Review and Consensus on Pharmacogenomic Testing in Psychiatry

Abstract

The implementation of pharmacogenomic (PGx) testing in psychiatry remains modest, in part due to divergent perceptions of the quality and completeness of the evidence base and diverse perspectives on the clinical utility of PGx testing among psychiatrists and other healthcare providers. Recognizing the current lack of consensus within the field, the International Society of Psychiatric Genetics assembled a group of experts to conduct a narrative synthesis of the PGx literature, prescribing guidelines, and product labels related to psychotropic medications as well as the key considerations and limitations related to the use of PGx testing in psychiatry. The group concluded that to inform medication selection and dosing of several commonly-used antidepressant and antipsychotic medications, current published evidence, prescribing guidelines, and product labels support the use of PGx testing for 2 cytochrome P450 genes (CYP2D6, CYP2C19). In addition, the evidence supports testing for human leukocyte antigen genes when using the mood stabilizers carbamazepine (HLA-A and HLA-B), oxcarbazepine (HLA-B), and phenytoin (CYP2C9, HLA-B). For valproate, screening for variants in certain genes (POLG, OTC, CSP1) is recommended when a mitochondrial disorder or a urea cycle disorder is suspected. Although barriers to implementing PGx testing remain to be fully resolved, the current trajectory of discovery and innovation in the field suggests these barriers will be overcome and testing will become an important tool in psychiatry.

Severe Pain in Chronic Pancreatitis Patients: Considering Mental Health and Associated Genetic Factors

“…Indeed, the role of genetic variants in drug-metabolizing genes (pharmacogenetics) is well established and is highly relevant for variable responses and even toxic outcomes in the treatment of pain and depression. [86][87][88][89][90][91] Genetic variant evaluation is a powerful tool since it can direct the analyst to specific mechanisms in the body that are likely to be dysfunctional under injury or stress, and other systems that are likely to be normal. 92 These tools are therefore most useful early in the course of disease before the damage of poorly managed pathogenic pathways becomes irreversible.…”

Pharmacogenetics in Psychiatry: Perceived Value and Opinions in a Chilean Sample of Practitioners

“…Also, given the added shipment days, turnaround times for results are long, limiting the ability to guide prescription decisions, especially in acute care settings. Finally, and although not explored in this study, the lack of standards for PGx panels results in differences in the available ones; this heterogeneity may also add to challenges in ordering decisions (Fan and Bousman, 2020;Bousman et al, 2021).…”

“…As stated in the introduction, the clinical value of PGx testing in psychiatry is still a matter of debate and an evolving issue. The recently published review and updated consensus on PGx testing in psychiatry by a group of international experts assembled by the ISPG might help change this perception and advance in expanding the use of PGx testing in clinical settings for specific validates genes and gene-pair drugs (Bousman et al, 2021).…”

“…Acknowledging this, the International Society for Psychiatric Genetics (ISPG) recommended in 2019 that PGx "should be viewed as a decision-support tool to assist in thoughtful implementation of good clinical care," and that evidence was still inconclusive to support widespread use (ISPG, 2020), but anticipated changes in the field. A more recent (2021) consensus by experts convened by the ISPG considers that current evidence does support the use of PGx testing for cytochrome P450 genes CYP2D6 and CYP2C19 to inform selection and dosing of commonly used antidepressant and antipsychotic medication, as well as testing for HLA-A and HLA-B when using carbamazepine, HLA-B for oxcarbazepine, PYP2C9, and HLA-B for phenytoin, and when a mitochondrial disorder or a urea cycle disorder is suspected, POLG, OTC, and CSP1 for valproate use (Bousman et al, 2021). Consequently, the authors predict that PGx testing will become a relevant tool in psychiatry.…”

Getting to Precision Psychopharmacology in Child Psychiatry: The Value of Adverse Treatment Effects

“…In point of fact, atypical antipsychotics are effectively used in medical conditions associated with cachexia or malnutrition, in part, because they so reliably result in improved appetite and weight gain (Couturier et al 2019;Roeland et al 2020). As well, many of the genetic variants associated with antipsychotic-induced weight gain are those associated with obesity in the general population (Zhang et al 2016;Bousman et al 2021).…”