Pharmacological and non-pharmacological interventions for irritability in autism spectrum disorder: a systematic review and meta-analysis with the GRADE assessment.

BACKGROUND: Numerous interventions for irritability in autism spectrum disorder (ASD) have been investigated. We aimed to appraise the magnitude of pharmacological and non-pharmacological interventions for irritability in ASD without any restrictions in terms of eligible interventions. METHODS: We systematically searched PubMed/MEDLINE, Scopus, and Web of Science until April 15, 2023. We included randomized controlled trials (RCTs) with a parallel design that examined the efficacy of interventions for the treatment of irritability in patients of any age with ASD without any restrictions in terms of eligible interventions. We performed a random-effects meta-analysis by pooling effect sizes as Hedges' g. We classified assessed interventions as follows: pharmacological monotherapy, risperidone plus adjuvant therapy versus risperidone monotherapy, non-pharmacological intervention, and dietary intervention. We utilized the Cochrane tool to evaluate the risk of bias in each study and the GRADE approach to assess the certainty of evidence for each meta-analyzed intervention. RESULTS: Out of 5640 references, we identified 60 eligible articles with 45 different kinds of interventions, including 3531 participants, of which 80.9% were males (mean age [SD] = 8.79 [3.85]). For pharmacological monotherapy, risperidone (Hedges' g - 0.857, 95% CI - 1.263 to - 0.451, certainty of evidence: high) and aripiprazole (Hedges' g - 0.559, 95% CI - 0.767 to - 0.351, certainty of evidence: high) outperformed placebo. Among the non-pharmacological interventions, parent training (Hedges' g - 0.893, 95% CI - 1.184 to - 0.602, certainty of evidence: moderate) showed a significant result. None of the meta-analyzed interventions yielded significant effects among risperidone + adjuvant therapy and dietary supplementation. However, several novel molecules in augmentation to risperidone outperformed risperidone monotherapy, yet from one RCT each. LIMITATIONS: First, various tools have been utilized to measure the irritability in ASD, which may contribute to the heterogeneity of the outcomes. Second, meta-analyses for each intervention included only a small number of studies and participants. CONCLUSIONS: Only risperidone, aripiprazole among pharmacological interventions, and parent training among non-pharmacological interventions can be recommended for irritability in ASD. As an augmentation to risperidone, several novel treatments show promising effects, but further RCTs are needed to replicate findings. Trial registration PROSPERO, CRD42021243965.

Incidence, prevalence, and global burden of autism spectrum disorder from 1990 to 2019 across 204 countries.

Autism spectrum disorder (ASD) substantially contributes to the burden of mental disorders. Improved awareness and changes in diagnostic criteria of ASD may have influenced the diagnostic rates of ASD. However, while data on trends in diagnostic rates in some individual countries have been published, updated estimates of diagnostic rate trends and ASD-related disability at the global level are lacking. Here, we used the Global Burden of Diseases, Injuries, and Risk Factors Study data to address this gap, focusing on changes in prevalence, incidence, and disability-adjusted life years (DALYs) of ASD across the world. From 1990 to 2019, overall age-standardized estimates remained stable globally. Both prevalence and DALYs increased in countries with high socio-demographic index (SDI). However, the age-standardized incidence decreased in some low SDI countries, indicating a need to improve awareness. The male/female ratio decreased between 1990 and 2019, possibly accounted for by increasing clinical attention to ASD in females. Our results suggest that ASD detection in low SDI countries is suboptimal, and that ASD prevention/treatment in countries with high SDI should be improved, considering the increasing prevalence of the disorder. Additionally, growing attention is being paid to ASD diagnosis in females, who might have been left behind by ASD epidemiologic and clinical research previously. ASD burden estimates are underestimated as GBD does not account for mortality in ASD.

Population-Based Epidemiology of Pediatric Patients with Treated Tic Disorders from Real-World Evidence in Korea.

Objectives: Although tic disorder (TD) is a common mental disorder in children and adolescents, epidemiological data based on real-world evidence (RWE) are insufficient. Using RWE, this study sought to examine the prevalence of treated TD, use of medical utilization, and use of prescription drugs among patients with TD with respect to TD type and comorbid psychiatric illness. Methods: We performed a retrospective cross-sectional study. Using the Korean Health Insurance Review and Assessment Service Pediatric Patient Sample data from 2009 to 2016, we analyzed 20,599 patients with TD (Korean Standard Classification of Diseases-6/7 code: F95.x) aged 2-19 years. Results: The annual average TD prevalence was 2.6/1000 population (95% confidence interval, 2.3-2.8/1000). Between 2009 and 2016, a slight increase in TD prevalence was observed from 1.9 to 2.9/1000 population. The TD prevalence rate in male patients was four times higher than that in female patients. Differences were observed in health care utilization and drug prescription types between patients with Tourette syndrome and chronic or transient TD. In addition, more than half of patients with TD had comorbid psychiatric disorders, and one-third of patients with TD had attention-deficit/hyperactivity disorder (ADHD). Patients with TD without comorbidities were frequently prescribed aripiprazole, while patients with TD and comorbid ADHD were frequently prescribed atomoxetine, methylphenidate, risperidone, and aripiprazole. Conclusion: This study described the epidemiological characteristics of TD based on recent RWE from Korea, and its findings can help establish future TD evidence-based clinical guidelines and related policies.

Cross-Cultural Aspect of Behavior Assessment System for Children-2, Parent Rating Scale-Child: Standardization in Korean Children.

PURPOSE: Our study aimed to examine psychometric properties and cross-cultural utility of the Behavior Assessment System for Children-2, Parent Rating Scale-Child (BASC-2 PRS-C) in Korean children. MATERIALS AND METHODS: Two study populations were recruited: a general population sample (n=2115) of 1st to 6th graders from 16 elementary schools and a clinical population (n=219) of 6-12 years old from 5 child psychiatric clinics and an epidemiological sample of autism spectrum disorder. We assessed the validity and reliability of the Korean version of BASC-2 PRS-C (K-BASC-2 PRS-C) and compared subscales with those used for US populations. RESULTS: Our results indicate that the K-BASC-2 PRS-C is a valuable instrument with reliability and validity for measuring developmental psychopathology that is comparable to those in Western population. However, there were some differences noted in the mean scores of BASC-2 PRS-C between Korean and US populations. CONCLUSION: K-BASC-2 PRS-C is an effective and useful instrument with psychometric properties that permits measurement of general developmental psychopathology. Observed Korean-US differences in patterns of parental reports of children's behaviors indicate the importance of the validation, standardization and cultural adaptation for tools assessing psychopathology especially when used in populations different from those for which the instrument was originally created.