Active monitoring of 12760 clozapine recipients in the UK and Ireland

Munro, Janet; O'Sullivan, D; Andrews, Christopher; Arana, Alejandro; Mortimer, Ann; Kerwin, Robert

doi:10.1192/bjp.175.6.576

Cited by 258 publications

(216 citation statements)

References 11 publications

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“…Although infrequent (0.7-3% of treated patients), 281,286,301 agranulocytosis is a potentially lethal side effect due to its clinical implications. Immune-mediated toxicity is one of the likely causes of neutropenia.…”

Section: Prediction Of Side Effectsmentioning

confidence: 99%

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Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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The last decade of research into the pharmacogenetics of antipsychotics has seen the development of genetic tests to determine the patients' metabolic status and the first attempts at personalization of antipsychotic treatment. The most significant results are the association between drug metabolic polymorphisms, mainly in cytochrome P450 genes, with variations in drug metabolic rates and side effects. Patients with genetically determined CYP2D6 poor metabolizer (PMs) status may require lower doses of antipsychotic. Alternatively, CYP2D6 ultrarapid matabolizers (UMs) will need increased drug dosage to obtain therapeutic response. Additionally, polymorphisms in dopamine and serotonin receptor genes are repeatedly found associated with response phenotypes, probably reflecting the strong affinities that most antipsychotics display for these receptors. In particular, there is important evidence suggesting association between dopamine 2 receptor (D2) polymorphisms (Taq I and À141-C Ins/Del) and a dopamine 3 receptor (D3) polymorphism (Ser9Gly) with antipsychotic response and drug-induced tardive dyskinesia. Additionally, there is accumulating evidence indicating the influence of a 5-HT2C polymorphism (À759ÀT/C) in antipsychotic-induced weight gain. Application of this knowledge to clinical practice is slowly gathering pace, with pretreatment determination of individual's drug metabolic rates, via CYP genotyping, leading the field. Genetic determination of patients' metabolic status is expected to bring clinical benefits by helping to adjust therapeutic doses and reduce adverse reactions. Genetic tests for the pretreatment prediction of antipsychotic response, although still in its infancy, have obvious implications for the selection and improvement of antipsychotic treatment. These developments can be considered as successes, but the objectives of bringing pharmacogenetic and pharmacogenomic research in psychiatric clinical practice are far from being realized. Further development of genetic tests is required before the concept of tailored treatment can be applied to psychopharmatherapy. This review aims to summarize the key findings from the last decade of research in the field. Current knowledge on genetic prediction of drug metabolic status, general response and drug-induced side effects will be reviewed and future pharmacogenomic and epigenetic research will be discussed.

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Section: Prediction Of Side Effectsmentioning

confidence: 99%

“…282 It is important to stress that NMS (incidence 0.3-2%) and agranulocytosis (0.7%) are rare events during antipsychotic treatment. 301,303 Hence the difficulty in gathering large enough samples to detect moderate genetic effects hinders progress in this area.…”

Section: Prediction Of Side Effectsmentioning

confidence: 99%

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

2007

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“…Thus, in adults, the risk of agranulocytosis increases with age, but the risk of neutropenia decreases with age. Agranulocytosis is more common in older Caucasian women and in those with a co-existing illness or abnormal blood count than in other patient groups (Alvir et al, 1993;Hall et al, 2003;Munro et al, 1999). A low baseline leucocyte count may be associated with future neutropenia, but not with agranulocytosis (Gillman, 2000).…”

Section: Clozapine and Neutropeniamentioning

confidence: 99%

Haematological toxicity of drugs used in psychiatry

Flanagan

Dunk

2007

Hum. Psychopharmacol. Clin. Exp.

193

154

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“…However, evidence from retrospective analyses of cohorts treated with clozapine and projected suicide mortality rates suggests that patients receiving this drug may have a lower rate of suicide than expected, [85][86][87] although one study designed to assess the impact of clozapine on suicide failed to demonstrate any positive effect. The mechanism for any such effect remains uncertain, although it has been postulated that improvement in symptoms, including depressive features, may be relevant, as might reduced extrapyramidal symptoms, better medication compliance, improved cognitive function, and greater involvement and support from the clinical team, partly related to regular blood testing.…”

Section: Clozapinementioning

confidence: 99%

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

Lewis

Davies²,

Jones³

et al. 2006

Health Technol Assess

134

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Active monitoring of 12760 clozapine recipients in the UK and Ireland

Abstract: The case register yielded valuable information for guiding research into the causes of the haematological reactions.

Cited by 258 publications

References 11 publications

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research

Haematological toxicity of drugs used in psychiatry

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

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