NYU Langone Insights on Psychiatry

Pediatric ADHD: Precision Strategies (with Samuele Cortese, MD, PhD)

April 16, 2024 Samuele Cortese Season 2 Episode 12
NYU Langone Insights on Psychiatry
Pediatric ADHD: Precision Strategies (with Samuele Cortese, MD, PhD)
Show Notes Transcript

For the final episode of Season 2, we're joined by Dr. Samuele Cortese, Professor of Child and Adolescent Psychiatry at the University of Southampton (UK) and Adjunct Full Professor at NYU Langone. Together we explore the intersection of pediatric ADHD and precision psychiatry, including the disorder’s genetic underpinnings and evolving treatment options.

00:00 Introduction
00:54 Dr. Cortese's Research Journey
02:11 Global Perspectives and Challenges in ADHD Treatment
03:51 Advances in ADHD Diagnosis and Treatment
06:41 Role of Genetics in ADHD
09:33 Precision Treatment and Stratification
12:17 Treatment Adherence and Shared Decision-Making
23:55 Connection Between ADHD and Obesity
28:39 Non-Stimulant Alternatives and Future Directions in ADHD Treatment
32:16 Non-Pharmacological Treatments
37:28 Advice for Clinicians and Closing Thoughts

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Podcast producer: Jon Earle

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DR. THEA GALLAGHER:
Welcome to NYU Langone Insights on Psychiatry, a clinician's guide to the latest psychiatric research. I'm Dr. Thea Gallagher. Each episode I interview a leading psychiatric researcher about how their work is shaping clinical care. For the final episode of Season 2, I'm pleased to welcome Dr. Sam Cortese to the podcast. Dr. Cortese is a professor of child and adolescent psychiatry at the University of Southampton and an adjunct full professor here at NYU. Like our last guest, Dr. Cortese is an expert on pediatric ADHD, but this interview goes in different directions. Dr. Cortese is deeply involved in bringing precision psychiatry to ADHD, and his work has uncovered an important link between ADHD and obesity. So, even if you listen to our interview with Tim Wilens, you'll find a lot more to think about here. Dr. Cortese, thank you so much for being on the podcast today.

DR. SAMUELE CORTESE:
Thank you.

DR. THEA GALLAGHER:
Can you give us an overview of your research journey and what drew you to focus on ADHD?

DR. SAMUELE CORTESE:
Right. So, I started my research journey, I would say probably more than 20 years ago as a clinician researcher. And my interest was from the very beginning around ADHD. I think I was fascinated by the fact that for this disorder we have therapists, in particular pharmacological treatments, which are very efficacious and effective in the real world. And so, since then, I've been trying to understand really better how best we should treat individuals with ADHD. And so, I collaborated and I'm still collaborating with a number of colleagues around the world. And currently, I am the chair of the European ADHD Guidelines Group, which is a very important network for me. And we are producing what I think is very interesting work to guide clinicians in their daily clinical practice.

DR. THEA GALLAGHER:
And it sounds like this is an issue that is important internationally. Can you tell us a little bit about that global perspective?

DR. SAMUELE CORTESE:
Yes. I think it's interesting, because, of course, we have evidence which is applicable at the international level. I mean, the findings of trials are applicable regardless of the country where you are in general. Meaning, that if we find that this specific medication is efficacious in a trial and well-tolerated, this is the case across countries. But what changes is the way clinical recommendations are implemented according to the specific setting. So, our remit as European ADHD Guidelines Group is to produce a guidance, which is, let's say a general guidance, but then this will need to be translated and shaped in specific.

DR. THEA GALLAGHER:
And what are some of the main challenges with global dissemination and implementation?

DR. SAMUELE CORTESE:
I think there are many challenges. The first is that, of course, not all interventions are available equally across countries, both in terms of pharmacological options. So, for instance, of course, the US market is quite broad, but in other countries there is just one medication for ADHD. But also ways in which the pathways for the management of ADHD are organized. So, it's really interesting to see this variety of clinical possibilities out there.

DR. THEA GALLAGHER:
It sounds like your work in part is focusing on that very important work of dissemination and implementation on the global level. And just getting more specific to ADHD. When you look back over the past 20 years of ADHD research, which advances do you feel like have been the most significant for both diagnosis and treatment?

DR. SAMUELE CORTESE:
Right. So, in terms of diagnosis, I think that a very important study finding has been the publication of the GWAS results of the genes which are involved in the theology of ADHD. So, of course, this is not yet applicable to clinical practice. This is more to understand the theology of the disorder, and so in the future to tailor the treatments according to this specific theology. But I think the discovery of these genes has been very important and it has highlighted that ADHD actually is not a simple disorder. There are many, many genes, each of which contributes with small effect sizes to the disorder. And of course, what we need to understand better is also the interaction among different genes, and between genes and environment.
The second finding, which I think has been important in terms of management and treatment of the disorder, is the understanding of the different role of pharmacological versus non-pharmacological treatments. This, in particular, I think the work we have done in terms of evidence synthesis in interpreting the evidence from all randomized control trials in the field for non-pharmacological approaches. Has been very helpful to highlight that possibly when it comes to non-pharmacological interventions, these are not tackling the ADHD core symptoms, but are very helpful for other issues, problems associated with ADHD. But when it comes to the core symptoms of ADHD per se, so in attention, hyperactivity and impulsivity, to date, we have evidence that only medication can really change the severity of these symptoms when we look at blind [inaudible 00:06:11].
So, I think this has been important really to guide a number of guidelines to support inform guidelines around the world. For instance, in the UK, where I work at the guidelines from the National Institute of Health and Care Excellence, the NICE, which do recommend parent training when there is a comorbid oppositional defiant disorder. They do not recommend parent training for ADHD itself. And this is a big change in relation to the previous guidance.

DR. THEA GALLAGHER:
And when interpreting, or making meaning, or doing anything about what we're learning from the genetic aspect of things, does it have an impact on diagnosis and treatment, or are we still at early stages of just seeing that there is information to show that something is happening but we don't know exactly what to do with it or how we would get closer to maybe a precision medicine treatment?

DR. SAMUELE CORTESE:
Right. So, that's a very important question. So, of course, the naive approach will be to say, "I know the genes of ADHD. So, to diagnose ADHD, I simply test, I do a blood test and I check these genes or a saliva test to check the genes." But this is not possible, because we're not talking about two, three or four genes. We are talking about a plethora of genes, each of which can interact with others. And if I take individual A with ADHD and another individual B with ADHD, they will not necessarily have mutations in the same genes, in the same set of genes. So, this is why right now there is no diagnostic test based on genetics. However, genetics, of course, is very important for the purpose that you mentioned, which is hopefully in the future we will be able to implement an approach which is similar to what for instance oncology has done in the past, which is to tailor the treatment to specific characteristics of the patient.
And we are not there yet at all in terms of ADHD and the other mental disorders. But the hope is that the more we know about the neurobiological correlates of this condition, the more we will be able to stratify the treatment according to specific characteristics of the patients. And so, genetics, of course, will play an important role in this, because one can argue that compared to other modalities, it may be cheaper to implement. One may think for instance, of the cost of an MRI and other advanced approach. Even though, ultimately, it's not just only a matter of cost, it's a matter of cost-effectiveness. So, even if there is a cost, if it is good to then provide the patient with a specific treatment, which is effective, one may also argue that it is cost-effective. So, it's not just a matter of cost.

DR. THEA GALLAGHER:
Well, it sounds like genetics are one way that you hope the precision medicine and precision approach for ADHD begins. And you've written about the need for precision tools for making treatment decisions for ADHD patients. So, can you give us the lay of the land for that aspect of things, the precision tools connected to treatment decisions?

DR. SAMUELE CORTESE:
Right. So, I think we are really at the beginning of all these. And I would say that right now my research really is focusing on stratification of treatment, which is a concept which is correlated to the framework of precision medicine. So, basically, as I said, I think it's still early days to use any predictor which is genetic, neurobiological, neurophysiological, to really treat to implement a personalized approach. So, what I think is possible to do, hopefully, and my main project right now is exactly on this, is to stratify the treatment according to specific clinical characteristics, which is easy to measure. We do this in the clinical practice every day. So, social demographic characteristics, comorbidities, other treatments, so all these information which is available to clinician. It doesn't add any burden, any additional cost. So, to stratify the treatment according to this, but also according to the personal preferences of the patient and their family.
So, we have now, from a number of methodologies, we have a ranking of medications, for instance, which should be considered first line, second line, or third line medication. This is a general recommendation, which means that the medication which is indicated as a first line in general may not necessarily be the best for a specific person. So, the question is how can we shape, how can we change this hierarchy, this order of medications based on specific clinical characteristics, but also based on specific preferences?
So, for instance, if a patient says, "For me it's very important to avoid headache, because for me headache is really an issue," then we can look at those medications which are more likely to give headache and factor these in the prediction model so that we can say, "Okay, given your characteristics and your specific needs, this medication may be the best for you." So, I think we can do this right now. We have the tools to do it, potentially. We are not yet in the position to say, "Given your genetic makeup, you should take this medication."

DR. THEA GALLAGHER:
And do you think personal preferences play a role in treatment adherence, and is that why it's a big focus for you with the stratification?

DR. SAMUELE CORTESE:
Yeah. I do think so. I think one of the main issues we have in the treatment of these children, and people and adults, is adherence, as you said. We have very good medications. So, if we look at the medications we use for ADHD, these are among the best we have in psychiatry and in general medicine, I would say, in terms of their effect sizes, how powerful they are in changing the severity of the symptoms. So, the problem is not having good medication, the problem is to be adherent to this medication. So, adherence is really an issue, big issue. So, we need to tackle this.
And there are different ways to tackle this, but I do believe that if we implement a system whereby there is a share decision-making between the clinician who will bring the result of the science, the result of research there and the preference of the individual, the individual will be more empowered and the adherence will really improve. I think of many of my patients, and sometimes I know I discussed this issue at the beginning where we started treatment, but when I see them after a year, they have already forgotten all this. And they don't see the point why they should take a medication. So, we really need to have the patient on board, more rather than just imposing a treatment, just because we know that this is recommended by specific guidelines.

DR. THEA GALLAGHER:
And understanding that this is a challenge is important. It makes me think of the use of a CPAP machine. We know it works, but the adherence is where it can get difficult and then figuring out ways to make that adherence more likely, it sounds like where a lot of your work is focusing. And are you gathering that data or do you think we should be gathering that data in advance of treatment, or having it be an iterative process with regard to how someone experiences the medication or both emotionally, physically, et cetera?

DR. SAMUELE CORTESE:
That's very important. So, I was recently funded by the National Institute for Health and Care Research, which is the NHR in the UK, it’s the main funding body for clinical research. Quite a large award really to basically develop and testing, initially testing a web tool device, so an app or a website which will help share decision making between prescriber and a patient. Whereby, really, the hierarchy of the medications will be informed by data from randomized controlled trials, data from observation studies, but also the choice of the final medication will be informed by the specific preference of the patient. So, it will be to be an ongoing process, rather than something which is established just at the beginning of the therapeutic journey.
So, I think this is really crucial to change and to have this perspective in the field, because we have not been good, I think, in the past in terms of involving really patient and hearing their voices, particularly the voices of children. And there is a lot to learn when we listen to them. And we know we have in our mind, as prescribers, we know everything which is written on the guidelines and on the formularies, and so on and so forth, but we should listen more to children and their parents.

DR. THEA GALLAGHER:
Yeah. And it sounds like you're tapping into more of a psychological principle of maybe motivation, and personal gains and trying to really bolster that instead of just here's your doctor telling you to do something.

DR. SAMUELE CORTESE:
Well, certainly, I think this is how we conceptualize care nowadays. And also, more specifically in terms of ADHD medications, we have done also research alongside my colleague, Steve Faraone, from SUNY Upstate, and on the placebo effect of this medication. Because we know quite a lot about the placebo effect of antidepressant, for instance, but not so much about the placebo effect of medications for ADHD. And we were looking at the data from randomized controlled trials of these medications. It's quite clear that part of the action of these medications is based on a placebo effect, which is not a negative per se. So, it's part of the action of the medication. So, psychological factors do have a crucial role ultimately in the success of these medications and we need to be aware of this.

DR. THEA GALLAGHER:
And what would you say are some of the major challenges you face when it comes to precision psychiatry and ADHD? Would you say it's the data, our understanding of the neurobiology or maybe getting health systems on board with this stratification model? What are some of the biggest barriers here?

DR. SAMUELE CORTESE:
I think everything you mentioned makes sense. To me, I think right now, as I said, I think we don't know yet a lot about the neurobiology. Actually, we know quite a lot and we know that it is complex. So, it's quite heterogeneous. So, we need to address this challenge. But right now, if we want, for instance, to implement the stratification model I was mentioning early on, which is the base of my NHR project, I think the key thing is really to have access to data, to a large data set, because we cannot do this with small data sets. So, what I'm in the process of doing right now is to hopefully having access to individual patient data from trials and observational studies, electronic health records. Because in order to build these personalized stratification models, we don't only need the aggregate level data, which is the summary of the data across the sample. We need data from each individual included in each trial that we include in this big model.
There has been a development in terms of data sharing and open access culture in the field, but arguably things are not really straightforward yet. But we need to appreciate that as a scientific community and including also manufacturer drug companies, sharing data is really crucial to build these models. And of course, there are a number of challenges, obstacles there, but I think overall the field is moving toward that direction. The project I submitted and then the application I submitted, it would be not conceivable probably 15 years ago where there was not at all a culture of data sharing. Now we have a platform such as Vivli, which allow us to request data from trials. And hopefully, this will make our research more impactful.

DR. THEA GALLAGHER:
And when you survey the field of ADHD research, are there some other efforts that also seem particularly promising?

DR. SAMUELE CORTESE:
Right. So, in general, in the field of ADHD, I think when it comes to treatment, for instance, I think that another interesting line of research is to understand the long-term effect of these medications. For instance, also non-pharmacological approaches, but the focus on the long term rather than the short-term. Because all the trials, for instance, we have in the field are short-term. So, we need really to understand better the long-term effects. And having a long-term trial is basically impossible, because it's not ethical to randomize somebody to placebo for years. So, we have a way to address this via withdrawal trials, but we have also interesting developments from the epidemiological field. Now we are able to model, for instance, the effect up to 10, 15 years using registries, such as the Swedish registries, for instance. So, there are emulated trial, target emulated trials. So, the methodology is advancing and is allowing us to understand the longer-term effect of medication. So, I think this is a very exciting development.
The other interesting development I think more generally in the field of ADHD, is I think its relationship with the concept of neurodiversity, which is really something that was not there when I was trained 20 years ago. Now, of course, it may potentially be a change in paradigm. We are not seeing any longer diseases within the lens of a medical model, but as a neurodiversity, so, a difference. And the problem is not due to the condition itself, it's how people address this condition externally. But arguably, this is very controversial and very complex concepts. So, I hope there will be serious research and discussion on this, because it may really change quite significantly things in the field.

DR. THEA GALLAGHER:
And you were talking about the controversial piece, from what I understand, of the perspective being that some people feel like they're meant to fit into a world that doesn't accommodate their neurodiversity, and that you have to be medicated to fit into the guidelines of society where hopefully there might be more general accommodations and understanding of that people work differently, think differently, act differently.

DR. SAMUELE CORTESE:
Yes. That's what, of course, is being discussed. But I think it's quite complex, because of course, we need to highlight, we need to fight stigma around this condition and we need to be aware of this. But arguably, many individuals have been really helped in the past by the medical model. The treatment they receive has helped them. So, I think it's not a question of black and white, it's a matter of seeing how we can in a way put together these two different models, the medical one and this neurodiversity model to make sure that ultimately the person, the individual, the patient is at the center. But I don't think that it's good to completely reject the medical model that has been used.

DR. THEA GALLAGHER:
Yeah. And hopefully the goal leads to greater quality of life and well-being for the patients and finding data to support that. Are they feeling better? Do they feel like they have some more maybe control over certain aspects of their lives? And switching gears a little bit here. You've been involved in many studies exploring the connection between ADHD and obesity, and we haven't really talked about that on our podcast. So, can you tell us about what you've learned and where that research stands?

DR. SAMUELE CORTESE:
Yeah. So, I would say this is within the more general framework of the relationship, the association between mental conditions, so to speak, and somatic or medical conditions. So, when I was trained, it was quite common to mention the psychiatric comorbidities of ADHD. So, everybody knew that ADHD is associated with opposition, defined disorder, anxiety disorder, mood disorders, and so on and so forth. So, that guidelines recommend to screen for this, and this is part of the assessment of ADHD. And that was quite clear and well-established. What was not clear at all and not mentioned in any of the guidelines and the text I used to study back then, was the association between ADHD and other somatic or medical conditions, such as actually obesity that you mentioned, probably has been the first one.
And to me actually came by chance, because when I was a trainee resident in Italy, I was collaborating with a pediatrician who was doing research on obesity. So, I was thinking, well, actually, this is quite interesting. There is not much research out there on ADHD and obesity, so we should try to explore this. So, it start really by chance, by this coincidence that I was working with this colleague. And then we started doing individual studies and meta-analysis, and then this developed quite as an important topic. And the reason why I think it was considered important is because arguably we are talking about two conditions, ADHD and obesity, which are both important, prevalent. And importantly, we have shown that the treatment, the management of ADHD in those individuals with obesity can help the management of obesity itself. So, I think there are clear implications out there.

DR. THEA GALLAGHER:
Are there more conditions, or symptoms, or other disorders that you would like to look at in the context of ADHD as well?

DR. SAMUELE CORTESE:
Well, I mean this is ongoing work and there's been already a lot of research on other disorders. So, for instance, after obesity we focused on asthma. And we showed actually meta-analytic evidence of significant association. And then we also did a very comprehensive broad umbrella review. So, umbrella review is a systematic review of meta-analysis. So, it's really the highest level of evidence synthesis. And by doing this, we saw really evidence for significant strong association between ADHD and obesity, asthma, rhinitis, and other conditions characterized by immunological alteration. So, it is possible that either there is a common genetic base and, or a common immunological mechanism alteration in the immune system, but also there is the role of stress. So, it's quite complex.
So, I would say that really I think this kind of research is also important because it highlights the fact that we don't need to do research in silos on specific topic. There is a complexity there, because the patient will come to our attention are not simple, are complex, they have many conditions. And we need to reflect system which are able to correctly and properly manage this complexity, rather than having the specific service for ADHD, the specific service for this and that. So, they should be more complex and comprehensive.

DR. THEA GALLAGHER:
And that's the precision medicine goal, to pull in all various data points, and make meaning, and have treatment recommendations and interventions based on the other pieces of the puzzle?

DR. SAMUELE CORTESE:
Yeah. And I would say that the pieces of the puzzle should actually include both what we traditionally see in psychiatry, but also what other colleagues in internal medicine they see.

DR. THEA GALLAGHER:
And although stimulant medications for ADHD are seen as quite safe. I know you were talking about there's the goal to have more longitudinal data, long-term follow-up data, but there is also a significant demand for non-stimulant alternatives. I think for a lot of parents, for their kids, even there's some stigma around stimulant medications, but just the hope that maybe there's something else. How would you rate existing non-stimulants and what is the pipeline currently looking like for new medications?

DR. SAMUELE CORTESE:
Well, I would say it's important to have stimulants, because we know that some individuals with ADHD, even though they're not the majority, but some of them, either they don't respond to stimulants or they don't tolerate. So, that's clear, we need to have stimulants. And the concern around possible abuse and misuse is also important. So, it certainly is important to have non-stimulant options. What we have so far are alternatives, which are second or third line, because in general they are less efficacious in trials compared to stimulant medication.
But as we mentioned earlier, this is general at the group level. For specific patients, actually, a stimulant and maybe the best option for other non-stimulant may be the best option. So, I think that right now we have three main non-stimulants on the market in the US. So, atomoxetine, the alpha-agonists, so clonidine, and guanfacine and fluoxetine, which is not present in other markets. And they are quite similar, I would say, in terms of effect sizes. So, we are moderate effect sizes. So, certainly, they will not probably be recommended as the first line in general, for the majority of the patient.
There are interesting developments in the field. We have actually recently conducted a systematic review of all the trials which have been registered in clinicaltrials.gov in the past 10 years. And there are a number of compounds in ADHD. However, when we looked at replicated data, so trials with positive finding that had been replicated in two or more trials, we couldn't find a lot of compounds, actually. There was a compound, but interestingly its development was stopped by the drug company in 2021. So, I think there is some movement I would say in the field, but it's quite difficult, I must say, to find something which can compete with stimulants, because stimulants have very high effect sizes.
So, ideally, we would like something with the same effect sizes as stimulants, but better tolerated. But so far to my knowledge, this has not been found. But the other interesting development in the field in terms of new compounds is alternative formulations of already existing medications. And this is extremely important, because for instance, we have a number of children with sensory sensitivities, autism and comorbidity, who are not able to swallow tablets or capsules. So, we need alternative formulations. So, injectable, ideally, but so chewable medication, liquid formulation, transdermal formulation. So, there is a lot of development in this, and it's very important.

DR. THEA GALLAGHER:
You're talking about how stimulants are the first-line intervention. What do you think about or what are the prospects around non-pharmacological treatments, maybe on their own or as an adjunctive, and that includes maybe both therapy, but also lifestyle changes, et cetera?

DR. SAMUELE CORTESE:
Yeah. So, this is extremely important, because of course, we know that stimulants are not curative. So, it's not that you take them once and ADHD goes away. So, the goal of many researchers, the dream I would say has always been to find something which is curative in the long term, and also something which is safe, which the concerns we have with medication is not there. So, I think there are mainly two broad areas on the one. And there are the non-pharmacological interventions, such as psychotherapies, cognitive training, neurofeedback and diet. For all these so far, we don't have a strong evidence of a meaningful effect on ADHD core symptoms, but some of them address other problems which are very important in ADHD. For instance, parent training has been shown to be efficacious and safe for oppositional, defined behavior, conduct disorder, improving parenting. So, these are not the classic outcomes for trials, but they are very important in clinical, in daily life.
The other big chapter is around neurostimulation. And so, this may potentially be promising in terms of providing a more lasting effect in the long term. And of course, many of our listeners may be aware that the FDA approved, gave license to the external trigeminal nerve stimulation, ETNS, as a treatment for ADHD. However, this was based back then only on one pilot trial. So, we need more evidence on the effect of this treatment, and also we need to understand better the underlying mechanism. So, for instance, in my center, we are conducting a trial in collaboration with colleagues in London. Actually, the PI is in London, Professor [Katya] Rubia, to better understand the effect of trigeminal nerve stimulation, which is a non-invasive approach for ADHD.
So, far we know that its effect size is moderate, so probably it will not replace current treatments, but it may be an alternative, but we need to understand better. So, also, colleagues in the US are studying this. So, the field is developing a lot. And finally, to highlight what you mentioned, also lifestyle is very important and related to this in part, is microbiota, so all these studies. So, we really need to have a more comprehensive approach. But I would say that the guiding principle in all this line of research is which outcome do we want to tackle, because we cannot say just treatment for ADHD in general. ADHD is much more than three core symptoms. So, do we want to improve ADHD core symptoms? Do we want to improve exact functions? Do we want to improve mood or mental health in general? Do we want to improve quality of life? So, depending on this, the result of the study will be interesting to point to specific outcomes.

DR. THEA GALLAGHER:
Yeah. It seems like having a number of different targets and hopefully pulling them all together would be the goal. But it sounds like because different treatments, lifestyle changes can maybe address different symptoms. It might be a combination of factors, which it sounds like the research is ongoing to figure out which combination of factors produce the best results for, again, greater quality of life and well-being.

DR. SAMUELE CORTESE:
Yes, indeed. The combination is not just considering this individual intervention in isolation, that's definitely... We need more head-to-head trials. And there are also advanced meta-analytic techniques which allow us to look at all the interventions available, and also the combination and combine them in kind of meta-analysis. So, we have a quite advanced tool to understand these comparisons.

DR. THEA GALLAGHER:
And on top of that, it sounds like also understanding maybe people have different needs throughout the lifespan in which symptoms are we targeting at different stages for individuals as well.

DR. SAMUELE CORTESE:
Exactly. Exactly. So, this is exactly the developmental approach that we need to have, because we're talking about a neurodevelopmental condition. So, it doesn't make sense really to see this in a static way.

DR. THEA GALLAGHER:
And for my final question, what advice would you give to clinicians working with people with ADHD right now to improve treatment outcomes?

DR. SAMUELE CORTESE:
Well, I would say, of course, you need to know the evidence, you need to know the guidelines, when available. But this is just one part of the picture. So, we know that there is a slide I always show when I talk about evidence-based approaches in the management of this disorder, which is a very simple slide with a triangle, which shows that there are three factors we need to consider in an evidence-based approach. One is, actually, as I said, the evidence. So, we need to stay abreast of the latest evidence. But the other factor is the specific characteristics of the patient and the other is the preferences of the patient. So, we cannot just look at the evidence-based. Is important, because in the past, in many contexts, this has been ignored and this caused a number of issues.
But we need to bear in mind that we're dealing with human persons, and beings with preferences and specific characteristics. So, I think, ultimately, I always say I learned together with my patient and their family what is best to do. I don't have the solution at the beginning. I can propose, I can say what I know based on what I study, I read, but we need to find together. And there is no way to model this complexity right now.

DR. THEA GALLAGHER:
Yeah. It sounds like collaboration is key, and that will likely only bolster more motivation and connection for the patient to their own treatment journey. So, thank you so much. I think that's a great piece of advice to leave with our clinicians. And thank you so much for being on our podcast today.

DR. SAMUELE CORTESE:
Thanks for inviting me. And I hope this will be helpful to stimulate a good practice in our colleagues.

DR. THEA GALLAGHER:
Thanks so much for that conversation, Dr. Cortese. If you enjoyed this episode, be sure to rate and subscribe to NYU Langone Insights on Psychiatry on your podcast app. This is our final episode of Season 2. Thanks to all of our amazing guests, to their support staff and to all of you for listening, of course, but more importantly for the work you do every day. From all of us in the Department of Psychiatry at NYU Langone, I'm Dr. Thea Gallagher. Thank you and take care.