Evidence-Based Reviews

Pharmacogenetic testing: Navigating through the confusion

Current Psychiatry. 2021 June;20(6):12-17 | doi:10.12788/cp.0131

References

1. Ellingrod, VL. Using pharmacogenetics guidelines when prescribing: what’s available. Current Psychiatry. 2018;17(1):43-46.
2. Ellingrod VL. Pharmacogenomics testing: what the FDA says. Current Psychiatry. 2019;18(4):29-33.
3. Ramsey LB. Pharmacogenetic testing in children: what to test and how to use it. Current Psychiatry. 2018;17(9):30-36.
4. Bousman CA, Dunlop BW. Genotype, phenotype, and medication recommendation agreement among commercial pharmacogenetic-based decision support tools. The Pharmacogenomics Journal. 2018;18(5):613-622. doi:10.1038/s41397-018-0027-3
5. Bousman CA, Arandjelovic K, Mancuso SG, et al. Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials. Pharmacogenomics. 2019;20(1). doi:10.2217/pgs-2018-0142
6. Nicholson WT, Formea CM, Matey ET, et al. Considerations when applying pharmacogenomics to your practice. Mayo Clin Proc. 2021;96(1);218-230. doi:10.1016/j.mayocp.2020.03.011
7. Krebs K, Milani L. Translating pharmacogenomics into clinical decisions: do not let the perfect be the enemy of the good. Human Genomics. 2019;13(1). doi:10.1186/s40246-019-0229-z
8. Greden JF, Parikh S, Rothschild AJ, et al. Impact of pharmacogenomics on clinical outcomes in major depressive disorder in the GUIDED trial: a large, patient- and rater-blinded, randomized, controlled study. J Psychiatr Res. 2019;111;59-67. doi:10.1016/j.jpsychires.2019.01.003
9. Haga SB. Integrating pharmacogenetic testing into primary care. Expert Review of Precision Medicine and Drug Development. 2017;2(6):327-336. doi:10.1080/23808993.2017.1398046
10. Ward KM, Taubman DS, Pasternak AL, et al. Teaching psychiatric pharmacogenomics effectively: evaluation of a novel interprofessional online course. J Am Coll Clin Pharm. 2021; 4:176-183.

Patient education is critical

Although the benefits of using pharmacogenetic testing information when making certain treatment decisions is promising, it is important for both patients and clinicians to understand that test results do not always change therapy. A study on the impact of pharmacogenetic testing on clinical outcomes of patients with MDD found that 79% of patients were already prescribed medications that aligned with recommendations.⁸ Therefore, switching medications based on the test results of a patient who is doing well clinically is not recommended. However, DSTs may help with clinical decisions for ambiguous cases. For example, if a patient has a genotype and/or phenotype that aligns with medication recommendations, the DST might not be able to identify a better medication to use, but may be able to recommend dosing guidance to improve the tolerability of the patient’s current therapy.⁶ It is also important to understand that the results of such testing may have a broader use beyond the initial reason for obtaining testing, such as when prescribing a common blood thinner such as warfarin or clopidogrel. However, for many of the pharmacodynamic genes that are included in these panels, their use beyond the treatment of depression may be limited because outcome studies for pharmacodynamic pharmacogenes may vary based on psychiatric diagnosis. Regardless, it may be beneficial to securely save and store patient test results in a standardized place within the medical record for future use.

CASE CONTINUED

You work with Mr. J to help him understand the benefits and limitations associated with pharmacogenetic testing. Assuming Mr. J is comfortable with the costs of obtaining testing, you contact the testing companies you identified to determine the specific pharmacogene variants included on each of these panels, and which would be the most appropriate given his race. If the decision is made to order the testing, provide Mr. J with a copy of his testing report so that he can use this information should he need any additional pharmacotherapy in the future, and also maintain a copy in his patient records using a standardized location for easy future access. If Mr. J is not comfortable with the costs associated with the testing, find out which medication his brother is currently receiving for treatment; this information may help identify a treatment plan for Mr. J.

Impact on practice

As psychiatry continues to gain experience in using pharmacogenetic testing and DSTs to help guide treatments for depression and other disorders, clinicians need to learn about these tools and how to use an evidence-based approach to best implement them in their practice. Many academic medical centers have developed continuing education programs or consult services to help with this.^9,10Just as the choice of which medication to use may be based partly on clinician experience, so too may be which pharmacogenetic test to use.

Bottom Line

Pharmacogenetic tests have not been examined in head-to-head clinical trials, which makes it nearly impossible to identify which test is best to use. Although the testing companies’ decision support tools (DSTs) often disagree in their recommendations, research has shown that using DSTs can facilitate implementation of relevant psychopharmacology dosing guidelines, assist in identifying optimal medication therapy, and improve patient outcomes. Clinicians should use testing panels with recommendations that best align with their individual practices, their patient’s needs, and FDA information.

Related Resources

PGx Gene-specific information tables. www.pharmgkb.org/page/pgxGeneRef
Clinical Pharmacogenetics Implementation Consortium. https://cpicpgx.org/guidelines/

Drug Brand Names

Aripiprazole • Abilify
Carbamazepine • Tegretol
Citalopram • Celexa
Clopidogrel • Plavix
Clozapine • Clozaril
Fluoxetine • Prozac
Imipramine • Tofranil
Paroxetine • Paxil
Sertraline • Zoloft
Warfarin • Coumadin, Jantoven