Efficacy of cannabinoids in neurodevelopmental and neuropsychiatric disorders among children and adolescents: a systematic review.

A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.

Sensory dysregulation in tic disorders is associated with executive dysfunction and comorbidities.

BACKGROUND: Tics are conceptualized as a sensorimotor phenomenon with a premonitory urge typically described by patients. As observed in other neurodevelopmental disorders, we have observed sensory dysregulation symptoms, such as tactile hypersensitivity to clothing, in children with tic disorders; however, formal clinical research in this area is limited. OBJECTIVE: To define the presence of sensory dysregulation symptoms in tic disorders, and their clinical associations. METHODS: Prevalence of sensory dysregulation in 102 children with tic disorders was compared to 61 age- and sex-matched healthy controls. Sensory dysregulation, executive function, and quality of life data were obtained through the Short Sensory Profile-2, Sensory Profile-2, Sensory Processing Measure, Behaviour Rating Inventory of Executive Function-2, and Strength and Difficulties Questionnaire and Pediatric Quality of Life Inventory. Tics were assessed with the Yale Global Tic Severity Scale. RESULTS: Children with tics, in the presence of comorbidity, had elevated sensory dysregulation compared to healthy controls (P < 0.001). There was a positive correlation between sensory dysregulation and global executive difficulties in children with tics and comorbidity (n = 87; rho = 0.716; P < 0.001) and a negative correlation of sensory dysregulation with quality of life (n = 87; rho = -0.595; P < 0.001). In children with tics, there was an association between sensory dysregulation and number of comorbidities (P < 0.001). CONCLUSION: In the presence of comorbidity, children with tic disorders have broad sensory dysregulation symptoms beyond the premonitory urge. There was a statistically significant association between sensory dysregulation and executive function difficulties and the presence of neurodevelopmental and psychiatric comorbidity. Sensory dysregulation can be considered neurodevelopmental symptoms, providing insight into the neurobiology of tics and opportunities for therapeutic intervention. © 2019 International Parkinson and Movement Disorder Society.

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial.

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain. Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders. Design, Setting, and Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017. Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks. Main Outcomes and Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables. Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21). Conclusions and Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference. Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392.

An exploratory study into an adapted use of the Alert Program for tic disorder in children.

OBJECTIVES: This preliminary study explored whether an adapted approach to the Alert Program, that uses sensorimotor strategies, might assist with management of tic disorders in children. The Alert Program, a program that uses sensorimotor strategies for self-regulation in children with neurodevelopmental disorders, had not been trialled with children with tic disorders. METHODS: Ten children with tic disorder were assessed using the Dunn Sensory Profile 2 (SP2), the Yale Global Tic Severity Scale (YGTSS) and the Parent Tic Questionnaire (PTQ). Participants attended three 60-90-minute appointments with an occupational therapist and clinical psychologist for implementation of the adapted Alert Program. RESULTS: The YGTSS showed tic reduction in all participants. The total YGTSS pre-intervention mean score of 46.5 improved to 17.7 post-therapy. Five participants reported no impairment post-therapy. PTQ scores reduced in nine participants. On the SP2, 30% of participants scored as having sensory sensitivities that impaired daily function. CONCLUSIONS: This exploratory study found trialling an adapted approach to the Alert Program that uses sensorimotor-based approach decreased tic severity in children with tic disorders. A randomised controlled trial is needed to establish the effectiveness and feasibility of this approach.

Psychiatric comorbidity is common in dystonia and other movement disorders.

OBJECTIVE: To determine rates of psychiatric comorbidity in a clinical sample of childhood movement disorders (MDs). DESIGN: Cohort study. SETTING: Tertiary children's hospital MD clinics in Sydney, Australia and London, UK. PATIENTS: Cases were children with tic MDs (n=158) and non-tic MDs (n=102), including 66 children with dystonia. Comparison was made with emergency department controls (n=100), neurology controls with peripheral neuropathy or epilepsy (n=37), and community controls (n=10 438). INTERVENTIONS: On-line development and well-being assessment which was additionally clinically rated by experienced child psychiatrists. MAIN OUTCOME MEASURES: Diagnostic schedule and manual of mental disorders-5 criteria for psychiatric diagnoses. RESULTS: Psychiatric comorbidity in the non-tic MD cohort (39.2%) was comparable to the tic cohort (41.8%) (not significant). Psychiatric comorbidity in the non-tic MD cohort was greater than the emergency control group (18%, p<0.0001) and the community cohort (9.5%, p<0.00001), but not the neurology controls (29.7%, p=0.31). Almost half of the patients within the tic cohort with psychiatric comorbidity were receiving medical psychiatric treatment (45.5%) or psychology interventions (43.9%), compared with only 22.5% and 15.0%, respectively, of the non-tic MD cohort with psychiatric comorbidity. CONCLUSIONS: Psychiatric comorbidity is common in non-tic MDs such as dystonia. These psychiatric comorbidities appear to be under-recognised and undertreated.

Pervasive developmental disorders and psychosis.

Pervasive developmental disorders (PDDs) and infantile schizophrenia were initially thought to be the same condition, but distinct differences were described in later research. However, attempts to identify psychosis in individuals with PDDs continue to be challenging and controversial. The two disorders share many similar features, including perceptual abnormalities, thought disorder, catatonia, and deficiencies in reality testing. Progress has been made in describing features of PDDs that can be confused with psychosis and in surveying the prevalence of psychotic symptoms in populations with intellectual disability, although there are fewer data on PDD populations. Further research is needed on the longitudinal course of PDDs and the relationships with adult disorders such as psychosis and mood disorders. This research would not only improve the diagnosis and treatment of these complex disorders but would help to unravel the complex brain pathways involved in the perception of the external world that is central to psychosis and PDDs.

Intellectual ability, self-perceived social competence, and depressive symptomatology in children with high-functioning autistic spectrum disorders.

Although social competence deficits in children with high-functioning autistic spectrum disorders (HFASD) are well documented, there is little research investigating self-perceptions of social limitations. This study replicated research showing a negative association between self-perceived social competence and intellectual ability and investigated associations between self-perceived social competence and depressive symptomatology. Participants were 22 children with HFASD, aged 7-13 years with intelligence quotient (IQ) scores of 82-141. Parent- (N = 18) and teacher- (N = 17) rated social competence was lower for children with HFASD compared with a normative sample. Higher age and IQ predicted lower levels of self-perceived social competence, and low self-perceived social competence predicted higher levels of depressive symptomatology. Almost a third of children rated themselves for depression; parent ratings suggested even higher levels.

'All that glitters is not gold': misdiagnosis of psychosis in pervasive developmental disorders--a case series.

The early literature established the validity of the distinction between early onset schizophrenia and autism. In the modern context of increasing recognition of pervasive developmental disorders (PDD) and a growing interest in very early onset schizophrenia and other childhood onset psychoses, this clinical distinction is often difficult to make. This article looks at problems arising from overdiagnosing psychosis in those with PDD. Four case examples of misattributed diagnosis of psychosis are described. The features that were mistaken for psychotic phenomena are described and explained and successfully treated in the context of a diagnosis of PDD. The article describes problems of reliability of ascertaining subjective mental phenomena and the range of mental phenomena that need to be recognized in PDD. The overlap of abnormal perceptions and cognitions in both these conditions is described with reference to the literature. It is evident that more needs to be done to improve diagnostic reliability of psychosis in PDD, by improving clinical awareness and research tools.

A Pilot Study for Understanding the Perceptions of Australian General Practitioners Regarding Psychopharmacology for Children With Autism Spectrum Disorders.

BACKGROUND: General practitioners (GPs) are increasing involved in the care of children with autism spectrum disorders (ASDs), and prescribe and/or manage psychotropic medications for these children. Few published reports of perceptions of GPs regarding use of these medications exist in the literature. OBJECTIVE: Qualitative analysis of comments by 177 GPs regarding psychopharmacology use in children with ASDs. METHODS: A postal questionnaire survey containing both close- and open-ended questions was conducted in New South Wales, Australia. RESULTS: Respondent GPs were more likely to be females graduated from Australian medical schools and reported an interest either in child or in mental health. The respondents demonstrated good understanding of the issues surrounding psychopharmacology use in children with ASD based on contemporary literature on this topic. The main themes included concerns regarding medication safety, evidence for their use, and role of these medications as an adjuvant to behavior management. GPs reported a lack of experience of these medications, and would often prescribe only under the supervision of specialists. GPs with greater confidence and involvement with children of ASDs prescribed more medications; whereas GP reporting more concerns with regard to medications prescribed less. CONCLUSION: Respondent GPs have good understanding of psychotropic medications but need support from specialists for managing these medications in children with ASDs. Future larger studies should explore the utility of collaborative models of care for GPs to work in close partnerships with specialists.

The Association Between Social Skills and Mental Health in School-Aged Children with Autism Spectrum Disorder, With and Without Intellectual Disability.

Autism Spectrum Disorder (ASD) is associated with social skills deficits and co-occurring mental health difficulties. ASD frequently co-occurs with Intellectual Disability (ID). There is scant literature exploring the association between social skills and mental health in children with ASD, with or without ID. Participants were 292 children aged six to 13 with ASD (217 without ID; 76 with Mild ID). Parents and teachers rated social skills and mental health using standardised questionnaires. Greater mental health difficulties were associated with greater social responsiveness difficulties and poorer social skills across the sample. Effect sizes were large. Social skills explained a significant proportion of the variance in mental health scores across the sample. The study has important implications for treatment and future research.

A Framework for Developing a Curriculum Regarding Autism Spectrum Disorders for Primary Care Providers.

INTRODUCTION: The prevalence of Autism Spectrum Disorders (ASDs) has increased and varies across age groups. Thus there is an increasing need for educational opportunities for General Practitioners (GPs) and other Primary Care providers to help in early identification and referral to specialist services. An earlier survey of GPs in New South Wales (Australia) demonstrated two broad domains for educational activities: (1) a general knowledge (important for early identification and referral) and (2) surveillance (important for ongoing management). AIM: To seek further evidence to these domains and synthesize the important contents for educational programs for GPs. MATERIALS AND METHODS: We conducted a (1) Confirmatory Factor Analysis (CFA) on our original survey data and (2) systematic review of the literature to identify important educational topics, using a life cycle approach. RESULTS: CFA and literature review support theoretical framework of two domains. Alerts and red flags for ASDs, knowledge of simple surveillance tools, communication of diagnosis with parents, referral pathways particularly to speech pathologists before a formal diagnosis is confirmed, and appreciation of vulnerabilities for identifying supports were important in the general knowledge domain, while supporting the families through transition points such as from pre-school to school entry, secondary school and adolescence, role of psychopharmacology such as medications for sleep issues, and for common co-morbidities of anxiety were important in the surveillance dimension. CONCLUSION: GP supervisors and medical and nursing educators can use findings from this paper for developing structured learning activities for training primary health care workforce regarding ASD's.

Children and adolescents with acute alcohol intoxication/self-poisoning presenting to the emergency department.

OBJECTIVE: To describe the presentations, characteristics, and follow-up care of children and adolescents aged 10 to 18 years who present to emergency departments (EDs) with acute alcohol intoxication/self-poisoning. DESIGN: Retrospective medical record review. SETTING: Five EDs in Western Sydney, Australia. PARTICIPANTS: Patients aged 10 to 18 years who presented to EDs with acute alcohol intoxication/self-poisoning between January 1, 1996, and December 31, 2000. MAIN OUTCOME MEASURES: Frequency of presentations; presentation characteristics; psychosocial characteristics; and presence or absence of follow-up. RESULTS: Two hundred twelve children and adolescents presented to EDs 216 times. Of the 212 patients, 49 (23%) were 14 years or younger, and the youngest was aged 10 years. The majority (82%) came after hours and were brought in by emergency services (77%). In 13% of presentations, verbal and/or physical aggression was present, and a threat of self-harm was present in 2% of cases. A mental health worker was consulted about the child or adolescent in only 6% of presentations. Most children and adolescents (85%) were discharged from the ED. Of concern, in 56% of presentations, a follow-up plan was not recorded. There was documentation of mental health follow-up in only 14% of presentations and follow-up from drug and alcohol services in only 1%. Forensic history, school functioning, and a history of past mental health problems were not documented in more than 60% of the medical records examined. CONCLUSIONS: When children or adolescents present to an ED with acute alcohol intoxication/self-poisoning, their risk factors for psychosocial dysfunction appear to be inadequately assessed, documented, and followed up. Clear guidelines for assessment and referral pathways must be established in EDs.

Quality of life of survivors of pediatric intensive care.

OBJECTIVE: Measuring outcome in pediatric intensive care is necessary to equate the high cost of treatment with benefits to the patient. Although mortality rates and morbidity are relatively insensitive measures of the benefits of treatment, quality of life measurement gives insight into the long-term outcomes. The aim of this study was to investigate the long-term quality of life outcome of children admitted to a pediatric intensive care unit. DESIGN: Prospective survey. SETTING: A 13-bed pediatric intensive care unit in a university-affiliated, tertiary referral children's hospital. PATIENTS: Patients were 432 children discharged from the pediatric intensive care unit between May 1992 and April 1994. INTERVENTIONS: Quality of life was measured by using the Royal Alexandra Hospital for Children Measure of Function. The scale has two components, the first part completed by the clinician after parent interview and the second part completed separately by the parent. MEASUREMENTS AND MAIN RESULTS: Parents of 432 children were contacted between 3 and 24 months after discharge. Twenty-seven children (6.3%) had died after discharge from the pediatric intensive care unit; 59.3% (256) had scores indicating a normal quality of life, and 32.4% (140) had a fair quality of life with ongoing health, social, or cognitive problems requiring some intervention. Two percent of survivors (nine children) had scores indicating a poor quality of life as they had continued to experience significant or disabling health problems requiring hospitalization or the equivalent. Predictors of poor quality of life included presence of comorbidities, increased length of stay, and a diagnostic category of malignancy. Diagnostic categories of respiratory, trauma, and cardiac dysfunction were associated with a better outcome. CONCLUSIONS: Our results indicate that the long-term outcome in terms of quality of life after admission to a pediatric intensive care unit is good or normal for the majority of surviving children. Those children with a poor outcome are likely to have significant comorbidities or a diagnosis of malignancy.

Telenursing: clinical nurse consultancy for rural paediatric nurses.

Videoconferencing is increasingly being accepted as a medium for health-care. Telenursing is in its infancy in Australia but has enormous potential for nursing care in remote areas. The Child and Adolescent Psychological Telemedicine Outreach Service (CAPTOS) began in 1997 and in its first evaluation recommended more support for paediatric nurses. CAPTOS telenursing began as a new initiative in late 2001. The telenursing project aims to link ward nurses to CAPTOS and local community teams, and to provide both clinical consultancy on nursing and interdisciplinary issues and locally based professional development Telenursing supports nurses via site visits, videoconferencing sessions, an interactive Website and sabbatical opportunities. Telehealth works with existing services to enhance the nursing care of young people with a complex mixture of psychological and physical health problems.

An Exploratory Survey for Understanding Perceptions, Knowledge and Educational Needs of General Practitioners (GSs) Regarding Autistic Disorders in New South Wales (NSW), Australia.

AIM: A survey was conducted to ascertain General Practitioners (GPs') perceptions, knowledge and educational needs regarding autistic disorders in childhood. METHODS: A concurrent mixed method approach was used for data collection and analysis. Exploratory factor analysis (EFA) of the data was done and groups were compared using appropriate statistical tests. RESULTS: There was more response from female GPs, Australian medical graduates and those with an interest in mental and /or child health. Variability was noted in how GPs perceived their competence and knowledge of autistic disorders. About 60% correctly believed that an early-individualised treatment programme was evidence based. Knowledge was inversely related to the number of years in practice and enhanced by personal involvement with children of these disorders and awareness of community resources. Parallel analysis of knowledge scale revealed a "general knowledge" dimension loading items helpful for early identification and referral and a "surveillance" dimension helpful for ongoing involvement of GPs for management of children with ASDs. CONCLUSIONS: Although further development and refinement of knowledge questionnaire using these dimensions for primary care physicians are needed these are relevant target areas for education.

A child in detention: dilemmas faced by health professionals.

A 6-year-old child, held in detention with his parents pending the outcome of their application for refugee status, manifested psychological distress by repeated episodes of refusing to eat or drink. This case presented clinical and ethical dilemmas for health professionals who were constrained from acting in the child's best interests by government policy of mandatory detention.

Telenursing: clinical nurse consultancy for rural paediatric nurses.

Videoconferencing is increasingly being accepted as a medium for health-care. Telenursing is in its infancy in Australia but has enormous potential for nursing care in remote areas. The Child and Adolescent Psychological Telemedicine Outreach Service (CAPTOS) began in 1997 and in its first evaluation recommended more support for paediatric nurses. CAPTOS telenursing began as a new initiative in late 2001. The telenursing project aims to link ward nurses to CAPTOS and local community teams, and to provide both clinical consultancy on nursing and interdisciplinary issues and locally based professional development. Telenursing supports nurses via site visits, videoconferencing sessions, an interactive Website and sabbatical opportunities. Telehealth works with existing services to enhance the nursing care of young people with a complex mixture of psychological and physical health problems.