In an interview with pharmacy times, Adriana Kekic, Ph.D., pharmacogenomics clinical specialist at the Mayo Clinic in Phoenix, Arizona, discussed presentations at the 2024 American Pharmacists Association (APhA) Annual Meeting and Exposition. Kekich said pharmacogenomics could help streamline the prescription and administration of psychiatric drugs, avoiding the trial-and-error process that is common with these drugs.

Q: How is the use of pharmacogenomics in psychiatry unique?

Adriana Kekic, PharmD: Well, I think psychiatry is probably the second area of ​​clinical practice that deals with a large number of drugs with so-called FDA pharmacogenomic biomarkers. So if you actually go to the FDA website and look at the drugs and genes table, or the drugs table that includes pharmacogenomic biomarkers, there are a number of drugs, particularly oncology drugs, and both of those have significant You will notice that there are several. Germline and somatic mutation biomarkers, pharmacogenomic biomarkers. But the second, just behind oncology drugs, are psychotropic drugs, which are used to manage mental health disorders such as major depressive disorder, generalized anxiety disorder, schizophrenia, bipolar disorder, and neurologically related disorders. It’s medicine. So, [there are] Numerous drugs with pharmacogenomic biomarkers.

Q: Why is there so much trial and error in psychiatric treatment?

Adriana Kekic, PharmD: Yes, this is a really good question. And my thinking is that we usually approach this from a pharmacological perspective rather than a disease or diagnostic perspective. But there are two things I always think about. One is that we know that different people react differently to drugs, so giving the same correctly prescribed drug requires a lot of trial and error. Let’s say you’re managing major depressive disorder and you’re following guidelines, clinical guidelines, and you’re giving someone an SSRI, for example. So it is prescribed correctly based on indication, weight and everything else. Clinical factors. Still, it is intuitive that many patients do not respond appropriately, meaning they become ineffective, meaning the drug does not work and symptoms do not improve. Or, on the other hand, some people may experience various problems, side effects, and even toxicity that prevent them from continuing the treatment and therefore simply have to discontinue the treatment. So from a genetics perspective, we actually have some answers, and we’ve been getting answers for years, about how genetics affect how people respond to drugs. Masu. We also know that there are individual differences in drug reactions. In other words, mutations, or more precisely, precise genetic variations, may exist. And when I say mutation and genetic variation, mutation simply means that there are rarer events, whereas genetic variation is actually mutations that are more common within a population. And that’s what we’re really aiming for. So we can now do pharmacogenetic testing and find out if someone has a mutation or mutation in a so-called pharmacogene, that is, a gene that is involved in pharmacokinetic proteins, or a gene that gives the instructions to make a pharmacodynamic protein. You can basically evaluate whether or not it exists. The reasoning behind it is very simple. If there is a significant mutation that significantly changes the way a protein is produced, it can affect pharmacokinetics or pharmacodynamics. Translation can affect how someone metabolizes and responds to drugs.

And this is seen with many antidepressants and psychotropic drugs in general. Here’s why: Many of these drugs, especially SSRIs, SNRIs, and tricyclic antidepressants, are processed by so-called CYP metabolizing enzymes, especially CYP2D6 and CYP2C19. These are like the two MVPs or VIPs of pharmacogenomics. Psychiatry, or the treatment of mental health disorders. The reason is that these two pathways metabolize the majority of these drugs. So the other part is that not only do they contribute to metabolism, but more importantly, these are what are called highly heterogeneous genes. In other words, if CYP2D6 and CYP2C19 are her 100-person room, [people]About half of us are very likely to be normal metabolizers, which means we won’t find major variations in these genetic pathways. But for the other half of us, we don’t know. We fall somewhere on the spectrum between having no enzymatic activity due to a specific mutation that causes enzymatic activity, and at the other end of the spectrum, perhaps having very enzymatic activity. You’ll probably end up doing it. Metabolic activity increases, which may cause the drug to be processed faster and become less effective.

Just a quick note: As you can see, I love pharmacology and genetics. But I really wanted to make a quick note. So, for example, if you think about a condition like major depressive disorder, which is very common in the United States, one in five of our girlfriends might actually have this disease. That’s it. And these situations are also very common worldwide. For example, major depressive disorder is a very diverse illness. And, you know, we use her ICD 9 or 10 code or the DSM manual to guide her to say, Major depressive disorder. ” However, if you peel back the layers at the molecular level, you will find that it has various characteristics and can be expressed differently depending on the person. And all of the drugs that we prescribe as first-line treatment, or that could be indicated as first-line treatment, are the most individualized, so to speak, most effective for those patients. It does not necessarily mean that it is a perfect treatment. Therefore, we need to better understand the molecular features behind these symptoms, and genetics is helping. And they can be better matched with currently available drugs, perhaps resulting in better treatment strategies to address those symptoms in the future.

Q: How will the introduction of pharmacogenomics benefit psychiatric patients?

Adriana Kekic, PharmD: Well, we’ve been doing pharmacogenetic testing for the medical community, the pharmacy community, the medical community for several years. How to do it is very simple. Typically, we identify patients who are difficult to administer medication, so this is a type of reactive test. For example, you may have a patient who may have tried antidepressants or anti-anxiety medications. But let’s say it didn’t work or you couldn’t stand it. So we order pharmacogenetic testing to find out if a person has a genetic mutation, either in the genetic pathway, like the drug-metabolizing enzyme pathway, or perhaps the serotonin receptor, serotonin transporter, You can find out if any of the pharmacodynamic genes, such as dopamine receptors. They can be identified through genetic and pharmacogenetic testing. The role that pharmacists currently play is not necessarily that of a test interpreter, but rather that of an individualized treatment guide. When those results come back, we consider genetics, what those tests are showing. [and] Determine whether someone is a normal metabolizer and overlay that with other patient details such as clinical factors, renal function, liver function, presence of other drugs, and indications. And we can give you direction here about what’s the best strategy, what’s the best drug, what’s the best dose.

And actually, here in the United States, we’re leveraging clinical guidelines, pharmacogenetic guidelines, from the CPIC (Clinical Pharmacogenomics Implementation Consortium). And many of us who are doing this are leveraging them, either reactively or preemptively, to have things like clinical decision support that can automatically give guidance to health care providers. There may be. If someone is prescribing a drug and that person’s genetics has an impact on that drug, we can use the CPIC guidelines to support clinical decision-making and decide whether to prescribe, not prescribe, or what to do. determine which is most effective. Based on that, what is the most effective dose for that patient?