Abstract
Clozapine is an efficacious atypical antipsychotic for treatment-refractory schizophrenia. Clinical response and appearance of adverse events vary among individual patients receiving clozapine, with genetic and non-genetic factors potentially contributing to individual variabilities. Pharmacogenetic studies investigate associations between genetic variants and drug efficacy and toxicity. To date, most pharmacogenetic studies of clozapine have been conducted through candidate gene approaches. A recent advance in technology made it possible to perform comprehensive genetic mapping underlying clinical phenotypes and outcomes, which allow novel findings beyond biological hypotheses based on current knowledge. In this paper, we will summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis. While there is still limited evidence on clozapine efficacy, recent genome-wide studies provide further evidence of the involvement of the human leukocyte antigen (HLA) region in clozapine-induced agranulocytosis.
Highlights
30% of patients with schizophrenia are treatment-resistant (Meltzer, 1997)
We summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis
Arransz and colleagues investigated an association between the T102C polymorphism in the hydroxytryptamine receptor 2A (HTR2A) gene and clozapine response for at least 3 months of treatment following clinical stabilization (N = 149), demonstrating that homozygosity for the C102 allele was more frequent in the non-responders than in the responders (Arranz et al, 1995a)
Summary
30% of patients with schizophrenia are treatment-resistant (Meltzer, 1997). Clinical practice guidelines recommend clozapine in treatment-refractory schizophrenia (Warnez and Alessi-Severini, 2014), given that it has been shown to be superior for those resistant to treatment (Siskind et al, 2016). Clozapine may cause serious adverse events, such as agranulocytosis, cardiomyopathy, and myocarditis (Alvir et al, 1993; De Berardis et al, 2012; Alawami et al, 2014), so careful monitoring is needed during clozapine treatment. Clinical response and the presence of adverse events vary among individuals taking clozapine. We summarize the studies on clozapine pharmacogenetics that have extensively examined clinical response and agranulocytosis
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