Mr. J, age 30, a Black man with major depressive disorder (MDD), has been your patient for the past year. At the time of his diagnosis, Mr. J received sertraline, 100 mg/d, but had little to no improvement. During the past year, he received trials of citalopram and paroxetine, but they were not effective for his recurrent depressive symptoms and/or resulted in significant adverse effects.
During a recent visit, Mr. J asks you about “the genetic tests that help determine which medications will work.” He mentions that his brother had this testing done and that it had “worked for him,” but offers no other details. You research the different testing panels to see which test you might use. After a brief online review, you identify at least 4 different products, and are not sure which test—if any—you should consider.
During the last few years, there has been a rise in commercial pharmacogenetic testing options, including tests available to clinicians at academic medical centers as well as direct-to-consumer testing (Table). Clinician and patient interest regarding pharmacogenetic testing in practice is often followed by the question, “Which test is best?” Although this is a logical question, providing an answer is multifactorial.1-3 Because none of the currently available tests have been compared in head-to-head clinical trials, it is nearly impossible to identify the “best” test.
In this article, we focus on the evidence-based principles that clinicians should consider when adopting pharmacogenetic testing in their practice. We discuss which genes are of most interest when prescribing psychotropic medications, the value of decision support tools, cost considerations, and patient education regarding this type of testing.
Which genes and variants should be tested?
The genes relevant to medication treatment outcomes can be broadly classified into those with pharmacokinetic vs pharmacodynamic effects. Pharmacogenes, such as those coding for the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4, and UDP-glucuronosyltransferase (UGT)2B1, may alter the rate at which medications are metabolized, thus varying the serum drug concentration across patients. Variants that impact the function of these enzymes are considered pharmacokinetic. Up to 40% of the variance in patients’ response to antidepressants may be due to variations in the pharmacokinetic genes.4 Alternatively, pharmacodynamic pharmacogenes impact drug action and therefore may affect the degree of receptor activation at a given drug concentration, overall drug efficacy, and/or the occurrence of medication sensitivity. These pharmacogenes may include:
- brain-derived neurotrophic factor (BDNF)
- catechol-O-methyltransferase (COMT)
- human leukocyte antigens A (HLA-A)
- serotonin receptor subtype 2 (HTR2)
- serotonin receptor subtype 2C (HTR2C)
- opioid receptor mu 1 (OPRM1)
- solute carrier family 6 member 4 (SLC6A4).
In articles previously published in Current Psychiatry, we outlined some of the evidence regarding these pharmacogenes, and resources available to clinicians to support their use of these tests.1,2
Currently, there is no standardization among commercial pharmacogenetic tests on:
- which genes to test
- which variants specific to a gene need to be included
- how the genetic data is translated to phenotype
- how the phenotype is translated to a treatment recommendation.
Continue to: Due to these factors...