We are the Association for Child and Adolescent Mental Health or ACAMH for short. And this is ACAMH Learn. My name is Maggie Sibley. And today, I'm going to be presenting on a review that spans pharmacological non-pharmacological treatments for adolescents with ADHD. This review is just published in 2025. The focus on the adolescent period comes from an interest in improving outcomes for young adults with ADHD. We can see that as individuals leave high school and enter the young adult years, there's a widening of the gap in their level of functioning compared to their peers. This data comes from the multimodal treatment of ADHD study. And you can see that the ADHD diagnosed group continues to have more and more severe impairments as they exit high school and enter the post-high school years, whereas the non-ADHD group starts to actually improve their level of functioning over that same time period. And the transition to adulthood is marked by a lot of very challenging experiences for many people with ADHD. One of the ones that sticks out to me the most is that young adults with ADHD are 11 times more likely to be both unemployed and not in school at age 19. Some of the challenges involve for those who enrol in University or college, a risk for not completing. For those who enter the workforce, unstable employment. And for those who are able to sustain a job after high school, having lower earning jobs, more difficulties. And that does translate into lower lifetime earnings. So all of this is something that we do find concerning in the population. Young adults with ADHD are more likely to live with their family. They're less likely to be accumulating some sort of financial savings. They have instability not only in their jobs, but also in where they live and in having their basic needs met, which translates into lower life satisfaction, higher rates of depression, and heavier uses of substances than their peers at this period of life, especially marijuana. In the period preceding young adulthood, we see that ADHD often escalates with new difficulties emerging that are different than the classic impairments known in childhood. Adolescents with ADHD not only have trouble in school, but have trouble with sleep. They have trouble with overuse of digital media, disengaging from healthy life activities, and becoming depressed using substances. And just overall demoralisation is something that a lot of teens with ADHD face, which can translate into high conflict relationships with others, especially parents. Unfortunately, we see that adolescents with ADHD seem less interested in obtaining help for their symptoms and impairments than during other age periods. So here we can see data seeing that a lot of teens with ADHD stop taking their childhood ADHD medications as they enter the middle and high school years. This is also data from the MTA study showing that by the end of high school, only about 30% of kids are still taking their childhood ADHD medications. And if you try to understand why this is happening, we learn that teens are just not as open to receiving help for their ADHD as their parents and teachers and health care providers are interested in them receiving that help. And that's not just about a certain type help they don't like. So it's not just that they don't like medication. They're also less interested in receiving psychosocial supports, educational supports, help for their ADHD in general. And when we enter this psychotherapy clinics, we also see something similar than what we see with medication. This is a study done almost three decades ago by Barkley and colleagues. What they showed is that it's easy to retain parents in treatment for a child's ADHD. But when you start involving the teen in the treatment, the whole family is more likely to drop out. And so this is tricky because in the period of adolescence, it's appropriate for kids to start being involved in their own care a little bit more than they might have been in childhood, and yet they don't seem interested in doing that. So how do we help without forcing something on people that don't necessarily want it? The review I'm going to be presenting on today has been published, as I mentioned, and here you can see a QR code that will allow you to access this paper. And I'll be walking you through and explaining what we found. Now this review was interested in a few research questions regarding all possible treatments for ADHD in adolescents. We are interested in not only understanding the efficacy of these treatments, both acutely when they're occurring and long-term after they've been withdrawn, but also the safety of these treatments. And if there are any moderators of what works, for whom, and why in the treatment of teenagers with ADHD. In general, if we look at our PICO systematic review inclusion criteria, we were interested in individuals who are between the age of 10 and 19 years. So samples in papers had to be inclusive of those years. We had an open door for the type of intervention that might be included in the review, as we were interested in seeing all that were out there. And this is a review that is only focused on RCTs. Randomised controlled trials are the gold standard for understanding the efficacy of a treatment for various methodological reasons. And because this literature has progressed to a point where there are lots of RCTs now for treatments, we decided to get clarity and internal validity of our findings. We were interested only in reviewing randomised literature. We're also coding all kinds of outcomes because we are very interested in how these treatments may help in different ways, depending on what their mechanisms of action are. So we did not just focus on ADHD symptom severity, but also impairments and other key targets that the research teams indicated were expected to change based on the intervention. So we'll go over some of that. Now I will be, in this presentation, summarising the findings of studies. And in some cases, I'll be making evidence designations for how strong we think the evidence is for a certain category of intervention. And it's important to know that when we found only one study that substantiated any of these research questions above, we described the study in our paper, but we did not feel confident enough drawing a conclusion in our review if there wasn't replication of that finding. So I will be only forming conclusions when there was at least two studies to substantiate a finding. Our search strategy was following kind of standard gold standard methods. So here we were searching in three different databases to find publications. We pre-registered our review in advance. So that's something that folks can take a look at if they're very interested in high level detail. We did restrict our search to the English language based on the language abilities of the research team. We use the Ryyan AI tool to help us organise and code studies as we identified them. And we started with the title abstract review, moved to a full text review after finding the titles and abstracts that appeared to be germane to our research question. We did have double coding at both steps of our review in order to ensure that we were making sound decisions, and they always exceeded 90%. Now one thing that really comes up in this literature is how to treat findings that are from blinded versus non-blinded studies. So this is important for me to handle up front. Some of the treatments that are going to be included in this review are going to be impossible to blind someone to. So, for example, it's really hard to blind someone to whether they have engaged in a high-level of physical activity-- they know they have done that. It's really hard to blind them to the fact that they have received a CBT intervention. They know they have done that. With ingested treatments, you can make a fake pill and somebody doesn't know whether they've taken an active treatment or not. And even with some of our digital therapies or therapies that involve something like neurofeedback, you can make a sham where the experience that the person has feels just like what it would be if they got the intervention and you can hide it from them that they haven't gotten it. But some of our treatments, you can't do that with. So that creates a situation where treatments that can be blinded are at an advantage in terms of how strong their literature is going to be considered compared to treatments that cannot be blinded. And so really our intention in this review was to lay out pros and cons of different designs and maybe point out places where the effect sizes may be related to design features, but not to categorically throw out studies or devalue studies because of design limitations that it is impossible to overcome. And so that is something that I'll try to talk about as I go through the results. And so we are careful and thoughtful about validity threats. So we can't create a sham controlled treatment and pretend that that's a valid sham control if what they're getting is also an active treatment that overlaps in features with the treatment itself. We also have to be thoughtful about what outcomes we choose. So blinded raters sounds really good, but if those raters are just observing someone for an hour, that's not really good information on that person's average behaviour across time context and in front of different people. And so we really have to think about all of these pros and cons to the different aspects of the design. So here is how we did our review. Now prior to this review, there were two in the series, one that was published in 2000, that included all the literature on the same research questions up to 2000, and then one that was published in 2014 that included basically the 2000 to 2012 time period. These reviews are going to be integrated into our current literature review so that we can take our latest science and then basically collate it with the earlier science. Now the older reviews-- Smith, 2000, Sibley, 2014, they included non-randomised studies as well, because literature was more in its infancy at that time. And so it was Helpful to go through a lot of these open trials that people had done without control groups. Here in, we have such a big literature at this point that we can let go of those studies that have more validity threats. And so if we go through our flow diagram here, you can see that in our search part, we got over 1,000 studies that we were able to identify, 100 got through our title abstract review, and 46 were included in the review after the full text. Now we took those 46 and we integrated them with the 27 that were RCTs that were pulled out of those two earlier reviews, and then we end up with 73 papers or 63 studies since some studies were split into multiple papers that we were able to review in this paper. And it's all RCTs. So that's great. Now, as far as where the studies were done, as you can see, likely due to our English language criteria, there was a bit of a over-representation here of North American papers. There was also papers from Europe, from Middle East, North Africa region, and from Asia. As far as the classes of treatments and how many studies, we found for each, you can see that the largest literature is for CBT and medication. These two treatment categories had the most papers by far. There was also multiple Papers for cognitive training, also called digital therapeutics for physical activity. And then we start to get into treatments that have far less papers or maybe only crossover papers, which is a bit of a weaker design than the parallel group RCT. And so here you can see we also found papers on neurofeedback, brain stimulation, nutrient supplementation, and occupational therapy. I'm going to start with CBTs. It had the most parallel group RCTs. And then I'll go on down to the literatures from there in order of their size. So a note about defining CBT. So we basically define CBT as any treatments that had classic behavioural elements, skills training, or cognitive components as in cognitive restructuring, not necessarily direct cognitive training. So using this broad term works for this literature because if you look at what these treatments are, they're always a combination of both. There's no sort of unit element treatment that's being used in this population. It's always this sort of multi-component with some cognitive pieces, with some behavioural pieces. And so it's very artificial to sort these treatments into just this is organisation skills training and this is behavioural reinforcement training, because all of these treatments have all of those pieces in them. And so I think-- and you see that as you move into the adult literature. We just call that collection of treatment CBT. And we would be applying that same logic here in the adolescent treatment literature. And so what we find in the CBT RCTs is that mostly these were parallel group. We did have about two dozen. Most of them were looking at the basic efficacy of a treatment. So basically, the treatment compared to not getting any treatment from the research team, although a fairly large amount of this literature is actually comparing two CBTs to each other. And so that has interesting implications for what kinds of conclusions can be drawn. There were a few studies that looked at adding CBT above and beyond something like medication, and whether there's an incremental effect there. And because we had so many of these comparative trials in CBT literature, you actually see a lot of CBT arms represented almost twice as many arms as RCTs total. And so there's a lot to learn here about what people are doing and a lot of variety to look at. The sample sizes of these RCTs have grown a lot in the last couple decades. Since the earlier reviews, we see that there are more studies with over 100 people in them in this RCT literature than under 100. So this is a greatly maturing literature. On average, there's 122 people in the samples of these studies. We applied the grade rating system to all of our studies, just to have a general sense of where the strengths and limitations are in the literatures. And as you can see within the CBT, the main limitation, as I already mentioned, is blinding. So although you can sometimes partially blind folks, especially in these comparative trials where you have two CBTs compared to each other, they don't know which of those CBTs you might be hypothesising is more effective or might have a bigger effect on one outcome versus another. That could be maybe partially blinded. But in general, people know they got CBT. So there's no real such thing as fully blinding that can really occur, unless you're having someone who's not participating in the treatment be the person measuring the outcome. So like the outcome assessors sometimes in an observation could be blinded. But then again, there might be other limitations to that kind of trial involving the validity of the outcome measure. So just a lot of pros and cons to look at here. In general, I think that the CBT literature is pretty good at a couple of things that other literatures weren't, which includes reporting all of their outcome measures that they had set out to look at having a broad range of outcome measures just beyond ADHD symptoms. And also reporting full data, so that even if there was a non-significant effect, we as a person doing a systematic review can come along and have enough information to still calculate the effect sizes is still look at what they found. So some strengths there in the way these studies were conducted. As this is a table that you don't need to stare at too hard. In fact, if you zoom out and look at the green and white patterns, it might actually be more informative to you. This is every single arm in a CBT study, and the name of the intervention that was studied in that arm. And we can see how much heterogeneity there is here and what people are calling CBT in this literature. So this could range from some of our treatments, I think the lowest was an hour and a half of treatment, 90 minutes, all the way up to programmes that were over 300 hours of treatment. So, obviously, we're going to have very different findings based on dose and then also who's involved in the treatment. So some of these are group treatments. Some of them are one-on-one treatments. Sometimes the parent is involved. Other times, the parent is not involved. Sometimes it's delivered in these studies in the community by real world practitioners. Sometimes it's delivered by the research team. Maybe graduate students. And as far as the main elements of these treatment goes, we saw a big reliance on behavioural principles. So using contingency management or modifying someone's environment to promote behavioural skills. Direct training of behavioural skills was in most treatments as well. And we're seeing an emerging trend here, especially in the more recent studies for also involving motivational interviewing in order to increase engagement. One of the issues we saw in the introduction of this presentation. And getting folks maybe more interested in getting help for their difficulties. So a lot of heterogeneity here in that literature. And now we're going to look at the medication studies and what's in that literature before I get to the results. So medication also has a similar number of RCTs total compared to the CBT literature. The medications have more crossovers I think owing to the fact-- than CBT, owing to the fact that there's a long history of conducting crossovers and also a lot of the early studies on medication were initially cross-over. So much more basic efficacy studies where we're looking at usually compared to placebo, a medication, some comparative efficacy where we're looking at either medications, different doses compared to each other, or different medications altogether compared to each other, a few incremental efficacy studies. So lots of medication arms as well. You can see many more than the actual studies because of different comparisons that were made in these studies. As far as what medications have been looked at in this population. So you can see it's a mix of immediate release stimulants, extended release or long-acting stimulants, and non-stimulant medications. And I think in our more recent years, we're seeing more non-stimulants being tested, as well as just a broader set of formulations for the long-acting and extended release medications, you can see them all listed here. The medication studies, similar to the CBT, there are more RCTs that have over 100 people than there are that have under at this point. The average size here is almost 150 people. So these are fairly big studies. And these are all specific to the adolescent age group. As far as the medication studies go, the strengths and limitations of the literature are different than the CBT study. So medication studies are outstanding at blinding for the most part. And you can see that, that is an easy thing for people to comply with when running medication studies. Where the medication studies are a little bit more limited is that often, they only look at ADHD symptoms as an outcome, rather than broader impairments or other targets for folks. And then one issue we ran into with some of the medication studies was that if something was non-significant, there was no more information than that included. So we didn't know the size of the effect or have enough data to be able to calculate that ourselves. And so that was the limitation of the literature that actually prevented us from calculating effect sizes for a lot of the outcomes that were in those studies. And you'll see that in a second. Now the other treatments that we found and reviewed in our study include cognitive training. So you can see the lists of the different programmes here that were looked at and what they targeted. Physical activity, similarly, you can see the different kinds of physical activity that people have done RCTs with. And also you can see the sizes of the studies here. A lot of them are smaller. Brain stimulation, specifically some work on transcranial direct current stimulation in the adolescent age group-- smaller studies. One nutrient supplementation study and one neurofeedback study, specifically with adolescents, one occupational therapy study. Among these other treatments, I sort of just put them all together here for ease of viewing-- really a mixed bag in terms of the strengths and limitations. These literatures show a bit of an easier time blinding for most of these modalities compared to something like CBT. Exercise is the exception that's pretty hard to blind that. And in some cases, there wasn't blinding of something like cognitive therapy also-- or sorry, cognitive training also. So other issues, I think, incomplete outcome data was also a big issue. And also using per protocol analyses instead of intent to treat, which means that if people dropped out of the treatment, you just didn't analyse them, which creates bias. So this literature in particular had issues with that, mostly because a lot of these studies are smaller, more preliminary RCTs that people were doing. Now let's look at our outcomes here. So I'm going to walk you through this. And we're going to look at this in different ways. As far as ADHD symptom outcomes goes. So as I mentioned, we did calculate effect sizes for each study that had enough data for us to calculate effect sizes. And we did reach out to authors twice if it wasn't in the study to see if we could get more information about means and standard deviations for outcomes. And here what we can see for our core ADHD symptoms, in pink, I've highlighted the medication effects. In yellow, the CBT effects. And if you look, you can see the less frequent treatments colours in the key at the left side of the figure. So what we see here is that there is a more consistent effect for medications on ADHD symptoms across the studies. And many of the medication studies, as I mentioned, did not give enough data for us to calculate those effects. So this is just those that are represented here. With the CBT treatments, it's more of an inconsistent effect. So some of those packages did find effects, but some of them didn't. And given the heterogeneity in those packages, it's not surprising we might see heterogeneity in effects. Other studies were not replicated. So if we see that green neurofeedback with that small study there, they have an effect. But on the other hand, there's only one study. So we really don't know if that replicates. One thing that we do see that is worth looking at is that in the orange, the cognitive training pretty consistently did not have an effect, although there was that one small study that had-- the Steiner study had 1 out of 13 measures, I think, have an effect on ADHD. So it's possible that there is some effect there, but it is not seeming to generalise. As far as the impairment outcomes go, you see a lot of yellow here for CBT. Yes, CBT seem to have a really strong effect on impairments, but also other treatment types are not including impairment measures in their RCTs. And so you can see that only a couple medication studies included impairment measures-- those are both really recent studies of viloxazine. So great work that those authors included impairment measures. And we had one brain stimulation study that had an impairment measure as well. As far as then other outcomes. So basically, we looked at what the authors designated as core targets for their treatments that maybe went beyond impairment or ADHD symptoms. So some examples might be executive function skills or academic improvement or substance use, because the specific treatment was also targeting a secondary issue or an issue from specific issue within ADHD like executive functioning. And you can see here, again, the CBT literature tends to involve multiple outcomes. And so you do see an overrepresentation of that literature in this graph. But you can see what comes out of here is that executive function skills in particular seem to have very robust effects with the CBTs in their RCTs. And then there's a kind of a collection that I'll describe in a minute of other effects here that might be of interest. So for CBT, to return to that for a second, no safety concerns were noted in any of these trials. But we will say a limitation is that most of these studies are not really systematically monitoring adverse events or safety. And so that's probably an important future direction for this literature. CBT had an inconsistent effect on ADHD symptoms, but it had a fairly consistent strong impact on impairment. You can see the range of effect sizes there. It also had a fairly strong consistent effect on executive function skills. So things like organisation skills, time management, planning. And it had a fairly modest but consistent impact on comorbid internalising skills. There was no evidence that CBT impacted cognitive task performance. And there were only really in the CBT literature where there are studies that extended the RCT phases of the study six months to several years to understand the long-term maintenance of effects. So sometimes, there'll be an open-label extension on the Med trials, but that's no longer RCT data. So here we can see from these 11 studies that there do appear to be some long-term effects of the CBTs after they've been discontinued, at least most strongly on the executive function skills. So lots of replication up to six months on that and two studies replicating up to three years on that. So that's something worth being aware of. And the long-term impact on ADHD symptoms, though, was inconsistent in line with the fact that it was inconsistent to begin with acutely. So I think that's interesting that maybe this is a period that begets longer term impact of treatment than childhood. Unfortunately, we only have a literature looking at this in CBT, so it'd be very interesting to look at this in other modalities as well and have long-term follow up. CBT was also the only literature that really looked at moderators of treatment, especially with those studies comparing two types of CBT. So if you look in the paper, you can see a whole list of different moderations. None of them were really a replicated moderation. But we do point out in detail in there about certain programmes that seem to work really well for certain kinds of kids. For medication, we saw all medications were well-tolerated as far as safety goes in the adolescent age period. There was definitely a focus on understanding the impact of the meds on sleep since adolescents are already vulnerable to sleep problems in general during this age of their life. But that was the most common adverse event reported across trials. There was very consistent, strong efficacy for the impact of medications on ADHD symptom severity. So that's a confident finding. The only exception to this was there was some inconsistency in the effects for the alpha 2 agonist extended release guanfacine, at least in this age group. There was no impact on impairment indices. So five studies that evaluate this, five studies found nonsignificant effects. Some of those studies didn't offer enough data to look at what the effect sizes actually were. But that is something that was found. And we would want more med trials to include impairment indices. So we can really understand this piece. There was a consistent modest impact on cognitive task performance. We couldn't calculate these effect sizes, unfortunately, because there wasn't enough data reported in the med trials to understand the nature of this. But there were studies that did significance test on cognitive task performance. And there were no studies looking at long-term impacts and no studies examining moderators. As far as the other treatments go, I put them in a table here just to take a look at what the literature is finding. So across these less common treatments, mostly there was insufficient literatures to draw any conclusions, which means either they didn't look at an outcome, or maybe one study did and there wasn't replication yet. A couple places where there were a little bit more confident findings, for cognitive training, remember, I think there were five cognitive training studies in this paper. There appeared to be no impact on ADHD symptoms overall, and there was an inconsistent impact on cognitive tasks. Not too surprising because different protocols were involved in targeting different aspects of cognition in these different studies. For physical activity, we're all very interested in this potential treatment, I think. There was a consistent, modest impact on cognition that didn't translate into ADHD symptoms or impairment. And there's also this question in that literature of whether we're just capturing the immediate acute effects of exercise, because a lot of these studies just have someone do a cognitive task as soon as they've exercised, versus more of a generalised impact on cognition when someone hasn't just exercised. So that's a future direction for that literature. And then brain stimulation, there was no impact on symptoms or impairment and an inconsistent impact on cognitive training-- or sorry, cognitive tasks. So again, more literature is needed there, I guess, to clarify when things work and don't work for some of these treatments. You can see no huge safety issues for any of these treatments, but some adverse effects that might be good for people to know about, especially maybe the motion sickness with cognitive training, which just came up in particular in a treatment that was looking at driving and cognitive performance. Maybe some issues with discomfort with the brain stimulation training as well and physical activity. So if we pull all the findings of this review together, what does it tell us about thinking about treatment approaches for adolescents with ADHD, especially maybe thinking about multimodal treatment approaches? And I think there's kind of a key model here that's emerging from these data. As far as medication goes, it seems that, that has the strongest impact on ADHD symptom severity, and that the main way that that's occurring is by improving cognitive performance directly. At the same time, if somebody does a CBT-like programme, it seems like particularly through developing executive function skills like organisation, time management, and planning, maybe better self-awareness of what you need to manage your own ADHD better in terms of your daily life choices, the environment you put yourself in. Those things that we would work on in CBT, those seem to have more of a direct impact on functional impairment. So if we're thinking about how to maximally help people, we probably would consider an approach that would use both cognitive behavioural and a medication together if we really want to have a big impact for folks. This sort of does medication in turn impact impairment? And does CBT in turn impact ADHD symptom severity? I think there's a question mark there still, but I think we know that both of these treatments are not having redundant effects, they're having complementary effects. So they do seem incrementally valid when you consider multiple outcomes. Now there's some limitations about this that, obviously, you're limited by the literature base that you're reviewing. So we decidedly did not meta-analyse because there was so much heterogeneity in the treatments in this literature base that we thought it was a better service to the field to observe that heterogeneity, note it, and discuss its impacts, rather than trying to maybe artificially lump things together and summarise things in a way that we felt would actually create too much oversimplification and lose the main important messages and findings and lessons in this literature. That was our choice. The strength of this review is also impacted by individual study limitations. So we talked about we have a blinding issue for some of these classes of treatments and they'll never be able to be fully blinded. So what do we do with that? And when I'm presenting this data showing robust effects for CBT on executive function skills and impairments, that is always with the caveat that the people who filled out the ratings knew, for the most part, that they were getting treatment targeting those areas. So you have to decide, as a consumer of this science, whether that to you is a deal breaker or whether that's just a validity threat that we have to keep an eye on. For me, I think the decision to throw out exercise and CBT is not helpful because you can't possibly blind them, probably is a worse evil because now you might be denying people things that could really help them because of a design flaw that can never be overcome in a research study, which doesn't feel great to me. So again, it's an interesting debate to have. We can't draw conclusions about the individual components of any of these interventions because we always tested them as a package. So we saw with the CBTs, there was always multiple pieces in those interventions. We don't know whether it was the behavioural part or the cognitive part or the engagement part that really drove the effect. Likely it was them working together. And you can say that about other kinds of treatments as well. Some of the cognitive training packages, we're looking at multiple cognitive targets. There was a working memory piece. There was a sustained attention piece. Again, we don't necessarily know what's driving the effect, just like in some medications that have multiple ingredients in them, we don't know exactly which ingredient may be driving the effect. Now, what does this mean in clinic? So I think, for me, I would say there's no reason to only reserve CBT for people who are medication non-responders. That's what some of the guidelines currently say. For this age group, I think we really need to look at those guidelines and ask ourselves if they actually reflect a holistic view of this literature or just maybe reflecting only looking at ADHD symptoms as an outcome. And you can see the differences in some of the global guidelines here depending on region. We also need to think about expanding the targets of treatments for adolescents with ADHD. So we have some great treatments that target academics and have shown effects in family relationships, for example. But some of the areas that need more attention are emotion regulation, safe behaviour with peers, responsible use of digital media, sleep. So really thinking about all of the aspects of the impairments associated with ADHD to broaden our treatments. And I do think, again, I'll say that it's critical that people try their best to conduct long-term follow up in an RCT format for their treatments, because we're seeing a signal that this period may beget long-term effects better than in childhood. But if we don't test that with lots of treatments, we don't know if that's just a CBT thing or if that's really true just because of the age for any treatment. And so really encouraging people to try to do that as much as they can. And quite surprisingly, there's never been a true combined treatment RCT for ADHD in adolescents. We're just making assumptions about what was true in childhood that it would also be true for teenagers when they have very different brains and very different lives. So I do think that, that would be a value to the field for somebody to do at some point. OK. That wraps up my presentation. This is my contact information. And I'm always happy to connect with people after the presentation to discuss it or to field questions. So thank you so much for your time today. [MUSIC PLAYING]