Pharmacogenomic screening for agranulocytosis and efficacy with clozapine

Aim: To review genetic biomarkers of agranulocytosis and efficacy with clozapine as a screening tool for the safe and effective use of clozapine. Methods: A PubMed search was performed using PRISMA guidelines for English articles. Separate searches were conducted using “clozapine” AND “agranulocytosis,” and “clozapine” AND (“response” OR efficacy “outcome”) AND “schizophrenia”. Eligible studies reported positive findings with genetic polymorphism(s) associated with clozapine-induced agranulocytosis (CIA) and clozapine’s efficacy. Case reports/series, abstracts, systematic reviews, and meta-analyses were excluded. Negative and genome-wide studies were not formally reviewed but included in the discussion. Results: Twelve out of 572 CIA studies and 32 out of 126 efficacy studies met the eligibility criteria for this review. Most reviewed studies were conducted in small samples of Jewish, Caucasian, and Asian populations using a candidate gene approach. Conclusion: Future research needs to address the limitations of the findings from the reviewed studies to enable a combined genetic screening for CIA and clozapine response to optimize the safe and effective use of clozapine without unnecessarily exposing potential clozapine nonresponders to CIA or neutropenia.