CNS Drugs

, Volume 18, Issue 4, pp 213–220 | Cite as

Antipsychotic-Induced Rabbit Syndrome

Epidemiology, Management and Pathophysiology
Therapy in Practice

Abstract

Rabbit syndrome is an antipsychotic-induced rhythmic motion of the mouth/lips, resembling the chewing movements of a rabbit. The movement consists of a vertical-only motion, at about 5Hz, with no involvement of the tongue. Usually, the involuntary movements associated with rabbit syndrome appear after a long period (in most cases months or years) of antipsychotic treatment; however, a few patients with the syndrome have had treatment histories with no antipsychotic involvement. The reported prevalence of rabbit syndrome ranges from 2.3 to 4.4% of patients treated with typical antipsychotics. There have been isolated reports of rabbit syndrome in patients treated with the atypical agents risperidone and clozapine.

Patients with rabbit syndrome are most often misdiagnosed as having oral tardive dyskinesia. In such cases the key for correct diagnosis is the involvement of tardive tongue movements, which does not occur in rabbit syndrome.

The treatment of rabbit syndrome is empirical, reflecting poor understanding of its neuropathology. The first step is to reduce the amount of antipsychotic treatment as much as possible. However, since, in most cases, full withdrawal of antipsychotic treatment is impossible, the syndrome cannot be completely abolished without additional measures. The next stage of treatment involves specific drugs that aim to control the syndrome. Anticholinergic drugs are the best known treatment. Rabbit syndrome does not respond to treatment with levodopa or dopamine agonists.

The most striking aspect of this syndrome is its specificity. Rabbit syndrome affects only the buccal region, and within this area it involves a highly stereotyped involuntary movement. This immediately focuses attention on the basal ganglia, in particular the substantia nigra pars reticulata, which is also implicated in oral dyskinesia. Continuing neurophysiological and pharmacological research of the basal ganglia holds the key to better understanding and treatment of this syndrome in the coming years.

Keywords

Levodopa Basal Ganglion Multiple System Atrophy Tardive Dyskinesia Antipsychotic Treatment 

Notes

Acknowledgements

The authors are indebted to Professor John Finberg at the Department of Pharmacology, Faculty of Medicine, Technion, Haifa, Israel, for his critical reading of this manuscript. No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

References

  1. 1.
    Villeneuve A. The rabbit syndrome: a peculiar extrapyramidal reaction. Can Psychiatr Assoc J 1972; 17Suppl. 2: SS69PubMedGoogle Scholar
  2. 2.
    Schwartz M, Weller B, Erdreich M, et al. Rabbit syndrome and tardive dyskinesia: two complications of chronic neuroleptic treatment [letter]. J Clin Psychiatry 1995; 56: 212PubMedGoogle Scholar
  3. 3.
    Jus K, Villeneuve A, Jus A. Tardive dyskinesia and the rabbit syndrome during wakefulness and sleep [letter]. Am J Psychiatry 1972; 129: 765PubMedGoogle Scholar
  4. 4.
    Miwa H, Sassaki Y, Hatori K, et al. Idiopathic rabbit syndrome: a case report. No To Shinkei 1999; 10: 907–9Google Scholar
  5. 5.
    Nishiyama K, Masuda N, Kurisaki H. A case of rabbit syndrome: its unique pharmacological feature. Rinsho Shinkeigaku 1993; 33: 663–5PubMedGoogle Scholar
  6. 6.
    Kamijo Y, Soma K, Fukuda M, et al. Rabbit syndrome following phenol ingestion. J Toxicol Clin Toxicol 1999; 37: 509–11PubMedCrossRefGoogle Scholar
  7. 7.
    Todd R, Lippmann S, Manshadi M, et al. Recognition and treatment of rabbit syndrome, an uncommon complication of neuroleptic therapies. Am J Psychiatry 1983; 140: 1519–20PubMedGoogle Scholar
  8. 8.
    Sethi S. Rabbit syndrome: an acute complication of neuroleptic medication. Indian J Psychiatry 2001; 43: 3Google Scholar
  9. 9.
    Schwartz M, Beny A, Sharf B. Risperidone-induced rabbit syndrome. Br J Psychiatry 1998; 173: 267–8PubMedCrossRefGoogle Scholar
  10. 10.
    Levin T, Heresco-Levy U. Risperidone-induced rabbit syndrome: an unusual movement disorder caused by an atypical antipsychotic. Eur Neuropsychopharmacol 1999; 9: 137–9PubMedCrossRefGoogle Scholar
  11. 11.
    Hoy JS, Alexander B. Rabbit syndrome secondary to risperidone. Pharmacotherapy 2002; 22: 513–5PubMedCrossRefGoogle Scholar
  12. 12.
    Nishimura K, Tsuka M, Horikawa N. Withdrawal-emergent rabbit syndrome during dose reduction of risperidone. Eur Neuropsychopharmacol 2001; 11: 323–4PubMedCrossRefGoogle Scholar
  13. 13.
    Sethi S, Bhargava SC. Clozapine-induced rabbit syndrome. J Clin Psychiatry 2003; 64(2): 219PubMedCrossRefGoogle Scholar
  14. 14.
    Fornazzari L, Ichise M, Remington G, et al. Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings. J Psychiatry Neurosci 1991; 16: 227–9PubMedGoogle Scholar
  15. 15.
    Damodaran SS, Thankamma JK. Reversal of rabbit syndrome with olanzapine. Aust N Z J Psychiatry 2000; 34: 172–3PubMedGoogle Scholar
  16. 16.
    Deshmukh DK, Joshi VS, Agarwal MR. Rabbit syndrome: a rare complication of long-term neuroleptic medication. Br J Psychiatry 1990; 157: 293PubMedCrossRefGoogle Scholar
  17. 17.
    Durst R, Katz G, Zislin J, et al. Rabbit syndrome treated with olanzapine [letter]. Br J Psychiatry 2000; 176: 193PubMedCrossRefGoogle Scholar
  18. 18.
    Inada T, Yagi G, Kaijima K, et al. Clinical variants of tardive dyskinesia in Japan. Jpn J Psychiatry Neurol 1991; 45: 67–71PubMedGoogle Scholar
  19. 19.
    Kakigi R, Kuroda Y, Shibasaki H. The rabbit syndrome induced by sulpiride: a case report. Rinsho Shinkeigaku 1982; 22: 557–62PubMedGoogle Scholar
  20. 20.
    Sovner R, Dimascio A. The effect of benztropine mesylate in the rabbit syndrome and tardive dyskinesia. Am J Psychiatry 1977; 134: 1301–2PubMedGoogle Scholar
  21. 21.
    Wada Y, Yamaguchi N. The rabbit syndrome and antiparkinsonian medication in schizophrenic patients. Neuropsychobiology 1992; 25: 149–52PubMedCrossRefGoogle Scholar
  22. 22.
    Weiss KJ, Ciraulo DA, Shader RI. Physostigmine test in the rabbit syndrome and tardive dyskinesia. Am J Psychiatry 1980; 137: 627–8PubMedGoogle Scholar
  23. 23.
    Yassa R, Samarthji L. Prevalence of rabbit syndrome. Am J Psychiatry 1986; 143: 656–7PubMedGoogle Scholar
  24. 24.
    Casey DE. Rabbit syndrome. In: Joseph AB, Young RR, editors. Movement disorders in neurology and neuropsychiatry. London: Blackwell Scientific Publications, 1992: 139–42Google Scholar
  25. 25.
    Nambu A, Tokuno H, Takada M. Functional significance of the cortico/subthalamo/pallidal ‘hyperdirectic’ pathway. Neurosci Res 2002; 43: 111–7PubMedCrossRefGoogle Scholar
  26. 26.
    Calabresi P, Centonze D, Gubellini P, et al. Acetylcholine-mediated modulation of striatal function. Trends Neurosci 2000; 23: 120–6PubMedCrossRefGoogle Scholar
  27. 27.
    Kaneko S, Hikida T, Watanabe D, et al. Synaptic integration mediated by striatal cholinergic interneurons in basal ganglia function. Science 2000; 289: 633–7PubMedCrossRefGoogle Scholar
  28. 28.
    Di-Chiara G, Morelli M, Consolo S. Modulatory functions of neurotransmitters in the striatum: Ach/dopamine/NMDA interactions. Trends Neurosci 1994; 17: 228–33PubMedCrossRefGoogle Scholar
  29. 29.
    Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 1990; 13: 266–71PubMedCrossRefGoogle Scholar
  30. 30.
    Smith Y, Bevan MD, Shink E, et al. Microcircuitry of the direct and indirect pathways of the basal ganglia. Neuroscience 1998; 86: 353–87PubMedCrossRefGoogle Scholar
  31. 31.
    Lang AE, Lozano AM. Parkinson’s disease: second of two parts. N Engl J Med 1998; 339: 1130–43PubMedCrossRefGoogle Scholar
  32. 32.
    Onn SP, West AR, Grace AA. Dopamine-mediated regulation of striatal neuronal and network interactions. Trends Neurosci 2000; 23(10 Suppl.): S48–56PubMedCrossRefGoogle Scholar
  33. 33.
    Parent A, Sato F, Wu Y, et al. Organization of the basal ganglia: the importance of axonal collateralization. Trends Neurosci 2000; 23(10 Suppl.): S20–7PubMedCrossRefGoogle Scholar
  34. 34.
    Hazrati LN, Parent A. The striatopallidal projection displays a high degree of anatomical specificity in the primate. Brain Res 1992; 592: 213–27PubMedCrossRefGoogle Scholar
  35. 35.
    Middleton FA, Strick PL. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Rev 2000; 31: 236–50PubMedCrossRefGoogle Scholar
  36. 36.
    Canales JJ, Gilmour G, Iversen SV. The role of nigral and thalamic output pathways in the expression of oral stereotypies induced by amphetamine injections into the striatum. Brain Res 2000; 856: 176–83PubMedCrossRefGoogle Scholar
  37. 37.
    Aosaki T, Kimura M, Graybiel AM. Temporal and spatial characteristics of tonically active neurons of the primate’s striatum. J Neurophysiol 1995; 73: 1234–52PubMedGoogle Scholar
  38. 38.
    Zhou F-M, Liang Y, Dani JA. Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum. Nat Neurosci 2001; 4: 1224–9PubMedCrossRefGoogle Scholar
  39. 39.
    Calabresi P, Pisani A, Mercuri NB, et al. The corticostriatal projection from synaptic plasticity to dysfunctions of the basal ganglia. Trends Neurosci 1996; 19: 19–24PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Department of NeurologyMiguel Schwartz, Bnai Zion Medical CenterHaifaIsrael
  2. 2.Faculty of MedicineTechnionIsrael

Personalised recommendations