by Dr. Adam Klapperich, DO
Pharmacogenomic testing is becoming more commonplace in the world of psychiatry, leading to “guided treatment” and “precision medicine.” Genetic information can be helpful in choosing medication, choosing starting and target doses, and in predicting/explaining adverse events. The evidence base for this testing, as far as clinical outcomes, has gaps. This brief article aims to help the primary care provider decide when obtaining pharmacogenomic testing is indicated, and how to interpret those results. This article will focus on guided antidepressant therapy.
There are multiple resources from which to obtain this testing, found in table 2 of this NIH paper. In my clinical practice, I tend to reserve pharmacogenomic testing for those who have failed at least two adequate medication trials for the same diagnosis, or has not tolerated typical therapeutic doses, though I do not necessarily always obtain testing in this situation. Some providers obtain a pharmacogenomic profile prior to initiation of the first medication. Though I do not personally advocate this for children and adolescents, this may have utility in achieving remission sooner.
For example, a 16 year old has had failed trials of both Fluoxetine and Escitalopram for depression and/or anxiety. Reasons for the failed trials include the possibility of this patient being a poor metabolizer at cytochrome 2D6, 2C19, and/or 3A4 and does not tolerate therapeutic doses, or an ultra-rapid metabolizer and is not achieving therapeutic plasma levels (though FDA label indicates Escitalopram should not be affected by a single cytochrome polymorphism or inhibition). SSRI medications may not be helpful or may not be tolerated due to a polymorphism in the serotonin transporter gene or the serotonin 2A receptor. At this point pharmacogenomic testing may help guide the next step in pharmacotherapy.
As far as interpreting the results of pharmacogenomic testing, some of the reports are easier to digest than others. One of the local providers has a liaison who is typically available to discuss results. Also the psychiatrists staffing the PAL service are more than willing to go over these reports with you. The most commonly utilized test in the Twin Cities is arranged in a green, yellow, red format, which is based on drug-gene interactions. The yellow and red categories do not imply that these medications cannot be used, but have the possibility of drug-gene interactions, which can affect dosing considerations and increase risk of side effects. A common problem is the “green” category containing only medications that are not FDA approved for children, and oftentimes not covered by insurance. In these cases, more careful interpretation of the results is necessary than basing treatment decisions solely on the color status. The pharmacogenomic test results are however reasonable justification for obtaining a prior authorization for second tier or off-label medications, especially if there have been failed trials of first-line medications.
Sources:
- Bousman, et al. Antidepressant prescribing in the precision medicine era: a prescriber’s primer on pharmacogenetic tools. BMC Psychiatry. 2017; 17: 60.
- Drozda et al. Pharmacogenomic Testing for Neuropsychiatric Drugs: Current Status of Drug Labeling, Guidelines for Using Genetic Information, and Test Options. Pharmacotherapy. 2014 Feb; 34(2): 166–184.
- Tantisira et al. Review of pharmacogenomics. Uptodate.com
- Lexapro FDA prescribing information.