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Effect of Anticholinergics in Preventing Acute Deterioration in Patients Undergoing Abrupt Clozapine Withdrawal

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Abstract

Background: The most serious adverse effect of clozapine, agranulocytosis, was described for the first time in Finland in 1975. It caused the immediate withdrawal of clozapine from the market and immediate discontinuation of this medication in all patients. It is now known that abrupt withdrawal of clozapine may cause a rapid deterioration in psychotic symptoms.

Objective: The aim of this retrospective study was to investigate the effect of abrupt clozapine withdrawal on psychiatric patients, and to examine whether anticholinergic drugs are effective in preventing acute deterioration.

Materials and methods: We reviewed the hospital case records from Pitkäniemi Psychiatric Hospital, Tampere, Finland, of the 28 patients with schizophrenia who had been receiving clozapine and from whom it was abruptly withdrawn due to the withdrawal of the drug from the market in the summer of 1975. We assessed the incidence of deterioration and whether or not patients in whom this occurred were receiving anticholinergic drugs.

Results: We found a rapid deterioration after clozapine withdrawal in almost half (46.4%; n = 13) of the patients. Patients receiving anticholinergic drugs (such as antiparkinsonians, tricyclic antidepressants and antipsychotics with anticholinergic properties) were significantly less likely to deteriorate than those not receiving these drugs (21.4% vs 71.4%, p = 0.008). The condition of the patients who deteriorated was poor for up to 1 month after discontinuation, but had improved slightly by the end of 1975.

Conclusion: Anticholinergic medication should be considered for preventing possible symptom deterioration when clozapine is abruptly discontinued.

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Acknowledgements

The authors acknowledge Ms Johanna Varsamäki for excellent secretarial assistance, Ms Anna-Maija Koivisto B.A. for statistical assistance, and Ms Virginia Mattila M.A. for language checking. Financial support for this study was received from Satakuna Hospital District Research Foundation. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Harjavalta Hospital, Satakunta Hospital District, Sairaalantie 14, FI-29200, Harjavalta, Finland

    Niko Seppälä

  2. University of Tampere, Tampere, Finland

    Carita Kovio & Esa Leinonen

  3. Tampere University Hospital, Tampere, Finland

    Esa Leinonen

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  1. Niko Seppälä
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  2. Carita Kovio
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  3. Esa Leinonen
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Correspondence to Niko Seppälä.

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Seppälä, N., Kovio, C. & Leinonen, E. Effect of Anticholinergics in Preventing Acute Deterioration in Patients Undergoing Abrupt Clozapine Withdrawal. CNS Drugs 19, 1049–1055 (2005). https://doi.org/10.2165/00023210-200519120-00006

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  • DOI: https://doi.org/10.2165/00023210-200519120-00006

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