Cytochrome genetic testing is quickly becoming a new fad in healthcare, and as with all trends, we must ask ourselves, “Is this popular because it benefits the injured person, or because it benefits certain commercial interests?” And again, like most fads, “fast metabolizers” and cytochrome genetic testing in pain medicine seem to be a lot of hype. A better understanding of the procedure and its limitations can help us discern if and when to consider application.

What is Cytochrome Genetic Testing?

We have long known that there are differences in how each person metabolizes any medication, whether for pain, hypertension, stomach ailments or anything else. The microscopic cytochrome system inside each cell is the cell’s powerhouse and the mechanism responsible for this difference. That’s because of genetic variation found in every trait of the human body. This is not a new concept.

BlueCross BlueShield of North Carolina issued a medical policy last year that defines it this way: “Pharmacogenomics is the study of how an individual’s genetic inheritance affects the body’s response to drugs. It may be possible to predict therapeutic failures or severe adverse drug reactions in individual patients by testing for important DNA polymorphisms (genotyping) in genes related to the metabolic pathway (pharmacokinetics) or signal transduction pathway (pharmacodynamics) of the drug. Potentially, test results could be used to optimize drug choice and/or dose for more effective therapy, avoid serious adverse effects and decrease medical costs.”

This is a complex system. The cytochrome P450 system in the liver is particularly important in drug metabolism, with more than 50 genes coding for the cytochrome P450 enzymes in humans. And the drugs themselves can increase or decrease the cytochrome enzyme function.

The question is whether a simple test can account for all the genetic variation, and non-genetic variation, in drug effectiveness to provide enough information to improve care decisions. With regard to pain medications, my response is no.

Exaggerated Claims

The people marketing the “genetic testing” are doing so under the umbrella of “personalized medicine.”

Though doctors and commercial interests generally like to simplify complex medical problems and offer quick fixes, their track record, especially in pain management, is terrible. That is because personalized medicine requires a great deal more nuance and adherence to the biopsychosocial model than simply prescribing a test or medication

What does this mean? True personalized medication management requires attention to a complex array of factors usually not systematically considered in busy day-to-day care. How a patient responds to a pain drug (determined by both objective measures and subjective report) depends on the specific medication, the medication’s metabolism, the person’s metabolism (cytochromes), the compliance with taking the medication, their diet, their age, other medicine they are taking that can increase or decrease absorption and metabolism, the placebo effect, their psychosocial profile, their weight and, for opioids, dependence and addiction.

All of these factors interplay to determine whether a pain medication is effective. It is the reason why we cannot simply attribute a poor drug response primarily to someone’s cytochrome makeup. In essence, the patient may be a fast metabolizer (clearing the drug quickly from the body) or a slow metabolizer, but a test will not provide any information about the patient’s response to the drug. Many high opioid prescribers, and likely some drug companies, are trying to make a not-so-subtle case that certain patients “need” higher doses based on their cytochrome enzyme profile. These same parties have yet to show any evidence that knowing this information positively and definitively affects clinical outcomes.

Unclear Applications

There is great risk in trying to justify high doses. And who needs high doses? The fast metabolizer may clear the dose and need an increased frequency of dose. The slow metabolizer may have great accumulation of the drug and require a lower or less frequent dose. Some opioids (and other drugs) are activated by metabolism, so a fast metabolizer may have a better response.  These examples are an attempt to illustrate that the issue is scientifically far more complicated than most physicians can easily synthesize and apply. Even if a physician makes an informed opioid choice, it likely has little effect on all the other biopsychosocial issues.

Personalized medicine is not a blood test. Rather, it is a concept best applied by pain physicians actually seeing and knowing their patient, being wary of addiction, making objective measures of effectiveness and ceasing medications that prove to not work. Proper treatment involves working with patients to address the reasons they do not take medications properly or follow through with their home exercise program. Knowing all this, how can we justify providing a doctor with additional, yet limited, out-of-context objective information, when his or her care plan does not include objective measures to begin with? Unfortunately, physician reimbursement often does not promote time spent with patients or for complex decision-making. But over-simplifying complex medical issues is not money well spent.

Learn more about treatments for complex pain by visiting the Paradigm Outcomes’ website and joining the conversation on LinkedIn and Twitter. Complex pain is a whole-person problem that requires a holistic, biopsychosocial solution. Paradigm’s comprehensive approach, team management and physician consultative services all contribute to injured workers making real improvement over manageable time spans.

About the Author

Steven M. Moskowitz, MD, is the Senior Medical Director and supervisor of Paradigm Outcome’s complex pain program. Dr. Moskowitz is a specialist in physical medicine and rehabilitation with clinical expertise in complex musculoskeletal and neurologic rehabilitation including spinal cord injury, multiple sclerosis and chronic pain.