The Schizophrenia Puzzle is Solvable

There’s a care model for schizophrenia that actually works—why isn’t it everywhere? On this episode, W. Gordon Frankle, MD, MBA, Vice Chair of Psychiatry at NYU Langone Health, shares how his team in Brooklyn is building a new model for treating serious mental illness—one rooted in long-term, relationship-driven, team-based care. From wraparound services to precision psychiatry, this conversation explores what happens when you bring humanity, structure, and innovation to a population too often left behind.

Also discussed:

• The first novel schizophrenia drug in over 50 years (Cobenfy)
• Why clozapine is underused—and how that may finally change
• The potential of brain imaging and biomarkers in psychiatric treatment
• What a real community mental health system looks like
• Why trust, not just treatment, is essential for recovery

🔍 Topics Covered

00:00 Introduction
00:30 Dr. Frankle's Current Work
01:08 Advancements in Schizophrenia Research
02:29 Challenges and New Treatments in Schizophrenia
05:02 Precision Medicine in Psychiatry
05:59 PET Scans and Brain Energetics
09:46 Barriers to Effective Treatment
11:51 Clozapine and Treatment Access
13:38 Wraparound Services and Community Care
14:46 Early Screening and Public Health Interventions
18:32 Mandated Treatment and Patient Engagement
30:08 Homelessness and Mental Health
34:54 Future Directions in Schizophrenia Treatment
38:09 Conclusion

📚 Related Resources

W. Gordon Frankle, MD, MBA
Schizophrenia care at NYU Langone
NYU Langone Hospital—Brooklyn
3 Things to Know About Cobenfy (Yale Medicine)

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Executive Producer: Jon Earle

Transcript

DR. THEA GALLAGHER:  Welcome to the Insights on Psychiatry podcast. I'm excited to introduce our guest today, Dr. Gordon Frankle. Dr. Frankle is an associate professor of psychiatry at NYU Grossman School of Medicine and here at NYU Langone Health and the Vice Chair of Psychiatry at NYU Langone Medical Center and the Chief of the Psychiatry Service at NYU Langone Hospital in Brooklyn. Dr. Frankle, thank you so much for being on the podcast. 

DR. W. GORDON FRANKLE:  Thank you so much, Dr. Gallagher.

DR. THEA GALLAGHER: Can you just tell us a little bit about what you're currently doing, the overview of your work right now? 

DR. W. GORDON FRANKLE:  Really, I have two main focuses to my work. The first, I do imaging research and schizophrenia, specifically receptor imaging research using a technique called positron emission tomography. And the second big area of my work is really program development and overseeing the program in Brooklyn, trying to develop systems of care for individuals with mental health issues and to try to treat the community that we serve in Brooklyn.

DR. THEA GALLAGHER:  We're going to get into some of what that program looks like. We're going to start with some of the significant developments in your research with schizophrenia and some of the neurological underpinnings over the past five years. So where do we stand with some of that research and what's the current state of that? 

DR. W. GORDON FRANKLE:  I think we're at a really exciting time in research in schizophrenia and mental health in general, but in schizophrenia specifically. We're starting to understand really the circuitry that's going wrong in this illness and what's happening in the brain when people start to develop the symptoms of schizophrenia, which include the psychotic symptoms, the things people understand as being associated with this illness, you know hearing voices, delusions, paranoia. And so what it appears now that we're learning from the imaging research is that there's an excitatory and inhibitory imbalance in the brain in patients with schizophrenia that tends to result in increases in dopamine release in certain brain areas, particularly the subcortical brain areas in the striatum, and a deficiency of dopamine in some of the frontal cortical brain regions. And some of the circuitry allows for trying to develop new medications and new treatments to target these circuits to really try to improve treatment for the illness. 

DR. THEA GALLAGHER:  And there hasn't been too much that's been new with schizophrenia treatment in the last number of years, or do you feel like this is an exciting time because there is more research and hopefully kind of more advances? 

DR. W. GORDON FRANKLE:   Yeah, I think you raise a good point. There hasn't been too much that's been new in treatment of schizophrenia as far as medications go. We've largely been using what are called the typical antipsychotic medications, which are the D2 blockers or medications which impact the dopamine system. This is up until recently. Just in December, however, a new drug was introduced which has a different mechanism of action for treatment of schizophrenia that's called Cobenfy. That's its trade or brand name. And it impacts the muscarinic system. So it's a bit of a different mechanism of action and that's what I mean when we're starting to understand the circuitry and where we can impact that circuitry differently with different medications to try to improve the symptoms. So I think that that's really exciting and that's the first drug that's been released in 50-something years, which doesn't impact the dopamine system yet shows improvement in patients with schizophrenia. 

DR. THEA GALLAGHER: Is it surprising, these findings, how are they going to impact things differently? Just understanding that there might be more ways to address these challenges? 

DR. W. GORDON FRANKLE:  So one, it is kind of surprising because there's been other drugs which have been tried to impact these circuitry in schizophrenia, which have not been successful when they've gone all the way to clinical trials. So drugs that have interacted with the glutamate system really haven't been effective or the glycine system have not been effective. Although there's been some promise when they get to the clinical trials, they just tend to not work in large-scale studies of schizophrenia. So to see a drug that has a new mechanism of action come out and actually work and get through clinical trials, that is kind of surprising. And so that's where I think we're going to start to look more specifically at these different circuits and which receptors we can target to impact schizophrenia and the different symptoms. And particularly both the psychotic symptoms but also the cognitive symptoms of the illness, which is really going to be an area that I think we're going to have to focus more on with treatments. We don't have a lot of treatments which show benefit for cognitive symptoms in schizophrenia.

DR. THEA GALLAGHER:  And is that important because you know we have this gold standard treatment of antipsychotics that have been successful with a lot of people. Is it for treatment refractory patients or just also thinking through maybe patients would benefit more from something different? 

DR. W. GORDON FRANKLE:  I think it's a bit of both. I mean, I think that if you can target better treatments to different patient populations, and this is kind of where we start to talk about what we're calling precision medicine and psychiatry, if you can have patients undergo maybe blood tests, genetic testing, imaging tests to identify in some patients which circuitry might be abnormal and if you had different treatments to target different circuits, you could really intervene at the specific spot for that specific patient and maybe show improvement for that individual. So I think that's something that's important. So it may not just be for treatment-resistant patients, but maybe more precision medicine for patients with schizophrenia. 

DR. THEA GALLAGHER:  And speaking of that prescriptive kind of nuance, with this circuitry, is it something that you're seeing develop over time? Is it episodic? What have you come to understand from these PET scans that you're utilizing? 

DR. W. GORDON FRANKLE:  What we tend to see is that there's a variability in the findings in the PET scans for patients with schizophrenia. Particularly when you look at abnormalities in dopamine, that's the area that's been most studied with positron emission tomography, where the studies have shown that in patients with schizophrenia, there's an excess of dopamine released when you give them a medication which causes the release of dopamine such as amphetamines or methylphenidate. We also see that there's an excess of dopamine production in the brain areas and schizophrenia when you compare it to controls. And so those are the findings that we're seeing. There's been less study than the other different circuits. We've done some studies looking at the GABA circuitry in schizophrenia. GABA is the main neuroinhibitory transmitter and we see differences in that in the brain regions in schizophrenia, which are related to cognition. So impairments in GABA transmission in patients with schizophrenia in the cognitive brain area, the frontal brain areas, which are important for cognitive functioning and memory and so forth. 

DR. THEA GALLAGHER:  And where are you hoping to see that research go from here? 

DR. W. GORDON FRANKLE:  So the next study we're working on now is to try to understand brain energetics in schizophrenia. That's a study that I've just started and we want to try to understand whether there are abnormalities in the brains of patients with schizophrenia and how they use energy and metabolize brain energy. So we have a study, we're looking at a specific enzyme in the mitochondria in schizophrenia to see if that might be altered in the disease. What we do know is that there are brain imaging studies which show that patients with schizophrenia have abnormalities in metabolizing glucose, abnormalities in how they activate different brain regions, particularly when they're doing cognitive tasks. And so one of the potential reasons this might be is abnormalities in the mitochondria, which the mitochondria are the main energy producers of the cell. And so if you have an abnormality in the mitochondria, you're going to have a deficiency in energy production. And so this might be one of the areas that could be targeted if we determine that there is such a deficit in patients with schizophrenia. 

DR. THEA GALLAGHER: And thinking of this as like a potential scalable intervention or a scalable way to get patients the treatment that they need, how do you hope to see that translate?

DR. W. GORDON FRANKLE:  We're at a point where we really have to try to find what we'll call biomarkers in schizophrenia. So for example, if we take the mitochondrial study that we're talking about, looking at the specific enzyme in the mitochondrial called the mitochondrial complex one, if there's abnormalities in that enzyme in some patients with schizophrenia, but not others, we might be able to detect that via PET scan. But what would be much better if we could develop a blood test to check that? Because PET scans are expensive, they take a lot of time, they expose patients to radiation for the study and so with some collaborators here, part of what we're also doing is starting to look at neuronal exosomes which are in the plasma and see if we can link that to some of the brain imaging findings in the mitochondria. So for example, that would be an interesting direction if it pans out to see if we could develop a blood test that could let us know if the mitochondria are abnormal and then are there specific drugs which we could use to target those abnormalities in patients with schizophrenia?

DR. THEA GALLAGHER:  Yeah, that seems exciting and it seems like kind of going from maybe that more complex big picture to something more, again, scalable that can be utilized with more patients and it seems like that is ultimately the goal if those correlations can be found and then the appropriate intervention can be utilized. 

DR. W. GORDON FRANKLE:   Yeah, that's exactly right. And I think you know that's been the goal of what we've been trying to do in schizophrenia for many, many years and I wouldn't say 100% effectively. 

DR. THEA GALLAGHER:  What would you say are some of the barriers? 

DR. W. GORDON FRANKLE:   So one of the barriers is the disease heterogeneity. There's a variety of different presentations in schizophrenia. I think that creates some complexity in identifying, are there specific subtypes of the illness? Is everything we're diagnosing with schizophrenia the same illness or are there different illnesses? Different illnesses isn’t the right word, but going back to the circuitry, different pathways impacted in different people, which result in the same symptoms, but they arise from different alterations in the brain.

DR. THEA GALLAGHER: And so the more that we can kind of, again, maybe get to this precision medicine model, even within this classification, could help individuals maybe differently? Is there the potential that there's different circuitry happening with different presentations who could maybe benefit from different interventions? 

DR. W. GORDON FRANKLE:  I think that that's one of the things we need to figure out. One of the most confusing things to me about patients with schizophrenia and treating the illness is that you can give a patient a specific antipsychotic medication and they can respond really well to that medication. You can give a different patient that same medication, same dose, and they won't respond at all. And so why is that? Why are there differences when the medication should be doing essentially the same thing in these different individual patients? Why does one patient respond to one medication and one patient not respond, or another patient not respond to that medication? I think some of that has to do with the heterogeneity of the disease and the different circuits, which might be abnormal into the different patients resulting in the same symptoms, but the cause for those symptoms might be different. 

DR. THEA GALLAGHER:  And it seems like that's the larger question, why is that happening? And then what can we do about it and are there different ways to intervene? 

DR. W. GORDON FRANKLE:  Yeah, exactly. 

DR. THEA GALLAGHER:  Again, we've talked about the success of the pharmacological treatments, but you're also talking that you know they don't always work for everyone. For those treatment refractory patients maybe that a clinician is working with, what do you suggest if they are utilizing these medications and then it's not being as effective?

DR. W. GORDON FRANKLE:  I think that one of the things, and this is fairly well-known in our field, is that we really need to use clozapine a lot more. Clozapine is our one antipsychotic medication that is effective in individuals who are treatment refractory and don't respond to the other antipsychotic drugs. It's really underutilized and really should be used more. One of the reasons it's underutilized is that it has what's called the risk evaluation and monitoring system, a REMS process whereby patients who are started on Clozapine have to get blood draws at regular intervals initially every week and then every two weeks and then every month. But just recently, this is another exciting development the FDA voted to get rid of the REM system for clozapine, which would make it a lot easier to prescribe and make it more available to patients than it currently is. Right now, you need a fairly decent infrastructure within a clinic to prescribe clozapine to get patients back in for those blood draws to monitor them. The pharmacies don't release the medication if there's not a recent blood draw, blood tests, the tests are for the white blood cell count. If those tests aren't on file, the pharmacy won't release the drug so that often results in delays in patients getting the next dose of medication. So I think the whole REM system is problematic, and that's been recognized by the FDA and I think it would be really good to see that system sunset and start to be able to prescribe clozapine more widely to patients with schizophrenia. 

DR. THEA GALLAGHER:  What are some of the barriers with even access to treatment itself, like to getting the care? We know with severe and persistent mental illness, that can be a challenge, even just getting to the place where they could access the resources. So can you talk about some of those barriers and what do you think can be done there? 

DR. W. GORDON FRANKLE:   Yeah. So that is one of the biggest barriers and I think that of all the things we're doing in treating severe and persistent mental illness and schizophrenia specifically, the areas we can probably have the most impact is the delivery of care and connecting patients into care. What we know is that the treatment systems that work really well for patients with SMI, severe mental illness or schizophrenia, are ones that provide really wraparound services where you have more than just one psychiatrist working with a patient. You have a whole team, a psychiatrist, a therapist, case managers, peer navigators, patient navigators, educational, vocational supports. And if you can put those wraparound services around a patient, they tend to do much better and you can engage them in care longer and in a more comprehensive manner. So that's some of the stuff that we've been trying to do in Brooklyn, and there's a lot of this work going on in the country, but it's unfortunately very expensive, as you can imagine, to put such a team around a patient. And so the reimbursement for that level of care is not where it needs to be. 

DR. THEA GALLAGHER: And is there the hope that this starts kind of in the primary care setting in some ways, like that it's identified maybe or diagnosed, or there are flags that you know this diagnoses might be on the horizon and then from there, people are connected with the right care that they need in this appropriate care team? 

DR. W. GORDON FRANKLE:  Yeah, I think that would be a great place to start. I think it would be good if we had better screening for mental illness in primary care. I know we're doing a lot of depression screening now is fairly common in primary care offices. Depression is so prevalent, it makes sense that that's screened fairly widely. I don't think we do a lot of screening and assessment for, are you at risk for developing a psychotic illness? And that's something we probably should do, particularly in adolescents and teenagers, to start to think about, well, how do we identify individuals who might be at increased risk for developing a psychotic illness or schizophrenia? And then what do we do for those individuals to monitor them kind of moving forward to ensure that if they do develop an illness, they can receive treatment pretty quickly, or they can take steps to mitigate the risks that they might have of developing the illness. And one of the best examples of that is reducing or eliminating cannabis use for vulnerable individuals, as there's a very high association between cannabis use and the development of schizophrenia. 

DR. THEA GALLAGHER:  And it seems like even the way that you're talking about this that there could be a system put in place even in the schools, like a screening day, or if you're kind of like, how do we monitor adolescents? I'm wondering if that's a place or even at your yearly physical in your primary care office. Is that something that you're hoping to see from like a public health perspective? 

DR. W. GORDON FRANKLE:   I think that would be wonderful to see something be implemented in schools where you have a screening day to try to identify individuals who have kind of prodromal symptoms of schizophrenia. And as I think many people know, prodromal symptoms of schizophrenia are pretty nonspecific for the illness. They actually tend to overlap with just being an adolescent, you know social withdrawal, some irritability, mood swings, maybe some mild psychotic symptoms. But if we could do some screening on a large scale, we could identify individuals who might be at risk, and then they could be tracked and have regular routine follow-ups with mental health professionals, you know much like we would do for individuals who might be at risk for other medical illnesses. 

DR. THEA GALLAGHER: And we were talking on another episode about predictors for PTSD, right? And being in an emergency room, if somebody's experienced a trauma, it's kind of like you can follow that a little bit more linearly. What would you say for schizophrenia, what risk factors or things that could be monitored or looked out for, even if maybe a clinician is working with an adolescent patient and they're starting to see some of these prodromal symptoms? 

DR. W. GORDON FRANKLE:  So I think the things you're going to want to look out for, be aware of family history. Is there a family history of any mental illness, but particularly a psychotic disorder or schizophrenia? That's something that's going to create a higher-risk environment for that individual that the clinician might be working with and then starting to look for social withdrawal, mood swings, irritability, anything that seems a little bizarre or maybe not fully psychotic, but a little paranoia or mild psychotic symptoms. Those are things that should raise some flags about whether or not this individual needs a little more attention and treatment. 

DR. THEA GALLAGHER: It seems like something that can be monitored over time and then the more information that we have over time can create that precision medicine model when we're collecting all these pieces of data over time.

DR. W. GORDON FRANKLE:  Yeah, exactly. 

DR. THEA GALLAGHER:  And I know it's somewhat controversial, but on a previous episode of the podcast last year, we kind of talked about mandated treatment for schizophrenia. Do you have any thoughts, feelings, perspectives on that? 

DR. W. GORDON FRANKLE:  It is a little controversial, but I do think that in schizophrenia, we enter into a strange area because we have individuals who, many of whom, particularly on the very severely ill patients with schizophrenia, that side of the spectrum, many of whom don't really understand that they actually have an illness. So it's very difficult to engage someone in treatment if they don't really acknowledge or recognize that they actually have this illness. And that's unfortunate because oftentimes when they're given treatment, they can do very well and they respond well to the medications. So I think there are specific times when mandated treatment is important, particularly when someone is at risk to themselves or at risk to someone else through violence or suicide or violent behavior.  In that case, you really have to take that as a priority and try to get them into treatment in a hospitalized setting. Now here in New York, we have an assisted outpatient treatment, which is really mandated, court-mandated treatment that individuals are kind of prescribed to or go through the court process to get onto. So I think that those individuals, we really do have to work towards mandating treatment. In other cases, what tends to happen is they might be mandated treatment kind of coming into a hospital and getting treatment while they're in the hospital and then when they leave the hospital, they end up stopping the treatment and relapsing. And I think that does represent a problem. I mean, one of the things we know about schizophrenia is that the more episodes you have and the longer those episodes are, the worse the disease becomes. So if you can shorten the psychosis, the psychotic episodes, and minimize the number of them, the prognosis is going to be much better for individuals with schizophrenia and that's why we really have to start early and really try to get them into treatment and engage well with patients with schizophrenia so that they can minimize those episodes of psychosis and stay on the medications. And I think to do that, when they leave hospital settings you really need what we were talking about before, that wraparound treatment program to engage them well and their families. It's also important to bring the families into the system of care. 

DR. THEA GALLAGHER: We were talking with regard to substance use disorder and even PTSD, something about talking to someone, that relationship that is built kind of contributes to adherence. Is there anything similar to that with schizophrenia or different or anything that you've found or we found that can impact treatment adherence over time? 

DR. W. GORDON FRANKLE:  Yeah, I think that it's building that relationship and I think that discounting that that can be built in patients with schizophrenia is a mistake. Many years ago, when I was working in Pittsburgh, I worked on the assertive community treatment team. I would go out a day a week and drive around the city and meet with patients with schizophrenia and other serious mental illness and really just making those connections with them fairly brief. You're not doing a long 50-minute therapy session. You're interacting with them, engaging them in their home or where they're living. You can really develop a connection and a rapport that helps them engage in the treatment and even take medications when they don't even acknowledge they have an illness, but they trust that you have their best interests in mind and that you're working with them and you have a collaborative relationship and then they're willing to kind of trust you and take the medication, which is really what we're looking for. 

DR. THEA GALLAGHER:  And it sounds like what you're kind of you know sidestepping or walking around is that there might be some stigma around these patients specifically that maybe that relationship isn't as powerful as with other conditions and it sounds like you think that that is a mistake and that those relationships are really powerful and can affect change over time. 

DR. W. GORDON FRANKLE:  First of all, there's absolutely a stigma around schizophrenia and the stigma that these patients can't engage as well with others and I think that's absolutely false. I think it's a different type of engagement for some patients, but you really can make those connections and they don't have many of those connections. They tend to have ended up being isolated oftentimes from family, from friends, because of the psychosis, because of the behaviors that that leads to. But you can make those connections, and you can really gain some trust and work collaboratively with patients with schizophrenia to their benefit and ultimately to the family's benefit. 

DR. THEA GALLAGHER: I think that's really exciting and also can break down some of that stigma as well. Any kind of future of the research or the development that you hope to see unfold in the next five to ten years? 

DR. W. GORDON FRANKLE:  I would like to see kind of more biomarkers develop for schizophrenia. It's something that the field has been working on for many, many years, and we have yet to kind of get to. It's still a diagnosis where we make the diagnosis by asking questions and observing behaviors and it would be good to have more biomarkers, whether that's imaging markers, genetic markers, blood tests. I think we're still a ways off from that, but that would be something that would be very, very helpful for us as a field. 

DR. THEA GALLAGHER:  Because schizophrenia, there is like a stronger maybe genetic component than other potential mental illnesses, it seems like that should have made it more easy to find these biomarkers. What do you think is like the challenge there? 

DR. W. GORDON FRANKLE:  That's a great question. I wish I had a good answer for that. I mean, it's a challenging question. It's a challenging problem in all of mental illness and psychiatry to find these biomarkers. I think the brain is a complex organ and it's difficult to identify what's going on in the brain and what's going wrong when something goes wrong. And so it's just been very difficult for us to crack that.

DR. THEA GALLAGHER: So even if someone's parent has schizophrenia, that would be helpful in you know maybe understanding the rates of them maybe developing the disorder, but it doesn't really help in understanding what piece is getting passed down. 

DR. W. GORDON FRANKLE:  That's exactly right. And even in the genetic studies that have been done, there have been fairly wide genetic studies, there are only a few genes which are associated with increased risk of schizophrenia, and they're only associated to a small degree. 

DR. THEA GALLAGHER: Well, that's, I feel, an exciting future direction and it seems like, again, that's where all psychiatry is hoping to move, is to see if we can make some meaning of these biomarkers and precision medicine, machine learning, to have better diagnoses and treatment. Kind of switching gears, as chief of the psychiatry service at NYU Langone in Brooklyn, you've also kind of been involved in just developing better care for many patients. Can you tell us about some of the lessons learned or what are the treatment systems that have been effective?

DR. W. GORDON FRANKLE:  I mean, I think that the one thing that I'm really excited about that what we did in Brooklyn is develop a program for patients with serious mental illness, not just schizophrenia, but depression with psychosis and bipolar illness in our outpatient clinic. We received a large grant from SAMHSA to put this together. And what we did, so right now, the wraparound services I talked about for schizophrenia, which really work well, that's been shown repeatedly to be the most beneficial type of care for those patients. Right now, those are implemented really in two phases of the illness. At the first episode, where it's called coordinated specialty care or on-track programs, where a patient has a first episode of psychosis, they can get into this on-track program and they have these wraparound services. Those services are time-limited over a certain number of years, and then they age out of the program. And that's a wonderful program and been shown to be very beneficial for patients and improve outcomes for patients. And then on the other end, when you have patients who are very severely ill and they've had multiple hospitalizations and they keep getting rehospitalized, they can enter into what's called assertive community treatment, what I mentioned before, ACT teams. But there's a fairly high barrier to get onto those ACT teams. Those ACT teams also provide those wraparound supports. But there's really nothing between those two systems to provide this kind of wraparound support for patients with severe mental illness. And so in Brooklyn, that's what we did with this program. We developed this program where we put wraparound supports for anyone with severe mental illness, not just schizophrenia and psychosis, and made it time unlimited, age unlimited, and we would just follow them indefinitely. And we had psychiatrists, therapists, care managers, peer navigators, vocational and educational supports for these patients. And so this program has been going on for about two and a half years now, and we have over 1,000 patients who have been enrolled in it. 

And what we saw, we just wrote up a publication and had presented it. What we saw is that patients do better with this, not unexpectedly. It's consistent with the literature that's out there. When we ask patients, how are they managing their mental health and how do they feel about their mental health, six months and 12 months after they've started, it's much better than when they first started the program when we asked that same question. They're much less likely to have a hospitalization at 6 months and 12 months than they are when they first come into the program. And then what's really important, we took this group of patients, 700-something patients that first started this program and tracked them over two years. They were about two times as likely to stay in care than kind of an analogous cohort that we looked at historically. So it really keeps patients in care, keeps them engaged, and improves their well-being. And I think that what we really need to do as a society is push for these types of programs and push for the funding of these types. We know they work, but we're not really devoting the resources to these programs that we really should be doing. It's one thing we're really confident works in this illness and other SMI. 

DR. THEA GALLAGHER: It sounds like you're really highlighting this aspect of community and care and a care team and maybe, again, a group of people who do care about them over time. I know in community mental health care, there are things like clubhouses too, where you can have that community involvement, and even maybe some community work, which can build self-efficacy. Is it about kind of bringing all those pieces together?

DR. W. GORDON FRANKLE:  That's exactly right. It's bringing those pieces together, being able to go out into the community and meet with patients in their homes or other places in the community to really engage them where they're at and make sure that they're part of the treatment system. 

DR. THEA GALLAGHER:  Yeah, because what seems so limiting, you know even having worked in crisis outreach is sometimes you'll go do a mobile outreach. They go to a hospital. And then, like you said, that's kind of where it ends, and then they're sent back into the you repeat the cycle.

DR. W. GORDON FRANKLE:   Then you do another crisis outreach. Yeah. 

DR. THEA GALLAGHER:  And so this seems more like long-term, and actually, it seems like it's cumulative, that they almost get better over time. 

DR. W. GORDON FRANKLE:  Yeah. And I think that that is true. They get better over time because they have fewer episodes. And if you reduce episodes of psychosis, you're going to have continued improvement. I mean, think about how really disrupting an episode of psychosis is for a patient, both for the patient, for the family. You can't be working. You can't be going to school. You've got to be in the hospital. It disrupts the family system. Family has to give up some time working to take care of the patient. So it's very disruptive. So not just in the biological way, but also in the psychosocial manner. And so if you can reduce those, you're really going to improve long-term outcome for patients and improve their quality of life. 

DR. THEA GALLAGHER: This kind of leads me to my next question about schizophrenia and severe mental illness and homelessness. There's been, I think, some talk about bringing back the asylum, safe places for people to go so that they aren't homeless when they're struggling with mental illness. But it sounds like your idea is maybe something in between that, kind of creating a larger network and structure and community that also is ongoing, that isn't just sending them back to business as usual.

DR. W. GORDON FRANKLE:  Yeah, I think we have to try to stop this cycle of hospitalization, discharge, relapse, hospitalization, discharge, relapse and for people with homelessness, often that cycle includes the criminal justice system. They get arrested, they get put into jail, they get treated there, maybe they get diverted to a mental health institution. So we have to try to stop that by really working with patients and putting these systems around them. This is where we kind of often get into the treatment of rejection area for individuals who are living on the streets, who are homeless. But I do think that you can still engage with patients and we have, I mean, New York City has a lot of very good street outreach for patients with mental illness who are homeless and to provide treatment there and so I think you can really engage with patients still, even if they're homeless. But trying to get them into a safe place in a safe environment where they can also receive the treatment, feel safe, not feel like they have to live on the street, not struggle with that.  And then I think the other big aspect of this is substance use disorder. Oftentimes, individuals who are on the street who are homeless are using substances for a variety of reasons. And that's another pattern that needs to be broken if we're going to kind of connect with and end up treating patients. 

DR. THEA GALLAGHER: You said there's a number of reasons. Is there any kind of theories about why? We were talking about dopamine? I don't know if there's anything structural, functional that makes it at more risk for substance use disorder with severe mental illness?

DR. W. GORDON FRANKLE:  I don't know if there's anything that makes it more risky. I mean, I think that if you're living on the street, using substances is a way to comfort yourself and to take away some of the anxiety and fear that goes along with that and it's kind of a self-perpetuating cycle. The more you're doing that, the more you end up not being able to kind of get out of that situation where you're homeless. So I don't know that there's some underlying neurobiological reason why individuals with schizophrenia might be using substances or not.

DR. THEA GALLAGHER:  Is it thought that if they're on an antipsychotic medication that might mitigate against the substance use disorder, or are there other kind of pathways or things that you think would help with that aspect to it? 

DR. W. GORDON FRANKLE:  I think that being on treatment can help with judgment and insight. So if you have treatment, you don't have the psychosis, you don't have the paranoia, you don't have the fear, you're probably going to be less likely to reach for the substance and less likely to engage in substance use. So maybe that's one way to break that pathway. I think without treatment, it's very tough to do that. 

DR. THEA GALLAGHER: Would you say it would be a two-pronged approach of specific substance use disorder treatment as well as maybe treatment for the schizophrenia? 

DR. W. GORDON FRANKLE:  Yeah, I think that bringing those two parts together is what's important. To have experts in treating individuals with substance use disorder because we do have good medications to help with specific substances and also people who are well-versed in treating psychosis and schizophrenia and making sure that they're on the same team and they're talking the same language and working with the patient the same way.

DR. THEA GALLAGHER: What seems really thematic from what you're saying and a couple other experts that we talked to with substance use disorder, PTSD, is this idea that what might be like a big theme in all of this is community and a team of care and continuation of care that that might help mitigate against all of these issues. 

DR. W. GORDON FRANKLE:  Yeah, I think that's absolutely right and you want to have a continuity of care. In Brooklyn at NYU, we have a really nice system where we have a large outpatient setting, we have an inpatient hospital, and we have really nice continuity of care where patients receive treatment in our hospital and then go to our outpatient setting and it's quite unique that we have that continuity. So we don't have to send patients to outpatient clinics that are kind of far out or difficult to connect with. They're all under one roof. We all have one EMR so we can see the medical record. And I think that makes a difference and I think that does help us to provide better care to patients. 

DR. THEA GALLAGHER: It seems like there's a care about them ongoing as well. 

DR. W. GORDON FRANKLE:  Yeah, exactly. 

DR. THEA GALLAGHER:  Looking ahead, what are you most excited about with maybe some of these more nuanced treatments and then some of these big-picture public health interventions for schizophrenia? 

DR. W. GORDON FRANKLE:  Yeah, so I think that the new treatment that came out , the Cobenfy, is going to be interesting to see how that works and what's the uptake of that medication and whether or not the success of that medication starts to spur on increased development, drug development in schizophrenia in different pathways. So I think that that's one area that's very exciting to see what comes out of there. 

DR. THEA GALLAGHER: Can I ask a quick question about that? Is it administered any different than the other medications that have been used, or is it the same but different? 

DR. W. GORDON FRANKLE:  This is a pill form. And you bring up a good point. There are different ways to administer medications for patients with schizophrenia. One of the ways is the long-acting injectable medications. This new medication doesn't have a long-acting injectable formulation, but many of the antipsychotic medications do. That's also another thing to consider. I mean, that has been shown, the use of long-acting injectable medication has also been shown to reduce relapses and improve long-term outcomes, be associated with reduced mortality in patients with schizophrenia. 

DR. THEA GALLAGHER: I don't know, everyone's talking about psilocybin, psychedelics, is there any hope for even maybe an intervention that could be two times and help long term? Or is that kind of what we understand likely not going to happen?

DR. W. GORDON FRANKLE:   I think likely not the right choice for patients with psychosis. 

DR. THEA GALLAGHER: But anything like that, you said like this long-acting, is there anything that they're hoping could be like you know maybe a shorter? 

DR. W. GORDON FRANKLE:  Just a single one or two? That's, I think, unlikely, just because of the course of the illness and how it is really a lifelong illness and something which needs treatment lifelong, much more of a chronic illness. 

DR. THEA GALLAGHER:  And I think maybe providing education about that. That's why it seems like this intervention that you have at the hospital, which is ongoing, is so important because of the nature of the illness. 

DR. W. GORDON FRANKLE:  Yeah, I think that's right. The education both of the patient and the family and to understand that this is really a lifelong illness and in most people, they need to take medication throughout their life and that's really going to result in the best outcome. We have some ability to do some disease mitigation by starting treatment early and trying to continue it throughout the life.

DR. THEA GALLAGHER: And then with community public health kind of interventions ongoing, what do you hope to see? 

DR. W. GORDON FRANKLE:  So some of the stuff we've been talking about would be wonderful to see. So some early screenings and assessments for individuals who might be at risk and then tracking to see who might be developing schizophrenia or psychotic illness. And then really, I'd love to see much more investment in the community setting for patients with schizophrenia, being able to provide these wraparound services, not just at the first episode or when they've had multiple hospitalizations, but throughout the life course. That, I think, will save money by reducing hospitalizations, even though the actual cost of the outpatient care is going to be more expensive because you have many more individuals involved in that treatment team. 

DR. THEA GALLAGHER: I think that it sounds like there's a lot of great work and great research happening that will hopefully be ongoing. So thank you so much for your time. 

DR. W. GORDON FRANKLE:  Thank you so much. It was a pleasure. 

DR. THEA GALLAGHER:  All right. And thank you to all of our viewers and listeners of the Insights on Psychiatry podcast. If you enjoyed this episode, please remember to rate and subscribe wherever you watch or listen to your episodes. And I'm Dr. Thea Gallagher, and from all of us here at NYU Langone Health, thanks for listening and viewing.