Rechallenge of late-onset neutropenia with clozapine

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States
Journal of Clinical Psychopharmacology (Impact Factor: 3.76). 05/2005; 25(2):185-6. DOI: 10.1097/
Source: PubMed
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    ABSTRACT: To identify the outcome of potentially serious adverse effects of clozapine, particularly those frequently cited as reasons for clozapine discontinuation, and to characterize management strategies for adverse effects that do not warrant discontinuation. A structured search was performed of PubMed and EMBASE from database inception until September 10, 2012, without any language restrictions, using clozapine as the search term. Reference lists of retrieved articles were cross-checked for additional relevant studies. Included in this review were studies that reported on the frequency of the specified clozapine-related adverse effects and that either reported on the grounds for or against clozapine discontinuation or reported on management techniques to maintain patients on clozapine or enable successful clozapine rechallenge. The following side effects were considered important for this review as potential grounds for clozapine discontinuation: neutropenia or agranulocytosis, leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, leukocytosis, QTc prolongation, electrocardiogram changes, atrial flutter, tachycardia, myocarditis, cardiomyopathy, fever, syncope, diabetes mellitus, diabetic ketoacidosis, diabetic hyperosmolar coma, neuroleptic malignant syndrome, ileus, liver enzyme elevation, or seizure. Study results that supported continuation or discontinuation of clozapine or that provided information on management techniques were abstracted. Of a total of 13,385 search results, data from 81 studies were included in this review. Results suggest that prompt discontinuation of clozapine without rechallenge is indicated for agranulocytosis, myocarditis, cardiomyopathy, and a QTc interval > 500 milliseconds that is confirmed and derived using the appropriate correction method. Clozapine discontinuation with potential rechallenge (provided there is appropriate surveillance and management or prophylactic therapy) is indicated for ileus or subileus, neuroleptic malignant syndrome, venous thromboembolism, and diabetic ketoacidosis or hyperosmolar coma. Neutropenia, leukocytosis, seizures, orthostatic hypotension, severe constipation, and weight gain and metabolic abnormalities, including metabolic syndrome and its components, as well as moderately prolonged myocardial repolarization, need to be managed but do not generally warrant clozapine discontinuation. Eosinophilia, leukocytosis, drug-induced fever, and tachycardia (provided that myocarditis and neuroleptic malignant syndrome are ruled out) can be managed and should rarely lead to clozapine discontinuation. A number of side effects commonly cited as medical reasons for clozapine discontinuation do not necessarily warrant such action. Management techniques are available that allow continuation or rechallenge in relation to a number of clozapine-related side effects.
    The Journal of Clinical Psychiatry 06/2013; 74(6):603-613. DOI:10.4088/JCP.12r08064 · 5.14 Impact Factor
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    ABSTRACT: A case is presented of a 23-year-old lady with treatment-resistant schizoaffective disorder who had responded well to treatment with clozapine. Fifteen months after satisfactory use of clozapine she had 'red alerts' from routine haematological monitoring indicating neutropenia. Clozapine was discontinued and she was admitted to the psychiatric hospital to manage the aftermath of discontinuing clozapine and start alternative treatment with other antipsychotics. Her mental health rapidly deteriorated. Adequate trials with amisulpride, haloperidol, olanzapine and flupenthixol decanoate yielded little improvement in her clinical state. After 9 months of non-response to other antipsychotic medications, she was rechallenged with clozapine, followed by improvement in her mental state. She was eventually discharged home after 14 months of hospitalisation in a stable mental state. She remained mentally stable in the community on clozapine for 18 months after rechallenge, with no further red alerts.
    Case Reports 01/2013; 2013. DOI:10.1136/bcr-2012-007172
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    ABSTRACT: Late-onset agranulocytosis is rare during treatment with clozapine, especially in monotherapy. The authors describe a case of agranulocytosis that emerged after 19 years of continuous clozapine monotherapy. The discovery of the agranulocytosis was due to the lifelong white blood cell counts that are now required for clozapine treatment. Despite the fact that this requirement probably saved the life of this patient, this monitoring is not evidence-based because the incidence of agranulocytosis does not exceed that of conventional antipsychotic drugs, for which no such requirement exists. For mentally competent and adequately informed patients, the Netherlands Clozapine Collaboration Group now permits quarterly monitoring after the first 6 months of clozapine treatment.
    American Journal of Psychiatry 04/2013; 170(4):366-9. DOI:10.1176/appi.ajp.2012.12081036 · 13.56 Impact Factor


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