Inside the GENOME

Myriad Live - Let's Talk Mental Health Genomics!

May 16, 2022 Myriad Oncology Season 2 Episode 10
Myriad Live - Let's Talk Mental Health Genomics!
Inside the GENOME
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Inside the GENOME
Myriad Live - Let's Talk Mental Health Genomics!
May 16, 2022 Season 2 Episode 10
Myriad Oncology

Myriad  Live episodes are recordings of an open-forum webinar hosted by Dr. Thomas Slavin. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, visit for a list of dates, times, and subjects.

References for this episode:

Show Notes Transcript

Myriad  Live episodes are recordings of an open-forum webinar hosted by Dr. Thomas Slavin. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, visit for a list of dates, times, and subjects.

References for this episode:



0:00:13.3 Dr. Thomas Slavin: Welcome. This episode of Inside the Genome is a recent recording of Myriad Oncology Live, a webinar hosted by me, Dr. Thomas Slavin, Chief Medical Officer for Myriad Genetics. The opinions and views expressed in this recording do not necessarily represent those of Myriad Genetics or its affiliates. To participate in a future recording, please visit Myriad Live for a list of dates, times and subjects. I look forward to exploring the world of genetics with you all.




0:00:40.9 DS: Hello, everyone, welcome to Myriad Live. I'm so happy that you're able to spend your afternoon and, or night time with us, depending on where you're at in the country. Today, we are doing a special Myriad Live, it's actually the first ever that we've done on mental health genomics. So very excited to get into a little background on what's going on in mental health and how genomics plays a role. A little housekeeping as always, to start, if this is your first time to Myriad Live, you might not know what it is, that's okay. We are a... This is a webinar-based platform that is just something we host at Myriad every two weeks or so. And the theme is really picked earlier, a few months usually in advance, we have our current schedule here, we have... We just went over let's talk oncology, spring oncology conference review, and then today is mental health genomics, we're gonna be, later this month coming around to emerging biomarkers for Li-Fraumeni syndrome screening. We have a bunch loaded up also in June and July that we're gonna put so if you know any of these are of interest to you pop on, you can register, you can just Google Myriad Live and and find this fairly easy. And all the registrations are right there.


0:02:13.6 DS: And this is just meant to be an open communication platform. So, we'd like to do some education. We try to keep it relatively unbranded and just want people to be able to learn and have a place where their questions can be answered in a safe spot. So if you have any questions whatsoever, let us know. We try to keep them theme based, so today's mental health. But if you have a burning question on PALB2 or something like that, feel free to let us know. And we will try to get it answered.


0:02:46.1 DS: Well, without further ado, I'm gonna stop sharing my screen here. Oh, also, before I... Two more things, actually, before I leave the screen. One, we have in all these, they are recorded. So feel free to unmute yourself, ask questions, whatever you want. But if you don't want to unmute yourself and ask questions, you can also send questions through the chat. Shelley, thank you so much as always for coming on. I will graciously ask you [chuckle] to run the chat, if able and thank you so much. So feel free to send questions to Shelly and she always, as people know, if you've been on this before, does an excellent job of making sure all these get addressed. And then also, because we do record these, one of the benefits is we can put the content up on a podcast. So we put them up on inside the Genome, which yeah, has been really taken off.


0:03:43.2 DS: So we just had 4500 downloads as of a couple days ago. So we see a ton of content here. And anything this is Myriad Live, is from these webinars, if it does not say Myriad Live, like we just posted the 9/11 is a very good podcast, for those that are just interested in what genetics companies do in general, when they're not doing sometimes the main thing that they say they're doing, like selling commercial testing, etcetera. When I came to Myriad actually was really surprised to know that, not... Surprised to know is not the right terminology. I just didn't even think to question that where all the survivor identification work was going on in this country during the 9/11 tragedy.


0:04:40.3 DS: And it actually was happening a lot at Myriad. We were a nationally rooted company heavy on genomics with massive capacity to collect samples nationally, and to do a lot of valuation. We had people here and expertise that knew a lot about family matching by really complex genomics. And it's... I sit down with two individuals that were here during that time. And this is just really, we go pretty deep into how this all came about, and what was done to really stand up and do the best for the country. So, definitely point that one for those looking for something to listen to. That's a pretty... It's heavy, so put it that way, but it's a very... You'll learn a lot, from going through it. And then... Yeah, any of the other ones again, that same year live, those are from the... So, usually we try to keep the non Myriad Live podcast to about 20 minutes or so. This one I think was a little longer, one of the longer ones, but these Myriad Live ones are about 60 minutes. So today, we have two special guests in particular. We have... Sorry, I'm trying to see all, what you sent me, Jay. So I just want to make sure I'm [chuckle] getting this all correct.


0:06:10.0 DS: We are privileged to be joined by Jay Elliot. He is the Vice President of Medical Affairs for Myriad Mental Health. And he is really integral to the GeneSight psychotropic test. He holds a PhD in Biological Psychology from UNC at Chapel Hill and has worked in pharmaceutical and biotech for 15 years. So he is an excellent advisor for our mental health unit. And then we are also privileged to have Dr. Rachel Earls. She's a senior medical science liaison for the GeneSight test. And she has a PhD in Neuroscience from the University of Georgia and was voted medical science liaison of the year for Myriad Health in 2021. So very excited to have you both on. And as I brought up originally, I mean this kind of came about because I was talking with Jay and he alluded me that mental health awareness, and this was many months ago, I don't remember, but yeah, he said mental health awareness month is in May, maybe we could carve something out.


0:07:24.0 DS: So that's how this all came to be. And really it's no shock to everyone here that's listening that mental health services are really just on the rise. Jay and Rachel gave me a little insight to one of the latest GeneSight mental health monitor surveys that were done nationally showing that two out of three women diagnosed with depression or anxiety say they've reached or are approaching their breaking point regarding mental health. And that this breaking point can be defined as negative impact or a significant strain on anything from social life to caring for loved ones at home, or any professional obligation problems. Four out of 10 women without a diagnosis of depression or anxiety say they have reached or are reaching their breaking points. So we have real crisis going on right now in this country with the state of COVID and just everything else going on, social media, etcetera. We have with that an increasing demand on our healthcare service providers. In December, 2021 they wanted me to bring up that the New York Times had a survey of 1,320 therapists who found that social workers, psychologists, and counselors from every state say they can't keep up with all the unrelenting demand that's going on in the field.


0:08:55.3 DS: And this is not only for adults, it's including children and people are just desperate for support. The ability to see all the people that need seen is really around just trying to find streamlined ways to do this. And a lot of that is hits on a consistent issue that continues to pop up, medication management. I mean, a lot of people know a lot of the pharmacology that's used and treatments used to take care of people with mental health conditions take a long time to kick in. And a lot often they don't work the first time. So that's a lot of what we'll talk about today. How genomics can play a role in that. And this trial and error it can take years. So what we're trying to do with the GeneSight psychotropic test is have something that can take years and make it a more streamlined and fast process where people can get matched to the right drug quickly. So I really appreciate you both being here today. Thank you so much for coming on. And I just wanted to hear after going through that a bit, your impression since you really live and breathe all of this, of the current mental health state in the country.


0:10:16.5 Jay Elliot: Sure. So, TJ, I guess I'll start. And I just wanted to likewise echo thanks to you for having Rachel and I on tonight. Very exciting to see everybody. And as you mentioned, it is mental health awareness month. So what better time than today to have a discussion about mental health and also link it to genetics, which is obviously the typical theme of Myriad Lives. So I guess with that, I'll just start with some sobering statistics. And just to, again, echo something you mentioned, it really is not an overstatement to say that there is a mental health crisis in this country. I know you mentioned a couple of articles. There was a big article of a big feature in the New York Times this weekend about adolescent mental health also reaching a crisis point.


0:11:00.2 JE: So the writing is all over the place. And I guess what I'd like to do just for a moment is focus on the burden to the provider. And also just the lack of available mental health services to many Americans. Just to focus on a couple statistics. Kaiser family foundation recently reported that there are nearly 130 million Americans who don't have adequate access to mental health specialists. So they just live in sort of mental health deserts, if you will. And that situation's likely to get worse because as we're seeing, there's a crisis of the need for mental health care. And there's also a paucity of people who are entering the mental health field. And so over time, it's likely that this progressive lack of providers combined with the increased need is gonna just make the situation worse over time. And in that absence of dedicated mental health specialists, the people who bear the load for that are primary care physicians, generalists, nurse practitioners, physician assistants, and that's shown because 80% of people who have some sort of behavioral health disorder consult their primary care physician in any given year. So the vast majority of people who've got a behavioral or mental health disorder are gonna talk to their primary care doc about it, and believe it or not 50% of all of the behavioral health visits.


0:12:22.3 JE: Nationwide are conducted in primary care. Interestingly, there's a group called the Primary Care Collaborative, they're focused on things like patient-centered medical homes. And when they look at the conditions that really are driving cost and burden to the healthcare system, depression pops up as number one, and that's because of its effect on work related productivity, medical costs, as well as pharmacy costs, not to mention just the intangible effects on quality of life. So Rachel, I know you spend a lot more time in the trenches talking to physicians, and I guess I would just wonder from your perspective, is this something you see? What is the State of the Union as far as the average healthcare provider with regard to mental healthcare? 


0:13:07.3 Dr. Rachel Earls: Yeah, absolutely. As part of the medical team for GeneSight, a big part of my job is talking with healthcare providers every day about the GeneSight report, how to utilize it, the science behind it. And so, many people think I would probably spend most of my time in psychiatrist office, but it's actually not the case. I spend the bulk majority of my time talking to primary care providers who are just inundated with an increase in seeing patients with depression, anxiety, ADHD. And in fact, our most recent GeneSight Mental Health Monitor that TJ mentioned, it was shown that nearly... I think it was 46% of patients said they would actually talk to their primary care physician first about their mental health concerns rather than going to a mental health specialist. It seems that there is, as Jay mentioned, an increase in demand, but there isn't a mental health provider for them to go to, so they're seeking out this help from their primary care. And that's where I spend a lot of my time educating.


0:14:03.6 JE: And I guess along with that, if we think about the drugs that are currently used for depression, anxiety and the vast majority of mental health conditions, these are old drugs. The vast majority of them are generic, the vast majority of them act through common mechanisms of action, and yet prescribing is... Well, because of that, prescribing is such a black box. And so it's one of the reasons that pharmacogenomics has really come online as an objective tool that can hopefully help providers get to effective treatments quicker, and so obviously our link to this is having such an offering in the gene psychotropic test.


0:14:40.6 DS: Yeah. And how have people really traditionally prescribed these medications, that's probably where we should start and then we can start talking about some of the pharmacogenomic solutions that have come to light.


0:14:55.3 JE: Absolutely. Well, the average diagnosis and treatment journey is obviously initially confirming a diagnosis and making sure that you at least have a provisional diagnosis of what it is that you plan to treat, and then clinicians will gather all sorts of clinical information and try to use that information to help tune their prescribing. And that could include other non-psychiatric medications the patient's taking, whether they previously tried and either done well on or perhaps not done so well on psychiatric meds, lifestyle, age, allergies, family history. And actually one of the bits of clinical information that probably carries the most weight is, if the patient has a family member that has previously had a psychiatric diagnosis and had some sort of experience with mental health meds, and often a positive experience with the medication in a family member is taken as a proxy that maybe that med might work well on a patient.


0:16:00.8 JE: And there's some good face validity kind of reason why that is a reasonable approach to take, but obviously, just because we share genes with our parents and our family members, doesn't mean that necessarily those meds are gonna work because obviously we get our genes from both our parents. And just as a personal example, I've been GeneSighted and I've had my son GeneSighted and our predicted gene drug interactions and our genotypes and phenotypes are quite different. Just as I wouldn't pick up my mother's glasses and put them on, because we don't share the same eye sight, we also don't share the same genetics as it relates to mental health disorders.


0:16:41.8 DS: Yeah, that's a good analogy.


0:16:44.0 JE: Oh, thank you. [chuckle] I'll credit somebody on our marketing team with that one, but I like it too. [chuckle] And so as a result, it is still a black box with the typical information that clinicians will use to make that initial prescribing decision, and so they usually start low and go slow, titrate up, have frequent visits with the patient to make sure that they're tolerating the medication and are showing some degree of symptomatic improvement. But as reasonable as that is, it can be really problematic, and that's because it's been shown in the largest study of depression and treatment strategies ever, that there really is diminishing returns with this trial and error approach. If you look at the first medication trial, it's roughly 40% of patients who actually undergo a clinical remission and their depression largely goes away, and for every subsequent medication trial, that rate of remission goes down even lower. It's 31% with the second trial and a shade under 15% with the third trial, and along with that increasing... Well, decreasing likelihood of having a clinically effective medication, the side effect burden also goes up. And so, where that leaves the patient is often on this ongoing journey where they're trying multiple meds that involves all sorts of different titration steps, waiting to have some sort of clinical relief, but that can take months or years and can be incredibly frustrating for patients, family members, caregivers and providers.


0:18:22.8 DS: Yeah. Yeah, and even titrating, titrating doses, then you have to wait for another four to six weeks to see if it even had an effect, 'cause it's really challenging. What does this really mean for the health systems and payers, what have you been seeing? I mean, this is a huge burden as we've been highlighting.


0:18:50.4 JE: No, absolutely. And so, reality is that medication failure means more burden on health systems, higher costs for patients, and overall cost to the system. And if you think of any chronic condition like diabetes or hypertension where there's polypharmacy, there's titration, you're looking at sort of clinical indicators to see how the patient's responding. Treating depression is just like that, where if you're not... You don't have an effective regimen, it means that you've got more visits, so more burden for the patient, more cost to the patient, more cost to the healthcare system. You've got the increasing of doses, which can then lead to wasted medication because, obviously you prescribe a number of doses if the medication doesn't work, those drugs get thrown out, you try something new. You can have to sometimes wean patients off ineffective medications, the SNRIs are a pretty good example of something that really shouldn't be stopped abruptly, so that will happen to be weaned down and/or cross-titrated. And needless to say, all of that can lead to distrust and frustration for the patients, and can lead to potentially less adherence, not wanting to carry on with treatment, disappointment, and undermine an otherwise really good patient provider relationship.


0:20:14.8 DS: Mm-hmm.


0:20:15.3 DE: Yeah, I would agree with that, I mean, for our patients, medication failures really could have significant ramifications. First of all, patients, if they don't feel like they're doing well on a medication, if they're having intolerable side effects, they'll stop taking them, so that means wasted medication costs for them, that's wasted time, and as you mentioned with these particular classes of medications, you don't feel the effects right away, it takes time, anywhere from 4-8 weeks is what we hear mostly in the field, so this is an investment in their time, and if it doesn't work for them, that's two months lost. So you think about that from the cost perspective, but you also think about it from kind of the more intangible losses as well.


0:20:53.3 DE: Many patients spend years on this journey trying to find medications that are actually... Work for them, that they don't have intolerable side effect profiles to. And this could have been time when they were enjoying life with their family or doing things they're passionate about. And then one thing I talk a lot about with healthcare providers, and we see consistently in the literature is that, depression rarely happens in a vacuum, depression tends to be comorbid with many other conditions such as cancer, stroke, heart attack and disease, and you kinda get in this positive feedback loop of, if you don't treat the underlying depression or anxiety, patients tend to have those increased comorbidities, they tend not to be as compliant. And so it's frustrating from the top down when this trial and error process continues on.


0:21:40.1 DS: Yeah, yeah, I know all around. And so, how did the field of pharmacogenomics pharmacogenomic testing come about? And yeah, I'd love just to learn a little bit more from your perspective of where all this is going.


0:21:57.9 DE: Sure. So, pharmacogenomics pharmacogenomic testing has roots in many different parts of medicine. To talk specifically about the pharmacogenomic test called GeneSight. So, essentially the premise, and Jay has already hit on this, is that not all patients respond to medications the same, whether they're on the same dose, same exact medication, we're seeing vast heterogeneity of response. And so one of the factors that scientists and researchers realized that may be affecting this variation in response is the genes that control how these drugs do their jobs. So whether it's the genes that control how a patient metabolizes a medication, which can have really big implications on dosing recommendations, or genes that regulate the mechanism of action of a drug, so how the drug does its job. And so what the GeneSight test does is that it takes all of that into account. So it's a pharmacogenomic test, and it analyzes clinically significant genetic variation, and how this may impact a patient's response to those drugs. So the GeneSight report, and I think we'll show you a little bit of what it looks like later, but it looks at 64 FDA-approved medications for the treatment of depression, and it categorizes them into different bins based on the expected impact a patient's genes may have on their response to those medications.


0:23:15.6 DE: And so the way we always frame this when we're talking with clinicians is that this is a tool, this is a tool that is meant to be used in conjunction with all of the other clinical factors that Jay mentioned previously, to try to arrive at the most appropriate medication for the patient. And it adds a level of objectivity, because as we all know, the patients genes aren't going to change. So it allows to have some objective data in that decision-making process. And specifically on GeneSight, one thing that's a big differentiator compared to other pharmacogenomic tests is the way that we analyze this genetic variation. So we use something that's called a combinatorial approach, so that's our kind of proprietary algorithm. And all that means is that we look at multiple genes that affect medication response, and we look at them in a weighted fashion.


0:24:03.5 DE: So we don't treat each gene as if it contributes equally, because we know that's scientifically not the case. We give each gene a specific weight. And our algorithm is based on a myriad, no pun intended, of published clinical studies, pharmacology, internal data, external data. And what's great and what I really have a lot of passion talking about is that the report is backed in scientific evidence, so we have multiple peer-reviewed publications, looking at the clinical utility, we look at economic utility as well. As we've mentioned here, being chronically sick and being on multiple medications is not cheap, and so we have data to show the utility of GeneSight in that realm as well, and so the way we... As I mentioned, the way we frame it is that this is a tool for providers to help with the medication selection process.


0:24:53.4 DS: Yeah, that's incredible. And was this one of the first tests to enter into the space? 


0:25:01.9 JE: So I think it's probably fair to say it was one of the first commercially available panels. There are certainly lots of academic labs that will do single gene analyses. But I think we are among the first, well, certainly the first to use this combinatorial approach, that Rachel described. And also I think when you see our report, unlike something that would just give you a genotype, if you ordered it from a local academic lab, obviously there's the richness of the report and the clinically actionable information that it provides.


0:25:29.9 DS: Yeah. Yeah. 'Cause that's kind of the big thing. Most... Like you said, Rachel, I mean, you're spending a ton of your time with general practitioners, and then even psychiatrists, these, these individuals are not geneticists. [chuckle] So it's gotta be something that's easy for people to, go through. How have you... How's the team been working on making it, simple for people to understand? 


0:25:58.2 JE: So TJ, I think I'm gonna take this one and I'm gonna share my screen.


0:26:03.6 DS: Yeah, sure.


0:26:04.8 JE: Yeah. I'm actually gonna take us all to Because it's actually a great place where we've got a sample report as well as a whole bunch of other information. And I guess to answer your question, I mean, there's really three things that I think make the test interpretable for the non-genetically inclined clinician. One is the fact that the report is designed in a way to give clinically actionable information and be easily interpretable. The second is that on, there are a ton of resources. There are white papers, other infographics and information that can help better understand the genes that underlie the test, the gene drug interactions, why we have some of the genes that we do. And then the third thing is that we have people like Rachel. So we have a whole team of people who are in the field like Rachel, who work with providers to help them better understand the test and we've got an in-house team of medical information specialists. These are all doctoral level professionals, who work very actively with clinicians to help them maximize the value of the test. And so from here, I'm gonna go to the four clinicians sites where we will find the a sample report. And just to confirm, everyone seeing my screen.


0:27:21.3 DS: Yeah.


0:27:21.8 JE: Alright. So just scrolling down from the four clinicians, you can see that there is this learn more about the report link, which has got nicely annotated, interactive report. And so this is page one of the GeneSight psychotropic report, and I'm gonna show you three different sections. So this first part of the report takes different classes of medications and based on the patient's genotypes bins the medications into either green, yellow, or red, which come across or which signify use as directed. So there aren't any known gene drug interactions that, are known to affect how the medication might work in the patient. Moderate gene drug interactions, which is kind of a use with caution or with certain considerations and then significant gene drug interactions, which might involve something like a labeled contraindication due to safety, or other factors that really should require, some significant sort of clinical thought before, considering those meds.


0:28:25.1 JE: But it's really important to say that it's not a guarantee that the meds in green will absolutely work, nor is it true that the meds in red are not suitable. I mean, you really do need to use all of those other clinical factors we talked about, also think about what conditions the patient is presenting with, what the drug, what, evidence base exists for the drugs. But in general terms, this information is what's used to then help with all those other clinical factors you plan on prescribing. And on top of that, the other thing that is in these pages, and you can see on the second page are these footnotes. And you can see for all of the yellow or red meds, there are footnotes that describe what those clinical considerations might be. So if you happen to be a slow metabolizer, that means that you may well have higher than expected levels of serum levels of the drug at which point it might be most appropriate to start low, go slow as we talked about earlier.


0:29:26.3 JE: You might be an ultra rapid metabolizer where you'd be predicted to have lower than normal levels of the drug. So they're starting with a higher starting dose and or titrating more aggressively may be more appropriate. So these clinical considerations, I heard one provider describe them as the juicy gold of the report in that they really do sort of help you understand whether it's a titration issue, whether you may be better off choosing another medication, etcetera. And so a lot of that information is given there.


0:29:57.6 DS: Yeah. Do most people follow levels over time? 


0:30:04.2 JE: No. In fact they don't. I mean, there, there certainly some drugs where you absolutely should follow levels like Lithium and that's just has to do with the therapeutic index of the drug and toxicity. There are places where you can order levels and for some drugs where there's a narrow therapeutic index or polypharmacy, it might be clinically relevant to do so, but in the vast majority of cases, people do not do not follow levels.


0:30:28.2 DS: Yeah. Yeah.


0:30:28.9 JE: And obviously there's depending on your lab there, they can be hard to order too.


0:30:34.3 Shelly: Hey, Jay, is... Are there any prospective or, or retrospective randomized control trials for these? 


0:30:45.2 JE: There are, now, I mean, what you will find is that there, there are, antidepressants anxiolytics hypnotics, antipsychotics and ADHD meds on the panel. Most of our clinical utility research is focused on Major Depressive Disorder and we have, oh geez, at least four RCTs plus the number of other open label studies that have been reported and have appeared in meta analyses. So yeah, I mean, there's an abundance of clinical data and we recently published a, yet another renewed meta-analysis that showed improved symptoms, higher rates of remission and higher rates of antidepressant response, with GeneSight compared to a control. Which in these studies is basically treatment as usual. So basically just clinical management without, without the test results.


0:31:40.1 DS: Mm-hmm.


0:31:41.5 JE: So just quickly back to the report, you can see then the next couple of pages have the genotypes and phenotypes, so you can dig in to what underlies those medication, the medication binning or buckets. And then in the final pages of the report, as Rachel said, there are more than one drug, or there's more than one gene rather, that affects the mechanism of action or the metabolism of a given drug. And so in these last pages, it really lays that out and shows which pathways are involved in the metabolism or action of a given drug and then which are affected in the individual patients. So it's a great place to sort of better understand how those medication binning calls have been made. And so, as I mentioned, lots of resources, the last thing I'll highlight is that getting in touch with our medical information group is super easy. You can see it on the top part of the report up here, there's an 855 number, and then just, and that can get you in touch with one of our medical personnel who would be happy to help with more specific interpretation questions.


0:32:50.4 DS: Yeah. No, that's great. Yeah, very easy to navigate for sure. Yeah, I was wondering, I know we were talking about RCTs, but one of the big trials was guided that was behind, at least, getting it into the payer landscape and things, can you tell us a little bit about that trial? 


0:33:17.4 JE: Sure. Rachel, do you wanna maybe...


0:33:19.2 DE: Yeah.


0:33:20.6 JE: Maybe take the first stab on that one? 


0:33:21.9 DE: Absolutely. So the guided trial is actually the largest randomized control trial for pharmacogenomics that's been conducted in mental health history. There were about 1100 patients in it across 60 different sites. And the big premise behind this trial, and Jay kind of alluded to this, is, or the question we wanted to address is, if a provider has access to GeneSight to help with medication selection, does this lead to better clinical outcomes for patients compared to the standard of care? So again, it's a bit unique. Normally in a drug trial, you have a treatment arm and a placebo arm; in this case, both arms were receiving active therapy. The only difference between the two is that those in the guided trial had this genetic test to help with medication management.


0:34:04.0 DE: And so the primary outcome that we looked at was symptom improvement, which looked at over eight weeks. And we also looked at response and remission rates. We did not see statistically significant improvements in symptom improvement, but we did see improvements in... Statistically significant improvements in response and remission rates. And what this indicated here was that when a provider has this genetic input to help with medication management, that it may lead to improved remission rates for patients as well. So we've done a plethora of post hoc analysis as well, which we've looked at specifically patients that came into this study with... On red category medications and found that if they get patients off of those, it can lead to better outcomes.


0:34:47.8 DE: But one question that I get a lot from providers based on this trial is who do I use GeneSight on? And when do I use it? And so the inclusion criteria for this trial is patients had to have failed at least one psychotropic medication with moderate to severe depression. So the clinical guidance we usually give on when do I use GeneSight is at least after one medication failure, but like many things on this test, we always say it's up to the judgment of the clinician. If they wanna use it after one medication failure, that's fine. If they wanna use it after five, that's fine too. And then why do I use GeneSight or who do I use GeneSight on? So these conversations happen a lot. And again, it's really the clinician's discretion, but some reasons that providers will use GeneSight on that I hear pretty consistently is they're trying to reduce the number of medications patients are taking, so reduction in polypharmacy, where to start in that process can be a bit daunting if patients are on numerous medications. If patients are having adverse drug reactions, so we hear this a lot in long-term care, but we hear this generally as well, and we've alluded to this, this entire talk, that side effects for these medications can be pretty intolerable. So if they're trying to reduce that side effect burden, that's another reason.


0:36:04.3 DE: And lastly, probably the third most common thing that I hear is, providers will use it, I've heard this term a few times, as a roadmap. So if they wanna know maybe where to go next and they wanna see which medications are more or less genetically optimal, GeneSight can help with that as well. But I think one of the probably most unspoken benefits of GeneSight that I love hearing about is how it can promote kind of a therapeutic alliance between clinicians and patients. As we mentioned, this mental health journey is not an easy one, it is not a linear path, and so it can kind of make patients question the treatment that they're getting. And so I think it really helps provide rapport and alliance between the provider and the patient as well. So a lot of patients to potentially use it on, and again, it really comes with the discretion of the provider.


0:36:53.4 DS: Yeah.


0:36:54.6 Shelly: Rachel, I have a question. There's a lot of sensitivity around genetics and the impact that that has on whole facet, but having it be known that something that you have is related to something that you've inherited. And then on top of that, the mental health stigma that is out there. So it seems like it could be very compounded. How have you, do you see that and how have you worked through that with GeneSight or any other way? 


0:37:26.6 DE: So to reframe your question to make sure I'm understanding it correctly. So kind of the first layer, is there a stigma around treating mental health? And then the second layer is maybe increased stigma due to genetic testing, is that what you're referring to? 


0:37:41.2 Shelly: Or a genetic predisposition to anything? And in this case, something that's happening...


0:37:48.2 DE: Sure.


0:37:48.3 Shelly: And then... In the family.


0:37:51.1 DE: Yeah, so I think one thing that's really critical with this particular test is providing clear education on what it can and cannot do, as Jay mentioned, this test is not going to tell you that this medication will work, or this medication will not work, this medication will tell you that, these medications may be less likely to work, they made need a dosage adjustment, so when we talk to healthcare providers and patients for that matter, we don't really frame it as a genetic predisposition, we just view it as, this is information that your genes are giving us to help with med management. So it's much less putting the blame on the patient I think for their genetic predisposition and looking at it more as increased information for the patient, so I think it's a lot about how you explain it to patients as well as their families and to that point, we do have genetic counselors that are available, if families do want more information on that, exactly what the test does and does not mean.


0:38:44.4 JE: And Rachel, it's probably worth noting that the genes on the test are really not designed to look at susceptibility to mental health conditions, they are specific to the action of the drugs themselves, there's active work looking at the genetics of depression and the genetics of mental health conditions, and needless to say, it's a big polygenic, kind of soup of different genetic influences with no one particular smoking gun, and so there's really not a lot of insight in terms of the aetiology genetic or otherwise from this test. And I think that's an important thing to note as well.


0:39:23.8 DE: That's a great question.


0:39:27.1 DS: Yeah, yeah. And How would you compare it to some of the other tests that are out there right now? What do you think is really like the secret sauce here then? 


0:39:43.0 JE: I think it's hard for Rachel and I to comment on other tests. We're GeneSight experts, so I guess just focusing on what GeneSight has to offer, we certainly have the largest bodied of evidence of any of the available tests as far as pharmacogenomics and mental health, the combinatorial approach is A, it makes sense. And B, there is published evidence that it predicts blood levels of medications better than just using a single gene, and so we do have evidence that combinatorial also makes sense. And I would say that the other thing is that, like other areas of the Myriad business, we provide an amazing customer experience in terms of how we support providers, patients and the overall mental health community. And it's certainly our job in the medical affairs group to generate and communicate the right evidence and make sure that we're supporting the clinical community and we're proud to do that.


0:40:43.8 DE: Yeah, absolutely, I would second everything that Jay said, and I think when I speak with providers, one thing that I think they find great value in is, we don't expect you to get this report and know all the ins and outs, that's why we have this team in place, it's a free service, we're available at any time. We cover all territories of the US, so I think first and foremost, it's the body of evidence and the body of literature supporting it as a tool, but also as Jay mentioned, just the ability for whether it's a patient, whether a provider, whether it's a patient's family members, there are a systems in place to be able to provide education along the whole way, so.


0:41:19.1 DS: Yeah, no, that's incredible. Let's take a pause there. See if there's any questions. Anyone? Feel free to unmute or you can put questions in the chat. I...


0:41:33.0 Shelly: There are no questions [0:41:36.7] ____.


0:41:41.2 DS: I think you said there are no questions.




0:41:43.1 Shelly: There have none. There have... Yes.




0:41:46.1 Shelly: I have terrible internet today, so I apologize.




0:41:49.5 DS: No problem Shelly, thank you. And right now so... We've been talking about depression, and I know this was just also launched for anxiety, what are... How do you see those as overlapping? Do you see them as very different? How have things been going since the launch of some of the anxiety additions? 


0:42:15.3 JE: Yeah, so anxiety per se, isn't really a new addition to the test.


0:42:20.7 DS: I guess... Yeah, sorry, I guess I should be saying, not anxiety, ADHD is what I was meaning to say. Sorry [chuckle] attention deficit, sort of.


0:42:29.4 JE: Absolutely so ADHD was part of the panel for several years, we then did some additional work on it and brought it back with additional evidence, and it was... It's actually incredibly popular among providers in particular since most of the ADHD prescribing exists in the adolescent segment and patients... Or parents rather were justifiably concerned about putting their kids on either stimulant meds, which are usually first line for ADHD and for the non-stimulants in particular, the drug Strattera, there are very well-known pharmacogenomic interactions through CYP2D6 that affect blood levels and medication and can really affect how well it works and how well tolerated it is, and so I think the feedback from the field and Rachel I'll just turn it to you 'cause I think you've had more of these individual conversations has been, providers are delighted to have it back, and I think it's used all the time, and frankly, ADHD, adult, adolescent otherwise does tend to cluster with anxiety in particular, but also this sort of whole slew of other mental health conditions including depression.


0:43:49.1 DE: Absolutely, I hear it day in and day out, providers are thankful that that information is back, as you mentioned, anxiety and depression are highly comorbid with ADHD, and then particularly within the pediatric space, patients want more for their... Or parents, want more for their children in terms of how to select a medication so highly useful, it's been wonderful to have it back, and as Jay mentioned, there are some really well-established genetic variations that can affect how these drugs do their job, so it's been great.


0:44:21.6 DS: Yeah, that's really interesting.


0:44:22.8 Shelly: I have a question. Jay, with the... And Rachel, with genes that are on GeneSight now, What kind of trajectory do we have with adding other candidate genes or other changes to GeneSight? And what does that look like? 


0:44:43.8 JE: Absolutely. So we do a full and formal review of our algorithm every couple of years. We are always looking at literature, we're also generating our own evidence. So we do have a research pool of candidate genes that we also look at. And we also monitor to see which therapies may be coming down the pipe soon, because obviously, we need to wait until a drug is marketed, and it's got a label in order to add it to the test. And I've just highlighted this year, we added three new medications to our panel just a couple of months ago, one ADHD Med, one med for insomnia, and Rachel, I may be blanking on the third or maybe it was just two.


0:45:26.7 DE: Two meds for insomnia and a calvary for ADHD for pediatric patients.


0:45:32.3 JE: Yeah, exactly. And these were new classes of anti... Rather insomnia meds, and so new mechanisms of action, and they were added to the test. And so something that happens on an ongoing basis, and we're always looking for additional refinements.


0:45:47.9 DS: Yeah. Do you allow the genes to overlap, like with these different indications? I would imagine.


0:45:51.4 JE: They do. So not universally with ADHD, when we brought it back, we added a new metabolic enzyme CES 1A1. But otherwise, it's the usual suspects from cytochrome P450 families, so...


0:46:06.2 DS: CYP families.


0:46:08.2 JE: Exactly CYP3A4, 2C9, 2C19, 1A2. So there is although we don't actively communicate data around non-psychiatric meds, needless to say, there's also overlap with medications that are used for non-psychiatric conditions.


0:46:24.8 DS: Yeah. And do clinical features come into the test, too.


0:46:30.8 JE: So give me an example. What would you...


0:46:34.8 DS: I eat four cups of pineapple a day? 


0:46:38.3 JE: No, but they are relevant. And so that should be a discussion and actually, well, we are actually looking actively to find... To incorporate certain lifestyle factors into the test. So there's some things that are not ready for primetime now. But what I would say is stay tuned. And maybe we can come back and update this audience when that goes live, hopefully later this year.


0:46:58.9 DS: Yeah. Interesting. Yeah, even... I don't know what kind of data we have around BMI, have you seen any correlations there with any of the work? 


0:47:11.0 JE: Not in any of the studies we've done. I don't think, Rachel that there's been any subgroup by BMI that's shown to be significant. So no, not specifically. But I think with anything in clinical medicine, understanding where there are potential moderating factors is hugely important. And really...


0:47:31.7 DS: I was thinking about the dosing too. Yeah, I don't even... I'm trying to remember how these SSRIs mean most of them are just route adult dosing if I remember off the top of my head.


0:47:42.5 JE: That's exactly it. There are a few examples. So Rachel, mentioned, Strattera. It's the ADHD non-stimulant drug. It's got the weight-based dosing for PEDs. But for the most part, these are just, fairly set it and forget it kinds of standard doses.


0:48:00.6 DE: But to that point, many of the meds that are prescribed very frequently have very common side effects of weight gain and [0:48:06.1] ____ profile. So BMI definitely comes into play there, and it comes up in conversation a lot.


0:48:13.4 S?: Have you noticed any differences across different ancestries? 


0:48:17.1 JE: Interesting, you should ask, the short answer is no. And if anybody is going to be at the American Psychiatric Association in a couple of weeks, we actually have a sub-analysis, looking at our guided data based on ancestral background, including African-Americans and Hispanics. As with any clinical trial, our trials are as diverse as most clinical trials, but probably not as diverse as they otherwise could be. And so we are beginning to look very actively at, are there gene variants that may be enriched in certain populations that could be added to the panel that would give more clinically actionable information. So we have an ongoing workstream on what we're calling diversity, equity, and inclusion genes, that will hopefully shed some more light on where ancestry might be a relevant factor or determinant.


0:49:08.3 DS: You definitely have specific alleles already built into the test that are more common in certain ancestries than other which is why it shows that it's performing well amongst the ancestries, 'cause obviously, if those alleles were missing, it would show a massive discrepancy.


0:49:25.7 JE: And actually, to share a really good example, we've got two seconds is the HLA so the immune system, the genes... The code for proteins in the immune system. There are variants in particular HLA*1502, where patients who have got that variant are like 60 to 80 fold, more likely to have Stevens-Johnson Syndrome or 10, in response to the drugs like carbamazepine, so mood stabilizers. And that is a gene that's enriched for in the Asian population. Although, interestingly enough, we have an African-American colleague who has one of those HLA gene [0:50:07.0] ____.


0:50:07.4 DS: Oh, interesting.


0:50:09.8 JE: Is not universal, obviously, this can pop up everywhere. And, that's an example where there's a catastrophic side effect. And if you've got that variant, you are 60-80 fold more likely and so hugely important to know that if you're dealing with patients who otherwise would benefit from [0:50:27.2] ____.


0:50:28.4 DS: Yeah, I actually consulted on somebody in Hawaii for a Tegretol dose, which is carbamazepine, who, had that allele and it was a mess, and it was Stevens-Johnson and then ICU.


0:50:41.4 DE: Yeah, actually if we see that on our report the medical team, it will elicit what's called a flag report and medical we'll reach out to the provider to ensure that they see that information is there.


0:50:54.4 DS: Yeah, and that's been a black box warning, I think for some time on that particular drug.


0:51:01.3 JE: So Shelly I'm seeing a question in the chat.


0:51:05.4 Shelly: Yes. So, I don't know if that went to everybody. Yeah it went to everyone. You wanna go ahead. You can read it just as easily as I can, Jay.


0:51:14.3 JE: Yeah. No, no, absolutely. So Raymond is asking if we can comment on the lack of significant clinical impact, for combinatorial pharmacogenomics in depressed adolescents. And yet, we did see significant effects in geriatric depressed patients. So, there are now three clinical studies on the use of GeneSight in depressed adolescents. I think Raymond's referring to one RCT that came from the Mayo clinic where surprisingly there was no effect, of GeneSight compared to treatment as usual in terms of depression outcomes. Those are contrasted with a couple of other studies, one, a naturalistic study and another a retrospective chart review study. That actually did show improved outcomes in adolescents using GeneSight. So I think we're at a point where, the utility of GeneSight and adolescents has not been fully established yet.


0:52:11.7 JE: And so it remains an active area of investigation. Of course, they're, generally far fewer data in teens as compared to adults anyway. But Raymond is absolutely right that there was a failed study but a couple of other supportive studies. So we continue to investigate why that may have been, and also to consider other research that might be worth funding. In geriatrics subgroup analyses, have shown that, geriatric patients benefit, as much as other adult patients. Rachel, I don't know if you've got other comments on our geriatric data, but certainly geriatrics is an area where we tend to focus just because, those are patients that, can be more susceptible to side effects and, or having negative consequences associated with side effects. And so when adding psychotropic meds, being particularly careful and, purposeful, is an area where we think GeneSight has particular value.


0:53:12.6 Shelly: I think there's, I had a private message to me that there is, seems to be a study, a veteran's administration study in the works. Do you have, any line of sight of when that might be published? 


0:53:27.1 JE: So we're super excited and to be clear, we have, zero insight into the data. This is a veteran's administration study that was funded by the VA and the federal government, where we just provided the testing. So it is a study of GeneSight compared to treatment as usual. So providers getting GeneSight results and it's actually a fully six-month study. So Rachel mentioned Guided the biggest study of its kind up until this new study, via Prime-care. Guided was 1100 patients, eight weeks blinded. This is almost 2000 patients blinded over 24 weeks looking at clinical remission of depression as the primary endpoint. So we do expect to see the data sometime this year TBD, and needless say those of us on the GeneSight of defense have our fingers firmly crossed that we will see positive results from that study.


0:54:24.9 Shelly: Thank you.


0:54:25.0 DS: Yeah, that's great. Well, I know we're coming up to time. Any other questions? This was fantastic discussion. I can't thank you enough, Jay and Rachel, Shelly for running the chat, but yeah, I mean good. I learned a lot, so [chuckle] it's and, even though, this, as I alluded to before we even got on the call today as we were kind of gearing up before the hour. I was saying that this is just usually historically for Myriad live, not our best time slot. So one, I appreciate everyone [chuckle] who is on today and, decided to spend their later afternoon or night with us. That's huge, but yeah, I mean, most of the Myriad lives, we, normally do these, a bit during the day and at first we were trying to do them at this time, but, yeah, just we would just not get the kind of audiences that we would get during the day. Which is honestly a little counterintuitive when I first started doing these you'd think that busy clinicians, that we're trying to get the information to would be more apt to jump on kind of after clinic.


0:55:36.2 DS: But, it seems a lot try to make time, during their day. So, hats off though, to those of you who, stuck it out. So I really appreciate it. And, hopefully you learned a lot about the field of pharmacogenomics and mental health. And again, circling back to the front of this is. This is a crisis. I mean, mental health is, we have a problem, not only in this country, but the world, there's just a lot going on. And, these are the kind of things that we can use in our tool belt to help providers take better care of their patients and people on this call to take better care of their patients. So, know this is out there. And I don't know, Jay, would you consider this standard of care or Rachel these days? 


0:56:23.3 JE: Standard of care is kind of a loaded term? I don't know, I'm gonna punt it to Rachel, just 'cause it's a difficult question.




0:56:33.1 DS: [0:56:33.6] ____.


0:56:33.9 DE: I think I may not be the best person to ask that because I go to offices where it is the standard of care. So I do talk to people who maybe don't see the [0:56:42.8] ____ as much, but a lot of the times I'm educating and collaborating with people who do use this in day-to-day practice. So I think there's a bit of sampling bias on my part. But so I think it depends on who you ask, but in my day-to-day world, it does seem to be that way.


0:56:56.7 DS: Yeah, yeah, yeah. And all the research that has come out and is soon to be coming out. I mean, this is all just very exciting and hopefully we'll continue to add just an immense amount of support to looking at pharmacogenomics instead of just kind of throwing darts at the dartboard and hoping that something hits. So, really appreciate everyone coming on again. Thank you so much. Please join us later in the month. We will be talking about novel of ways to screen for Li-Fraumeni syndrome. I see Betta on, so Betta, make sure you're there. [chuckle] Don't miss out. And we can also work in the life consortium as well, I promise. So thanks everyone, and have a great rest of their day and yeah, join us in the future.