Mental Health

Nonvalidated Pharmacogenetic Tests, Part I: Confessions of an Embarrassed Psychiatry Professor

Referenced article originally published October 26, 2016 in the Psychiatric Times:
Dr. de Leon
It is refreshing to read about a seasoned clinician backtracking on mistaken prior conclusions. I would opine to go further in limiting the need or utility of these tests.
For example, you want to do CYP2D6 and 2C19 before giving a tricyclic. What is the risk of giving someone 10mg BID of nortriptyline and increasing by 10mg BID every 2 weeks up to 40mg BID watching how the patient reacts vs the risk of delaying treatment and cost of the test? Poor metabolizers may easily tolerate titration to 20mg or 30mg BID and have a response after 6-8 weeks stopping the dose there anyway. If a rare patient will have trouble after a few 10mg BID doses they can just stop the medication. EVERY patient regardless of metabolic profile requires careful and slow titration of a tricyclic and should be advised to pause their drug dosing and contact their Dr if they have trouble. I really don’t see the risk-benefit ratio falling on the side of doing a costly test.
For CYP2C, Asians have a 3-4x increase number of poor metabolizers. Here in Japan, CYP is not tested, its start low and go slow with most every psychiatric drug. There seems to be little problem with this method as long as there is close follow up. Again, EVERY patient should be followed closely.
You also want to do HLA testing before giving CBZ to Asians, I assume to decrease the risk of SJS. The best approach is not to give CBZ to Asians, not do a test. Why not use oxcarbazepine if you need to? There are plenty of other drugs to use, even for seizure disorder treatment, then again your article was on “genetic tests in psychiatry” not neurology. CBZ isn’t used much in psychiatry in Japan nowadays. HLA testing isn’t done here either, though LFT and WBC should be tested a week into CBZ therapy regardless of HLA type.
Ok, maybe there is an exceptional case where we want to do a test, but it should be a rare case and tests are no substitute for careful and knowledgeable clinical monitoring. I vote that these tests stay in the research lab for pharmacology research, and in pharmaceutical company labs during drug development, not in clinical psychiatry.
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