Pharmacogenetic Testing in Pain Management: Where Do We Stand?
Pharmacogenetic testing has recently been introduced to pain management. Prior to its introduction, pharmacogenetic testing was the purview of oncology, cardiology, and psychiatry.
In oncology, for example, there are several drugs that are very effective if the patient has a specific genotype but useless if not. Cardiologists use this type of testing to help calculate coagulation therapy and in psychiatry it can be helpful when selecting the safest and most effective agents among potent antipsychotic and antidepressant regimens.
Given the relative success of pharmacogenetic testing in these specialties, commercial purveyors of the tests believed they’d find a natural place in pain management. Instead, pharmacogenetic testing has been stalled by controversy and confusion.
Lack of Guidelines
At this time, there is no universal agreement as to who, when, and why the testing should be done. For example, at the 2015 International Conference on Opioids, Andrew Somogyi, MD, gave a presentation titled, “Pharmacogenetics of Opioids: Clinical Translation is Premature.”1 He concluded that pharmacogenetic testing in pain management is not yet ready to be used.
In contrast, Inna Belfer, MD, recently published a review titled, Personalized Pain Medicine: Pharmacogenetic Testing for Pain and Opioid Addiction.2 With 160 references, Dr. Belfer describes about 24 genes that are involved with pain, opioid metabolism, and addiction. She concluded that, “There is a growing interest in the pain and addiction communities with regard to the rapid optimization of genetic testing services because they have the potential to dramatically improve the utility and efficacy of both current and future pain and addiction management strategies and serve as an essential basis for personalized pain medicine.”
The message is clear—pharmacogenetic testing in pain and addiction management has “potential” but no current practical application. Indeed, this in-depth article did not specify who, when, and why to test. Most critical is that there was no discussion about how the results of pharmacogenetic testing can and should alter treatment.
An unfortunate, but not unexpected result of current pharmacogenetic testing, promotion and utilization in pain management is that third party reimbursement has become scant. No wonder. To gain reimbursement, a diagnostic test must spell out who, when, and why to test as well as explain how the test will alter treatment.
Unfortunately, pharmacogenetic testing in pain management has essentially been promoted as a pre-treatment screen to select treatment agents and avoid drug interactions. The tests are expensive, take days to process, and are not considered a patient necessity.
In an ideal world, every patient would know their genetic profile and present it to a prescribing physician before starting any therapy. In the future, lower costs and increased availability of genetic testing may make this a reality. In the meantime, pain patients are typically started on analgesic agents in urgent clinical situations that involve uncontrolled muscle, nerve or joint pain.
There is little opportunity in pain management to pre-screen for genetic defects. Consequently, pharmacogenetic testing of pain patients is almost always performed on chronic pain patients who are not doing well on their current treatment regimen.
Role of Testing Today
Given the vagaries and missteps described above, does pharmacogenetic testing have a current place in practical pain management? And, should third party payors ante up? My answer is a resounding yes, and the purpose of this memo is to encourage identification of specific pain patient subgroups who should be tested.
In my practice I’ve used pharmacogenetic testing among chronic pain patients who are not finding adequate pain relief with daily opioid dosages of at least 80 mg to 100 mg of morphine equivalents in combination with ancillary neuropathic, anti-inflammatory, and antidepressant agents.
Please note that the current trend in opioid guidelines and regulations calls for evaluation and caution when daily opioid dosages of at least 80 to 100 mg of morphine equivalents are required. Chronic pain patients who are failing to adequately respond to usual opioid dosages should be pharmacogentically tested and third party payors should pay for the test since the results will likely alter treatment.
For example, multiple cytochrome P450 defects in the intestine and liver may mean that the patient can’t well assimilate oral opioids and must find a non-oral administration route.3 Cytochrome P450 defects may require the practitioner to prescribe analgesic agents that don’t require cytochrome P450 metabolism.4 Defects in opioid receptor binding or abnormal catecholamine enzymatic activity may call for ultra-high opioid dosages.5
Besides the chronic pain patient who isn’t finding pain relief with standard opioid dosages, there may be other specific patient subgroups that would benefit from pharmacogenetic testing. Practitioners should identify these subgroups and the specific treatment changes that will occur based on test results.
There is an old adage in diagnostics: “If the test result won’t change the treatment, don’t do the test.” We need pharmacogenetic testing, but unless we identify specific patient subgroups who need the testing to alter and improve their pain treatment we risk losing reimbursement for it.