Dr. Timothy Wilens is a Professor of Psychiatry at Harvard Medical School and Chief of the Division of Child and Adolescent Psychiatry at Massachusetts General Hospital. His research interest include the relationship between ADHD, bipolar disorder, and substance use disorders; ADHD pharmacotherapy; and stimulant medication misuse.
On this episode, Dr. Wilens discusses the importance of early diagnosis and intervention in ADHD, as well as its lifelong implications. He takes us through the evolution of ADHD treatment, from behavioral therapies to modern pharmacological interventions, including stimulant and non-stimulant medications, and the application of digital therapeutics. The conversation also touches on the stigma surrounding ADHD, the role of precision medicine, and the future of ADHD research.
00:00 Introduction
02:50 Evolution of ADHD Treatment
04:43 Stigma and Misconceptions
12:18 Importance of Early Intervention
15:02 ADHD Symptoms and Treatment Approaches
30:02 Addressing Concerns About Stimulant Medications
35:50 Navigating the Complexities of ADHD Medication
41:22 Future of ADHD Research and Treatment
43:20 Conclusion
Visit our website for more insights on psychiatry.
Podcast producer: Jon Earle
Dr. Timothy Wilens is a Professor of Psychiatry at Harvard Medical School and Chief of the Division of Child and Adolescent Psychiatry at Massachusetts General Hospital. His research interest include the relationship between ADHD, bipolar disorder, and substance use disorders; ADHD pharmacotherapy; and stimulant medication misuse.
On this episode, Dr. Wilens discusses the importance of early diagnosis and intervention in ADHD, as well as its lifelong implications. He takes us through the evolution of ADHD treatment, from behavioral therapies to modern pharmacological interventions, including stimulant and non-stimulant medications, and the application of digital therapeutics. The conversation also touches on the stigma surrounding ADHD, the role of precision medicine, and the future of ADHD research.
00:00 Introduction
02:50 Evolution of ADHD Treatment
04:43 Stigma and Misconceptions
12:18 Importance of Early Intervention
15:02 ADHD Symptoms and Treatment Approaches
30:02 Addressing Concerns About Stimulant Medications
35:50 Navigating the Complexities of ADHD Medication
41:22 Future of ADHD Research and Treatment
43:20 Conclusion
Visit our website for more insights on psychiatry.
Podcast producer: Jon Earle
NOTE: Transcripts of our episodes are made available as soon as possible and may contain errors. Please check the corresponding audio before quoting in print.
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. Today I'm pleased to welcome Dr. Tim Wilens, Professor of Psychiatry at Harvard Medical School and chief of the Division of Child and Adolescent Psychiatry at MGH. An expert on pediatric ADHD, Dr. Wilens walks us through the latest research, making the case for early intervention and addressing concerns about the long-term use of stimulant medications. Dr. Wilens, thank you so much for being on the podcast today.
DR. TIMOTHY WILENS:
Oh, thanks for having me.
DR. THEA GALLAGHER:
Can you give us an overview of your research journey and what led you to focus on pediatric ADHD?
DR. TIMOTHY WILENS:
Absolutely. I've been a researcher for a number of years and have been very interested in common disorders that affect individuals and one of the most common disorders is ADHD or attention deficit hyperactivity disorder. I was particularly interested as a child and adolescent psychiatry person to really be able to examine the roots of ADHD and ultimately the treatment of ADHD, but with a lifespan perspective. Given that ADHD starts so early, it starts in preschool years. I really was interested in studying it from preschool all the way through the lifespan. And again, it is a very common disorder and why not study a common disorder? If you can help educate, if you can help describe things that are potentially affecting kids adversely, it's going to have a huge impact. And so that's where my journey began. I was very lucky to be part of a research team that studied ADHD through the lifespan and it was a wonderful collaboration through my life to be part of this team.
DR. THEA GALLAGHER:
And what do you think makes it so important about studying it through the lifespan?
DR. TIMOTHY WILENS:
It's a disorder that starts very early, but persists in at least half the kids so that adults manifest this disorder. And there's not been an adult I've ever evaluated with ADHD who doesn't talk about their childhood. So I think it's important. The other reason it's important is because anything that you have very early on that then persists through your life is going to cause a lot of impairment, struggling, and suffering. And so to help people understand what it is and to come up and help be part of teams that come up with treatments is very rewarding because you're going to help ameliorate that struggling and suffering and hopefully some of the sequelae that occurs if you don't treat ADHD.
DR. THEA GALLAGHER:
Yeah. We're going to get into more of what you've learned over the years, but how would you say the field has evolved even since your beginning research attempts in terms of understanding diagnosis and treatment?
DR. TIMOTHY WILENS:
Yeah. There's been a huge evolution in the field. First of all, in terms of where we are as a society. When we first started, people really pushed back against kids having any type of neurobehavioral disorders. Kids could have seizures, but they couldn't have ADHD. Kids, by the way, also couldn't be depressed or have other major psychiatric illnesses, even though we know for other major psychiatric illnesses, 50 percent of it onsets by the age of 18. Yet people pushed back. And so we had a lot of resistance about is ADHD real. And then there started to be toeholds in realizing that ADHD is real, but then the pushback was adolescents don't have ADHD and then adults don't have ADHD. So there's been a lot more recognition of the disorder across the lifespan. And a lot of that has come through systematic studies, getting the word out from researchers, to public health experts, to the general lay public as well as to our other professionals that treat ADHD to help arm them in understanding the disorder.
From that, then it became important to start treating it and there was a lot of pushback about the treatments we used. And subsequently, I think more and more people are on board with the various treatments we use. And there's been more and more movement in expanding the treatment repertoire, studying both medication and non-medication treatments, understanding the role of each of them and things like that. And that's been very helpful to the community that diagnoses and treats ADHD as well as of course, to the patients who suffer with ADHD and their families.
DR. THEA GALLAGHER:
Yeah. And do you feel that it's become less stigmatized? I'm The Sopranos, and I feel like everything relates back to this show, but there's a portion where the principal's talking to the parents about how they suspect that he might have some ADHD tendencies, and it's taken as a real affront to both their parenting. And like you said, it used to be stigmatized to even have depression or anxiety or ADHD. But I still have parents of kids that I work with who it seems like there's still an element that's stigmatized, but do you think we're getting closer to people understanding, accepting and then being willing to treat?
DR. TIMOTHY WILENS:
Yeah. I think everything you just said is absolutely operant, which is that it used to be people had shame about the disorder. Certainly a lot of adults felt a lot of shame as kids if you talk to them. They knew something was different. They weren't the same as their peers. They were underperforming. And I always say that I haven't met an older kid or an adult who hasn't reported still feeling shamed and feeling something different about them and self-esteem issues that track back to childhood. But I think we've moved forward. I think that people now talk about ADHD. ADHD has hit the main media. It's hit TikTok. It's everywhere. And I think people talk about it. People are much more open to discuss it. Schools are much more likely to suggest evaluation for it. Pediatricians and nurse practitioners and physician's assistants are much quicker to screen for it, talk to parents about it, get it treated. And I also think parents are a lot more open to knowing the diagnosis and dealing with it.
It's no longer I think a disorder that is underground or is in the closet. I think people in some ways may in certain circumstances, overindulge others in knowing about their ADHD. I think it's nice that people are self-actualized around it, but I certainly don't want that ever being held against people. And I do think that that does continue a little bit. I think as kids age, when they start getting their jobs or they're starting in trades or whatever, I recommend to people that they may not want to offer to individuals sitting across from them during interviews that they have ADHD because I do still think that there's some stigma. People are worried about underperformance or absences or people are just ignorant and don't know what to expect, but that they just are like, "I don't know what this is, this ADHD. I just don't want it."
The last thing I'll say is we have a saying in our department, which is “no family goes untouched.” There's so much ADHD out there that pretty much every family has dealt with it either directly or indirectly. Either their friends know somebody who has ADHD, a cousin, an uncle, a parent, or one of the children have ADHD. So once people start talking about ADHD, it's rare that I meet a family that doesn't have some connection to ADHD.
DR. THEA GALLAGHER:
Yeah. It is amazing. Or doesn't have some knowledge of what it looks like and whether you've seen it with a friend or a family friend or a family member, you can also see it in the media. And you were even talking about places like TikTok. And this makes me wonder, do you think the pendulum has swung too much in the other direction? Do you think it's fueling overdiagnosis or also do you wonder if there is maybe a spectrum to the severity of symptoms and maybe we're realizing different people, there can be more nuance in the diagnosis?
DR. TIMOTHY WILENS:
Yeah. I think it's all of the above. I think that there is a popularization of it. And the overdiagnosis, if you look systematically, there are pockets of overdiagnosis, but in general, we're still under diagnosing the disorder. If you look at CDC data for example, we're still missing up to half the cases. I can't defend bad medicine people who just make a diagnosis in two minutes, that's not good medicine. But the same could be said about ear infections and kids have otitis media. There's an overdiagnosis and overtreatment with antibiotics. But in general, we're doing a good job with ADHD. These media like TikTok and stuff, in some ways destigmatizes ADHD. It definitely increases self-questions about ADHD. And there's where a healthcare professional sitting across from somebody can help that individual understand, hey, this may not be ADHD. You could have just normal activity and normal functioning and there's a lot of people like that. It could be executive function issues that are not ADHD like organization or time management. That's not ADHD. It could be something else. It could be a reading disability or some type of a mathematics disability or something that's getting confused. But that's really the role of the healthcare professionals.
I see the TikTok as bringing people to the table or asking about it or these things that people do online. But ultimately any kind of a screen tends to over read the diagnosis. Screening should over read diagnosis. That's what they do even in a professional's office. It's sitting across from somebody and honing down to understand are those the active symptoms? Do they have the developmental presentation? Are they associated with impairment? Is this not something else? That's all the burden of the healthcare provider to help articulate with the patient.
DR. THEA GALLAGHER:
Yeah. And if we were to follow the thread, TikTok is mostly adults. So I'm wondering if we're saying, Hey, it had been underdiagnosed in the past and now all of these adults are saying, "Oh my gosh, that's what I was dealing with as a kid and still impacts me today." So it seems like as much as there can be maybe some problematic self-diagnosis, maybe there's some accurate self-diagnosis going on where people say, that's how I felt and no one believed me or my parents didn't want to hear it, or no one thought it was an issue. Especially I know with females you could be pretty high performing and still struggle because you don't maybe have that very obvious feature of the hyperactivity. Yeah. What are your thoughts of maybe there are people who were not diagnosed appropriately and now are saying, this is how I felt?
DR. TIMOTHY WILENS:
Yeah. No. I absolutely agree with you. And I think they may have had in addition to that, been in a very structured school or had parents that helped them a lot and they were able to get by. But to your point, we see older adolescents who watch TikTok or other media. They're always online, so they pick it up and they self-present saying ... And I've had that not that long ago, an evaluation of an adolescent who came forward and he was a smart kid who didn't have a lot of the hyperactive impulsive symptoms, but had virtually all of the inattention symptoms and was really struggling and it really helped to get treatment. So I think that that's the case. And the older you get, the more likely it was that in the past you could have been passed up or not treated. The other group, by the way, are people who were diagnosed but not treated. Parents, to your point, the stigma, we see a lot of people who weren't treated as kids who present because their parents didn't want them to, or they present late in adolescence because the parents didn't want to give them meds when they were younger because they had heard all these negative reports about the various medication classes we use for ADHD.
DR. THEA GALLAGHER:
Yeah. And speaking of that, you're talking about some people are diagnosed and not treated. Is early intervention important and what age are we talking?
DR. TIMOTHY WILENS:
Yeah. Identifying ADHD early in, at least setting up educational accommodations can be very helpful for children with this condition. And it can be as simple as just having the child sit more forward in the class, reducing the distraction, having the individual have a buddy so that they know that they're getting the assignments and somebody they can touch base with if they miss things. Having teachers check their work, ensuring that if there's any problems, parents are notified right away. Simple things like that can make a big difference in a kid with ADHD’s life. We have longer-term data on treatment, and most of that treatment is focused on stimulants but not exclusively. Also, the non-stimulant class of medications. That shows over time treatment does have an impact at reducing the sequelae of untreated ADHD. Be it academic improvement, be it motor vehicle accidents, injuries, concussion, things like that that accrue over time if you don't treat ADHD are better.
And we have a few studies that triangulate to looking at when was treatment started and where was the best outcome? So most of this data comes from cigarette smoking and substance use issues, but it seems to triangulate around the age of nine years, which typically puts kids around fourth grade or so. Nine years of age. And if treatment started before nine as opposed to between 10 to 14, you can see incremental improvements in ultimate outcomes for cigarette smoking and substance use disorders. And it's not just one study, it's multiple studies that seem to show that. So when I talk to parents given that signal and we're getting signals about other impairment at that level, that's where I say, look, probably if you've identified it early, probably by third grade or so, you really ought to start thinking about treating your child because we are starting to see over time it may have a more positive effect on outcome.
DR. THEA GALLAGHER:
Yeah. And so catching it early, diagnosing it early, treating it early, can have a lot of benefits in the long term. And we were talking just recently about the different presentations of ADHD. We're not going to get into every single symptom. But even for maybe clinicians or psychiatrists, psychologists, therapists who are treating these patients, what do you see as maybe distinct presentations that you would want clinicians to be aware of and not to miss in their diagnoses?
DR. TIMOTHY WILENS:
Yeah. Absolutely. And I think the first thing to realize is attention deficit, that first two ... Attention deficit. By the way, it could have been called attention dyscontrol. A lot of people argue it should be attention dyscontrol. But that component, the attentional attention, distractibility, shifting, not completing tasks, that group is what we consider the core cognitive group of ADHD, the thinking group. And 95 percent of children who have ADHD have core cognitive deficits. And now remember, these are behaviorally diagnosed. It's not like you do a neuro-psych test. It's—you notice that the kid doesn't pay attention or the kid says, I have problems paying attention. Or they shift activities frequently or they get distracted by noise outside or distracted by thoughts in their head. They have problems completing tasks. Have organization issues. But my point is that 95 percent of ADHD has a core cognitive component. So that to me is the most important issue around ADHD.
Now, some people may or may not have the prominent, hyperactive, impulsive symptoms. Sitting still, moving around, feeling and on edge. Or impulsivity, active before you think, being very frustrated and having a real low tolerance for things. Most people have a few of those who have ADHD, but some people have a lot of them. It used to be that we put a lot of effort into subtyping ADHD. You had the more just cognitive parts of it, the inattention distraction like I reported, or you had that plus the hyperactivity impulsivity. So you would have either the inattentive subtype, which was the former or the combined subtype, which was both the inattention distractibility, but a lot of the hyperactive impulsive fidgety symptoms. And what we realize now is there's probably not a lot of difference between them except those people who have more symptoms that would be those with inattention and hyperactivity tend to have a little bit more severe ADHD and those who have fewer, just the inattentive symptoms have less severe ADHD. So that's another diagnostic thing. We don't agonize over the subtypes as much as we used to.
DR. THEA GALLAGHER:
Yeah. And do you see that with all of this information about maybe females being diagnosed less. Are there fewer females who have ADHD and or are we realizing that more do have it, they just need to be diagnosed in a more nuanced or specifically focused way, maybe on those cognitive symptoms more?
DR. TIMOTHY WILENS:
Yeah. I think your point is well taken. I think it's a little of both. It used to be that the number of boys as opposed to girls presenting with ADHD was literally 10 boys for every one girl. And once our group and other groups started studying girls with ADHD realized that girls with ADHD report a lot fewer of the major co-occurring issues like oppositional or conduct disorder, which almost invariably gets people picked out in school right away and referred. They may not have as much impulsivity and hyperactivity. And people would apply the diagnostic scales to them without accounting for girls tend to have just baseline fewer hyperactive impulsive symptoms. So if you require the same number of hyperactive impulsive symptoms for girls with ADHD as boys, you really got a more severe presentation in the girl because they just naturally have fewer hyperactive, impulsive inattentive symptoms than boys and fewer amounts.
So where it used to be 10 boys for every girl, it's now three boys for every girl. Closer to three to one. Is it really one-to-one. There's clearly a group out there that think that I think we're probably getting close to the proper distribution of boys to girls. And it's not unknown and unreasonable and child psychiatry to see equal distribution of different disorders in boys and girls. We see that for a lot of different disorders. But it's a very different story than was being told let's say one to two decades ago.
DR. THEA GALLAGHER:
Yeah. You're adding seven more people to the ratio, so it's pretty impressive. How does the brain of a child with ADHD, how is it different? Because if you're saying this is a disorder developed in childhood, is it a neurological condition? Is it a genetic condition? What do we know about what's happening even functionally in the brain that's different?
DR. TIMOTHY WILENS:
Yeah. Great question. First of all, we know that it runs in families. That doesn't mean necessarily things are genetic, but we also know genetically we ascribe about three quarters of ADHD to being genetic. That's based on looking at twins and they come up with a fancy term called heritability. But the bottom line is probably three quarters of cases have a heritable component to them. So it's a highly genetic disorder. It's not as much as height, but it approaches autism spectrum and other things that we know are highly genetic. Part B to that, there's an environmental component. For example, we know that the most likely reason for non-genetic ADHD is smoking while pregnant. So just the exposure of nicotine really we think creates 10 percent of cases. And we've known that epidemiologically by studying large populations of people. But we've also used rat models to replicate that and find that.
Fast forwarding, it is a brain-based disorder and there's a lot of aggregation of the findings with ADHD. The front part of the brain, the prefrontal areas don't seem to be working as well. And the deeper areas of the brain called the striatal areas have different systems like reward systems that are different in ADHD kids. And what we seem to ... A neurocircuit way of seeing this is that there's less executive oversight problem-solving inhibition on general activities, but also on deeper things such as emotions, rewards such as substance use and nicotine use, which is higher in ADHD untreated versus general populations. So we think that those are there. And there's a number of other structural areas that are involved in thinking processes that seem to be less active. There's an older study we did that I found very helpful clinically, which is if you look at the brains of individuals with ADHD who are asked to do cognitive tasks, certain areas of the brain light up that are not the most efficient areas to be doing those cognitive tasks compared to people who don't have ADHD. If you give people treatment for their ADHD ... Let's say in this case Methylphenidate, which is one of the treatments we use for ADHD as a medication, we find that it reverts the brain from the less efficient brain to the more efficient brain. Re shifting through the anterior cingulate in this case.
So what I remind people a little bit about is it's a little bit like driving to work in the good old days when we would go to work in person. And you take your major road to get there, you find out there's an accident or construction and you have to take a bypass road. The ADHD person is constantly taking that bypass road, which means you'll get there, but it's going to take you longer and it's going to take more wear and tear on you than if you had the more direct route, which is what happens to people who don't have ADHD or if you treat the individual with ADHD, it's almost like you opened up the direct route to work and the brain becomes more efficient.
DR. THEA GALLAGHER:
And are the parts of the brain that you are addressing with treatment? What's the gold standard treatment? Psychostimulants, maybe executive functioning skills groups, some CBT. What's happening now with these treatments? Have they changed a lot or are they the same that they've been across the board? And are they helping to make some of these changes in the brain?
DR. TIMOTHY WILENS:
Yeah. So we're still relying a lot on many of the things we did previously. So using from a non-pharmacologic standpoint for kids who have a lot of behavioral issues using behavioral treatments. Using cognitive behavioral treatments as they get older are a little bit more helping them with skills to build that are more cognitively based as opposed to just behaviorally. And there's good evidence that at least in treated individuals, partially responsive to meds, they do make a big difference in terms of the individual's ability to deal with the remaining symptoms and how they compensate. We still rely non-pharmacologically on people who have a lot of organization, time management and other problems. Executive function coaching. We call that executive function. I always call it Wilens-ism. It's the secretary of the brain. And that secretary isn't working great and we help and it's really coaching and stuff.
From that standpoint, some of the bigger breakthroughs have been refining our executive function treatments and starting to utilize online systems to deliver some of these programs. There's been gamifications and systems that really target some of the cognitive components of that to help hone it, to refine it. These are FDA approved, they've been replicated, they've been shown in controlled trials to be effective. So there's evidence that these computer driven, computer administered treatments can be helpful. I think that the price is reasonable, so it's something that is available to all people who have bandwidth at home or can access that. Pharmacologically we still are utilizing the same stimulant class agents, methylphenidate class or amphetamine class. There's been a lot of refinement in the formulations and preparations, which have made them a lot more tolerable. We've essentially eliminated the need for in-school dosing. We can pretty much target how much of the data we want to cover and very effectively do that with the various stimulant preparations. They come in all different types. So if you have somebody who can't take pills, you can open capsules, you can give them solutions, you can do it sublingually. There's a lot of different things. You can use patch technology.
So there's been a lot of formulation breakthroughs. And the other component is abuse liability. We've got lower abuse liability stimulants than we did previously. Probably the bigger breakthroughs are in the non-stimulants. And we now have three FDA approved classes of non-stimulants that are somewhat different from each other. They help not only ADHD, but each one seems to work on specific co-occurring problems with ADHD. And then there's a pipeline of new non-stimulants in development. So there's been movement. It's new. I think we're still working to try to come out with a non-stimulant that has tremendous efficacy, that's better efficacy than a stimulant. It's hard to beat a stimulant. We haven’t done that but like I said, we have a lot of non-stimulants that are working pretty well and are available that weren't available a decade ago.
DR. THEA GALLAGHER:
And for the digital therapeutics and the non-stimulant medications, can you just list what those are for our listeners in case they want to utilize them as an adjunctive to their practice and maybe ADHD isn't their specialty?
DR. TIMOTHY WILENS:
Yeah. So the one that I'll mention is the FDA approved one. It's through EndeavorRx and it's Akili who makes it. And it's a gamified cognitive approach to assist with ADHD. And like I said, that's FDA approved. There's other ones that you can help with different aspects of cognition that may be part of executive function, like the one that's been tested the most is Cogmed and they have various types of Cogmed that you can tap into and utilize. The other treatment that's FDA approved, but not a medicine that some people use is a NeuroSigma. It's a minor electrical thing that people wear at night and it helps treat. There's a lot of movement now in using neuro-therapeutics. So it's a neurotherapeutic and it's been FDA approved in an NIH study that was done. So those are major non-med, non me non ... That are available. Some of them on the internet, some not.
In terms of non-stimulants, the FDA approved ones. One of them is Atomoxetine also called Strattera. It's been around for a number of years. Seems to help with ADHD. Helps with anxiety with ADHD. Helps with tics with ADHD. We have a class of medicines called ... And that's a noradrenergic agent. Another noradrenergic agent that just came out, relatively new is Viloxazine XR. It's actually a medicine that was used in Europe as an antidepressant. And it seems to work well for ADHD. Some recent data showing it works for executive function. Again, that hierarchical thinking organization that sometimes doesn't work well with stimulants or doesn't respond. And it also may be helpful for co-occurring problems like anxiety or depression. Alpha-agonists, Guanfacine extended release, Clonidine extended release. These are two class agents that help. We use them often in younger children.
They show that they work across with inattention and hyperactive impulsive. A lot of people think ... Clinicians think they work more for hyperactivity impulsivity. But these can be very good base medicines. We've learned that you can use them in adolescents and they've even been studied in adults now, and so you can use them across the lifespan. And we use them in combination often with stimulants. So you can. And using alpha-agonists with stimulants is actually FDA-proof. You can do that. That's an FDA-proof thing. So that continues to be the major classes. We have medicines that are off-label like Wellbutrin, Bupropion, tricyclic antidepressants like Nortriptyline, or Desipramine, or Imipramine. Those are also very effective but they're off label. We don't use them as first-line agents. We use them as second or third line and they do have a role when other things aren't working.
DR. THEA GALLAGHER:
Mm-hmm. And if you have comorbid conditions for sure. And in talking about the gold standard first-line treatment of stimulants, is there any reason to be concerned about the long-term use of stimulant medications?
DR. TIMOTHY WILENS:
That's certainly one of the biggest questions that comes up. And what I would say to that is that these are among the best-studied agents in all of medicine. There've been multiple studies. Amphetamines have been around since the 1930s, methylphenidates since the 50s. And ever since they came out they've been concerned. Probably the biggest things we still watch really closely is height and weight. There's some evidence that there's heigh and weight decrements, especially in the first two years. Then there's other evidence to show that there's catch up. And it seems to be clinically if people seem to be struggling a bit with that, you can use extra supplements, but also medication breaks or drug holidays as people like to call them, if the person can tolerate. It seems to abrogate that.
There were concerns about other things like cardiovascular risk factors. But there've been multiple, multiple studies, big studies by the Food and Drug Administration in our AHRQ organization, another government organization that seems to dispel that notion. On the other hand, we still monitor for any cardiac symptoms that may exist and maybe that stimulants exacerbate underlying cardiac structural problems. It's a tip off that that person should be evaluated if they develop these types of symptoms. Chest pain, chest discomfort, shortness of breath, feeling like they're going to pass out. One of the biggest concerns used to be ... And this is a big area of our lab's work. Is the issue that these medicines are controlled substances. In fact they're controlled II substances. And do they increase the likelihood for a later stimulant use disorder? Are you going to develop cocaine or methamphetamine or misuse or does it kindle substance use disorders? And in fact, the vast majority of patients in different studies, registry studies show just the opposite, that treating ADHD actually reduces the likelihood to smoke cigarettes or have stimulant or other substance use disorders. And that again, the earlier you start, the more protective effect you have against that.
So I think everybody agrees that they don't increase the risk. And I think most of the big registry studies that can marry people's use of medicines, et cetera, are showing that. And we're talking like the largest study in the United States was with over three million individuals with ADHD and showed robust differences between treated in untreated times for individuals. Those times they were untreated, higher rates of substance use. Or if you looked at groups that were treated versus groups not treated for their ADHD, higher rates of substance use in that group. So it's a big deal. The last thing-
DR. THEA GALLAGHER:
You realize that you're getting to the core of the problem and then not self-medicating.
DR. TIMOTHY WILENS:
I would agree. Yeah. There's some people who think that it has something to do biologically with attenuation of dopamine systems because giving people meds that work that way. And then there's other people who say exactly what you did that you're getting to the core symptom. You're helping people academically achieve, you're helping their self-esteem, you're helping their competence and that route is what's helping with substance use.
And I'm not sure we know exactly the mechanism, but we keep seeing that. But I did want to say that we'd still worry about people who misuse stimulants because these are controlled substances and there is misuse of stimulant medications. And we've been studying this for over a decade now. And a couple of comments is first of all, if people who are prescribed stimulants are misusing a stimulant, it puts them in a whole different category in terms of later substance use. No longer is it protected, but if you're misusing your medicine, that's a flag that you're at increased risk for all kinds of substance use, including methamphetamine and cocaine. We just published a paper on that. Or if you're out in the general public and you're misusing stimulants, you're getting your stimulants from somebody else or buying them or they're given to you and you're misusing stimulants, it's a flag that you could have a substance use disorder that's going to unveil itself in the next few years. So we still need to keep an eye on the abuse liability of stimulants.
DR. THEA GALLAGHER:
Yeah. And my experience as a clinician is that especially with the younger kids, sometimes it's hard to actually get them to adhere to taking the treatment. They feel like, “Hey, it makes me boring. I'm not as fun or exciting. I don't feel as good.” So it's interesting that these medications have the word meth in them. And I had a patient recently say to me like, oh, am I supposed to go on meth? But it tends to be that the experience a lot of people who need these medicines when they're taking them actually find that they may be more focused mellowed out. So what are your thoughts there about that misnomer or misconnection?
DR. TIMOTHY WILENS:
I think that that cannot be stated loud enough, and I'm so glad you mentioned that. The vast majority of issues we have with stimulants in kids with ADHD is adherence. And the adherence is either the kid just says, I don't want to take them because I don't know if I have it. And that's a common thing that most kids who are adolescents are going to deal with and that's a discussion with their clinician. Or it's what you said. They feel different, they don't have appetites, they don't like the feeling on them. Which by the way, it's time to think about another stimulant or a different preparation within class. I always say my office is a “no zombie” zone. I don't want kids feeling that way. I don't want feeling a huge personality change. Adherence over time is the biggest concern we have. Some of the data are pretty devastating, showing that you can do everything right and do all this evaluation and get them in and treat them. And we lose 70 percent of kids and that goes through the lifespan over one year. Only 30 percent are still taking their medicines. And you're right, they're not doing that because of the abuse that they like because they don't like them because it's doing something to them.
DR. THEA GALLAGHER:
We talk a lot on this podcast about precision medicine and it seems like maybe the medications themselves haven't changed too much, but you've figured out how to dose them, how to administer them, how to be highly specific in the hours during the day that it's most important to have these things. But you're also following people through the lifespan. You change developmentally, physically, hormonally. How often should people be getting a reassessment of their medication or maybe should we be taking it in a different manner or a different way? What are your thoughts on, as you follow through the lifespan, what changes should be made or how regular should the check-ins be about maybe adjusting the protocol?
DR. TIMOTHY WILENS:
Yeah. It's a real important point because I would say you're talking at least yearly. And for most people where there's ... For most kids for example, I like to see them three times a year at least. And that is if everything's going well. If it's not going well, I'd like to see it monthly until we make things better. And I really want to underscore something you said about making adjustments and getting the right medicine dose, the right formulation of the medicine you're on, etc. We have so many available now. That's the good news. And I always comment that what we're trying to do now with ADHD is go from just symptom reduction to wellness. We really are aiming at wellness. Getting people well is different. We've done studies that look at functional improvement. Outside metrics of how well you're doing. And it turns out you really have to drive symptoms down and you're going to have to work with people and really getting it right.
And the metaphor I use for this is for those people that are old enough to have old analog tuners for radios, the old radios that you would dial in, it isn't good enough anymore to just get close to the station with some static. We like to get the station perfect. You dial it perfectly and the static goes away and you have a great signal from the radio and the music is clearer. And that's where we're at with A DHD now. People should not be satisfied with it's sort of working and I sort of have a lot of side effects if you haven't tried other ways around it. Other things. There's a lot of things we can do to make people's lives better with ADHD. Make them clearer, focus, better ADHD control with more tolerable side effects.
DR. THEA GALLAGHER:
Yeah. And so it sounds like it should really be an iterative process and you should look at it like that because it's going to be a long journey on some medication, likely if you're starting as a child and continuing to maybe see that as part of the process and accepting that as part of the process. Not seeing that as maybe a treatment failure either.
DR. TIMOTHY WILENS:
Yeah. And the other component of that is when you're working with the family and the kid ... Now when they're younger, you're going to be listening more to the parents, but the kid is in the room and they're hearing that conversation. The kid starts to take it over when they're like 13, 14. You'll start to have more the kid is reporting and the parent is consulting. And then when the kid goes to college or to the trades or to the military, and if they're off their meds, go back on them, then they're going to need to have a lot of say in what's going on. And I always say thinking about treatment through the lifespan, one of the most important points is helping kids with transitions as they go from elementary to middle to high school, high school, on to the other. And that all starts with things such as understanding your disorder, understanding what we're trying to treat, getting a sense of the treatment itself as well as other components of that.
For example, doing your work during the day if you're on stimulants while the stimulants are working. Not relying on after school treatment when the stimulants may be working out. And if you're going to college, that's going to be a very important strategy for you to keep up with your class work. Also, if you're in the trades, there's a tremendous amount of intellectual component of trades now. And you're going to have to learn and how do you learn to do your work while you're on your medicine? And that all is the conversation around tolerability when the meds work, when they don't work. And that's that process that you have with the kid that starts early and continues as they grow up.
DR. THEA GALLAGHER:
And with ADHD meds, you have more of these options then you have say with an SRI. Because like you said, you can kind of tinker with the dose each day or throughout, again, the times of the day that you want to be most productive, times of the week, you want to be most productive. It seems like there's that ability to have that nuanced relationship with your doctor and with the medications to navigate that.
DR. TIMOTHY WILENS:
That's absolutely correct. One of the important points ... I was on a call with the Food and Drug Administration and they were asking about some analysis we were doing and they were saying, "Well, can't you just put people in one class that they use this dose of this extended release, etc?" And what we realized when we were doing our analysis looking at our electronic health records, there's literally no two individuals, kids with ADHD that are on the same preparation, dose, time. They're all on various derivatives of that. And I actually think that's a very good thing. It's not that we're destroying practice by everybody doing their individual thing. I think we're individualizing our treatment for the patient, which goes back to your comment about precision medicine. And that really is the foundation to precision medicine. And there's more of that occurring now.
DR. THEA GALLAGHER:
And you're allowed to be more precise with these medications, which again, not all medications have that option. And so for my last question, ongoing or future research that you believe will have implications for treating ADHD?
DR. TIMOTHY WILENS:
Yeah. A couple of things. We're continuing to look at long-term, et cetera, but our lab is right now focused on treating executive functioning in ADHD. What is the best way to treat these secretary of the brain deficits that also exist in 20 to 25 percent of kids with ADHD. And so we're really focused on what do you do there? And we think it's going to be a combination. It's probably going to be some kind of physiologic thing like exercise. It's probably going to be some type of an online cognitive enhancement system. And it's probably a medication, a combination of let's say a noradrenergic medicine, like a non-stimulant and a stimulant or something else. But we're trying to figure out what is the best intervention that we can start telling people to use when you have prominent executive function in ADHD? We know that not treating that creates a lot of noise difficulties for individuals. That's where we're turning our labs and our light. We just published a paper looking at a full review of the literature at what treatments exist currently for executive function and now we're whiteboarding what combination are we going to propose and we're going to study it.
DR. THEA GALLAGHER:
Yeah. And what seems to set ADHD aside is that it sounds like you're getting to do research on things that you can maybe add to what already exists and just making it better. Not necessarily we have to recreate the wheel or start from scratch. We get to build on what's already there, which I feel like is exciting in psychiatry.
DR. TIMOTHY WILENS:
I absolutely agree. Most of our work with ADHD has been incremental, but over time it's really added up. So yes, I agree. And I think waiting for a major shift or something with a different treatment is great, but right now we need treatments for our kids.
DR. THEA GALLAGHER:
Wonderful. Well, thank you so much for being on the pod.
DR. TIMOTHY WILENS:
Thanks for having me.
DR. THEA GALLAGHER:
Thanks so much for that conversation, Dr. Wilens. If you enjoyed this episode, be sure to rate and subscribe to NYU Langone Insights on Psychiatry on your podcast app. For the Department of Psychiatry at NYU Langone, I'm Dr. Thea Gallagher. See you next time.