Introduction to PGx for Behavioral Health
Aegis offers pharmacogenetic testing, with a majority of the available tests focusing on medications prescribed in behavioral health. The testing menu includes medication/gene pairs that are supported by clinical guidelines, FDA-approved labeling, or clinical studies and must be graded as level A or B by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
Many in the healthcare industry agree that personalized medicine, which is based on the premise that medical treatment should be tailored to patients’ unique needs, is one way to improve patient care. Ideally, this approach will streamline therapy and reduce therapeutic failures and adverse effects by identifying the best medication regimen for each patient at initiation of therapy. Discussions surrounding personalized medicine often focus on genetic testing. Pharmacogenetics refers to the study of specific genes and their impact on patient response to medication. The terms “pharmacogenetics” and “pharmacogenomics” are often used interchangeably, although they technically differ. Pharmacogenomics is a broader term that refers to the impact of genes on medication response. Pharmacogenetics generally refers to the study of specific genetic alterations and their effect on medications.1
Pharmacogenetic testing often revolves around the detection of single nucleotide polymorphisms (SNPs) in genes encoding for receptors or metabolizing enzymes. SNPs are defined as “the most common genetic variations in human DNA, occurring once approximately every 300 base pairs.” Humans typically possess two alleles (one from each parent) encoding for receptors or enzymes, and each allele may carry different SNPs. The presence of SNPs may be associated with an increase or decrease in receptor or enzyme function, or no change at all. Other types of genetic mutations may result in duplicated alleles, potentially leading to increased receptor or enzyme function. The specific alleles present are described in a patient’s genotype, and the predicted function associated with that genotype is called a phenotype.2
Drug metabolism generally occurs in two phases: phase I and phase II. In phase I, compounds are transformed to facilitate the process of drug elimination. Most of this activity is associated with a superfamily of enzymes called the cytochrome P450 (CYP450) enzymes.3-7 The CYP450 enzymes are divided into different families, many of which are known to be involved in drug metabolism. Numerous medications rely on these enzymes for activation and/or detoxification.8 Aegis’ testing includes CYP2D6, CYP2C9, and CYP2C19. At this time, genetic testing for behavioral health drugs primarily metabolized by phase II enzymes lacks supporting evidence
The CYP2D6 enzyme is involved in the metabolism of 20-30% of all medications.9 In psychiatry, the tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and antipsychotics are the drug classes most impacted by CYP2D6 polymorphisms, but it also is important in the metabolism of atomoxetine, dextromethorphan, and quinidine. While CYP2C9 is involved in the metabolism of many drugs in general, phenytoin is the primary drug of concern in neurology. Additionally, the CYP2C19 enzyme is highly important in the metabolism of selected TCAs and SSRIs. Depending on a patient’s genetic variation, a dosage adjustment at initiation of therapy may be necessary to avoid adverse effects or therapeutic failure, as a patient’s metabolizer status may cause therapeutic drug levels to be too high or too low at a typical starting dose.
Although changes in metabolizing enzymes typically exist over a continuum, which could be impacted by drug-drug interactions, predicted metabolism phenotypes are usually classified as follows:10
- Poor metabolizer (PM): absent or minimal enzyme function
- Intermediate metabolizer (IM): decreased enzyme function
- Extensive metabolizer (EM): normal enzyme function
- Ultrarapid metabolizer (UM): increased enzyme function
The following is a summary table of current behavioral health gene-drug pairs, for which testing is offered at Aegis:
All pharmacogenetic offerings at Aegis meet level A or B grading by CPIC. CPIC is one of the most widely-recognized expert groups providing genetic testing information; in addition to examining scientific literature and drafting evidence-based guidelines, their goal is to provide the clinician with reliable resources to foster understanding of the clinical impact of various pharmacogenetic tests. Aegis is devoted to providing test offerings that are clinically meaningful and have the ability to positively impact patient care.
NOTICE: The information above is intended as a resource for health care providers. Providers should use their independent medical judgment based on the clinical needs of the patient when making determinations of who to test, what medications to test, testing frequency, and the type of testing to conduct.
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10. Hicks J, Swen J, Gaedigk A. Challenges in CYP2D6 phenotype assignment from genotype data: a critical assessment and call for standardization. Curr Drug Metab. 2014;15(2):218-32.