Pharmacogenetic testing combines pharmacology and genomics with the intent of discovering effective and safe medications and doses tailored to a person’s genetic makeup. A number of commercially available panel tests (e.g., GeneSight® Analgesic, Proove® Opioid Risk Panel, Pain Medication DNA Insight™, Millennium PGT™, IDgenetix®) have been proposed as an aid in pain management.
Individual or panel tests relevant to pharmacogenetics could include testing of the following genes:
5HT2C (serotonin receptor gene)
5HT2A (serotonin receptor gene)
SLC6A4 (serotonin transporter gene)
DRD1 (dopamine receptor gene)
DRD2 (dopamine receptor gene)
DRD4 (dopamine receptor gene)
DAT1 or SLC6A3 (dopamine transporter gene)
DBH (dopamine beta-hydroxylase gene)
COMT (catechol O-methyltransferase gene)
MTHFR (methylenetetrahydrofolate reductase gene)
γ-aminobutyric acid (GABA) A receptor gene
OPRM1 (μ-opioid receptor gene)
OPRK1 (κ-opioid receptor gene)
UGT2B15 (uridine diphosphate glycosyltransferase 2 family, member 15)
Cytochrome p450 genes: CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP2B6, CYP1A2
Pharmacogenetic testing for the treatment of pain is considered investigational.
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
No high quality studies were found in the published literature that validates the use of pharmacogenetic testing for the treatment of pain. At present, the clinical utility of pharmacogenetic testing in pain management is poorly defined.
American Academy of Neurology. (2014). Opioids for chronic noncancer pain a position paper of the American Academy of Neurology. Retrieved January 22, 2019 from www.AAN.com.
Bell, G. C., Donovan, K. A., & McLeod, H. L. (2015). Clinical implications of opioid pharmacogenomics in patients with cancer. Cancer Control, 22 (4), 426-432. (Level 4 evidence)
BlueCross BlueShield Association. Evidence Positioning System. (11: 2018). Pharmacogenic testing for pain management. (2.04.131). Retrieved January 18, 2019 from https://www.evidencepositioningsystem.com/. (7 articles and/or guidelines reviewed)
CMS.gov: Centers for Medicare & Medicaid Services. Palmetto GBA. (2018, October). CYP2C19, CYP2D6, CYP2C9, and VKORC1. (LCD ID L35072). Retrieved January 18, 2019 from https://www.cms.gov.
Crews, K. R., Gaedigk, A., Dunnenberger, H. M., Leeder, J. S., Klein, T. E., Caudle, K. E., et al. (2014). Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update. Clinical Pharmacology & Therapeutics, 95 (4). (Level 5 evidence)
Kapur, B. M., Lala, P. K., & Shaw, J. L. (2014). Pharmacogenetics of chronic pain management. Clinical Biochemistry, 47, 1169-1187. (Level 2 evidence)
Owusu, A., Hamadeh, I., & Smith, M. (2017). Review of Opioid Pharmacogenetics and Considerations for Pain management. Pharmacotherapy, 37 (9), 1105-1121. Abstract retrieved January 22, 2019 from PubMed database.
Scarpi, E., Calistri, D., Klepstad, P., Kaasa, S., Skorpen, F., Habberstad, R., et al. (2014). Clinical and genetic factors related to cancer-induced bone pain and bone pain relief. Oncologist, 19 (12), 1276-1283. (Level 3 evidence)
ORIGINAL EFFECTIVE DATE: 9/13/2015
MOST RECENT REVIEW DATE: 2/14/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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