Genetic Testing in Workers’ Compensation: A Clinically Sound Strategy for Improved Outcomes

In previous discussions, we’ve explored the clinical and financial impact of specialty medications—those requiring specialized handling, high-touch service models, or advanced monitoring protocols. But let’s be honest: in workers’ compensation, “monitoring” has traditionally been synonymous with deterrence, less about clinical stewardship and patient outcomes.

That’s changing.

As the industry moves closer to value-based care, and as more complex treatment regimens enter the workers’ comp ecosystem—from oncology and transplant medicine to advanced therapies for autoimmune disorders—the need for pharmacogenomic (PGx) testing and broader genetic insights is becoming unavoidable.

PGx testing provides a proactive method for tailoring drug therapy based on a patient’s genetic profile, reducing the likelihood of treatment failure, adverse events, and prolonged disability. Despite strong clinical support, PGx remains underutilized in workers’ compensation—where outdated, trial-and-error prescribing still drives significant cost and delay.

Below are several clinical scenarios where PGx testing can add value across key therapeutic categories commonly seen in workers' comp.

Opioids: Addressing Genetic Variability in Pain Management

Opioids are frequently prescribed for managing acute and chronic pain in injured workers. Yet their metabolism and efficacy vary significantly based on CYP2D6 enzyme activity—an area where PGx testing provides clear clinical value.

• Poor Metabolizers (loss-of-function CYP2D6 alleles): These individuals cannot effectively convert codeine to its active form, morphine, resulting in inadequate pain relief and risk of inappropriate dose escalation.

• Ultrarapid Metabolizers (gene duplications of CYP2D6): These individuals convert codeine too efficiently, rapidly accumulating morphine and increasing the risk of respiratory depression and overdose.

PGx testing can identify these genetic profiles upfront, allowing prescribers to select safer, more effective analgesics and adjust dosages accordingly—minimizing risks and supporting better outcomes.

Anticoagulants: Reducing the Risk of Hemorrhagic and Thrombotic Events

Anticoagulants are commonly used post-injury or post-surgery to prevent thrombotic complications. Two medications—warfarin and clopidogrel—carry well-documented pharmacogenomic considerations.

• Warfarin Sensitivity: Variants in VKORC1 and CYP2C9 impact drug metabolism and sensitivity. Slow metabolizers may require lower doses to avoid excessive anticoagulation and bleeding events.

• Clopidogrel Activation: This prodrug must be metabolized by CYP2C19 to be effective. Patients with CYP2C19 loss-of-function variants may experience therapeutic failure, placing them at higher risk for stroke or myocardial infarction.

PGx testing helps guide therapy by identifying genetic non-responders or high-risk individuals. This supports more effective medication choices and reduces the likelihood of emergency interventions and hospital readmissions.

Psychiatric Medications: Accelerating Mental Health Recovery

Psychotropic medications—used to treat PTSD, depression, and anxiety—are frequently prescribed in workers’ compensation claims. However, therapeutic response and side effect profiles often vary widely based on genetic makeup.

• CYP2D6 Ultrarapid Metabolizers: May rapidly clear medications like paroxetine, rendering them ineffective at standard doses and prolonging untreated symptoms.

• Poor Metabolizers: May accumulate excessive levels of SSRIs like fluvoxamine, increasing the risk of adverse drug reactions unless doses are reduced.

Psychiatric medications typically require 4–6 weeks to evaluate efficacy. When medications fail, the trial-and-error cycle restarts, delaying recovery and return-to-work. PGx testing enables more targeted initial prescribing, reducing the need for multiple medication changes and enhancing adherence.

Cost-Effectiveness: PGx Testing as a Risk Mitigation Strategy

Despite the compelling clinical evidence, PGx testing is not yet standard in most workers’ compensation formularies. Coverage varies, often due to concerns over upfront testing costs. But these short-term expenses must be weighed against longer-term cost avoidance:

• One failed prescription can delay functional recovery by months.

• An opioid-related overdose or psychotropic-induced adverse reaction can lead to catastrophic claims.

• The cost of a single genetic test is minimal compared to the cost of prolonged disability, ER visits, or litigation.

Forward-thinking payers are beginning to treat PGx testing not as an ancillary service, but as an integral part of high-risk medication management.

Conclusion: Precision Prescribing is the New Standard of Care

The old model has historically absorbed the costs of reactive, generalized prescribing—tolerating prolonged disability, suboptimal outcomes, and preventable complications. But today’s evolving landscape demands a more nuanced, evidence-driven approach.

Pharmacogenomic testing provides a clear path forward. It enables clinicians to make more informed prescribing decisions, reduces unnecessary utilization, and supports faster, safer recoveries. As treatment regimens grow more complex and individualized, genetic testing will be not just appropriate—but expected.

The question is no longer whether PGx testing should be included in workers’ comp—it’s how long we can afford not to.

By Marissa Harle

PharmD Candidate (P4)

For questions, e-mail pharmd@prodigyrx.com 

References 

• Bousman, C.A., Arandjelovic, K., Mancuso, S.G., Eyre, H.A., Dunlop, B.W. Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials. Pharmacogenomics. 2019;20(1):37-47. 

• Brandt, J.T., Close, S.L., Iturria, S.J., Payne, C.D., Farid, N.A., Ernest, C.S. 2nd, Lachno, D.R., Salazar, D., Winters, K.J. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost. 2007;5(12):2429-36. 

• Charlier, C., Broly, F., Lhermitte, M., Pinto, E., Ansseau, M. & Plomteux, G. Polymorphisms in the CYP 2D6 gene: association with plasma concentrations of fluoxetine and paroxetine. Ther. Drug Monit. 25, 738–742 (2003). 

• Crews, K. R., Gaedigk, A., Dunnenberger, H. M., Leeder, J. S., Klein, T. E., & Caudle, K. E. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2D6 and codeine therapy. Clinical Pharmacology & Therapeutics, 2014;95(4), 376–382. 

• Dean, L., Kane, M. (2012) Codeine Therapy and CYP2D6 Genotype.[Updated 2025 Jan 17]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK100662/ 

• Dean, L. (2012) Warfarin Therapy and VKORC1 and CYP Genotype. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US); Available from: https://www.ncbi.nlm.nih.gov/books/NBK84174/