Abstract

Effective pharmacologic treatments for psychiatric disorders are available, but their effect is limited due to patients’ genetic heterogeneity and low compliance-related to frequent adverse events. Only one third of patients respond to treatment and experience remission. Pharmacogenetics is a relatively young field which focusses on genetic analyses in the context of the metabolism and outcome of drug treatment. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs. Recently, a clinical guideline was authorized by the Dutch Clinical Psychiatric Association (NVvP) on the clinical use of pharmacogenetics in psychiatry. The main goal was to provide guidance, based on current evidence, on how to best use genotyping in clinical psychiatric practice. A systematic literature search was performed, and available publications were assessed using the GRADE methodology. General recommendations for psychiatric clinical practice were provided, and specific recommendations per medication were made available. This clinical guideline for caregivers prescribing psychotropic drugs is the product of a broad collaboration of professionals from different disciplines, making use of the information available at the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) so far. We summarize the relevant literature and all recommendations in this article. General recommendations are provided and also detailed recommendations per medication. In summary we advise to consider genotyping, when there are side effects or inefficacy for CYP2C19 and CYP2D6. When genotype information is available use this to select the right drug in the right dose for the right patient.

Highlights

  • Effective treatments for mental disorders are available, but their effect is limited due to patients’ heterogeneity and poor treatment compliance due to frequent adverse events

  • There is some evidence that pharmacogenetic-guided treatment with antidepressants results in a higher chance of remission of depression and better treatment response than standard care

  • Sources: Hall-Flavin et al (2012); Hall-Flavin et al (2013); Singh (2015); Winner et al (2013); Perez et al (2017); Bradley et al (2018); Greden et al (2019) No studies were found investigating the effect of pharmacogeneticguided treatment compared to standard care in psychiatric patients using antipsychotics

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Summary

Introduction

Effective treatments for mental disorders are available, but their effect is limited due to patients’ (genetic) heterogeneity and poor treatment compliance due to frequent adverse events. Pharmacogenetic testing can help in this process by determining the person-specific genetic factors that may predict clinical response and side effects associated with genetic variants that impact drug-metabolizing enzymes, drug transporters or drug targets (Porcelli et al, 2011; Altar et al, 2015; van Westrhenen et al, 2020). Pharmacogenetics is a discipline that investigates genetic factors that affect the absorption, metabolism, and transport of drugs, thereby affecting therapy outcome and pharmacogenetics might include the study of genes involved in the mechanism of action of a drug. These genetic factors can, among other things, lead to differences in the activity of enzymes that metabolize drugs

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