppl 1985; 419: 62–70.
Raymond J, Dememes D, Nieoullon A. Neurotransmitters in vestibular pathways. Prog Brain Res 1988; 76: 29–43.
Dewaele C, Muhlethaler M, Vidal PP. Neurochemistry of the central vestibular pathways. Brain Res Brain Res Rev 1995; 20: 24–46.
Serafin M, Khateb A, Waele C, et al. In vitro properties of medial vestibular neurones. In: Shimazu H, Shinoda Y, editors. Vestibular and brainstem control of head and body movement. New York: Karger, 1992: 111–21.
Darlington CL, Smith PR The effects of the N-methyl-D-aspartate antagonists on the development of vestibular compensation in the guinea pig. Eur J Pharmacol 1989; 174: 273–8
Fröscher W, Bürlan P, Burr W, et al. Double-blind placebo controlled trial with flunarizine in therapy-resistant epileptic patients. Clin Neuropharmacol 1988; 11: 232–40.
Barton JS, Huaman AG, Sharpe JA. Muscarinic antagonists in the treatment of acquired pendular and downbeat nystagmus: a double-blind, randomized trial of three intravenous drugs. Ann Neurol 1994; 35: 319–25.
Kumoi K, Saito N, Tanaka C. Immunohistochemical localization of gamma-aminobutyric acid and aspartate-containing neurons in the guinea pig vestibular nuclei. Brain Res 1987; 416: 22–33.
Spencer RF, Wang SF, Baker R. The pathways and functions of GABA in the oculomotor system. Prog Brain Res 1992; 90: 307–331.
Nerveen JV, Pompeiano O, Collewign H. Depression of the vestibulo-ocular reflex and optokinetic reponses by intrafloccular microinjection of GABA-A and GABA-B agonists in the rabbit. Arch Ital Biol 1989; 127: 243–63.
Cohen B, Helwig D, Raphan T. Baclofen and velocity storage: a model of the effects of the drug on the vestibulo-ocular reflex in the Rhesus monkey. J Physiol (Lond) 1987; 393: 703–26.
Takeda N, Mashahiro M, Hasegawa S, et al. Neurochemical mechanisms of motion sickness. Am J Otolaryngol 1989; 10: 351–9.
Bouthenet ML, Ruat M, Sales N, et al. A detailed mapping of histamine H1 receptors in guinea-pig central nervous system established by autoradiography with (I125) iodobolpyramine. Neuroscience 1988; 26: 553–600.
Wood CD. Antimotion sickness and antiemetic drugs. Drugs 1979; 17: 471–9.
Vibert N, Serafin M, Crambes O, et al. Dopaminergic agonists have both presynaptic and postsynaptic effects on the guinea-pig’s medial vestibular nucleus neurons. Eur J Neurosci 1995; 7: 555–62.
Zee D. Perspectives on the pharmacotherapy of vertigo. Arch Otolaryngol 1985; 111: 609–12.
Gilchrist D, Smith P, Darlington C. ACTH (4–10) accelerates ocular motor recovery in the guinea pig following vestibular deafferentation. Neurosci Lett 1990; 18: 14–6.
Harker LA. Migraine and vertigo. In: Sharpe JA, Barber H, editors. The vestibulo-ocular reflex and vertigo. New York: Raven Press, 1993: 355–9.
White JC. Epileptic nystagmus. Epilepsia 1971; 12: 157–64.
Hallpike C, Cairn H. Observations on pathology of Méniere’s syndrome. J Laryngol Otol 1938; 175: 527–9.
Norris C. Drugs affecting the inner ear. A review of their clinical efficacy, mechanisms of action, toxicity and place in therapy. Drugs 1988; 36: 754–72.
Grad A, Baloh RW. Vertigo of vascular origin, clinical and electronystagmographic features in 84 cases. Arch Neurol 1989; 46: 281–4.
Caplan L. Vertebrobasilar disease: time for a new strategy. Stroke 1981; 12: 1111–4.
Ruckenstein M, Rutka J, Hawke M. The treatment of Meniere disease: Torok revisited. Laryngoscope 1991; 101: 211–8.
Peppard S. Effect of drug therapy on compensation from vestibular injury. Laryngoscope 1986; 96: 878–98.
Smith P, Curthoys I. Mechanisms of recovery following unilateral labyringhectomy: a review. Brain Res Brain Res Rev 1989; 14: 155–80.
Bonner T. The molecular basis of muscarinic receptor diversity. Trends Neurosci 1989; 12: 128–51.
Abeln W, Bienhold H, Flohr H. Influence of cholinomimetics and cholinolytics on vestibular compensation. Brain Res 1981; 222: 458–462.
Price N, Schmitt L, McGuine J, et al. Transdermal scopolamine in the prevention of motion sickness at sea. Clin Pharmacol Ther 1981; 29: 414–9.
Steer R. Transderm scotch-patches for prevention of motion sickness. N Eng J Med 1984; 311: 458–69.
Cohen B, de Jong J. Meclizine and placebo in treating vertigo of vestibular origin. Relative efficacy in a double-blind study. Arch Neurol 1972; 27: 129–35.
Bickerman H. Drugs for disturbances in equilibrium. In: Modell W, editor. Drugs of choice 1978–1979. St Louis (MO): CV Mosby Co., 1978: 502–11.
Gilman A, Rall T, Nies A, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: Pergamon Press, 1990: 585
Wood C, Stewart J, Wood M, et al. Effectiveness and duration of intramuscular antimotion sickness medications. J Clin Pharmacol 1992; 32: 1008–12.
Jackson RT, Turner JS. Astemizole — its use in the treatment of patients with chronic vertigo. Arch Otolaryngol Head Neck Surg 1987; 113: 536–42.
Schmidt J, Huizing E. The clinical drug trial in Meniere’s disease with emphasis on the effect of betahistine SR. Acta Otolaryngol Suppl 1992; 497: 9–188.
Meyer J, Mathew N, Hartmann A, et al. Orally administered betahistine and regional cerebral blood flow in cerebrovascular disease. J Clin Pharmacol 1974; 14: 280.
Halmagyi GM. Vertigo and vestibular disorders. In: Eadie J, editor. Drug therapy in neurology. Edinburgh: Churchill Livingstone, 1992: 383
Arrang JM, Garbag M, Quach T, et al. Actions of betahistine at histamine receptors in the brain. Eur J Pharmacol 1985; 111: 73–84.
Timmerman H. Histamine agonists and antagonists. Acta Otolaryngol Suppl 1991; 479: 5–11.
Unemoto H, Sasa H, Takaoi S, et al. Inhibitory effect of betahistine on polysynaptic neurons in the lateral vestibular nucleus. Arch Otolaryngol 1982; 236: 229–36.
Tighilet B, Leonard J, Lacour M. Betahistine dihydrochloride treatment facilitates vestibular compensation in the cat. J Vestib Res 1995; 5: 53–66.
Timmerman H. Pharmacotherapy of vertigo: any news to be expected. Acta Otolaryngol 1994; 513: 28–32.
Brunton L. Agents affecting gastrointestinal water flux and motility, digestants and bile acids. In: Gilman A, Rall T, Nies A, et al., editors. Goodman and Gilman’s the pharmacological basis of therapeutics. New York: Pergamon Press, 1990: 914–32.
Laborit H, Huguenard P, Allvaume R. Un nouveau stabilisateur végétatif, le 4560 RP. Presse Med 1952; 60: 206–8.
Swazey JP. Chlorpromazine in psychiatric: a study in therapeutic innovation. Cambridge (MA): M.I.T. Press, 1974.
Petrosini L, Dell’Anna ME. Vestibular compensation is affected by treatment with dopamine active agents. Arch Ital Biol 1993; 131: 159–71.
Brogden R, Carmine A, Heel R, et al. Domperidone: a review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Drugs 1982; 24: 360–400.
Pope HG, Keck P, McElroy S. Frequency and presentation of neuroleptic malignant syndrome in a large psychiatric hospital. Am J Psychiatry 1986; 143: 1227–33.
McCabe B, Sekitani T, Tyy J. Drug effects on labyrinthectomy nystagmus. Arch Otolaryngol 1973; 98: 309–14.
Baloh R. The dizzy patient, symptomatic treatment of vertigo. Postgrad Med 1983; 73: 317–24.
Hain TC. Treatment of vertigo. Neurologist 1995; 1: 125–33.
Haefely W. The GABAA-benzodiazepine receptor: biology and pharmacology. In: Burrows G, Roth M, Noyes R, editors. The neurobiology of anxiety. Handbook of anxiety. Amsterdam: Elsevier, 1990: 165–88.
Ryn J, McCabe B. Effect of diazepam and dimenhydrinate on the resting activity of the vestibular neuron. Aerospace Med 1974; 45: 1177–9.
Kawasaki K, Matsushita A, Satoh M, et al. The lateral vestibular nucleus is a site for the depressant action of benzodiazepines on the crossed extensor reflex. Brain Res 1988; 461: 282–9.
Schaefer K, Meyer D. Aspects of vestibular compensation in guinea pigs. In: Flohr H, Precht W, editors. Lesion-induced neuronal plasticity in sensorimotor systems. Berlin: Springer, 1981: 197–207.
Rall TW. Hypnotics and sedatives; ethanol. In: Gilman A, Rall T, Nies A, et al., editors. Goodman and Gilman’s the Pharmacological basis of therapeutics. New York: Pergamon Press, 1990: 345–82.
Woods J, Katz J, Winger G. Abuse and therapeutic use of benzodiazepines and benzodiazepine-like drugs. In: Bloom F, Kuppler D, editors. Psychopharmacology, the fourth generation of progress. New York: Raven Press, 1995: 1777–91.
Holmes B, Brogden R, Heel R, et al. Flunarizine: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use. Drugs 1984; 27: 6–44.
Rascol O, Clanet M, Montastruc JL. Calcium antagonists and the vestibular system: a critical review of flunarizine as an antivertigo drug. Fundam Clin Pharmacol 1989; 3 Suppl.: 79s–87s.
Towse G. Cinnarizine, a labyrinthine sedative. J Laryngol Otology, 1980; 94: 1009–15.
Greenberg D. Clinical channel antagonists and the treatment of migraine. Clin Neuropharmacol 1986; 9: 311–28.
Zissis N, Alevizos V, Dontas A. Flunarizine, an inhibitor of Ca2+-induced vascular constriction in geriatric patients. Current Ther Res 1981; 29: 395–400.
Lee J, Watson L, Boothby G. Calcium antagonists in the prevention of motion sickness. Aviat Space Environ Med 1986; 57: 45–8.
Shapak A, Doweck I, Gordon C, et al. Cinnarizine in the prophylaxis of seasickness: laboratory vestibular evaluation and sea study. Clin Pharmacol Ther 1994; 55: 670–80.
Oosterveld W. Vestibular pharmacology of flunarizine compared to that of cinnarizine. ORL J Otorhinolaryngol Relat Spec 1974; 36: 157–64.
Ell J, Gresty M. The effects of the ‘vestibular sedative’ drug, flunarizine upon the vestibular and oculomotor systems. J Neurol Neurosurg Psychiatr 1983; 46: 716–24.
Sans A, Etchecopar B, Brehier A, et al. Immunocytochemical detection of vitamin D-dependent calcium-binding protein (Ca BP-28K) in vestibular sensory hair cells and vestibular ganglion neurones of the cat. Brain Res 1986; 364: 190–4.
Prigioni I, Masetto S, Russo G, et al. Calcium currents in solitary hair cells isolated from frog crista ampullaris. J Vestib Res 1992; 2: 31–329.
Tolu E, Mameli O, Caria MA, et al. Improvement of vestibular plasticity in the guinea pig with a calcium entry blocker. Acta Otolaryngol Suppl 1988; 460: 72–9.
Gilchrist D, Darlington C, Smith P. Effects of flunarizine on ocular motor and postural compensation following peripheral vestibular deafferentation in the guinea pig. Pharmacol Biochem Behav 1993; 44: 99–105.
Alving J, Kristensen O, Tsiropoulos I, et al. Double-blind placebo-controlled evaluation of flunarizine as adjunct therapy in epilepsy with complex partial seizures. Acta Neurol Scand 1989; 79: 128–32.
Montastruc JL, Llau ME, Rascol O, et al. Drug-induced parkinsonism: a review. Fundam Clin Pharmacol 1994; 8: 293–306.
Lean O, Ducrot R. Action de l’acetyl-leucine sur le vertige expérimental de la souris. C R Seances Soc Biol Fil 1957; 151: 1365–7.
Celice J, Lean O, Ducrot R, et al. Essai de traitement des vertiges labyrinthiques par l’acetyl-dl-leucine. Therapie 1958; 374: 274–83.
Freyss G, Vitte E. Stratégie, diagnostic et thérapeutique devant un sujet atteint de perte soudaine de la fonction vestibulaire. Cah Otolaryngol 1990; 15: 569–82.
Haguenauer JP, Cantenos F, Koskas H, et al. Traitement des troubles de l’équilibre par l’extrait de Ginkgo Biloba. Presse Med 1986; 15: 1569–72.
Denise P, Bustany P. The effect of an extract of Ginkgo Biloba (EGb 761) on central compensation of a total unilateral peripheral vestibular deficit in the rat. In: Lacour M, Toupet M, Denise P, et al., editors. Vestibular compensation: facts, theories and clinical perspectives. Paris: Elsevier, 1989: 201–8.
Ez-Zaher L, Lacour M. Effect of post-operative treatment with an extract of Gingko Biloba (EGb761) on vestibular compensation in the cat. In: Lacour M, Toupet M, Denise P, et al., editors. Vestibular compensation: facts, theories and clinical perspectives. Paris: Elsevier, 1989: 210–23.
Yabe T, Chat M, Malherbe E, et al. Effects of Ginkgo Biloba Extract (EGb 761) on the guinea pig vestibular system. Pharmacol Biochem Behav 1992; 42: 595–604.
Petrosini L. Behavioral recovery from unilateral vestibular lesion is facilitated by GM1 ganglioside treatment. Behav Brain Res 1987; 23: 117–26.
Milne RJ, Heel RC. Ondansetron: therapeutic use as an antiemetic. Drugs 1991 Apr; 41 (4): 574–595
Rice GP, Ebers GC. Ondansetron for intractable vertigo complicating acute brainstem disorders. Lancet 1995; 345: 1182–3.
Bergenius J, Borg E. Audio-vestibular findings in patients with vestibular neuritis. Acta Otolaryngol 1983; 96: 389–95.
Dix M, Hallpike C. The pathology, symptomatology and diagnosis of certain disorders of the vestibular system. Proc R Soc Med 1952; 45: 341–54.
Baloh RW, Honrubia V, Jacobson K. Benign positional vertigo. Clinical and oculographic features in 240 cases. Neurology 1987; 37: 371–8.
Brandt T, Daroff RB. Physical therapy of benign paroxysmal positional vertigo. Arch Otolaryngol 1980; 106: 484–5.
Brandt T, Steddin S, Daroff R. Therapy for benign paroxysmal positioning vertigo, revisited. Neurology 1994; 44: 796–800.
Torok N. Old and new in Ménière’s disease. Laryngoscope 1977; 87: 1870–7.
Brandt T. Vertigo: its multisensory syndromes. London: Springer-Verlag, 1991:48–9
Fraysse B, Bébéar JP, Dubreuil C, et al. Betahistine dihydrochloride versus flunarizine. Double-blind study on recurrent vertigo with or without cochlear syndrome typical of Meniere’s disease. Acta Otolaryngol Suppl 1991; 490: 3–10.
Fife TD, Baloh RW. Desequilibrium of unknown cause in older people. Ann Neurol 1993; 34: 694–702.
Hawkins JE. Antibiotics and the inner ear. Trans Am Acad Ophtalmol Otolaryngol 1959; 63: 206–18.
Brien J. Ototoxicity associated with salicylates. Drug Saf 1993; 9: 143–8.
Prazma J. Ototoxicity of diuretics. In: Brown R, Daigneault P, editors. Pharmacology of hearing. New York: John Wiley and Sons, 1981: 197–229.
Harpur ES. The pharmacology of ototoxic drugs. Br J Audiol 1982; 16: 81–93.
Collaborative Group for Epidemiology of Epilepsia. Adverse reactions of antiepileptic drugs: a follow-up study of 355 patients with chronic antiepileptic drug treatment. Epilepsia 1988; 29: 787–39.
Masur H, Elger C, Ludolph A, et al. Cerebellar atrophy following acute intoxication with phenytoin. Neurology 1989; 39: 432–3.
Ghatak N, Santoso R, McKinney W. Cerebellar degeneration following long-term phenytoin therapy. Neurology 1976; 26: 818–20.
McLain L, Martin J, Allen J. Cerebellar degeneration due to chronic phenytoin therapy. Ann Neurol 1980; 7: 18–23.
Flohr H, Abeln W, Lüneburg U. Neurotransmitter and neuromodulator systems involved in vestibular compensation. In: Berthoz A, Melvill Jones J, editors. Adaptative mechanisms in gaze control, facts and theories. Amsterdam: Elsevier, 1985: 269–77.
Smith P, Darlington C. Neurochemical mechanism of recovery from peripheral vestibular lesions (vestibular compensation). Brain Res Brain Res Rev 1991; 16: 117–33.
Flohr H, Lüneburg U. Role of NMDA receptors in lesion-induced plasticity. Arch Ital Biol 1993; 131: 173–90.
Schaefer KP, Meyer DL. Compensatory mechanisms following labyrinthine lesions in the guinea pig. A simple model of learning. In: Zippel JP, editor. Memory and transfer of information. New York: Plenum, 1973: 203–32.
Gilchrist DP, Darlington CL, Smith PF. A dose response analysis of the beneficial effects of the ACTH (4–9) analogue, Org 2766, on behavioural recovery following unilateral labyrinthectomy in guinea-pig. Br J Pharmacol 1994; 111: 358–63.
Ishii M, Igarashi M. Effect of thyrotropin — releasing hormone on vestibular compensation in primates. Am J Otolaryngol 1986; 7: 177–80.
Bienhold H, Flohr H. Role of cholinergic synapses in vestibular compensation. Brain Res 1980; 195: 476–8.
Ishikawa K, Igarashi M. Effect of atropine and carbachol on vestibular compensation in squirrel monkeys. Am J Otolaryngol 1985; 6: 290–6.
Smith PF, Darlington C. The NMDA antagonists MK 801 and CPP disrupt compensation for unilateral labyrinthectomy in the guinea-pig. Neurosci Lett 1988; 94: 309–13.
Berthoz A, Young L, Oliveas F. Action of alcohol on vestibular compensation and habituation in the cat. Acta Otolaryngol 1977; 84: 317–27.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rascol, O., Hain, T.C., Brefel, C. et al. Antivertigo Medications and Drug-Induced Vertigo. Drugs 50, 777–791 (1995). https://doi.org/10.2165/00003495-199550050-00002
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-199550050-00002