Peer Reviewed

1

Document Type

Article

Publication Date

11-2016

Keywords

Personalized Medicine, Pharmacogenetics, Treatment Resistant Psychosis, Clozapine, Pharmacokinetic, Pharmacodynamic

Funder/Sponsor

FG has received honoraria for advisory work and lectures from Roche, BMS, Lundbeck, Otsaka, and Sunovion, is a collaborator on an NHS Innovations project cofunded by Janssen, and has a family member with professional links to Lilly and GSK, including stock.

Comments

This article is also available at https://www.dovepress.com/index.php

Abstract

Up to 30% of people with schizophrenia do not respond to two (or more) trials of dopaminergic antipsychotics. They are said to have treatment-resistant schizophrenia (TRS). Clozapine is still the only effective treatment for TRS, although it is underused in clinical practice. Initial use is delayed, it can be hard for patients to tolerate, and clinicians can be uncertain as to when to use it. What if, at the start of treatment, we could identify those patients likely to respond to clozapine – and those likely to suffer adverse effects? It is likely that clinicians would feel less inhibited about using it, allowing clozapine to be used earlier and more appropriately. Genetic testing holds out the tantalizing possibility of being able to do just this, and hence the vital importance of pharmacogenomic studies. These can potentially identify genetic markers for both tolerance of and vulnerability to clozapine. We aim to summarize progress so far, possible clinical applications, limitations to the evidence, and problems in applying these findings to the management of TRS. Pharmacogenomic studies of clozapine response and tolerability have produced conflicting results. These are due, at least in part, to significant differences in the patient groups studied. The use of clinical pharmacogenomic testing – to personalize clozapine treatment and identify patients at high risk of treatment failure or of adverse events – has moved closer over the last 20 years. However, to develop such testing that could be used clinically will require larger, multicenter, prospective studies.

Disciplines

Medicine and Health Sciences | Psychiatry and Psychology

Citation

Lally J, Gaughran F, Timms P, Curran SR. Treatment-resistant schizophrenia: current insights on the pharmacogenomics of antipsychotics. Pharmacogenomics and Personalized Medicine. 2016;9:117-129.

DOI Link

https://doi.org/10.2147/PGPM.S115741

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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