So this talk is part of the Clinical Updates track, which is a new track within, well, it's the second year within the APA meeting, so the goal is that you can attend all of them. They're labeled on the app, and you'll get a very global update as a practicing psychiatrist. All of these are going to be live-streamed on the virtual meeting, so when I take questions, I'll be alternating between in-person questions and then online questions so that people who are watching the meeting from home are also going to interact with us. So just a quick bio, and then we'll jump into the meat of the talk. Dr. McGuff is a professor of clinical psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior. He is a distinguished fellow of the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry, and he is currently chair of ACAP's program committee, so we know how hard you work, given that I'm also on the SPC of this meeting. And he has been a principal or co-principal investigator at over 50 clinical trials, including for both the NIH and the industry, and he has authored over 150 research publications, reviews, and book chapters, and one with particular emphasis on pediatric psychopharmacology of ADHD. So we're very lucky to have an expert to talk about this important topic, and without further ado, we'll get started. All right, Jackie, is my mic on? Are we good? How about now? Challenges. Okay. Well, you know, I was telling Jackie, I came to my first AP meeting. I was a third-year med student. We had our AV person. Apparently I'm not audible. We'll make this work. How about now? I could stand, but I'm old, and I get wobbly. How about can we... There we go. All right, that took the wind out of my compelling introduction. So I was saying, I was a third-year med student, and I came to my first APA. I think it was like 1985 in Dallas, and I had such a good time. And I remember as a resident also coming, in fact, to San Francisco one year. When you're a resident, coming to an APA meeting is very much a nice change of pace. I run the child meeting, so it's an all-encompassing job. So kudos to Jackie. This is like five times as big as ours. There's a lot of faces I don't typically see, so it's nice to be here. The only other thing before I really plunge into it, and let me say, I have learned that... Actually, in the years of Zoom learning, we've made our talks shorter and shorter and shorter. I'm going to talk for like 50 minutes, and we'll have another 30 to 40 minutes, because I think your questions are probably what you're going to take away, in terms of my answers for those. But my last comment, as a Californian, I can welcome all of you. I actually live 500 miles down the coast, right off the Pacific as well. People get very confused when they come to Southern California, and it's June, and the sun doesn't come out until like 4.30 in the afternoon. This is what the surfers call June gloom. And last night, as I walked around, I remembered, I believe Mark Twain said, the coldest winter I ever had was my summer in San Francisco. So I hope you're enjoying your time here. Okay, let's get started. So I'm going to talk about ADHD across the lifespan. And again, when I was 30 years ago, the idea that ADHD was a lifespan disorder was completely novel, right? And now that has very much changed. We have learned a lot, and I'm going to do my best to share the highlights for you. I do not do any... I have no dealings with pharmaceutical companies on the commercial side. I am on a DSMB for Synovium. I have testified in actually several patent trials with Eli Lilly, Takeda, and Trisforma. And I get material support for an NIH-funded research project for trigeminal nerve stimulation from NeuroSigma. But I have no commercial entanglements whatsoever. All right, at the end of this medical education activity, you should be able to, one, identify two personal and or social consequences of ADHD, secondly, identify at least one standard tool useful in ADHD assessment, and finally, describe three evidence-based ADHD treatments. I was taught once that every good talk has three parts. I don't know if that's... if it was Chaucer or Cicero or some famous teacher. But anyway, this talk has four-plus questions, so forgive me that. But we're going to go over the background and impact of the disorder, something about its ideology. Let's talk about assessment strategies and then treatment. You know, I appreciate you may correct me if I'm... Well, let me back up a little bit more. I think, I'll be really honest, child psychiatrists are the best people managing ADHD because it's most of what we do. I think adult psychiatrists can get really good at it, but I think, like, in the adult training program right now at UCLA, you get two hours of instruction from me on ADHD in your four years. So I recognize that you have probably all heard more and more about this, and I'm going to do my best not to bore you with the super, super minutiae, but give you the big picture so that tomorrow you have more to think about when you get back to your offices. So again, we'll talk a little bit about the ideology, how to go about assessing this, and then really into some nuts and bolts about treatment. Just some quick facts. Now, there are books written... There have been books written sort of about the joy of ADHD and the blessing of... ADHD is not joy and it's not a blessing. It's not the worst thing, and I've had times where I've had parents... I remember very distinctly once I had a mom. As I'll tell you later, the first thing I do after I make an assessment is I say, I want you to know this as much as I do. I begin this process of psychoeducation, and part of that is talking about the brain basis of the disorder and some of the risks that I'll get into in a second. I had a mom start to cry once. She's like, good God, I could be saying your child has autism or your child has... all sorts of things. Your child could have leukemia. ADHD is not the end of the world, but it's not really a blessing. Some quick facts. About 3% to 10%, maybe 3% to 12% of the child population around the globe is affected with ADHD. Let's say it's about 10% of school-age kids. It doesn't matter where you are. It doesn't matter how smart you are. It's just there. About half of those people seem to have the disorder as adults. About 4%. So many of you probably in your practices see a lot of people with depression, and I think the lifetime incidence of depression is maybe one out of four people has one episode of depression, but it comes and it goes, and a lot of people have it once. Well, if you're an adult with ADHD, you've got ADHD. It's not going away. So probably one out of four people, or one out of 25 people that you see in your office is likely to have had ADHD or been affected by it. Certainly everybody knows somebody who has ADHD. In school-age clinic populations, boys are more represented. Boys are more hyperactive and impulsive. They're more behaviorally disordered. Attention is cast on them. Nine to one, boys or girls. But in community samples, it's more like three to one. Testosterone, I'll just say it, does not do great things to the brain in many ways, and this is one more area where boys are more affected, along with learning disabilities, autism, things like that. In adult clinics, though, we see about equal numbers of men and women. Now, as opposed to community samples, where there's still about a three to two prevalence, and perhaps not being, this isn't a joke, maybe some of those men are dead or they're in prison or they're just not coming in for care. So we do see more equal numbers of people in our clinics at the adult level. I know there's a little, you can up these numbers now for inflation. In 2007, there were about six million people with the diagnosis, only about a third of those are on meds. So these ratios hold true. We are still not giving medicines out to near the number of people that we have, and that's not a judgment, but that is to say we're not over-medicating this disorder. And the cost to the economy is now three to four hundred billion dollars per year. All right, one thing with ADHD. As I'm going to get into in a minute, I'll say this a couple of times. ADHD is a brain-based neurodevelopmental disorder, and I'll tell you about some of the brain findings in a minute. It creates risk for other disorders, and ADHD has lifetime risk for all sorts of other psychiatric comorbidities. The highest numbers are other oppositional and conduct disorder behaviors, the disruptive behaviors, and substance abuse, very, very common in kids growing up with ADHD, and also depression and anxiety disorders. Psychosis, there's not a lot of psychosis, unfortunately not a horrible overlap with bipolar disorder, but depression, anxiety, substance abuse are the main risk factors. To the point of substance abuse, in general there's about a one to two times chance compared to not having ADHD that you'll have some problem with substance use. There's this idea that maybe people are self-medicating. That's not really true. What seems to happen is people with ADHD get hooked on substances that are in their environment. Lots of problems with nicotine, lots of problems with alcohol, lots of problems with cannabis, and by problems I don't mean use. I mean getting stuck and having problems as a result of your using. That's what we're talking here. For those of you who see individuals who have substance use disorders, you ought to be thinking how many of these actually have ADHD. Then other risks. Again, these kids growing up are impulsive, they're hyper, they fail the marshmallow test, they don't delay very well, and they have higher rates of pregnancy and contraceptive failure and more partners sexually at young ages and school failure and occupational failure and not going to college and having arrests and having your license revoked Again, this is not really typically a virtue. That's what I'm going to say about the impact. Again, the big lesson here is let's not think this is a blessing, it's not the end of the world, but people with ADHD have added risks. It probably isn't well-suited to 21st century living. All right, let's talk a little bit about the etiology. I always like to... I think I was reading something in the New Republic once and it was written by a... I don't want to... Getting into politics isn't too important, but I will say... Well, I'll just say it. So apparently Rush Limbaugh once said that ADHD was a feminist conspiracy to turn boys to girls. That is not true, but the conservative columnist of this article actually had had a child diagnosed and he was very grateful for it. But let me talk a little bit about the various risk factors associated with really making it worse. So there's psychosocial risk, early developmental risk, things in the environment, genetic risk, and then I can talk to you a little bit about our brain imaging findings. And honestly, any one of these topics could be a whole talk or symposium, but I'm going to... Again, I want you all to have some take-homes for tomorrow. I was really poor as a medical student. I actually worked as a phlebotomist and sold myself for every drug study I could at those days. And so for three years, I went in every day at 5.30 to draw blood before I started whatever. We had Grand Rounds in medicine. It was at 7 in the morning. So I was there. I went. And I thought then, well, if I can remember one thing from this Grand Rounds, tomorrow it was a success. So that's my hope for all of you, that you can remember one thing from my talk today, tomorrow, and then it was worth your time. All right. The psychosocial risks. So again, a little history. In DSM-II, this was referred to as hyperkinetic reaction of childhood. That's what it was called in the 60s. And the idea was that this hyperactive syndrome, mostly in boys, was a reaction to bad parenting, which for those of you... I was alive in the 60s, and many things were a result of bad parenting then, I guess. But what they found is when they... Again, they were blaming marital difficulties. Then they found when they medicated the kids, the marital difficulties improved. But nonetheless, as with everything, if you live in chaos, if you are lucky enough to have two parents, or if your parents aren't supported, lower SES, more economic stress, large family size. I'm the oldest of eight. I'm having a father in prison, a mother who's depressed, being abused, being in foster care. This all tends to make the syndrome worse. So it's not going to give it to you, but in these circumstances, the phenotype, I think, is more out of control. And that's all I'm going to say about the environment. In terms of really developmental risk, again, these are all associations, but we know that prenatally, maternal smoking, maternal alcohol use, being exposed to PCBs and DDTs, which certainly isn't too common, thankfully. Interuterine growth delay. So I've had patients where, you know, come 20, 22 weeks gestation, their uterus starts to... or the placenta starts to fail. Those kids have a different etiology, but you do see the syndrome in them. And then perinatally, poor maternal health, older moms. Kids born under 32 weeks gestation almost invariably have what looks like ADHD because of sort of the birth trauma around that. Excuse me. Long labor, fetal distress, being really tiny, having anoxious seizures, brain hemorrhage. These are probably etiologies of the syndrome. They don't really represent the garden variety of ADHD. Again, in psychiatry, I like to say, you know, in the child world, we've had all these debates over the last 20 years about what juvenile bipolar disorder looks like. And we decided it looks just like bipolar disorder looks in a 30-year-old. But wars were fought over this. And I actually wrote an editorial when... We've made all this stuff up. So let's not get too hung up about what we're calling things. This is the syndrome. These are some things that can cause a syndrome of ADHD, but they don't represent the bread and butter ADHD that we're mostly going to talk about. Environmentally, again, if your child eats paint, if you live in an area where that's a problem, you can test for it. We can fix that. A lot of thought. We don't even talk about this anymore. But for a time, whole preoccupation about artificial dyes in food and kids eating sugar, none of that really affects things. There's really no role or evidence that vitamin deficiencies or sugar or any of those things have anything to do with this. And they've done this in... They've done studies where they blended everything in liquid and fed kids shakes, and some shakes have zinc and some don't. It's all the same. So none of this stuff is important. But where we do get to be important is the heritability. So the heritability, just to be really clear what this is, it's the percent of variance in expression that's due to basically family causes or genetic causes. ADHD is of the most heritable psychiatric conditions. So it is far more heritable than IQ or depression or panic disorder. It's about as heritable as height. So again, this was a disorder which wasn't even acknowledged as a disorder. It is so genetically driven. It is about as genetically driven as schizophrenia or autism. And as I'll tell parents, it's about as heritable as height. So tall parents typically have tall kids, and short parents have short kids. Love and food has some impact, but it's mostly in your DNA. And that's kind of what ADHD is. Now, we've had a series of ongoing genetic findings, and I've been a part of this group. There was a time 20, 30 years ago, we thought one candidate gene, like for the dopamine receptor, if you had the wrong allele, you had ADHD. That did not pan out at all. What we know now is ADHD is a complex trait. In the last version of the genome-wide association study, there's 27 regions of the genome that have been associated with increased risk for ADHD. We found possibly 76 different genes that all contribute very tiny amounts of risk towards developing this. And interestingly, almost all of these genes also create risk for schizophrenia, bipolar disorder, autism. So there's just a set of genes that seem to create developmental risks, and really all of us are seeing the results of those. Now, there is disagreement about this, but I have my own theory. These genes are present in the human genome. They clearly evolved a long time ago. And some would argue there has to be some reason these genes have survived, and I would argue in some circumstances they're useful. And sometimes, honestly, when I'm talking to patients who really feel bad about themselves, I'll tell them this. Yeah, when your job is to sit in class all day, yeah, this sucks. But, you know, maybe there are some instances where having these genes is a benefit. And what I think is one thing typical of people with ADHD, it's not so much a problem of I can't focus, but they don't shift focus properly. So as I'll get to in a minute, you have to pay attention to what's important, but you also have to pay attention to what's going on around you. Right? A kid is going through the forest looking for food, and he's looking for berries, and suddenly, you know, pushes a branch away, and there's a tiger there, a mountain lion. You've got to stop thinking about the berries and get out of there. You're not going to feed your family. You're not going to reproduce. So it's this shifting. And people with ADHD actually don't shift well, and a lot of times what we'll hear is they overfocus. So what I think of is like, well, you know, it's D-Day, and you've got to make it up the hill, and there's the bombs and the smoke and the blood and the, you know, whatever. Maybe an ability to overfocus or hyperfocus is useful. Michael Phelps has been public about having ADHD. I mean, maybe before a race he's just in some super zone where he's really on task. Right? So anyway, I don't like people to feel like they're damaged, so I talk about the genes, but I am sure in some circumstances these genes are useful. All right. Talk a little bit about brain imaging findings. Mostly we're going to get to your questions. Well, 30 years ago, let me actually dial back to be really clear. All of our brain imaging findings are based on group data. Okay? Groups of people with ADHD and groups of typical people. An individual brain scan yields you nothing. Right? I'm sure if we took a poll, I'm going to go out on a limb here. Let's say if we took a poll of, you know, average bench press, let's say. I suspect the guys would have a higher average in this room, maybe. Guys would have a higher bench press than women, but I would not bet that there aren't some women who can bench more than guys can. Right? Or anything, anything. Right? So it's all around a mean. So let's not think we can image anybody and get a diagnosis, 30 years ago in imaging adults and kids with ADHD, they found that certain areas, the prefrontal cortex, for example, underworks. Right? It wasn't metabolizing as well as typical kids. And there were areas of the brain, particularly the frontal cortex, the basal ganglia, that were smaller in groups of people with and without ADHD. And then very interesting, it was about 2008, Phil Shaw at NIH had a great study where they followed kids in fMRI longitudinally, and what they found is if you look at eight-year-olds, groups of eight-year-olds with ADHD against typical kids, there was less myelination in those kids in the prefrontal cortex. And if you follow those kids over time, a typical kid completes their prefrontal cortex myelination by about age 10. There's a three-year delay in the ADHD kids. It's about three years later. They're 13 before their brains normally myelinate. And I actually have this video on my desktop, and I show it to families. It's like you can download it. You know, it's 12 seconds, but you can see the patterns of growth are the same, but these kids develop more slowly. Okay? And people enjoy seeing that. It makes sense to them. That's why my kids are so immature. Right? So this is what we knew 30 years ago, 20 years ago. But now we have newer imaging findings, making use of things like diffuser tensor imaging, where we can actually look at connections in the brain. And one very compelling theory is that there are certain circuits which underperform. And I don't have a good picture of this. I wish I did, but let me just visualize in your mind. So there's the ventral attention network, which basically says, this is what's important. Look here. And there's the dorsal attention network, which is like just paying attention around you in case that, you know, mountain lion shows up and you've got to shift. And then there's the default network, which is where you go when you're chilling, right? Okay. It's where you go when you daydream. You're not thinking about anything. And we all have these. Well, it seems like in people with ADHD, that default network, the daydreaming center of their brain intrudes onto the pay attention to this center. Right? So, it knocks it out of balance. So, people with ADHD, the connections to their brain are such is that they wander into the zone where they're just chilling. Right? So, we're seeing this on brain imaging. Again, the brain-based neurodevelopmental disorder. That's not the final answer, but in terms of groups, people are wired a little differently when they have this disorder. Okay. So, part one, key points. ADHD has a high risk of comorbidity, functional impairments, economic cost. It's a brain-based neurodevelopmental disorder largely arising from genes with some interactions with the environment. And there are measurable differences in brain structure, function, and cognitive circuitry in affected versus unaffected groups. Okay. Now, let's talk about assessment. One big area where child psychiatrists are a little different from adults. You know, I think my sense of adult psychiatry is mostly you interview your patient and you base your diagnostic assessment on that. Children don't give great histories. So, the bias of child psychiatrists is to get information from a whole lot of different sources. And honestly, I do this with adults as well. It's just the way I, you know, approach things. So, the easiest way to get a lot of information efficiently is to use rating scales. And I'll point out a couple in a minute, you know, I think probably every adult ought to be screened for ADHD at least once. They can sit in their office and take four minutes and fill out a form, and you can look at it in 12 seconds and get a sense if you need to pursue, you know, that as an idea. So, we make, and then on the child side, of course, parent rating scales, teacher rating scales, because you want to sit and get information from as wide a view of sources as you can. The interview itself really is, though, the key. Perhaps based on the symptoms, you know, and on the ratings, it's really going through the DSM. There are 18 symptoms. I don't think I'm going to list them. You can look at your book. The issue with them is they occur, each of those symptoms occurs to a degree that's more than typical for one's developmental level. Yeah, first graders run around a lot, but it's a kid who runs around where the teacher says, like, holy God, like this kid is out of control, right? That's what the disorder is. And you see impairment in most settings. I'm not going to treat anybody unless they're really complaining of some impairment. Now, again, I don't know what the typical new evaluation is. I have, I spend at least an hour with my new patients, and then I mostly do med management. I really like, in that first hour, I tell our trainees, you know, get a sense for what's it like having dinner with these people, you know? Is it an intact family? Do they eat dinner together? Is it crazy, you know? What, take that first opportunity and know as much about this person and their relationships and their social environment as you can, because when the problems emerge later, you need to have some basis. Because once you get to the 20-minute med checks, you don't get into this, right? So, the interview is important. I'm a physician. I suspect most of the people in the room here are physicians. Let's not forget this. It's important to be sure that their medical, general medical needs are being addressed. I spend time on their medical history, significant past history, certainly in younger kids, height and weight, measuring blood pressure is good probably for everybody, all those things are good. And also, again, really to get at risk factors, including cardiac risk factors, which I'll mention in a second. So, you can go to, and I don't know if there are many psychologists here. Some psychologists' diagnosis is the same way we do. Psychologists that work, many psychologists are prime, they do testing. And so, they'll do a whole battery of different tests. That doesn't really give you a diagnosis. It can give you a sense of learning disabilities and executive function deficits, which I see as supportive and informative to the diagnosis. But it's not essential to the diagnosis. So, if someone comes in and they've seen a psychologist, great, take advantage of their report. You still need to do your DSM interview and then you can move on. Okay. All right. So, the person who asked me about rating scales. So, there are rating scales that you can buy and there are rating scales that are free. I would support your use of whichever ones you're comfortable with. In terms of the pediatric world, the ADHD rating scale is five. You buy the book, look at it at Amazon, it's 30 bucks. Once you get it, you can Xerox it forever. That's fine. The SNAP rating scales are the ones they used in the NIH Child Studies. You can get those online. You get to pay for the Connors scales. Vanderbilt rating scales are the pediatric version. They're put out by the American Academy of Pediatrics. They're downloadable. They need those free as part of their pediatric toolkits. So, that's all good. In the adult world, and this is maybe of most use to you, the World Health Organization has a screener that's online. So, simply use your search engine of choice of WHO adult ADHD screener and it's there. You can download it. You can use it. There's a more sophisticated one that you can use in follow-up. You can buy that. But this screener is great and honestly, we're having people in primary care fill it out and you can read how to score it and it will at least signal to you if it's worth pursuing that as part of your general evaluation. Okay. With kids, we always look to get more information. School, you know, parents, whoever. That's a little trickier with adults because of HIPAA stuff. But if you have a significant other who cares to, you know, inform you or even if they have old school records or you get reports that they're trouble at work, all that sort of helps confirm the, you know, that it really is ADHD. As I said, medical assessment is important. You know, of course, any current illness, any major life illness is important. Surgeries, here's that, I won't tell the whole story about my son and his preschool graduation, but he has that scar under his chin that I think is almost pathognomonic of recklessness in childhood. What meds are they on? Concussion history, lots of accidents, all that. Again, it just supports the history that this is someone who's had a lifetime of kind of impulsive, not so thoughtful activity. And then it's really important, I think, now again, I in the adult world, I guess you probably all have come to your equilibrium about this, but certainly with teenagers, on the initial outgo, I want to know about nicotine and drugs and alcohol. It's my chance to talk to them. You know, I acknowledge they may be having sex, maybe not. Seat belts, contraception, I bring all that up, even with teenagers for sure. You bring it up, it gives them permission to bring it up, at least in terms of if your person is engaged in risky behaviors, it gives you a basis to give them some good counseling or to help them with that. So again, at initial assessment, I would ask about those things. Medically, again, weight, blood pressure, pulse every six months. You don't need to do a physical. I actually still do physicals, but if they have primary care, if you're the only doctor in wherever, maybe you do physicals and take care of that yourself. There is no indication for an EKG, and EKG has no value, so don't feel the need to do that. What you do need to do in younger individuals at least is assess for that risk of congenital cardiomyopathy, basically, of which there is a baseline risk. So we always ask the same questions, and I ask people these questions, and I'm more developed, you know, I treat younger people. But if a person is under 30, any history of syncope, any family history of sudden cardiac death, any cardiac abnormalities that are known, if any of those things are true, I'll send these people to a cardiologist before assessing, or before, certainly before starting them on a medication. Again, EKGs are not worthwhile. I mentioned neuropsych testing. Really, if there's issues about academic functioning, if they're in school, that having a sense of that can be useful, even into adulthood. Executive function tests also can be very informative. There's a rating scale called the BRIEF, which, again, your patient can fill out, and it will give you a sense of whether they're in the clinical range for working memory deficits or impulse control deficits. We've actually found that rating scale can predict outcome on certain treatments. So that's an easy thing to do. It doesn't give you a diagnosis, but, you know, when I have somebody who has ADHD symptoms, especially inattentive ones, and then I also note they have executive function deficits, to me, that makes sense, right? So it's a picture that makes sense. All right. Summary number two. We base this on DSM criteria using as much information as we have. There is no diagnostic or clinical role for brain imaging, genetics, or pharmacogenetics testing. In spite of what you hear downstairs, there is no evidence to support any utility of that. In fact, some studies suggest that if you follow a clinical trial, some studies suggest that if you follow their guidelines, some people get in trouble. If you use some of those commercial tests, you end up choosing treatments that are less evidence-based than people who don't look at those sources of information. So at this point in time, not going to help. Educational cognitive testing can be useful, again, to confirm executive function stuff or really to help with learning problems, but you don't make your diagnosis there. All right, let's talk about treatment. All right. My view is you treat everybody the same in this way. So again, this is the child psychiatrist systems view of the world. I think psychoeducation is critically important. You want to engage your families or your patients in what you're doing. It promotes compliance. It's better care. Then I think about family-focused interventions, school or work-focused interventions, and then patient-focused interventions. So again, the classic child schema is, you know, you've got family, you've got school, you've got friends, you've got the person. You can kind of up that, make your adult versions of the same thing. But that's my framework. Let me just pause a second to mention some equity and diversity concerns because we need to talk more about that. ADHD prevalence is equal, again, across all groups. Again, this is rooted in the human genome and it has nothing to do with any other demographic. It is diagnosed less frequently in non-whites, but there are reasons for that. There does seem to be some decreased awareness about the medical basis of ADHD, at least according to this one study, in some black families. And some non-white groups certainly have a lot of suspicion about the medical establishment, I think justifiably so or understandably so. There can be less access to care, lower levels of trust in MDs, more concerns about side effects and the risks of abuse. And most of our clinical trials have been done in white males. So again, there are some concerns there. Okay. We just have to do better here, but good education, I think, is a part. Psychoeducation, again, I like to, as I said earlier, when I finish, I want you to understand this the way I understand this. And I start a dialogue. And what I like to do, honestly, is I think a little bit about what the person told me in their story, and I find, honestly, if you can weave some of their history into what you know about the disorder so that they're getting a sense of, yeah, that's me, this makes sense, you actually can give a lot of relief to people. And especially a lot of adults, they grow up feeling like they're damaged, like they're lazy, they're stupid. And I've had, you know, many adults feel really supported by knowing, no, this is a real thing, this is a real thing. And in fact, you're not weird, you're really typical. So I like to do that. It's good to convey didactic information. You can direct them to good sources. And then, you know, future answer questions, support groups, lectures, there's good information and bad information. But it's part of our job, I think, to direct people. Now, for kids, again, parenting is very important. We're talking about those family interventions. There are real evidence-based parent management programs. I don't know how many of you are parents who have been parents. The parenting that's good for ADHD kids is the parenting that's good. We actually do know what we're doing here. It has to be done correctly. These are all, like, manualized programs. I actually think, I don't know if there are any pediatricians here, but our family med docs, I think every primary care office in the country should have access to a good parent training program. Whether it's at a local hospital, it's like 10 sessions. And this should be implemented at a young age. Okay. The concomitant to that, I think, for older folks, I don't have a slide on it, but again, in talking to this person, if they're having relationship problems, whether it's in a marriage or otherwise, if you sense that's an area of concern, then a referral to work on that may make sense, right? But I think that's on an individual. Every seven-year-old needs good parenting. Every, you know, 27-year-old may or may not need help with their relationships or not. But you can, again, don't ignore that. And I think not that you'll do family therapy, but you can certainly direct them. Moving on to school and work, if you have a diagnosis of ADHD as a kid, you can get what's called 504 accommodations. That really means you can sit in front of the class, you get more time in your exams, and you get to pee if you need to. But more importantly, if they're still doing SATs, I don't think they're doing that in California, you get more time on those tests, and even, you know, later, taking your step exams. If you're shown to have this early on, you can carry those accommodations forward, and then really with, you know, repeated testing and verification you have this, you are entitled to accommodations. So be somewhat mindful of that. And then in terms of work accommodations, I chatted with somebody last week. He actually works in a, in like an open area, this is so Silicon Valley, like an open area with like 15 people in a glass room. I was like, you know, I would lose my mind. So that may not be the best work environment for him. You don't necessarily need an office next to the vice president on the corner of your office, but give some thought to what their work environment is. And also some thought to are they, you know, have they found their vocation? People with ADHD who are adults can do really well if they hit the niche that they're good at, right? I'm a terrible basketball player. I don't play basketball, but I'm a pretty good swimmer, right? I have found that in my life. I had a guy once who was a watch repair person. I could not believe he could do that with having ADHD. But I treat a lot of investment bankers and a lot of attorneys and a lot of physicians who, you know, they're really motivated to get a goal and strike it big. So a little bit of career guidance at that career deciding phase can be important. All right. Other kind of school work interventions, again, behavioral class management, testing accommodations, vocational, academic counseling, work accommodations. Again, this is fairly standard early on. As people become older, you got to think a little bit more about their own needs. In terms of patient-focused psychotherapies, therapy for eight-year-olds is not really, like for ADHD, is not really helpful. But there are some really good evidence-based therapies now for adolescents and adults that make use of organizational skills training and also CBT. There's actually a group I work with in, they're in Beverly Hills. They do adult CBT. It's like a 10-session course. You can get, you can buy these books online. Again, I don't know how many psychiatrists actually do CBT themselves, but if there are CBT therapists here, this is really effective. And I have sent dozens and dozens and dozens of adults to this group. I've had one person not like it. People tell me they like it, they use it. It's really good. So find somebody who can do CBT for ADHD. And these days, they do it online. So that's something we really, again, we need to think about. It really does add something to what we can do in terms of the medication. All right, and here we go to the meds. And let's see how much time, we've still got 15 minutes. All right, here's the cartoon or something like the cartoon that you probably learned in med school at some distant part of your past, right? So the idea, basically, you know, you've got a presynaptic neuron and a postsynaptic neuron. You see my, does my pointer show? Yeah, sort of, right? Presynaptic neuron, postsynaptic neuron. And there are these vesicles of catecholamines, you know, either epinephrine or dopamine. They're in a vesicle. The transmission comes down. The little vesicle floats to the edge and releases into the synapse. It floats away. And then, you know, across the synaptic cleft, it interacts with a receptor at the postsynaptic neuron. Key in a lock propagates the wave. And the way our medicines work, so the stimulants, both methylphenidate and amphetamine block the reuptake, just the way fluoxetine blocks serotonin reuptake. Methylphenidate and amphetamine block the reuptake leading of the catecholamines, leading to more catecholamine in the synapse. And then the idea, of course, would be, well, that would be more to push this downstream. Right. That's kind of the classic model. Amphetamine does a couple of other things. Amphetamine also directly stimulates the postsynaptic receptors. Amphetamine inhibits monoamine oxidase, which inhibits the breakdown of the catecholamines. And amphetamine can actually displace the catecholamines from the presynaptic neuron into the synapse. So that's why the amphetamines are stronger. But basically, it's a reuptake blocker. That was sort of the thinking. And that really fits well with how we view the world. And that is absolutely wrong. OK, so a more nuanced view of what seems to be going on is none of this is direct catecholamine activity. The catecholamines act as modulators of the glutamatergic system. So most of the activity, the prefrontal cortex is mediated by glutamine transmission. And as I said earlier, the brain's got to do two things. You got to focus on what's important and you got to focus on what's around you. Right. So the part that tells you to focus on the signal and what's important is mediated by epinephrine. So when you block the norepinephrine reuptake from that presynapse, there's more epinephrine floating around. But what it does on the post-synaptic norepinephrine neuron isn't really important. That neurotransmitter is available to interact with the adrenergic receptor on a glutamatergic neuron, which it closes the channel. All right. So it closes the channel that where the ions are leaking out. So it increases the signal of that glutamatergic neuron. Makes sense. OK, so you've got these glutamatergic neurons, prefrontal cortex, they're leaking potassium ions. And then when the norepinephrine hits it, which this is also why the adrenergic agents like atomoxetine or clonidine, for example, work on this. It closes that channel. There's more potassium, the signal stronger. So you've increased the importance of the signal on the dopamine side of things. Dopamine is what mediates you're paying attention to what's around you. Dopamine, when dopamine gets increased in the synapse, goes across to the prefrontal cortex. On those glutamatergic neurons, it opens the channels. So dopamine causes leakage of ions and a weakening of the signal that's paying attention to the noise. So what you're doing with these medicines is you're shifting the balance. You're increasing attention to signal and you're decreasing attention to noise. And sometimes this causes problems because sometimes people get too focused on the medicines or, you know, parents come in and the kid's too focused. Good God. You know, he's like a Stepford child. Well, it's unfortunately sometimes that's what you get with this. And it's intrinsic to the meds. I don't know how to get around it. But so that's what the meds are doing. They're acting indirectly on the glutamatergic neurons by either modulating attention to signal or decreasing attention to noise. All right. Now we're going to enough basic science. I you know, we could do a whole. Month on all the ADHD medicine, so I'm going to give you a really high, high level. If you're curious, you know, we have a PDR and you can read and there's lots of stuff written, but very basically, there are FDA approved and they're off label meds that we use to treat ADHD of the FDA approved ones. We have the stimulants and we have the non stimulants, the stimulants. And actually, this is the talk I have with everybody. When I first see this, I start explaining meds. The stimulants work the best. They are safe. You can see right away if they work or not. There's no lag time. They're flexible. And basically, in a brief amount of time, they work or they don't. Within the stimulants, I just say there are two families. Forgive me for using brand names for a second, but that's what's known. I'll say to the family, there's the Ritalin family. There's the Adderall family. What I'm really saying is just methylphenidate and there's amphetamines. And then I've listed the various ones here for the methylphenidates. D-L-methylphenidate is the traditional Ritalin. D-methylphenidate. They took the L out because it doesn't do anything. It's Focalin XR. Right. And then there's dextroamphetamine. And then, of course, mixed amphetamine salt, which is one of the dominant ones. And then, of course, there's now lisdexamphetamine, which is a prodrug amphetamine. And there's seridexmethylphenidate, which is a combination of, it's a pro-drug combo with an immediate-release methylphenidate. So that's what we got on that side. In terms of the non-stimulants, adamoxetine is a adrenergic reuptake inhibitor. The extended-release alpha-2 agonists, quantadine, guanfacine, are direct agonists on the epinephrine, on the adrenergic receptor that I was just describing before. A new compound, valoxazine, is just released. It also has some serotonergic blockade. And you can go downstairs and learn all about it, and maybe you'll get an espresso. I don't really, the only off-label one I tend to use is immediate-release alpha-2 agonists. So short-acting, quantadine, guanfacine. These others are used, I don't find much use to them, but I just list them there to be complete. In the world of choosing these medicines, here's only my bias. In a perfect world, in younger, littler people, I like using the methylphenidates. And why? Well, they're kind of kinder and gentler. The side-effect profile is better, the appetite loss is better, okay? Bigger, older people, the amphetamines are stronger, they act longer. So in a perfect world, that's how I would go. But I make it really clear to parents, because all of us have managed this, or we deal with this. You give your best advice, and then you find out, well, this generic drug that I'm recommending is going to cost you $470 a month. Your insurance company wants it, so I'll tell them, we're going to go with what, I'm not going to saddle you with a $300 a month pharmacy bill, right? So I work with what they have. But just as an example, this was in March. These were the cost estimates that I got through GoodRx, and you can see there's a wide variety. Most of the ADHD meds now are generic, and in a sensible world, they're not that expensive anymore. Now, you can see, now Vyvanse was $400 a month in March, it's now gone generic, it's list as amphetamine. So there is variety, and I just mention this because I think worrying about the financial health of our families is important. Now unfortunately, I cannot address, I can't address any questions about Adderall shortages, we have all really suffered, and I'm about to lose my mind. They keep promising it's going to be better. I can explain why it happened, but I don't have an answer for you there. Anyway, those are the costs. So this is a very basic algorithm, and what do you think, I have like 10 minutes? All right. I think you all have access to these slides. So I'm just going to give you the big view, and then, yeah, let's just do that. So the basic algorithm, you make your diagnosis, you consider all the non-med treatments that are appropriate to this patient, and then you start. Start with the stimulant, whether it's methylphenidate or amphetamine, your choice. You need to pay attention not only to, you know, does it have efficacy or not, but is it tolerated or not. Some of the different formulations have different durations of activity, you need to consider that, match it to the patient's needs. If it just isn't working, you probably ought to try the other class. You should give a try of both classes. About 70% of people will respond well to whatever stimulant you choose. The other 30%, 70% will respond to that one. So about 90% of people have a pretty good response. If you fail with your stimulants, go to your non-stimulants. Atomoxetine probably has the most evidence. Voloxazine, which is a new compound, also has pretty good data behind it. And then there's the alpha agonist, clonidine, guanfazine. They are not wonder drugs. Often I use them in combination with other things. You don't want to go there unless everything else fails. And if all this fails, you know, call up a child psychiatrist, you know. All right. All right. But here's some real clinical. Now, I think is my, I gave you my handout, right? Okay. All right. So you've made the decision to start a stimulant. So what not to do? Unfortunately, some pediatricians do that because they're so busy. They'll write a prescription for a low-dose medicine and say, come back in three months and tell me how you're doing. What you really need to do is take a couple of weeks and figure out what dose and med is right for the person. So what I say is, okay, we're going to start a medicine, but I'm not treating you yet. I need to know how you react to this medicine, and this is what we're going to do. Now, I've given you my handout, which includes instructions on writing scripts, at least in the paper world. You can go into Epic, do whatever you want. And also instructions to patients. So this is what I'll do. Let's just say we're going to try mixed amphetamine salts, which is Adderall. I will write a script for Adderall XR, 10 milligrams, one per day, dispense 30. All right. That's a little magic to get it paid for, and the insurance company will say fine. But then I say to the patient, this is what I want you to do, though. Don't follow directions. What I want you to do is take one a day for five days, then two a day for five days, then three a day for five days. And actually, in my little handout, which you're free to use, I give this to them, right? And I say, okay, so we're going to take you over three ranges of this, five days each, but it's the normal range. I'm not over-medicating you, because I need to know how you respond, okay? And I'll say, I don't know. You could take one pill, and it's like, glory, hallelujah, I'm Albert Einstein. Or you may get to three and not feel a thing. The meds ought to kick in in about a half hour to an hour, and they ought to last for eight to 10 to 12 hours, right? But all we're doing right now is getting information. You might run out of meds before you see me again. Don't page me. It's not an emergency. It might be good to see how you do off the medicine. That's fine. Do this. Do it every day. We're just getting more information. The flip side is an hour or two. You know, after you take it, you may feel like you're on rocket fuel. I treat surfers. I say, ride the wave. You'll be fine. If you're really upset, call me. But what you want to do, practically, is you just want to say, you want to take two or three weeks, have the patient do this, have them come back, and then you ask them, well, how'd you do on one? How'd you do with two? How'd you do with three? And then typically, you can find, more often than not, what's the sweet spot, what works for them. And then what I do is I say, okay, or I might say, oh, 10 milligrams, you felt nothing. 20 was a little strong. We can try you on a 15, right? And this works for all of these medicines, right? So we pick a dose, and then I say, okay, let's try that dose for a month. And let's see, oh, high school student, let's see if you're, you know, does this cover you for, do you have a lot of homework after dinner? Maybe I need to give you an immediate release in the evening. Or, you know, you're treating, I treated a neurosurgeon. He never slept, right? So you kind of find the sweet spot, then you try that out for a month. And then if you've made it work, you see them every three months, right? Now there is, well, this is the changing rule. Two weeks ago, the DEA was going to require all first visits to be in person. We have been doing this in telehealth very, very successfully. The DEA has waived that. So at this point in time, if you're doing telehealth, you can still do it. Just document everything in your chart. And I think what's really important, again, in adults is document the impairments and the symptoms you're treating. And then have them come back in three weeks, and then, you know, I do this in 20 minutes. Try to find the right dose, okay? Now once you get the right dose, I see people every three months. Now the DEA also requires an assessment every 90 days. You can give 90 days of medicine. There's another place where we've got to fight the insurance companies. Some people let us give 90 days. Some people, you've got to do three separate 30-day scripts. I write them all today, but one can't be filled until, you know, June 20th. Whatever game you play, you know how to do that. But I do make people come in every three months. And some people will not ever want to come and see you again. But honestly, these days, I tell people, you can sit in your car for 12 minutes and talk to me. But the law requires that I assess you before I give you more than 90 days of medicine. So stick to that, because otherwise it just takes you time, and you'll get reimbursed for it. When do you stop? Well, most people stop anyway. So that does give you a chance to ask, and I always do, well, are you better on the med than not? And typically people say, oh yeah, for sure. But most people, I actually treat one child psychiatrist, I've been treating him for 27 years. I think if he misses a dose, he hears about it from his wife. So you get people like that, and then you have people where it's like a gym membership, you see them twice, and then you don't. But that's okay. It's their choice. As long as you can document improvement against your impairments, I'm completely comfortable giving them meds. All right. I've got to shoot. I've just gotten more chatty than I wanted to be. All right. Summary points for three, and then I'm just going to scroll ahead, we get to your questions. Treatment is likely to be multimodal, meds, and targeted psychosocial interventions. Test them once in a while off med, just to confirm you're still there. Long-term maintenance is really improved when you have a relationship and you insist people come in and talk to you. It's really hard to solve a problem when you haven't seen people in 18 months. I've included these diagrams. You can look at them basically, ADHD with anxiety, ADHD with depression. The basic issue there, anxiety, you can start, treat the anxiety, you can treat the ADHD. I usually start with the ADHD because, again, in three weeks, you'll know about 10% of people have clinically meaningful improvement on stimulant alone. If not, you can go ahead and use an SSRI just like you would with any other impairing anxiety, but honestly, CBT for anxiety is probably the best way to go. With depression, it depends on what's worse. If people are really in a major depressive episode, I treat the depression first, and I see them in six weeks. Then once that's improving, we do the ADHD. It's okay to treat people with bipolar disorder as long as they're euthymic and that they're on mood stabilizers. Otherwise, you just follow the usual thing. The issue with substance abuse is there's a little bit less broad buy-in to this, but this is what I do. You need to assess the problem. There's a difference between use and abuse, for sure, as I think you're aware. Cannabis is legal in many places now. Let's not penalize people for that. I would not not treat somebody. I had a buddy. He was an Olympic swimmer, and he told me that the swimmers at his D1 university were as stoned as can be. Every Saturday night, okay, fine. I wouldn't hesitate to give those guys their ADHD treatment. If someone is on opioids, someone is intoxicated all the time, maybe that gets cleaned up first, but I don't preclude ADHD treatment because there's some intermittent cannabis or alcohol use. It doesn't phase me at all, but you need to come to your own terms there. Very quickly, because this seems to be the ... I don't know if it's ... Honestly, sometimes I think it's out of the innate lack of confidence some adult psychiatrists have with ADHD. They come up with excuses like, I think I'm being manipulated. I think these people are just cajoling me for medicines. All sorts of reasons that, in fact, you're just not comfortable doing this. But there is misuse of these medicines. Misuse being, it's mostly people using it for academic or other performance enhancements. Honestly, I don't lose sleep over this. It's not the end of the world. But if you really think your person is misusing the meds, then you have reason to perhaps use a non-stimulant. We do know the profile of who tends to misuse these meds the most. It's mostly white male students at competitive Northeast colleges, members of fraternities, who also use nicotine, alcohol, and other drugs, and who are not doing well at school. I can tell you what my roommate used to take to stay up all night to write papers. I don't think it ever helped him. And there's no real evidence that these meds ever helped him either. But that's mostly what this problem is. Most commonly, you can grind this stuff up. You can snort it. It turns into cocaine. It's not so common. But if you're really concerned, I had one boy once. This is, he's a 17-year-old. Month after month, he'd come into our clinic. He was so high, I mean, in the clinic. And he just, oh yeah, I want my, you know, I just became convinced. You know, after he told me he had to pay for his third girlfriend to have an abortion, I thought, you know, I don't really trust this kid's judgment. No, you're not going to get any more Adderall, which I'm sure you're selling. But you know, that's a real extreme. Typically, until I think someone is misleading me, you know, we're taught if someone complains of pain, you believe them. If someone complains of ADHD, if they have a good history for it, you believe them. Now, I did have one 65-year-old guy who really wanted to see me. And I was just checking the database. Here in California, there's a controlled substance database. He was on all these benzos and all these opioids. And he showed the classic story for somebody who was malingering. At 65 years old, he came in and he complained of 9 of 9 inattentive and 9 of 9 hyperactive symptoms. That's not what adults show. They show symptom decline. And this guy had a diagnosis of drug seeking on his chart. And I finally said, dude, I'll, we say dude in Southern California, but maybe you do in Freehold, New Jersey, too. I'm not sure. But I'll refer you to CBT, but you're not getting, he complained to the chance. But he was, so that's who you worry about, that all of a sudden at age 45, this person has ADHD and they've got 9 symptoms and, you know, that's, have a little skepticism. But typically when people come in and they have a good story and they're in pain and they're distressing, you can see it, I believe them and I would treat them until I see that they're, the very few times that, you know, they're jerking me around. All right. There is, I think, do all states have a, have a controlled substances database now? I know we certainly do in California. Use it. Look at it. It's really useful. Every time I send kids off to school, I counsel them. These are your meds. Don't share them. You know, I at least get a verbal commitment for them to use this properly and you document what you prescribe. Just very briefly, we've only got minutes, there's some new research that shows to the substance abuse question, kids with ADHD are at increased risk for substance abuse. Kids who are treated at earlier ages and more continuously have normal rates of substance use issues in early adulthood. Kids who are not treated until later or who are treated less so have more substance use issues. The meds aren't causing addiction. The ADHD is what causes this. And this is some evidence that there's real long-term benefit to being on this. I'm going to mention very briefly because I did it. This was an NIH-funded study on trigeminal nerve stimulation. It's the first non-med treatment approved for ADHD. It's no risk. Kids wear a patch on their forehead that's attached basically to a little TENS unit in their sleep. And some of these kids had responses at the level of what you see in stimulants. And this is where actually we showed kids on the brief that executive function rating scale, the ones who have executive function deficits may actually be the ones who respond. So we're doing a second study. This is put out by NeuroSigma. If you want more information about it, you can go to their website. I'm not endorsing the project just for more information. If you're curious, you can check on that. This hasn't been tested yet in adults. In terms of complementary therapies, and we're almost done, the only food supplement that is shown to have any utility is omega-3s. The effect size is like 0.01. So Cohen himself, who devised this statistic, said basically an effect size of 0.7 is a big effect. Anybody can see it. An effect size of 0.5, a clinician can see it. An effect size of 0.2, God can see it. So basically, if you give 5,000 kids fish tablets, one of them has improved ADHD. I'd rather say eat tuna, right? None of the other dietary interventions have no relationship to this. Neurofeedback has not been shown to be effective. There are some other neuromodality things. I don't know, again, what they'll tell you downstairs. None of them really have sufficient evidence yet. There are two cognitive training programs. Cogmed is one. Akili is one. They have been shown to improve cognitive functioning, not ADHD, but they are available. They are FDA-approved. Okay, unproven things, neurofeedback, brain balance. Cogmed works for memory training, not for ADHD. Mindfulness approaches are wonderful, but they have not shown to be useful for ADHD. Dietary supplements and restrictions, no value. Pharmacogenetic testing, absolutely of no value. Okay, key points, and we're going to have talks. Various levels of evidence inform treatment of ADHD once in comorbid conditions. Sorry, I didn't have time to talk about those, but you can look at those slides. The risk of stimulant abuse and misuse is generally manageable. Again, I have more details on the slides, but I want to get to your questions. Most complementary and non-med approaches do not have any empirical support, but the risk-benefit usually supports the evidence-based treatments we have. I only have 25 minutes for questions, but that's where we're going to go. So let's do that. Now, we are sharing time with the virtual world, and welcome everyone out in the stratosphere. Let's try to answer your questions. Yes, sir? My first rhetorical question is, could we have you teach some of our other speakers how to give a perfect presentation? Thank you very much. All right. Well, thank you. What about the durability of benefits over the course of time, and particularly for adults who have been on stimulants for many years? And is there a corollary normative loss of executive function as people get older? Well, you gave me a very loaded question. So you do have to be aware of the possibility of long-term cognitive decline. I mean, I have some patients now, and I've treated them for decades. And so that remains an issue, but I think we're used to that. The big picture is, the simplest answer is that you don't get tolerant to the stimulant effects. That once you get the proper dose, it works for you. Now there's an exception. The amphetamines actually have a long, this is a whole complicated lecture. Methylphenidate is out of your system by the evening. Amphetamine actually accrues in your system. If you're on mixed amphetamine salts, we show this in our study, if you were on the 30 milligram dose of mixed amphetamine salts, you had more ambient amphetamine in your body the next morning than the highest 10 milligram dose the day before. And that's not helping you. And sometimes on higher doses of amphetamine, you do get kind of an acute tolerance effect. So when a patient comes in and says, you know, doctor, it's worked, but now it's like just not so sure. What I basically say is, look, let's try, take a day off a week, is my general advice. And more times than not, it clears, you know, you're not really working Sunday. You don't need it. Take Sunday off. Typically, you'll reboot Monday morning and that's what happens. So it's extremely rare for people's doses or meds to change over time. But sometimes with the amphetamines, you might just need a break. Again, everybody can take a day off. Yes. Okay. So we're going to go next to the most upvoted question. What are your thoughts about adult onset ADHD with no clear symptoms in childhood? So there was a study about six years ago that some very well-regarded investigators, actually international team from Duke and other places came out describing new onset ADHD. And it causes the whole sort of stir because this wasn't supposed to happen. And it was a real hullabaloo for a couple of months. But when they looked more closely at those data, they didn't really check for impairment and they didn't screen for other comorbidities. So that's really not informative. The important thing is, technically the DSM says you have to have evidence of symptoms by age 12. But what we know, and remember we made all that up, what we know is most hyperactive impulsive kids are showing difficulties by age 4 or 5. But individuals who only have the inattentive presentation, it can often be much later. And going back to my training director, Danny Cantwell's view, it's better to be more intelligent than less so. It's better to have resources. Some kids are protected. Sometimes it doesn't really start to show impairment until kids are in college or kids are in med school or law school. So my view is I trust people until I don't. And if someone has a story where they're very bright, they've gone to good schools, you can't say anything bad about a student or a resident these days. So maybe they didn't get that negative, sorry to any of you here. So I don't see a need to be too rigid. Be flexible. Again, the case I mentioned, the 65-year-old who's got a history of opioid and benzodiazepine dependence who out of the blue at age 65 has nine symptoms, come on, that's absurd. They would be in the Atlantic Ocean in terms of impairments from here. But in general, don't be too rigid. Yes sir. Hi. First of all, I think it was a very comprehensive overview of an ADHD across lifespan. I'm a neurodivergent neurodevelopmental psychiatrist working across the lifespan in the UK. So I've got a few questions, very short questions in total. Just one question, okay. What do you think of the QB test in childhood and adult ADHD coaching in adults? What do I think of the QV test? QB. Yeah, so that's like an electronic brain scan, so I don't put anything in it. That would be the simple answer. ADHD coaching is not so evidence-based, but some people on an individual basis certainly find it helpful. So I typically, organizational skills training is evidence-based, DBT for ADHD is evidence-based. Some people find value in working with a coach, you know, more power to them, but that's not one of my general recommendations because there's not a whole lot of data, you know, on a higher level to support that it's useful. Thank you. Okay, from the beyond. So this question is, so somebody, he cites somebody, so thank you for that. I've heard from Barkley and others that executive function problems are the core problems of ADHD. So could you explain a little further why you think this is not as important? So Dr. Barkley and I are, we are friends, we are colleagues. He had this view about 20 years ago, and he wrote, you know, several things about it, but we did subsequent work, and actually my closest collaborator at UCLA is a woman, Sandra Liu. She is the, I think, the queen of ADHD, EEG, and cognitive functioning. We did a very large study. Our studies have shown about half of, again, syndromatic DSM-5 diagnosed kids with ADHD have executive function deficits, but the other half don't. So we are finding now that's really a subgroup. It is not pathognomonic for the disorder. The trigeminal nerve stimulation work that I've told you, we have an NIH grant right now. We're testing the hypothesis that executive function deficits predict response, but it is not part and parcel with ADHD. You know, the vision, of course, in X amount of years, all these, you know, the DSM should fade away, and we will have disorders of circuitry, etc., etc. You know, we used to, I don't know now that, I'll be like Frodo and in the West before this happens here, but I think the time will come where we will realize, like, the master of medicine, these are just syndromes, and we'll really be getting to what's going on, but EF is not equal to ADHD. Yes, ma'am. Thanks for a great talk. Quick question. Continuous performance testing for diagnostics. There's MOXO, which is a computer program to test for hyperactivity, impulsivity, distractibility, attention. What are your thoughts? So, and Keith Connors was one of the proponents of that. The problem with CPTs, every time I get an eye exam, I feel, you know, they flash the so the problem, so continuous performance tests, they basically measure errors, so they flash a signal and you're supposed to push a button, and it shows basically, are you responding too quickly, or are you missing the signal? The problem, it's just not specific. So, you know, what do kids do these days? Kids live looking at screens and pushing buttons these days, so it's just, it's just really not clear. I, you know, what I base a diagnosis on is, you know, observable symptoms and impairments. Now, some people, I think they feel better, but what happens if your CPT is negative? It doesn't mean a thing, because maybe your kid is really good at Minecraft, right? So, I don't, I don't, I don't see the, my son taught himself to read playing Pokemon, so I'm not dissing video games, but I don't see, we don't use them. Sometimes they're used in research studies as an outcome, but it's, it's, it's a mixed bag. This is another across-the-lifespan question. What is your thoughts on women who report to develop ADHD symptoms after menopause? So, again, there's a difference between symptoms and disorder. I am not an adult, like I, well, yeah, I, I trained in adults, but I am not, I'm not at all an authority in, in non-ADHD things in adults, and there are cognitive issues associated post-menopausally. I think there are some real experts on that. I would not diagnose that as ADHD. I think it's something else. Now, whether or not our ADHD medicines are useful, again, I would look to our experts in women mood disorders to look at that, but again, I, I don't, I'm pretty, um, I'm pretty relaxed with my, I gotta say, I, with, with a lot of my patients, I talk to, especially the young guys, I see the way I talk to them at the gym, but I'll, I'm refraining from using that language here. I don't care what DSM thing you have. If I see a constellation of symptoms and someone's in distress, I'll use these medicines. I'll call it ADHD unspecified, and I think that may be worth a trial, but, you know, I might look to you. I mean, maybe modafinil is useful, maybe, you know, but I would include these in the armamentarium, but I wouldn't call that ADHD. Yes, yes, ma'am. Actually, thank you for your presentation. I'd like to, I was going to ask about your comment on off-label use of modafinil. So, I actually was the principal investigator of the, um, the, we did a modafinil trial for adult ADHD about 25 years ago, and it didn't separate from placebo, but there are some problems with the trial. Modafinil was later shown in some pediatric studies to be effective, but there were safety issues, so the DEA did not approve it. I, I, I, again, there may be other uses of modafinil. I don't use it for ADHD. I think, again, and I don't want to, uh, who am I to judge? I think a lot of adults, practitioners, they just look to the non-stimulants because they're worried about prescribing schedule two. They're worried that they're being cajoled, so they prescribe things like bupropion, modafinil, etc., etc. I, you know, I'm comfortable with, I would encourage you to get comfortable with stimulants. There are, it's probably better evidence for bupropion, but those meds don't work anything as well as the stimulants, so I would, my advice is use the guidelines I've given you. Use my handout. Feel free, and if it works, and you're tracking, and you trust your patient, you can be comfortable with that. Sure. Yes. Do you have any specific recommendations for books for patients with ADHD or CBT manuals that people can take away with your expertise? Well, no, actually, so, so, so Steve Safran has an excellent manual for CBT, Safran, S-A-F-R-O-N. Steven, it's on, it's on Amazon. It's a very good manual. He's a psychologist. He developed this. What I'm telling you, so I'm very mindful this is CME. I'm not here to show anything I've done. You know, I listed a book as one of my references. I'm not telling you to buy my book. I'm not at all, but it's very simple, and it was really written at a level for med students. So there are some good sources. You could, you could read Dr. Barkley's book, who is the encyclopedia, if you're a physician interested in that. Chad is a very good source of information. It's a support group. They have online information. There's plenty of good information out there. Yeah, so I have a patient who has severe ADHD diagnosed clinically and then supported with neuropsych testing. I'm saying supported here. The thing is he is globally impaired to the extent that we are actually pursuing guardianship for him. He's been tried on a couple different stimulants with no improvement. There's nothing on neuropsych testing that suggests an underlying major neurocognitive disorder, although we all suspect, I mean a neurodegenerative disease, even though we suspect it. Imaging also has not been conclusive for anything but ADHD. He does have some other risk factors which I'm not going to go into for purposes of privacy. I'm curious if you've seen this global impairment with ADHD to the extent of even needing guardianship. So I'm assuming this person, and I probably can't comment too specifically about individual patients, but this person doesn't have any intellectual disability. They're not impaired with their IQ or anything like that. You know, I've had, typically not. How old is this person? He's in his 50s. He's in his 50s? Okay, well, it's never been previously diagnosed. Well, again, the questions I would ask is, you know, has he declined since his 20s? You wouldn't, you would expect to see symptomatic improvement with time. Typically, you have, so if you're 12, you need to have had 9 inattentive symptoms. If you're, if you're 30, you need to have 5 because the natural course is for these symptoms to get better. I would be worried that that person may be having some, some other cognitive decline or some other neurological issue. I had one kid I saw a year or so ago that was, just not to be pejorative, I'll use a technical term like basket case. I mean, he was in his early 20s. He was a, he was a disaster, but he was a disaster because he had an indulging, you know, wealthy family who coddled him. But that's not typical. People with ADHD struggle, but they're not, you know, they're not without potential to contribute in real ways. So I would look to something else. Thank you. We've got two questions on this. Do you have any opinions on what are the safest stimulants to use in patients with cardiac disease? And somebody specifically saying about like adult patients with arrhythmias. You know, interestingly when I was, so I trained in the, I think fluoxetine came out when I was a second year resident. So we were using TCA's all the time, which really had cardiac risks. And back then we used the amphetamine in geriatric, we used dextroamphetamine. Dextroamphetamine was used in geriatric depression because it was felt to be safer cardiovascularly. There is a baseline, you know, in younger people there is this congenital risk. You know, you read once a month there's a Olympic swimmer or a football player or a cheerleader or somebody in the band drops dead suddenly on a football field. You know, I mean that's an issue. And so we do screen for that cardiac risk. The data in terms of being on these stimulants is very, very good. There have been longitudinal studies in tens of thousands of adults with no increased cardiovascular risk. But if someone has a known arrhythmia, I would probably do that only in concert with a cardiologist. No need to take, you know, at that stage of the game. I would, I would not do that. And I probably wouldn't treat unless, unless there was no choice, I think. I somehow wandered into treating a lot of adults with congenital heart disease, like single ventricle and valvular issues. And for true risk of arrhythmia, the cardiologist will put that patient on the whole term monitor for seven days. But if they don't think there's a risk, they're just like, whatever, prescribe whatever you want. So there seems to be a large spectrum and what cardiologists say. Okay. I have a related question. So for people, or what's known about the lifetime and health risks of long-term stimulant use, or how do you educate patients in informed consent around that? Basically, if used as prescribed, there are none. It's safe, right? Now I'm not saying if you go out and you take a hundred tablets of something, but there are really, really good data. In fact, the best long-term data we have, if anything, says people who are treated with stimulants have less substance abuse risk, right? I showed you some studies about that. There are, there's no evidence of increased cardiovascular risk. So tens of millions of these meds are written for each year, and we've been using amphetamine since 1939. So we're going like on 80 years. These meds are safe. I tried to read about it and find more, but what you're saying basically is you can tell someone that they're not going to have any cardiac changes over their lifetime, worries about... So what you get, so what you get is you can get a couple, a couple of beats increase in your pulse per minute. You can get a little bit of increase in your blood pressure, but none of those seem to be, you know, clinically, clinically meaningful. So I've, so I don't get a lot of questions about that, but, but here is some, here's a little, here's my clinical observation. I think people who have anxiety, I put it this way, people who have anxiety are very in tune with their bodies, and they really get wigged out with side effects, right? You know, I actually, I, I do a lot of swimming. I, my, you know, my pulse is like 40 in the morning, and I throw in a topic beat every once, like I get an escapee, right? But, you know, somebody who's anxious has a palpitation, and they go crazy. So you, that's where, I mean, again, if I got a question like that from somebody, I would really be concerned. So in people who are anxious, I actually start them on really low doses, and in part, my strategy is like, it's exposure and response prevention. So, of course, I recognize the concern. I wouldn't dismiss them, but I would do everything I can to really help them realize that the meds are, are really safe. Are there other long-term benefits, like dementia, you know, reduction or anything like that? I'm sorry? Like dementia reduction, or are there any long-term benefits? Not aware of anything like that. Yeah. All right, we have five minutes left, so it's probably around two questions. So do you have an opinion on prescribing stimulants above the FDA-approved ceiling, and do you think it takes a certain amount of time to reach the, like, maximal clinical effect on certain doses? So I'm gonna answer the second part first. Whatever you're gonna get, you're gonna get, and this is what I tell patients. So on one hand, whatever you're gonna get, you're gonna, it's gonna kick in an hour, it's gonna last for whatever. The reason I do five days in my titration, though, is sometimes the universe smiles on us, and sometimes the universe frowns on us, and I don't want a single random event to, like, be the basis of our judgment. So we go for five days, right, to get a better sample. I do a lot of work with the FDA. What you see in the label simply reflects what the clinical trials did when they submitted them, but we have other evidence to say, so for example, I think the FDA for mixed amphetamine salts, it might say 40 or it might say 60 milligrams, but we have, there's clinical papers saying you can certainly go to 80, you know, one milligram per kilogram for amphetamine, you know, is reasonable. So I won't go on to infinity, but I'm very, I am very comfortable going, going above label in that regard. So again, I think there is a literature, when I give a farm lecture, actually, I include that some of my limits that I will have on a slide exceed, you know, what the FDA says, but you do need to keep in mind the FDA simply, simply is just responding to what was submitted for approval. That doesn't mean something else isn't safe or worthwhile. There are a couple questions, oh wait, sorry, in person. I got mixed up. Okay, we'll let you go to the in-person. Just, do you have any comments on bipolar disorder and, because somebody asked about family history and prescribing stimulants. Yeah, so my good friend Tim Willans at Mass General would probably give a very different answer, but I do not think it is a common thing. You know, common things are common, but rare things occur. So I, you know, I treat kids where there is a family history. Of course, again, you know, the first thing whenever I hear somebody's, especially in Los Angeles, some celebrity's bipolar, I just kind of take a breath and say, well, yeah. You know, I have learned when I hear somebody's bipolar, well, you know, have they ever been hospitalized? Like, what was this like? And, you know, so bipolar isn't necessarily bipolar. But there are times where I have kids who do have very idiosyncratic reactions. They do have sleep disturbance, but until I see it, I would not worry too much about it. In kids, the debate in kids is that bipolar disorder looks like adult bipolar disorder. There are distinct periods of altered mood, possibly irritability, interspersed with euthymia, as opposed to about a third of kids with ADHD that are chronically irritable. They have outbursts, they're dysregulated. That's a different story. That's not bipolar disorder. So I treat what I see. I'm gonna answer all your questions, guys. So my, this was true, I'm sorry, forgive me. My wife's grandmother was truly bipolar. I mean, she really was. It was very tragic. And actually horrible me. We were getting married. I thought, God, do I need to worry about this? We've been fine, but it did cross my mind. And I've told, she kids me about that now. Forgive me that. Anyway, I, if I see it, I believe it, but I don't worry about it until I do. Okay. Yes, we will go. One, two, three. Yes, sir. Hi, just a quick little background. My mom's family's German, and I got to just looking at the difference, you know, diagnosis rates for ADHD and stimulant prescriptions, just in northern European countries. Notice there's a pretty big difference between, you know, how they diagnose there and here. How do you interpret that difference? So I'd have to look at that more specifically. So, you know, in Europe, they, you know, they base it on the latest ICD, you know, we use, and they work to harmonize them, but they're just, there's some subtle differences. But if you use, to my point before, you know, if you base it on the same criteria, you get the same results. So I, I don't think it's more or less in, amongst Germans than, than anything else. And also, the EU has different availability of meds, etc., etc. Most of the meds we have are approved there, and they're used, although there are some cultural biases in different countries about, like, I believe in Spain, or I actually did work in Finland, and at the time I was there, like, two people in the entire country were on a stimulant, something like that. Yeah, that exists in Germany, too. What's, it's, sorry? The cultural, the cultural sort of ground on. It may be, yeah. So, but I think, again, in terms of the genetics and such, it's the same. Thank you. Yes, ma'am. Hello. I thought your trigeminal nerve stimulation study was pretty interesting. Could you speak to developments in transcranial magnetic stimulation and the use of ADHD treatment? So there's, as I said, there have been, I don't have all those facts at my fingertips, but there have been about a half-dozen studies of various forms of neuromodulation, and I believe that is one of the ones. If you, I've, I have a reference from, for that paper, and I know I summarized that in there. Yeah, so I think it's, it's a work in progress. It's worth looking at, and we have to kind of see. Thank you. So I work in an early intervention first episode psychosis service, and it's not at all unusual when you're assessing someone aged 22, 23, to get a background history that strongly supports that they've grown up with ADHD, probably unrecognized, and now they have what looks like schizophrenia, and we're quite nervous about prescribing stimulants. Should we be? Yeah, I think you should. So, yep, I think so too. So do you have any other advice? Well, I think so, so for a couple of reasons. I had one man I treated who had schizophrenia, and, you know, people with schizophrenia have, have cognitive, have real issues with cognitive processing. That's been a real struggle in the schizophrenia world. So he came in, and he had an ADHD-like picture, and I tried, actually, he was stable on his antipsychotic, but I wasn't able, I wasn't able to give him any relief. I would be, again, I think that's a really delicate stage, and you want to push them one way, not the other. I think at that point they probably have other more compelling issues, and I would be hesitant to, to start giving, I mean, just someone who really has reached that level of, you know, pre-psychosis, I would, I would, I would wait. Cognitive training might be useful, and CBT would certainly be useful, but I think they have bigger fish to fry than their ability to sit in class, I would suspect. Listen, it's really nice seeing everybody. I hope this was good. I hope you enjoy your week.

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