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This is Why Your COMT Gene Result May Not Help Personalize Your Antidepressant Medicine


The gene COMT has made its way onto some multigene panels for antidepressant therapy personalization.  Does it pull its weight, though?  What does your COMT test result tell you about which medicine might be right for your antidepressant treatment?

COMT is the catechol-O-methyltransferase gene.  The protein that it makes helps break down certain neurotransmitters in the brain like dopamine, epinephrine, and norepinephrine.  Everyone inherits two copies of the COMT gene, and there are several forms which you can inherit from one or both of your parents.  There have been a number of studies looking at the relationship between a person’s inherited copies of COMT and development of psychiatric conditions.  Yet even with all this information that seemingly relates to antidepressant therapy, your COMT gene result may not provide much help for your doctor in choosing the best medicine to treat depression.  Let me explain why.

Even if a gene is involved in the pathway of a medicine, such as COMT and the breakdown of neurotransmitters, this doesn’t always translate to a relationship to the correct medicine to use or to the right dose.  Several societies have published guidelines about how to use pharmacogenetic test results to personalize a person’s antidepressant therapy.  They include CPIC (www.cpicpgx.org), the Dutch Pharmacogenetic Working Group (https://upgx.eu) and the International Society of Pyschiatric Genetics.  Each of these 3 societies have looked at the evidence in the scientific literature for COMT and antidepressants and each of these societies have determined that there’s not a strong evidence base for how to use your COMT test result for choosing therapy.  There’s no dose or medicine that your doctor could focus on adjusting based on this result.

Your COMT genotype could be interesting to know, however.  The most widely studied copy of the COMT gene is a single nucleotide change at position 158.  The change from a G to an A in the DNA causes a substitution of the amino acid valine (Val) with methionine (Met) and results in low activity of the COMT protein.  Experts have labeled this change in the COMT gene the rs4680 allele.  There have been studies associating rs4680 with the development of PTSD, with major depressive disorder, and with schizophrenia.  However, it seems that for every study that finds an association, there’s a published study that looks for an association but doesn’t find one.  Nevertheless, if you and your doctor do have your COMT test result from a multigene panel, it could open up dialogue about the likelihood of you developing depression after exposure to adverse life events or during stressful periods.  But for medications to target based on this gene result, the evidence from scientific studies is too weak for COMT to be helpful in choosing medication therapy.

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