Pharmacogenetic Insights: A Conversation With John J. Miller, MD
Explore the complexities of pharmacogenetic testing in psychiatry, uncovering its current limitations and future potential in personalized medicine.
BRAIN TRUST: CONVERSATIONS IN PSYCHOPHARMACOLOGY
-Series Editor Joseph F. Goldberg, MD
Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sits down with Psychiatric Times' very own editor in chief, John J. Miller, MD, to discuss the current state and future directions of pharmacogenetic testing.
"Pharmacogenetics is almost like a Rorschach test in the eyes of many practitioners and patients. It is thought to be a projective that you sort of identify in various ways. It is going to tell me things about myself. It is going to make predictions. It is going to help me guide treatment. It is going to override
clinical factors, patient specific features that influence outcome, and really get to the heart of things," said Goldberg.
Miller shared his initial reactions to the introduction of this testing: "When pharmacogenetic testing first became available about 12 to 14 years ago, I was excited. And then, as I learned more about it, read the literature, and became aware of the institutions that exist to vet genes and whether or not they are clinically actionable, I became very frustrated by how overly adoptive pharmacogenomics has become when really the evidence base is not there. In fact, as we have learned more, it has become less evidence based in terms of clinical applications."
The International Society of Psychiatric Genetics published a review article on genetics and psychiatry, and they concluded that there are 4 genes that are evidence based and actionable: CYP2D6, CYP2C19, HLA-B*1502, and HLA-A*3101.1,2
"I think there is a mythology that all you have to do is do the gene testing, and you can choose a drug based on the results," shared Miller.
When it comes to testing, Miller believes we need to alter the thinking around testing in psychiatry: "We are very selective, and we do it for a reason, because we have a hypothesis. Maybe there is atrophy. Maybe we have some neurological sign. It really should spark the curiosity of the clinician to think, would a test—any test, for that matter—be informative to answer a question. That is how I always think about any test in medicine."
Together, Goldberg and Miller stress the importance of therapeutic drug monitoring and personalized medicine, while acknowledging the limitations and ongoing evolution of pharmacogenetic testing.
"We have a common goal. We want to do a test that is scientifically informative for you. If there is a test out there that I think will help us answer a question, I promise you, I will order it, but not everything comes down to a particular test, right? There are certain clinical impressions we have in medicine. How do you diagnose migraine headaches? There is no test for that. How do you diagnose your bowel syndrome or tinnitus? There is no test for that. So we look for tests to someday enhance or augment what we think is an observation that we would like some corroboration for," said Goldberg of speaking to patients about testing.
Miller agreed, concluding that, "We do not want to put the car before the horse, and so let's stick to the what the experts who really know this stuff are guiding us, and then incrementally use what becomes clinically actionable or evidence based."
Dr Goldberg is a clinical professor of psychiatry at The Icahn School of Medicine at Mount Sinai in New York, NY and the immediate-past president of the American Society of Clinical Psychopharmacology.
Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric Times; Volunteer Consulting Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.
References
1. Besterman A, Alnor MA, Castaño M, et al.
2. Nurnberger JI Jr, Austin J, Berrettini WH, et al.
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