The psychotropic panel looks at genes for liver enzymes that are responsible for the metabolism of most neuropsychiatric medications. It tests for various gene alleles and classifies the possible phenotypes as ultra-rapid, extensive, intermediate, or poor metabolizers. The panel also tests for a few genes not related to hepatic metabolism of psychotropic drugs, which are receptor polymorphisms with potential pharmacodynamic implications.
Genomind has one panel, the “Genecept Assay.” The assay includes genes encoding the serotonin transporter, calcium channel, sodium channel, serotonin receptor 2C, melanocortin 4 receptor, dopamine 2 receptor, catechol-O-methyltransferase, alpha-2A adrenergic receptor, MTHFR, brain-derived neurotrophic factor, μ-opioid receptor, and glutamate receptor, as well as a number of the hepatic cytochromes. According to Dr. Dowd, Genomind has received the most positive feedback from clinicians regarding the serotonin transporter gene (SLC6A4) and the 2 weight-gain–related genes on the panel (5HT2C and MC4R). Dr. Dowd asserts that certain serotonin transporter gene alleles identify people with lower response and remission rates and more adverse effects when treated for depression with SSRIs and that certain alleles of 5HT2C and MC4R imply a significantly higher risk of weight gain if the patient is treated with an atypical antipsychotic drug.
Words of caution
Shaun Purcell, PhD, Associate Professor of Psychiatry at HMS and a genetic epidemiologist who was involved in some of the studies to identify genes as risk factors for mental disorders, believes psychiatrists have ample cause to be cautious about using genetic testing. “To me, the evidence is underwhelming to say the least. It’s definitely concerning that these kinds of tests are being pushed prematurely.”
For the non-metabolic genes on the panel, Dr. Purcell says, “I’d question the basic assumptions and science behind the panel. As far as I’m aware, these genes are coming from studies of disease risk.” He adds, “It’s a different thing to have an association in the literature and to have it be clinically meaningful.”
Dr. Purcell continues: “The associations of major psychiatric illness with common variants in CACNA1C are unambiguously sound. They say nothing about what implications these variants have, if any, for guiding treatment.” He adds, “There is a fundamental disconnect between what is being claimed and the extant evidence base for CACNA1C.” He also questions the premise that any of the other non-metabolic genes tested on the GeneSight and Genomind panels have clinical utility. “There’s no evidence that these variants are going to be clinically actionable in terms of guiding treatment.”
Dr. Fogel, who is generally in favor of clinicians considering pharmacogenomic testing for difficult-to-treat patients, agrees with Dr. Purcell that the clinical relevance of some of the genes on the panels is questionable. He says, “Will getting a gene associated with BDNF actually make more of a difference than getting a BDNF level? I don’t think so.” Regarding Genomind’s listed “treatment impacts” for the MTHFR and BDNF genes, Dr. Fogel says, “A methylfolate supplement and exercise would usually be good for a patient no matter what their genotype.”
Dr. Allen is a Clinical Fellow in Neuropsychiatry, Brigham and Women’s Hospital, Boston, MA. Dr. Allen reports no conflicts of interest concerning the subject matter of this article.
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