19. Personalized medicine, pharmacogenetic testing: Is it ready for prime time?

Can we use information from our DNA to predict which medication will work for each of us? In this episode, Dr. Elise Fallucco talks about the latest information about pharmacogenetic testing and personalized medicine, and how they can (or cannot) be useful for treating ADHD, anxiety, and depressive disorders. She shares when and how pharmacogenetic testing can be useful.  In addition, she introduces Sequence2script, an online tool to help translate pharmacogenetic test results into clinical prescription recommendations. 

Dr. Elise Fallucco is a child psychiatrist, mom, and host of PsychEd4Peds.  She is a Professor of Pediatrics and Child and Adolescent Psychiatry with over 14 years experience in training pediatric clinicians to identify and treat mental health problems.

Check out our website PsychEd4Peds.com for more resources.
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Transcript

Dr. Elise Fallucco: 0:21

Welcome back to PsychEd4Peds. I'm your host, Dr. Elise Fallucco, child psychiatrist and mom. Today, we're talking about a little bit of a hot topic, which is pharmacogenetic testing and personalized medicine or personalized mental health treatment. And so in today's podcast, what we're going to do is talk about can pharmacogenetic testing help us choose the right med for ADHD or anxiety or depression, what information can this clinical tool give us and what's the best way to use this information to help us help our patients Pharmacogenetic testing is usually marketed to families with the idea that this simple test can tell you what medicine is going to work for their child. The promise of this type of personalized medicine is that we'll be able to know from the start, which med is going to be the best fit for somebody. And I'm sure your patients asked you questions about this. I even have some of my friends who were asking me questions about this, is this useful? Is this ready to go? Is it worth the investment. when I think of pharmacogenetic testing, I think of the stoplight with the red, yellow, and green colors. And for those of you who have already ordered it from some of the commercial companies, what happens is you'll get your patient's DNA sample and they'll run the testing and then they'll come back and they'll give you an answer in one of three columns that either there are red meds that you really should try not to use for the patient. There are yellow meds that can be used with caution, And there are green meds that can be safely used for the patient. Now, this would be great if we could take this red, yellow, green information at face value. The hope is that we could use this information upfront to be able to dictate which medication is going to be effective and well tolerated for our patients. And this could be helpful for ADHD when we're thinking about stimulant trials or perhaps most valuable for treatment of anxiety and depression, where we're thinking about the SSRI medications. SSRI trials can be really lengthy because we know it takes four to six weeks for these medications to take effect in your body. And so the question is, could we speed this up? Wouldn't it be great to know at the beginning, which medication is going to be most helpful or most successful and best tolerated for an individual? If we're thinking about medications for ADHD, unfortunately, this testing is not ready for prime time. We don't have any actionable data or actionable evidence based on PGX or pharmacogenetic testing that can really help us choose which medication is right for which person. And I hate to be the bearer of bad news, but when it comes to finding medications for youth, with anxiety and depression, the science is not there yet. As far as the red yellow and green distinctions Sometimes meds that are listed in the green section, are not even meds that have been well studied and or approved for the use for depression or anxiety in children, adolescents. Almost always in the green box is desvenlafaxine which is Pristiq and Pristiq is great. It's an SNRI. But we don't have a lot of evidence for that. And if somebody has anxiety or depression, that's not really our first line treatment for children and adolescents. And so green doesn't mean go. Pharmacogenetic testing gives you more data about pharmacokinetics, meaning about how your body metabolizes certain medication. And it provides less information about pharmacodynamics, which is how the drug or medication works in your brain. It's telling you which medications are you more likely to develop side effects for so that you have to dose them lower or, accordingly. But not telling you which medicines are evidence-based treatment for depression and anxiety. The gold standard of care is always when choosing a medication to think about, what are the current target symptoms that somebody has. Then you look at the evidence-base and think about what are the meds that we really have good data to show her effective in this particular condition and then thirdly, you really ask about family history of response to meds. Does mom or dad take a medicine that's really been helpful for them or on the other hand, is there something that someone in the family has tried that has not been very helpful? And then you use this information to guide your treatment decision. Okay, fine. So we know that this information is not going to tell us which medication is the best one. That's going to work the best. For our kids with anxiety and depression. But The big question is whether or not this particular testing can give us an edge or a leg up. Assuming that we're using the gold standard of care to choose a medication by thinking about these principles that we just discussed. How does that compare to gold standard of care plus having access to pharmacogenetic information? Well, I'm so glad you asked, because in fact, there's actually a randomized control trial of adolescents with depression that seeks to find the answer to that exact question. we have this really elegant, randomized controlled trial that was recently done by Jeff Strawn and his colleagues where they randomized adolescents with depression to treatment as usual or a gene informed arm where the clinicians were given extra pharmacogenetic data. And they took almost 200 adolescents ages, 13 to 18 with depression and they checked outcomes at eight weeks and at six months. And the hope is that this extra information would lead to more rapid response or perhaps better outcomes. But what they found is that there were no differences between the two treatment arms between the gene informed arm. And the treatment is usual arms at eight weeks or at six months in terms of improvement in symptoms, side effect burden, or family satisfaction. Pharmacogenetic testing for depression based on this trial was not more effective than treatment as usual for adolescent depression. And in fact, there were fewer adolescents in the gene informed arm that was getting the red, yellow, and green stoplight information who were actually on SSRI. Which are FDA approved. And they were more likely to use off-label medications. Which is what we were worried about with the advent of pharmacogenetic testing, which is that this oversimplified red yellow and green thing might override our clinical wisdom. So now I'm going to add a little curve ball just to make this more complicated. We're starting to have emerging evidence that when we're prescribing two medications in particular Citalopram which is Celexa or escitalopram, which is Lexapro that this data can be helpful for guiding dosing and titration. I'm going to share that they're both metabolized by. The two C 19. Cytochrome system, which makes me really happy. And nobody else cares about this level of detail, but I'm sharing it anyway. And so the reason why this is interesting is that in our typical adolescent population, there's actually a fair percentage of people who are not normal metabolizers of this particular cytochrome. So they're either ultra rapid or potentially ultra slow. And so what that means is if you're an ultra rapid metabolizer and you eat up the medicine really quickly than a standard dose will seem like a low dose in your body. And on the other side, if you happen to be a really slow metabolizer, then a standard dose of this medication may actually feel much higher in your body because of how your liver and your body are breaking it up. If you happen to be considering using either of these two meds for your patient, and you happen to have pharmacogenetic results available, then it can guide you in terms of how you should dose and titrate these meds. There happens to be a new free tool that's available online for clinicians And it essentially helps you translate pharmacogenetic test results into clinically useful recommendations. and it's called Sequence2script. So it's sequence the number two script. Dot com. This particular website is very evidence-based. And it incorporates C pick guidelines. CPIC is the clinical pharmacogenetics implementation consortium. So it's incredibly, evidence-based recommended by, a number of experts in the pharmacogenetics field and it's fairly straight forward. And can give you information about dosing. If the patient happens to have pharmacogenetic testing. And you have the results available. You enter information about the various genotypes for these cytochromes and then you enter their current medications. And then you finally enter the medication you're considering which in this case would be citalopram or escitalopram. And a magical formula will spit out the information that you need to know. Based on the patient's results from pharmacogenetic testing it could say something like Consider starting at a much lower dose of these meds. And you may need to max out at a lower dose than you would expect because your patient is a really slow metabolizer or on the other hand, if you happen to have somebody who's a super fast metabolizer. Then you may want to start out at a higher dose than you would consider and even titrate above the max recommended dose that we typically use in adolescents who are not ultra rapid metabolizers. And I'm trying to synthesize this information because. In some ways, it seems a little contradictory. On the one hand, we don't need pharmacogenetic data to help us choose which medication might work for somebody. However, if you're thinking about prescribing one of these two medications, it might be helpful to know if somebody is going to be extra prone to side effects because they slowly metabolize it and can easily build the medication up in their system. Or on the other hand, if they're going to be somebody who rapidly metabolizes the medicine so that we're not going to expect to see responses at lower doses and we may need to get to higher doses. What was really interesting is that when I was listening to this information about pharmacogenetics at this conference, that I was just at one of the people in the audience, raised their hands and said, this is a lot of steps. You've got to get the testing and wait for the testing to come back and then use it to guide dosing. And how long is this going to take? And their question was what is wrong with start low and go slow. This is the process that we have typically used for dosing medications in psychiatry, start at a very low dose and then gradually increase the dose as tolerated until you notice an effect and you're not hitting side effects. So Jeff Strawn, who's one of the leading experts in pharmacogenetics and psychopharmacology for children, adolescents in general had a beautiful response. And what he said is here's what's wrong with start low and go slow. If they're a poor metabolizer, even low, maybe too high. And so you may want to consider choosing a different medication entirely because they could be so such a poor metabolizer that even a low dose may feel like a toxic level dose to their system. On the other hand. What if they're an ultra rapid metabolizer? If you start low and go slow, that's going to be too slow. It's going to take you forever to get up to the point where you're at an effective dose. And in the meantime, this is weeks of life, months of life lost. To morbidity. For the teenagers and the kids that you're taking care of. So his response was if we can get someone better, more quickly and you can reduce morbidity, why wouldn't you do that? Big take-home point. We're not at the level where pharmacogenetic testing can guide which medication is going to work for our patients with ADHD or at this point with anxiety and depression. There are only certain cases in which this information can really be clinically helpful for you to guide dosing and titration for the two specific medications. Citalopram and escitalopram, where we would expect to see gene related variations in metabolism of these meds. So if a parent comes to you with this data or ask you questions about it i hope you feel more confident responding to them and i also hope that you know now where to go to translate any of these findings into actual prescription recommendations Available online at sequence. The number two script.com. and i'll have some more information about this on our website psyched the number four paeds.com. so I'm really curious to hear what your experiences have been with this, or if you try this. In your practices and what you think and how useful it is, or is it clunky? And also, I just want to do a quick shout out. What questions do you have? What are the controversial issues in the field? What do you want to learn about? So please email me at info at Psyched4peds.com or visit. Our website at Psyched4Peds.com and send me a chat or a message through the website. And let me know what you're interested in. I also feel free to DM me on Instagram with questions, ideas, topics, responses. And again, thank you so much for listening. Thank you for tuning into psyched for paeds and see you next time.