Dr Soumitra Datta Hello, I’m Soumitra Datta, Consultant Child Psychiatrist and we would continue learning about management of psychosis in children and adolescents. Earlier, we had learned about, you know, presentation of psychosis in children and adolescents, how do you differentiate various conditions which may have psychotic symptoms, and how do you tie it together while coming to a diagnosis? A current lesson, we would learn about the evidence base for treating psychosis in children and for childhood onset schizophrenia, which is rare, and treating adolescents with psychosis with medications, and adolescents with psychosis with psychological interventions. And we’ll end by, you know, looking into how do you, you know, apply these evidence base into your day-to-day practice? So, I’ll take you back to the early days, when we started working on childhood onset schizophrenia and atypical and typical antipsychotic medications. And we found that, you know, the trials, which were few, because it’s not easy to conduct a clinical randomised controlled trial with children who have schizophrenia and have an onset below 13. You know, first of all, these – this is rare and to – you know, family members incredibly stressed, understandably, our Clinicians are worried, to do a randomised trial is not easy. So, there is very limited evidence and we saw that, you know, actually, the data did not support one drug over the other. Even typical and atypical antipsychotics could – were not very different for this, as regards efficacy in terms of the mental state, in the review which we did. When it, well, it comes to adolescents, of course, you know, the evidence is a bit more robust, and we looked into the evidence base for atypical antipsychotics for adolescents in psychosis. However, we were, again, surprised to see that there is not much of difference between atypical and typical antipsychotics. Now, the TEOSS Study, which if you see, the authors had, you know, sort of, compared molindone, olanzapine and risperidone, and they found that response rate or the magnitude of symptom reduction did not have much difference for these two – these three groups of children who were on either of the drugs. However, olanzapine and risperidone were associated with weight gain. You know, that’s very crucial, because this is an age group where you are wanting peer validation and you would not want to gain weight. I think that’s true for any age group, but it’s probably one of the reasons for poor adherence to treatment in psychosis in adolescents. The follow-up for the patients who were recruited into this particular well designed, well done, study, was that only 12% of the adolescent had continued in the study. And for those who continued, there was no significant difference in terms of treatment response for each of the groups. So, you know, that’s an interesting story in itself. Now, moving on, we – when you see the recent reviews, there is a meta-review published last year, and yeah, people have said, of course, you know, “We all use atypical antipsychotics today and they’re comparably safe and efficacious options.” The meta-review of Lopez-Morinigo talks about aripiprazole, lurasidone, molindone, risperidone, paliperidone, quetiapine. Olanzapine was pointed out about the high-risk for weight gain and haloperidol for extrapyramidal symptoms. The authors also suggested that for treatment-resistant patients in this age group, should be offered clozapine and that is also, you know, supported by evidence base. However, the authors did point out some unmet needs in the research, which had – which is present, up-to-date. Most of the trials are short-term and they don’t have much data to support long-term efficacy, and there is very little data on adherence and acceptance of the treatment by adolescents. Many trials overlooked negative symptoms. There is very limited evidence on cognitive symptoms and there is a lack of reporting of outcomes, like, you know, school absenteeism, or employment for older adolescents, suicidal behaviour or mortality. Service use, like admissions, A&E presentations, outpatient appointments, how many somebody is requiring and, you know, cost effectiveness, almost always, you know, there is some off-label prescriptions. So, these are often not commented upon and the dosing there is very little evidence on. So, these are – even as you can see, that there is a lot of, sort of, areas, which need further research in – while we are looking at evidence base for adolescents with psychosis. Now, if evidence base is so limited, it’s a good idea to see what Child Psychiatrists actually do. And we did a survey about antipsychotic prescribing around ten years ago and we found that, you know, that most Child Psychiatrists actually started with a low dose of atypical antipsychotic. They wanted to make sure that they had got the diagnosis right. There is no tests, as such, to confirm the diagnosis of psychosis, so you need to rely on a good history and a mental state examination, so that’s vital. And starting on the young person on a low dose medication, start low and go slow. Risperidone, olanzapine, quetiapine, aripiprazole were the drugs which were popular amongst Child Psychiatrists in UK and clozapine, people had opined, could be offered for treatment-resistant patients. Depot antipsychotics, you know, there is no evidence base for that, but could be a last resort for adolescents where adherence is poor. This needs to be, you know, looked into the context of preferences of the child, of the family, you know, how much you are, sort of, wanting to – this is more intrusive treatment. So, how much are you actually sure that you need to go down that route? So – however, you know, the – if you keep this in mind that – what do you do when you see a early-onset schizophrenia on an adolescent with psychosis, I think this would make you – you know, sort of, give you some pointers. What about lived experience of adolescents who had been on antipsychotic medications? You know, adolescence is an age group where people might think that “If I have a problem, I’d rather beat it myself than breaking down or letting something else taking over it,” which is, you know – could be, you know, a service or could be medications. And there is a pressure to conform to the youth culture. “I went off my pills by choice because I had an issue with taking them. I don’t mind taking them now.” So, this was a, yeah, a study done in Canada and the quote citing, they’re quite poignant and, you know, have taught me a lot about how adolescents think about treatment with medications and antipsychotics. Some of the adolescents, you know, also mention that, you know, “I do have friends, but they’re very different,” and that, well, you know, struck me very differently. In one way, it is that these adolescents felt supported, but at the same time, it does throw up about the stigma of psychosis in this age group. So, I think, you know, in today’s world, it’s important that we look into the, sort of, the lived experience and the patient experiences of somebody being treated for a particular condition. Now, while treating individuals with antipsychotic medications, you could actually look at various ways how you minimise side effects. So, we published that for not specifically adolescents, but for all age groups, so even if, you know, there is a pre-existing cardiac disease, you need to be more cautious about antipsychotics. So, having a baseline ECG would help and, you know, if there’s a history of a disease like Down’s syndrome, which is not unusual to have comorbid psychosis, and you do need to be mindful that there might be ventricular septal defects or other cardiac conditions, which might predispose them to have more side effects. So, like this – in this particular paper, we had discussed about – over each common side effect or adverse effects of antipsychotics and how this could be minimised over time. Now, follow-up dose of the antipsychotic medication that could be lower than the dose at which you had treated the adolescent or the child when they were having the acute psychotic symptoms. So, one should be careful about having good medical evi – you know, medication adherence. And sexual dysfunction in boys, because of hyperprolactinaemia, or weight gain in adolescents, you know, boys and girls both, you know, these are things which you need to actively monitor while following up, so that, you know, you don’t, sort of, ignore these very important issues for treating – while treating children and adolescents. “Retrospective Review of Clozapine Use in Children and Adolescents,” you know, this is a study, which was published recently, and it did show that the people who was tried on clozapine were almost always an inpatient and it required around two months of stay in an inpatient unit. So, by the time this has been thought of, this is pretty specialist area. So, I think it’s good practice, if you have the resources, to have an adolescent inpatient setting and starting of clozapine be left to a specialist who are used to doing that. And, you know, it is a, you know, a good treatment for treatment-resistant psychosis or schizophrenia in adolescents. What about psychological interventions for psychosis? You know, we are Child Psychiatrists, and we are treating children, vulnerable families. So, our recent review in 2020, we looked at kind – all kinds of psychological interventions available and we found that, you know, there are trials on psychoeducation, cognitive remediation therapy, computer assisted cognitive remediation therapy and non-structured group therapy, family therapy. All these patients who were participating in the trials, they were also on medications, but the details of the medications are not reported by the authors, so that is something which we have suggested in future studies to be done. So, some of the findings suggested that, you know, cognitive remediation therapy versus treatment as usual, only short-term memory improved in the CRT group, but no difference in terms of PANNS, which is mental state, or you know, the global state. Similarly, group therapy versus treatment as usual, the global state slightly improved and you could intuitively make sense of that. You know, these are adolescents who might have deficiencies in social skills, so group therapies, in a way, might work. However, this did not make any impact on the mental state. But, you know, even though there is very little evidence, be it cognitive remediation therapy or any other specific modes of therapy, against something else, it is important that we have a psychological mindset while we are treating adolescents with psychosis, or children with psychosis. People have tried all sorts of, you know, interventions, psychological interventions, for this age group. Very little has been shown to be – you know, if there are two active – both groups have improved. So, it’s not like that they’re useless, but it didn’t show that non-structured group therapy was superior or inferior to psychoeducation and fam – multifamily treatment. So, I think it’s still important to remember that, you know, you do need medications, at the same time, have a psychological mindset for you to engage the child and the family so that they follow-up with the services. You reduce the risk, you instil hope in the parents, because, you know, they are going through a grief of having a child who is, sort of, being treated for psychosis, and, you know, the parents might be upset. So, having a psychosocial approach to the entire scenario is important. However, medication still remains important and the mainstay of treatment. So, psychological care of education, supportive psychotherapeutic interventions, need further trials, and there is almost no evidence about one particular medication being superior to other. However, the practice follows that you need to start these – you often start these adolescents and children on atypical antipsychotics, on low doses, and titrate it slowly, as you go along, according to the symptoms, response and side effects. I hope your understanding of management of psychosis in children and adolescents is better, and we would encourage you to share this with all your friends and colleagues who might benefit from this educational interventions.