Pharmacogenetic Testing in Psychiatry 9/14/2017

There has been increasing interest in the use of pharmacogenomic testing to help with medication choice when treating psychiatric conditions. Advocates are claiming they can be helpful for personalizing prescribing, improving outcomes, and reducing costs. Some of these commercial tests are now covered by some insurance companies. While clinicians would love to have a way to prescribe the right medication at the right dose without having to use trial and error, we are not there yet, at least not with psychiatry. On the other hand, genetic testing has been shown to be quite useful in cancer chemotherapy. Therefore, it would be helpful to review where we are at with pharmacogenomic testing in psychiatry to see how close we are to that goal.

 The choice of a psychotropic medication is based on a variety of factors. These include: age of the patient, FDA approval for a particular diagnosis, past medication trials, specific symptoms and illness characteristics, co-morbid psychiatric and medical conditions, side effect profile, frequency of dosing, onset of action, medication compliance, drug-drug interactions, to name a “few” of the many factors. Unfortunately the information gathered from pharmacogenomics testing does not really address these factors.

 The idea behind pharmacogenomics testing is to use available genetic testing to help guide which medications a patient is likely to respond well to versus which ones he/she would not respond well to. Most commercial tests target two broad categories: genes associated with drug metabolism and genes hypothesized to be involved with the mechanisms underlying the therapeutic/side effect profile of a medication. Current genetic testing provides a significant amount of data but it remains unclear how useful the data is to clinical practice. The data provided can include the level of activity of various drug metabolizing enzymes (including commonly CYP2D6 and CYP2C19) and metabolizer status (ultra-rapid, extensive, intermediate, or slow).

 Of course, genetic variation influences drug metabolism and response. Unfortunately the genetic variants that are currently being tested in psychiatry are not really providing clinically useful information for the population at large. One of the issues is that blood levels of a psychotropic medication are not very predictive of treatment response. Another issue is that knowing how quickly or slowly a patient will metabolize a medication does not inform if the medication will be helpful or not. Current testing does not really inform if a patient will tolerate a particular medication, even if the dose is increased slowly.

There are limited studies to assess the use of pharmacogenomic testing in informing the choice of medication. Many of the studies that have been done were conducted by the genetic testing companies themselves. Additionally most of the studies were for treatment-resistant depression and did not include a racially diverse population of subjects.

 The problem is that the variants currently being tested do not inform clinical practice the way we would like them to. More clinically relevant variants need to be studied. Additionally more rigorous studies need to be done to assess the effect on clinical practice.

 For now, pharmacogenomic testing can be helpful in cases of treatment resistance, particularly treatment-resistant depression, and in cases with patients with abnormal side effect profiles, but has limited use for now in general practice.



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