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Shad. J Transl Genet Genom 2023;7:141-65 Journal of Translational
DOI: 10.20517/jtgg.2023.11
Genetics and Genomics

Systematic Review Open Access

Pharmacogenomic screening for agranulocytosis
and efficacy with clozapine

Mujeeb U. Shad 1,2,3
1
Department of Psychiatry, The University of Nevada, Las Vegas, NV 89138, USA.
2
The Department of Psychiatry, The Touro University of Nevada College of Osteopathic Medicine, Las Vegas, NV 89138, USA.
3
The Valley Health System, Las Vegas, NV 89138, USA.
Correspondence to: Mujeeb U. Shad, MD, MSCS, DFAPA, The University of Nevada, Las Vegas, NV 89138, USA; The Touro
University of Nevada College of Osteopathic Medicine, Las Vegas, NV 89138, USA; The Valley Health System, 779 Etter Creek
Street, Las Vegas, NV 89138, USA. E-mail: mujeebushad@gmail.com

How to cite this article: Shad MU. Pharmacogenomic screening for agranulocytosis and efficacy with clozapine. J Transl Genet
Genom 2023;7:141-65. https://dx.doi.org/10.20517/jtgg.2023.11

Received: 17 Feb 2023 First Decision: 19 Apr 2023 Revised: 27 Apr 2023 Accepted: 7 Jun 2023 Published: 20 Jun 2023

Academic Editor: Sanjay Gupta Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
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.

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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