Implications of Pharmacogenetic Testing in ADHD


Stephen Faraone, PhD; Theresa Cerulli, MD; Craig Chepke, MD, FAPA; and Andrew J. Cutler, MD, discuss implications of pharmacogenetic testing in ADHD.

Theresa Cerulli, MD: Something we haven’t talked about yet, because it is often misunderstood, is what do we mean by genetic testing? And I can’t tell you how many times this has come up when I’m doing a presentation, where clinicians are misunderstanding that somehow that helps you pick the right medication, or the right class of medication for patients. I want to emphasize the genetic testing that exists is simply metabolism. DNA-based evidence for how one might metabolize the medications we have available in psychiatry. And certainly, the amphetamines versus the methylphenidates. But it can’t choose the most efficacious medication. It can’t necessarily predict who truly is going to tolerate or not tolerate. It’s just a guide in thinking about how the individual patient may metabolize, faster or slower, that given drug that you’re about to prescribe. That’s it.

Andrew J. Cutler, MD: Well, that’s not entirely true. These tests are mostly geared towards pharmacokinetics, as you’re talking about. But there are some pharmacodynamic tests embedded in there. And one that helps me with ADHD, believe it or not, is COMT. COMT is catechol-O-methyltransferase. That’s the enzyme that breaks down dopamine. Most of the time, an enzyme with a mutation is less effective. This is a mutation that makes it super charged. And it will chew up dopamine, especially in the prefrontal cortex. And patients who have that mutation, I have found, sometimes do better with an amphetamine, which is a little more potent at releasing dopamine, believe it or not. Now, it is true that you can use these tests to look at pharmacokinetics. For instance, methylphenidate is metabolized by CES-1, which is genetically variable. Amphetamine is mostly metabolized by CYP2D6, which we know is genetically variable. But you’re right. In general, they’re not as good at helping us pick the exact medication, with a couple of caveats. And these tests are evolving. I’m not an apologist. I’m not- I’m just trying to be realistic about them.

Stephen Faraone, PhD: I’ve studied this a lot in my own career of pharmacogenetics. And number one, it’s very clear from all of the professional societies that are interested in this as The American Psychiatric Association, The American Academy of Child and Adolescent Psychiatry say that pharmacogenetic testing for everybody is not warranted at this time. The associations differ on whether it’s useful in specific cases. And I would say there’s some agreement that, in certain cases, it can be very useful. Particularly difficult cases, where- being hard to figure out what medication would work well. Maybe with, for example, this patient who’s tried so many drugs, and has failed so many drugs. In some cases, pharmacogenetics will discover a genetic variant that may explain what’s happening, and guide treatment. But it’s not going to be for everybody. In fact, there have been studies showing that people that use them on all patients can sometimes go outside of guideline treatment. Because if they’re used in a either too much of an algorithmic way, because they’re not, the evidence base for them is weak, sometimes it points somebody to a medication that actually wouldn’t be a first or a second-line treatment. And that’s not a good thing.

Transcript edited for clarity

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