Haematological toxicity of drugs used in psychiatry.
Robert J. Flanagan,Louisa R Dunk +1 more
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Almost all classes of psychotropic agents have been reported to cause blood dyscrasias, and agranulocytosis is probably the most important drug‐related blood Dyscrasia.Abstract:
Almost all classes of psychotropic agents have been reported to cause blood dyscrasias. Mechanisms include direct toxic effects upon the bone marrow, the formation of antibodies against haematopoietic precursors or involve peripheral destruction of cells. Agranulocytosis is probably the most important drug-related blood dyscrasia. The mortality from drug-induced agranulocytosis is 5-10% in Western countries. The manifestations of agranulocytosis are secondary to infection. Aggressive treatment with intravenous broad-spectrum antimicrobials and bone marrow stimulants may be required. Of drugs encountered in psychiatry, antipsychotics including clozapine (risk of agranulocytosis approximately 0.8%, predominantly in the first year of treatment) and phenothiazines (chlorpromazine agranulocytosis risk approximately 0.13%), and antiepileptics (notably carbamazepine, neutropenia risk approximately 0.5%) are the most common causes of drug-related neutropenia/agranulocytosis. Drugs known to cause neutropenia should not be used concomitantly with other drugs known to cause this problem. High temperature and other indicators of possible infection should be looked for routinely during treatment. Clozapine is well known as a drug that can cause blood dyscrasias, but olanzapine and other atypicals may also cause similar problems. In addition to genetic factors, there are likely to be dose-related and immunological components to these phenomena. Important lessons have been learnt from the haematological monitoring that is necessary with clozapine and the monitoring has been very successful in preventing deaths related to clozapine-induced agranulocytosis. Continuing research into the mechanisms of drug-induced neutropenia and agranulocytosis may serve to further enhance the safe use not only of clozapine, but also of other agents.read more
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Physical illness in patients with severe mental disorders.I. Prevalence, impact of medications and disparities in health care
Marc De Hert,Christoph U. Correll,Julio Bobes,Marcelo Cetkovich-Bakmas,Dan Cohen,Itsuo Asai,Johan Detraux,S. Gautam,Hans-Jurgen Möller,David M. Ndetei,John W. Newcomer,Richard Uwakwe,Stefan Leucht +12 more
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Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided?
TL;DR: 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.
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References
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Journal ArticleDOI
Clozapine-induced agranulocytosis. Incidence and risk factors in the United States
TL;DR: The increasing risk of agranulocytosis with age and the reduced incidence after the first six months of treatment provide additional guidelines for the prescription and monitoring of clozapine treatment in the future.
Journal ArticleDOI
Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience.
TL;DR: Valproate is generally regarded as a first-choice agent for most forms of idiopathic and symptomatic generalised epilepsies, and prescription of a broad-spectrum drug such as valproate has clear advantages in this situation.
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Neutropenia and agranulocytosis in patients receiving clozapine in the UK and Ireland.
TL;DR: The use of a patient monitoring service kept the haematological risks associated with using clozapine within acceptable limits, particularly in view of the benefits of this medication in treatment-resistant schizophrenia.
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Active monitoring of 12,760 clozapine recipients in the UK and Ireland. Beyond pharmacovigilance.
Janet Munro,Desmond O'Sullivan,Christopher D Andrews,Alejandro Arana,Ann M. Mortimer,Robert Kerwin +5 more
TL;DR: The case register yielded valuable information for guiding research into the causes of the haematological reactions in subjects receiving clozapine, and the risk for agranulocytosis in Asian subjects was 2.4 times that in Caucasians.
Journal Article
Reducing Clozapine-Related Morbidity and Mortality: 5 Years of Experience With the Clozaril National Registry
TL;DR: The estimated impact of the CNR on clozapine-related morbidity and mortality over the first 5 years of commercial experience in the United States is reviewed.