Professor Samuele Cortese Hi, my name is  Samuele Cortese. I am an NIHR Research Professor,   Professor of Child Adolescent Psychiatry at  the University of Southampton in the UK. Also,   Professor of Child Neuropsychiatry at the  University of Bari in Italy and at the   University of New York in the United States. So,  this presentation will focus on the “Evidence on   the Non-pharmacological Treatment of ADHD.” Before  moving to the actual presentation, this is the   disclosure of my potential conflict of interest,  and let’s move now to the presentation itself. So, in terms of the non-pharmacological  management of ADHD, of course, we know   that in addition to medications, we do have  several non-pharmacological options. However,   it is important to appreciate the role of these  non-pharmacological approaches in the overall   management of ADHD. So, if we look, for instance,  at the NICE guidelines, released in 2018, they   recommend that non-pharmacological approaches,  in particular, behaviour interventions,   parent training, should we used only if there is a  comorbid oppositional defiant disorder, or conduct   disorder, or in adolescence, if symptoms are  still impairing after pharmacological treatment,   or, if, of course, non-pharmacological  options are the preference of the patient. So, why did NICE come up with  these recommendations? So,   this is based on evidence from NICE trials and  from meta-analysis of these trials. In particular,   I would like to show you a very important  and seminal work in the field, which we,   as European ADHD Guidelines Group, published  more than ten years ago now. This really set   the ground for these recommendations, and  this meta-analysis has been subsequently   updated, but its results actually have  not changed significantly over time. So, in this meta-analysis we looked at the  evidence on key non-pharmacological treatments,   such as parent training, diet, neurofeedback,  cognitive training and, importantly,   we looked at outcomes rated by two types of  raters. What we call “most proximal,” so these   are raters which are involved in the delivery  of the treatment, so they have expectations   around its effectiveness. And, also, we looked  at ratings of symptoms rated by people who were   not proximal to the delivery of the treatment,  so there were more, we could say, impartial. And, interesting, we saw that the  results of – around the effectiveness   of these treatment really change according  to the type of rater. So, let me give you an   example which will allow me also to show  how NICE made those recommendations. So,   if we look at behavioural interventional, more  commonly referred to as the “parent training,” we   did a meta-analysis of all the randomised trials  that tested the effect of this intervention. And,   as you know, in a trial, we measured the  severity of the symptoms of ADHD, in this case,   at the baseline, before treatment, and at the  end of the trial, with the treatment effect. And in terms of measuring the severity of  symptoms, we can ask, as I mention early,   several types of raters. So we can ask parents, we  can ask Teachers, we can ask children, adolescent   and themselves, and so and so forth. So, we  found that pulling together data from trials   and looking at the ratings from parent, which we  called in this case, “most proximal” because they   were involved in the delivery of the treatment,  there is a significant effect of parent training. As you can see, I guess you are familiar with  how to read a forest plot. If you are not,   I will briefly remind you that in the  forest plot, each line represent the   effect of a study. The dot is the effect  size, so the effect of the intervention,   and the confidence interval is the 95% confidence  interval within the real effect it’s supposed to   be 95% of times. And every time the line  crosses the vertical line, it means that   there is no difference between intervention  and control. Every time the confidence interval   is entirely on the right hand side, it means  that the treatment is better than the placebo. So, if we pull together the data from all these  trials on parent training with outcomes rated   by parents, it turns out that the final effect,  the meta-analytic effect, and this one, it turns   out that actually parent training is better than  control. So, it does work in terms of decreasing   the severity of the symptoms of ADHD, with a size  of effect which is moderate, around .4. However,   if we look at the ratings, pre and post,  provided by Teachers, who are not involved   in the behavioural parent training, so they  don’t have expectation effect, it turns out that   Teachers don’t see any significant improvement  in the severity of the symptoms of ADHD. So, look at rigorously blinded ratings, we  cannot conclude that parent training is an   effective treatment for ADHD. However, parent  training, as we showed in another meta-analysis,   it’s important to tackle additional  problems, additional dimensions,   that are associated with ADHD, even if they are  not the core symptoms of ADHD. In particular,   in this meta-analysis, and we found – I appreciate  this is a very busy slide with many forest plot,   but I will guide you through this,  we found out that actually looking   both at proximal but also probably blind  ratings, there was a significant effect   of parent training on conduct problems,  oppositional defiant and conduct problems. And, also, there was a significant effect, once  again, both in terms of most proximal and, also,   probably blind, also, on parenting, in  terms of improving positive parenting   and decreasing negative parenting. So,  parent training, per se, is not the treatment   according to this data for ADHD symptoms, core  symptoms, but it is very helpful to address   problems related to oppositional behaviour,  conduct problems and to improve parenting. We did the same – we applied the same approach  to test the effects of cognitive training and,   unfortunately, once again we found that cognitive  training, while according to most proximal raters,   it seems to work in terms of improving ADHD  symptoms. As you can see here, it does not work,   you see here the confidence interval line crosses  the line – the vertical line, so it means there is   no effect, no significant difference, when we look  probably blind raters. So, there is once again no   solid evidence to support the use of cognitive  training as a treatment for ADHD core symptoms. And this was also the finding we  had in the most recent update of   this meta-analysis that we published  in 23. No effect on ADHD. The only   effect of cognitive training were in  terms of improving working memory,   verbal and visual spatial working memory. This  may be important, of course, in some children,   but it is not the treatment of ADHD, per  se, it may improve executive dysfunctions. The same conclusion applies to neurofeedback,  and we are also conducting another meta-analysis,   and results do not seem to change, even in  the most recent updates. So, once again,   for neurofeedback, there is evidence that  when we look at most proximal raters,   it seems to work, but actually when we  look at more – most – the most rigorous,   probably blinded raters, there is no evidence that  it can significantly improve ADHD core symptoms. In addition to these treatments, of course, there  are other types of non-pharmacological treatments,   in particular, all the treatments which go  under the broader term of “neurostimulation”   and “neuromodulation.” There is no evidence so  far that approaches like transcranial magnetic   stimulation or transcranial direct current  stimulation, can improve ADHD. The only type   of treatment, or neuromodulation treatment,  which may eventually have a role in H – ADHD   according to current data, is the so-called  “external trigeminal nerve stimulation.”   This is stimulation to the externina – external  trigeminal branch and delivered by a small device,   as the one you see in the figure, is non-invasive,  and you wear during the night for four weeks. And, interesting, you may note that this  device was approved by the FDA in the   United States as a treatment for ADHD.  Interesting, that approval was made only   just on the basis of one pilot randomised  controlled trial, conducted in California,   where it was seen that the use of this device  compared to a control condition which we call in   this case a “sham condition,” was better in terms  of decreasing the symptoms of ADHD. Actually,   this is a graph which represents this, and you see  here is the active device in orange, and the sham,   so the non-active device, there is a difference in  the severity of the symptoms at the beginning and   at the end of the trial, with a number needed to  treat of three, so, it’s a quite moderate effect,   similar to the effect size for atomoxetine,  or Cohen’s d of .5, so moderate effect. However, this was a pilot  trial, so our colleagues in the   United States are conducting a larger trial, and  we are, also, in the UK conducting a larger trial,   alongside Professor Katya Rubia at  King’s College, and so, hopefully,   we should have the results in a couple of years,  and – to check really, to confirm, as to whether   this external trigeminal nerve stimulation  may or not be an option for ADHD treatment. And I think this was my last slide, so, of course,  the topic is quite broad, but I tried to select   the most important studies and the most important  non-pharmacological treatments. Thank you.