Rechallenge with clozapine following leucopenia or neutropenia during previous therapy

Histopathology Department, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, UK.
The British Journal of Psychiatry (Impact Factor: 7.99). 03/2006; 188:255-63. DOI: 10.1192/bjp.188.3.255
Source: PubMed


Further treatment with clozapine is contraindicated in any patient who has previously experienced leucopenia or neutropenia during clozapine therapy.
To investigate the results of such a rechallenge in 53 patients.
An analysis was made of the demographic, haematological and outcome data of patients in the UK and Ireland who were rechallenged with clozapine following leucopenia or neutropenia during previous clozapine therapy.
Of 53 patients who were rechallenged, 20 (38%) experienced a further blood dyscrasia. In 17 of these 20 patients (85%) the second blood dyscrasia was more severe (P<0.001), in 12 (60%) it lasted longer (P=0.0368) and in 17 (85%) it occurred more quickly on rechallenge (P<0.001). Of the original 53 patients, 55% (29 patients) are still receiving clozapine.
No clear risk factor for repeat blood dyscrasias was identified. Despite this, after risks and benefits have been considered, rechallenge may well be justified in some patients.

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Available from: Louisa Dunk, Jan 06, 2014
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    • "Recurrence of neutropenia on restarting clozapine is not rare. An analysis reported that 38% of 53 patients (not on cancer chemotherapy) who previously experienced neutropenia, when rechallenged with clozapine, experienced recurrence of neutropenia, most of them occurring more quickly on rechallenge (Dunk et al. 2006). Our experience with case 3 was in keeping with this finding. "

    Psychiatria Danubina 12/2013; 25(4):419-22. · 1.30 Impact Factor
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    • "There have been few case reports or expert reviews on this topic, although a recent case report was published in 2012.14 A manuscript in the British Journal of Psychiatry serves as good guidance for clinicians embarking on rechallenging patients on clozapine.15 Patients were required to have a break for at least a week in order to qualify as a rechallenge patient. "
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    ABSTRACT: We describe a case of a patient whose clozapine was discontinued after a "red result" following R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemotherapy for large B-cell lymphoma. In some cases, manufacturers grant permission, on compassionate grounds, for clozapine to be continued or reinitiated following assessment by their consultant hematologist. Other than a recent case report, there is not much literature surrounding this medical issue. However, since the two leading causes of mortality in schizophrenia are cancer and cardiac disease, this is not an uncommon occurrence. Clinicians are reluctant to prescribe clozapine in view of its side-effect profile, despite its proven efficacy for managing treatment-resistant schizophrenia. The alternative is to prescribe two antipsychotics to manage symptoms. This approach may be associated with increased side effects, and evidence for actual benefits is scant. The consequences were disastrous in this case, as the individual not only relapsed following clozapine discontinuation, but the therapy for this treatable form of lymphoma had to be delayed. He was eventually admitted to an inpatient unit after having been stable for 15 years. We managed to stabilize him with olanzapine and aripiprazole which enabled the heme-oncology group to resume R-CHOP therapy with filgrastim (granulocyte colony-stimulating factor). Even so, he continued to exhibit severe psychotic symptoms, with religious delusions and auditory hallucinations. We therefore applied for permission to rechallenge him on clozapine. Permission was granted when protocol conditions were met, and reinitiation went without any adverse events. The patient's symptoms showed improvement within a few weeks, and the other antipsychotics were discontinued once clozapine was titrated up to 300 mg. The decision to reinitiate clozapine following a red result is not to be taken lightly, but needs to be considered in terms of the risks versus benefits. More literature surrounding this issue would be of great benefit to clinicians, patients, and their families.
    Neuropsychiatric Disease and Treatment 08/2013; 9:1267-71. DOI:10.2147/NDT.S49028 · 1.74 Impact Factor
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    • "The plight of clozapine-dependent patients has prompted attempts at clozapine rechallenge, but there are still some patients who have to be taken off clozapine the second time it is tried. As an example, in a series of 53 patients rechallenged with clozapine after a first episode of neutropenia, a total of 20 (38%) had repeat agranulocytosis [3]. For a few other patients, clozapine has been continued in the face of ongoing agranulocytosis by administering either granulocyte colony stimulating factor (GCSF) to increase proliferation of neutrophils or lithium carbonate which stimulates migration of mature neutrophils into the circulation [2] [4] [5]. "
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    ABSTRACT: The atypical antipsychotic clozapine is very effective for treatment of schizophrenia, but it causes agranulocytosis requiring drug cessation in up to 2% of cases. There has been some success rechallenging with clozapine at a later date or giving granulocyte colony stimulating factor or lithium while continuing clozapine. However, there are still some patients for whom these strategies do not work yet who cannot be controlled on other medications. This paper proposes that for such individuals, cerebroventricular administration of clozapine via Ommaya catheters could allow continued use of clozapine therapy. Direct infusion into cerebrospinal fluid means far smaller amounts of drug would be needed for efficacy, and clozapine concentrates in the central nervous system where it would not be exposed to bone marrow stem cells to cause agranulocytosis. This treatment paradigm would also provide a means for court-ordered clozapine therapy and a possible delivery system for future therapeutics based on trophic factors such as brain-derived neurotrophic factor.
    Medical Hypotheses 07/2012; 79(4):497-9. DOI:10.1016/j.mehy.2012.06.033 · 1.07 Impact Factor
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