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Reintroduction of clozapine after diagnosis of lymphoma

Published online by Cambridge University Press:  02 January 2018

J. Hundertmark
Affiliation:
Flinders Medical Centre, Bedford Park, South Australia 5042, Australia
P. Campbell
Affiliation:
Flinders Medical Centre, Bedford Park, South Australia 5042, Australia
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Abstract

Type
Columns
Copyright
Copyright © 2001 The Royal College of Psychiatrists 

The atypical antipsychotic clozapine has been shown to be of value in some patients with treatment-resistant schizophrenia. The drug is now only used with careful blood monitoring after fatalities were noted in the early 1970s when the drug was initially released. Alvir et al (Reference Alvir, Lieberman and Safferman1993) estimate the incidence of agranulocytosis to be about 0.9% at 1 year. The following case demonstrates that a patient may suffer blood dyscrasias for reasons other than the known effects of clozapine and that the drug can be successfully reintroduced with a coexistent haematological malignancy.

A patient with a history of treatment-resistant schizophrenia was started on clozapine. After several months she developed asymptomatic agranulocytosis. On admission, investigations were normal apart from a bone marrow biopsy which showed agranulocytosis and mild myeloblastic changes attributed to an acute drug effect. Clozapine was ceased and short-term treatment with granulocyte colony-stimulating factor appeared to be successful.

The patient's mental state deteriorated after treatment with chlorpromazine and quetiapine. During her subsequent psychiatric admission, fevers were noted and a further general hospital admission was arranged. She was found to have severe hypercalcaemia and hyperphosphataemia and reported bone pain. Bone marrow aspirate revealed a diffuse large B-cell lymphoma, which was treated with intensive combination chemotherapy over three cycles.

The patient was initially managed with haloperidol and diazepam. Relatively large doses of these medications were used to provide sedation during the initial phases of chemotherapy. After discussion with the patient, her relatives and the treating haematology team, it was decided to reintroduce clozapine seeking better antipsychotic control. The drug was restored with good effect and continued, despite very significant neutropenia secondary to the chemotherapy.

The case illustrates that clozapine can be ceased because of suspicions that it has lead to agranulocytosis while an underlying more sinister cause is not immediately detected. Subsequently, the drug was reintroduced with good antipsychotic effect in a patient who was severely medically ill.

References

Alvir, J. M. J. Lieberman, J. A. Safferman, A. Z. et al (1993) Clozapine-induced agranulocytosis: incidence and risk factors in the United States. New England Journal of Medicine, 329, 162167.Google Scholar
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