Skip to main content
Log in

Rebound insomnia after abrupt clozapine withdrawal

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Rebound insomnia has been reported upon discontinuation of benzodiazepines. We describe the first case of a sleep polygraphically documented rebound insomnia with an unusual somatic fatigue syndrome after long-term use of clozapine in a 30-year-old schizophrenic male. The withdrawal symptoms occurred the first day after drug discontinuation and could be stopped by readministering clozapine. In our opinion, the sudden occurrence of the withdrawal symptoms cannot be explained by a dopaminergic hypersensitivityor a cholinergic rebound, but indicates an involvement of GABAergic and perhaps antiglutamatergic properties of clozapine.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alphs LD, Lee HS (1991) Comparison of withdrawal of typical and atypical antipsychotic drugs: a case study. J Clin Psychiatry 52:346

    Google Scholar 

  • American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders (DSM-III-R), 3rd edn, revised. American Psychiatric Press; Washington, DC

    Google Scholar 

  • Anderman B, Griffith RW (1977) Clozapine-induced agranulocytosis: a situation report up to 1976. Eur J Clin Pharmacol 11: 199–201

    Google Scholar 

  • Baron JC, Martinot JL, Cambon H, Boulenger JP, Poirier MF, Caillard V, Blin J, Huret JD, Loc'h C, Maziere B (1989) Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels. Psychopharmacology 99:463–472

    Google Scholar 

  • Borison RL, Diamond BI, Sinha D, Gupta RP, Ajiboye PA (1988) Clozapine withdrawal rebound psychosis. Psychopharmacol Bull 24:260–263

    Google Scholar 

  • Cambon H, Baron JC, Boulenger JP, Loc'h C, Zarifian E, Maziere B (1987) In vivo assay for neuroleptic receptor binding in the striatum: positron emission tomography in humans. Br J Psychiatry 151:824–830

    Google Scholar 

  • Chouinard G, Jones BD (1980) Neuroleptic-induced supersensitivity psychosis: clinical and pharmacologic characteristics. Am J Psychiatry 137:16–21

    Google Scholar 

  • Dickson R, Williams R, Dalby JT (1994) Dystonic reaction and relapse with clozapine discontinuation and risperidone initiaton. Can J Psychiatry 39(3):184

    Google Scholar 

  • Drew KL, O'Connor WT, Kehr J, Ungerstedt U (1990) Regional specificity of clozapine and haloperidol on GABA and dopamine release in rat basal ganglia. Eur J Pharmacol 187:385–397

    Google Scholar 

  • Ekblom B, Eriksson K, Lindstrom LH (1984) Supersensitivity psychosis in schizophrenic patients after sudden clozapine withdrawal. Psychopharmacology 83:293–294

    Google Scholar 

  • Eklund K (1987) Supersensitivity and clozapine withdrawal. Psychopharmacology 90:135

    Google Scholar 

  • Gillin JC, Spinweber CL, Johnson LC (1989) Rebound insomnia: a critical review. J Clin Psychopharmacol 9(3):161–172

    Google Scholar 

  • Graham SR, Kokkinidis L (1993) Clozapine inhibits limbic system kindling: implications for antipsychotic action. Brain Res Bull 30:597–605

    Google Scholar 

  • Klimke A, Klieser E (1995) The atypical neuroleptic clozapine (Leponex): state of the art and recent clinical aspects. Fortschr Neurol Psychiatrie 63:173–193

    Google Scholar 

  • Krupp P, Barnes P (1992) Clozapine-associated agranulocytosis: risk and aetiology. Br J Psychiatry 160 (Suppl 17):38–40

    Google Scholar 

  • Lidsky TI, Alter E, Banerjee SP (1991) Effects of clozapine on glutamatergic transmission. Soc Neurosci 17:686

    Google Scholar 

  • Lieberman JA, Alvir JM (1992) A report of clozapine-induced agranulocytosis in the United States. Drug Safety 7 (Suppl 1): 1–2

    Google Scholar 

  • Luchins DJ, Freed WJ, Wyatt RJ (1980) The role of cholinergic supersensitivity in the medical symptoms associated with withdrawal of antipsychotic drugs. Am J Psychiatry 137(11): 1395–1398

    Google Scholar 

  • Meltzer HY, Bastani B, Ramirez LF, Matsubara S (1989) Clozapine: new research on efficacy and mechanism of action. Eur Arch Psychiatry Clin Neurosci 238:332–339

    Google Scholar 

  • Parsa MA, al-Lahham YH, Ramirez LF, Meltzer HY (1993) Prolonged psychotic relapse after abrupt clozapine withdrawal. J Clin Psychopharmacol 13(2):154–155

    Google Scholar 

  • Perenyi A, Kuncz E, Bagdy G (1986) Early relapse after sudden withdrawal or dose reduction of clozapine. Psychopharmacology 86:244

    Google Scholar 

  • Rechtschaffen A, Kales A (1968) A manual of standarized terminology, techniques and scoring system for sleep stages of human subjects. Public Health Service, Washington DC, NIH, Pub No 204. US Government Printing Office

    Google Scholar 

  • Simpson GM, Lee JH, Shrivastava RK (1978) Clozapine in tardive dyskinesia. Psychopharmacology 56:75–80

    Google Scholar 

  • Staedt J, Stoppe G, Kögler A, Riemann H, Hajak G, Munz DL, Emrich D, Rüther E (1995) Nocturnal myoclonus syndrome (periodic movements in sleep) related to central dopamine D2 receptor alteration. Eur Arch Psychiatry Clin Neurosci 245: 8–10

    Google Scholar 

  • Ungerstedt R, Ljungberg T (1977) Behavioral, patterns related to dopamine neurotransmission: effects of acute and chronic antipsychotic drugs. In: Costa E, Gessa GL (eds) Advances in biochemical psychopharmacology, vol 16. Raven Press, New York, pp 193–199

    Google Scholar 

  • Zapletalek M, Preiningerova O, Hanus H (1980) Does clozapine cause dependence? Agressologie 21(A):19–22

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Staedt, J., Stoppe, G., Hajak, G. et al. Rebound insomnia after abrupt clozapine withdrawal. Eur Arch Psychiatry Clin Nuerosci 246, 79–82 (1996). https://doi.org/10.1007/BF02274897

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02274897

Key words

Navigation