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Letters To the Editor

Genotype Testing

Although we all recognize that genotype clearly plays an important role in medication selection, it has not entered routine clinical use (except as an excuse to blame patients’ metabolisms for failure of medications to work, or as patients’ excuses for negative urine testing).

There are some commercial tests available. I’ve read articles written by Dr. Forest Tennant on the topic of genotype variation. Are you aware of any good review articles that I could use in my journal club to educate people on this topic and whether it is ready for prime time?

Thanks, and thank you for continuing to address topics that are important but often ignored.


—Daniel Graubert, MD
Northern New Hampshire

Dear Dr. Graubert,

Births, weddings, graduations, and new lab tests may arrive with an exuberance that later has to be tempered as experience becomes available. Such it is with cytochrome P450 (CYP450) testing.

A little over 1 year ago, CYP450 testing arrived with a vengeance because third-party payors, particularly Medicare, began to pay for it. During the ensuing months, pain practitioners everywhere have been experimenting with CYP450 testing for various reasons.

In the main, CYP450 testing has proven to be contributory only to the management of a subset of pain patients. The basic reason is that medical treatment of chronic pain is a step-wise model that is typically initiated with non-opioid drugs and therapies such as anti-inflammatory agents, topical creams and gels, muscle relaxants, physical therapy, and electromagnetic measures. If this step isn’t satisfactory, antidepressant, neuropathic, and opioid agents are added. As the treatment steps are ascended, agents that are ineffective or have side effects are discarded. Since our menu of treatment agents isn’t very long, CYP450 testing doesn’t help much in selecting therapeutic agents from our small pool of options. Also, pain treatment is always initiated and continued at multiple clinic sites, including primary care offices, emergency rooms, hospitals, and specialty practices. In summary, CYP450 testing is not yet a “standard of care.”

To me, the best CYP450 testing use is to help determine which opioids may be most effective or ineffective for patients who are taking 2 to 4 different opioids but getting little relief. CYP450 testing may give you a clue that this condition may be present since CYP450 enzymes are ubiquitous in the intestine and necessary for gastrointestinal absorption of opioids. We covered how to interpret and select opioids based on CYP450 testing in the January/February 2013 issue of Practical Pain Management.1 Your journal club may find it helpful.

There are two key points about CYP450 testing. If a patient is doing fine on their current regimen, don’t bother to test or change therapy based on a test result. The old axiom, “Don’t run a test unless you will change treatment based on the results,” is quite operative here. Another axiom that fits here is, “If it isn’t broken, don’t fix it.”

Genetic testing will not hit “prime time” until the testing profiles include far more assays than are currently available, become less expensive, and our menu of treatment options grows a lot longer. Until that time, CYP450 testing is principally the purview of pain specialists who must diagnose and treat complex cases. What’s more, such specialists will have to take tutorial classes or other instruction beyond the written or Internet word, as CYP450 testing is complex.

Forest Tennant, MD, DrPH

Last updated on: August 15, 2013
First published on: August 1, 2013