Due to these factors, the FDA has advised clinicians to consult the dosing recommendations provided in a medication’s package insert for information regarding how genetic information should be used in making treatment decisions.2
The value of decision support tools
Researchers have assessed how various manufacturers’ decision support tools (DSTs) (ie, the reports the commercial testing companies send to the clinician who orders the test) agree on genotypes, predicted phenotypes, and medication recommendations.4 Overall, this research found varying levels of disagreement in the medication recommendations of the testing panels they studied, which indicates that not all tests are equivalent or interchangeable.4 Of the actionable recommendations for antidepressants, 16% were conflicting; the recommendations for fluoxetine and imipramine were most frequently in disagreement.4 Similarly, 20% of the actionable antipsychotic advice was conflicting, with the recommendations for aripiprazole and clozapine most frequently in disagreement.4 Researchers also reported a situation in which 4 testing panels agreed on the patient’s phenotyping status for CYP2C19, but the dosing recommendations provided for the CYP2C19 substrate, amitriptyline, differed.4 Thus, it is understandable why DSTs can result in confusion, and why clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.
Additionally, while the genes included on these panels vary, these testing panels also may not evaluate the same variants within a specific gene. These differences may impact the patient’s reported phenotypes and medication recommendations across DSTs. For example, the FDA has recommended HLA gene testing prior to prescribing carbamazepine. However, few of the available tests may include the HLA-B*15:02 variant, which has been associated with carbamazepine-induced severe cutaneous reactions in patients of Asian descent, and fewer may include the HLA-A*31:01 variant, for which testing is recommended prior to prescribing carbamazepine in patients of Caucasian descent.4 Additionally, some of the CYP enzymes—such as CYP2D6*17 and CYP2C19*3 variants, which may be more common in certain populations of patients who are members of ethnic or racial minority groups—may not be consistently included in the various panels. Thus, before deciding on a specific test, clinicians should understand which gene variants are relevant to their patients with regard to race and ethnicity, and key variants for specific medications. Clinicians should refer to FDA guidance and the Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines to determine the appropriate interpretations of genetic test results.1,2
Despite the disagreement in recommendations from the various testing companies, DSTs are useful and have been shown to facilitate implementation of relevant psychopharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. A recently published meta-analysis of randomized controlled trials (RCTs) of pharmacogenetic testing found that DSTs improved symptom remission among individuals with MDD by 70%.5 This suggests that pharmacogenetic-guided DSTs may provide superior treatment compared with treatment for DSTs were not used. However, the RCTs in this meta-analysis only included patients who had previously failed an antidepressant trial.5 Therefore, it is currently unknown at what point in care DSTs should be used, and whether they would be more beneficial if they are used when starting a new therapy, or after several trials have failed.
Consider the cost
The cost and availability of pharmacogenetic testing can be an issue when making treatment decisions, and such testing may not be covered by a patient’s insurance plan. Recently, the Centers for Medicare & Medicaid Services announced that Medicare would cover FDA-approved genomic tests that encompass broad gene panels if the evidence supports their use. Similarly, commercial insurers such as UnitedHealthcare have begun to cover some pharmacogenetic tests.6 Medicare or Medicaid plans cover some testing panels’ costs and patients do not incur any out-of-pocket costs; however, some private insurance companies require patients to pay at least a portion of the cost, and many companies offer financial assistance for patients based on income and other factors. Although financial coverage for testing has improved, patients may still face out-of-pocket costs; therefore, clinicians may need to weigh the benefits of pharmacogenetic testing vs its cost.7 Clinicians should also determine what timeline best suits their patient’s financial and clinical needs, and test accordingly.
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