The Bewildering Terminology of Genetic Testing
A most welcome and needed happening in pain practice in 2012 is the arrival of commercial genetic testing. Although the term genetic testing covers a wide array of tests for many disorders, pain practice is primarily interested in cytochrome P450 abnormalities. To those of us who prescribe opioids, these new tests are a great guide to help us select the safest and most effective opioid.
While genetic testing is essential, the terminology is bewildering because it is in the vernacular of genetic science and not standard medical practice. For starters, the term “polymorphism” simply means, “to exist in several different forms.” Cytochrome P450 is an unfortunate term. A much better easier-to-understand name would be “drug metabolizing enzyme system.” Cytochrome enzymes derive their name from the heme pigment (deep red color), which absorbs light at a characteristic wavelength of 450 nanometers.
The most critical “need to know” is how to interpret test results that are reported to us by the testing laboratory. A cytochrome P450 analysis is graded as “extensive,” “intermediate,” “ultra-rapid,” or “poor.” What this really means in standard medical terms is “normal,” “deficient,” “hyper,” or “hypo.” Then there are inducers and inhibitors. The inducers are really accelerators. An inhibitor speaks for itself. To assist, Table 1 provides a translation from genetic terms to standard medical meaning.
The sales and marketing people who are pushing genetic testing, as well as some pharmaceutical companies selling opioids that bypass the cytochrome system, constantly threaten a drug–drug interaction if the physician doesn’t choose the right opioid. If you bother to ask the purveyors of these admonitions what they mean by a drug–drug interaction, chances are they really don’t know. A drug–drug interaction just means “toxicity” or an “overdose” that may produce such symptoms as sedation, psychosis, dysphoria, itching, or dizziness.
A drug–drug interaction may also cause a lack of effectiveness of the prescribed drug. The worst drug–drug interaction in pain practice in recent times has been cardiac asystole and death when methadone has been given with an antidepressant or benzodiazepine to a patient who has a defect in the cytochrome(s) that metabolize methadone. The other relevant case involves the cytochrome that metabolizes codeine and hydrocodone. In these cases the patient took an antibiotic or antifungal agent that inhibited the cytochrome and caused a severe toxic reaction. Some genetic testing companies are supplying with each test result a computerized print out of possible drug–drug interactions plus a list of inducers and inhibitors. Just how needed and helpful this information may be has yet to be determined. The advice here is simple. Until we know more about genetic testing and what actions to take when we get the results, stick to some sound opioid-prescribing practices that have emerged in recent years:
- When it comes to dosages start low and go slow
- Use methadone as a last resort
- Beware of mixing opioids with benzodiazepines and antidepressants
- Believe the patient when they tell you an opioid doesn’t work or causes side effects
Laboratories now marketing genetic cytochrome testing are popping up like dandelions in Spring. Their major sales pitch is couched in such phrases as “personalized medicine,” “personalized care,” “genomic medicine,” “personalized prescribing,” and “pharmacogenetics.” These phrases are well meaning but confusing—they just mean, “pick the safest and most effective drug.” Although the intent of these marketing phrases is good, they imply a poor understanding of pain practice. To hear these marketing pitches you get the idea that the genetic testing laboratories believe a physician starts at ground zero and simultaneously picks one opioid, benzodiazepine, antidepressant, anti-inflammatory drug, and neuropathic agent on the same day and time as the pain is first discovered. In reality pain treatment is a step-wise progression in which treatment agents are started, added, and subtracted over an extended time period. Genetic testing will essentially never be done prior to initiation of pain treatment. It might surprise the unenlightened, but doctors can’t withhold analgesia while waiting for a lab result.
Don’t let the bewildering terminology hold you back. Just like urine testing when it first arrived, it will take us some time to decipher all the new terms and determine which genetic tests have bona fide merit in pain practice. Remember, the jury is still out. Practical Pain Management will try to give you some ways to interpret test results and actions to take. Here is a major caveat: the new genetic tests are an aide, not a directive, to therapeutics. They are not a substitute for clinical judgment in determining precisely which opioids, antidepressants, or other agents should be used. Stick with the patient.