Clozapine for Severe Treatment-Resistant Disruptive Behaviors in Youth with Autism Spectrum Disorder: A Prospective Real-World Interventional Study.

From Early Diagnosis to Individualized Care in Children and Adolescents with Autism Spectrum Disorder: A Narrative Review

Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition characterized by deficits in social communication and the presence of restricted or repetitive behaviors and interests. Increasing prevalence rates underscore the importance of early identification and timely intervention. This review examines current and emerging diagnostic and management approaches to ASD. Standardized diagnostic frameworks, such as the DSM-5 criteria, remain central to clinical assessment. Recent advances in screening tools have enhanced early detection. Due to the heterogeneity of clinical presentations, individualized care is necessary. Management strategies commonly integrate behavioral and developmental interventions, educational support, family involvement, and, when appropriate, pharmacological treatment for associated symptoms. Functional outcomes are further improved by strategies, such as executive function training, occupational therapy, technology-assisted therapies, and caregiver-mediated programs. Research indicates that extensive family involvement and coordinated, interdisciplinary care lead to improved long-term outcomes. To maximise functioning, engagement, and quality of life, the existing literature generally supports a comprehensive, flexible, and person-centred approach that takes into account each person's unique needs and strengths.

[Focusing on profound autism: validity of clinical taxonomy and management of treatment-resistant symptoms].

This review systematically summarizes the conceptual definition and clinical phenotypes of profound autism and emphasizes the need to shift the intervention focus toward managing serious comorbidities and establishing augmentative and alternative communication systems.

Severe self-injury in a young girl with autism spectrum disorder and Helsmoortel-van der Aa syndrome responding to naltrexone.

Comparative efficacy of pharmacological, adjunctive, and non-pharmacological interventions across behavioral domains in children and adolescents with autism spectrum disorder: a network meta-analysis.

OBJECTIVE To systematically compare the efficacy of pharmacological, adjunctive, and non-pharmacological interventions across multiple behavioral domains in children and adolescents with autism spectrum disorder (ASD), including irritability, hyperactivity, social withdrawal, stereotypic behavior, and inappropriate speech. METHODS Following the 2020 PRISMA guidelines, five databases were searched from inception to March 2026 for randomized controlled trials (RCTs). A frequentist network meta-analysis was conducted to estimate the comparative efficacy and ranking probabilities of different interventions across behavioral domains (PROSPERO: CRD420261368925). RESULTS Sixty-seven RCTs (N = 4,203) were included. For irritability, structured exercise ranked highest (SUCRA = 88.0%; SMD = - 1.48, 95% CI -2.24 to - 0.73), followed by risperidone plus adjunctive anti-inflammatory agents (SUCRA = 72.9%) and neuromodulatory agents (SUCRA = 67.8%). For hyperactivity, pharmacological interventions were most effective, with other antipsychotic/ADHD medications ranking highest (SUCRA = 95.1%; SMD = - 1.85, 95% CI -2.50 to - 1.20), followed by structured exercise (SUCRA = 76.1%). Similarly, for stereotypic behavior, pharmacological treatments dominated, with other antipsychotic/ADHD medications achieving the best performance (SUCRA = 92.0%; SMD = - 1.10, 95% CI -1.67 to - 0.52). In contrast, for social withdrawal, structured exercise emerged as the most effective intervention (SUCRA = 98.9%; SMD = - 1.28, 95% CI -1.96 to - 0.60), followed by risperidone plus neuromodulatory agents (SUCRA = 75.3%). For inappropriate speech, structured exercise (SUCRA = 80.1%) and probiotics plus oxytocin (SUCRA = 76.4%) demonstrated the highest rankings, with structured exercise showing a significant effect (SMD = - 0.80, 95% CI -1.40 to - 0.19). CONCLUSION This study establishes a domain-specific treatment hierarchy for ASD, demonstrating that intervention effects vary substantially across behavioral domains. Pharmacological approaches are more effective for hyperactivity and stereotypic behaviors, whereas structured exercise shows superior benefits for irritability and social withdrawal. Combination strategies consistently rank highly across multiple domains, supporting the value of multimodal interventions. These findings underscore the importance of individualized, symptom-targeted, and mechanism-informed treatment strategies to optimize clinical outcomes in ASD.

Longitudinal course of sensory processing difficulties in pediatric obsessive–compulsive disorder: A preliminary naturalistic observational study

Abstract Aim Sensory processing difficulties (SPDs) are common in pediatric obsessive–compulsive disorder (OCD), but their longitudinal course remains undercharacterized. This retrospective naturalistic observational study examined 25 children and adolescents with OCD, including eight with comorbid autism spectrum disorder (ASD), who received specialist outpatient care in Japan. Analyses according to ASD status were exploratory. Methods The study was designed to characterize longitudinal changes in caregiver‐rated SPDs rather than to evaluate treatment efficacy. Baseline and follow‐up assessments included the Short Sensory Profile–Japanese version (SSP‐J), Children's Yale–Brown Obsessive Compulsive Scale, and Children's Global Assessment Scale. Results Caregiver‐rated SPDs decreased over time, with a significant main effect of time on SSP‐J scores (F(1, 23) = 5.66, p = 0.026, ηp2 = 0.197). SSP‐J scores were higher among participants with ASD across assessment points (F(1, 23) = 8.67, p = 0.007, ηp2 = 0.274), but the time × ASD interaction was not significant (F(1, 23) = 1.48, p = 0.236, ηp2 = 0.060). OCD severity decreased, and global functioning improved. Changes in SSP‐J scores were not significantly associated with changes in OCD severity or global functioning. Conclusion In this sample, caregiver‐rated SPDs decreased over time. Participants with ASD had higher SSP‐J scores across assessment points, but the nonsignificant time × ASD interaction did not provide evidence of differential longitudinal change; ASD‐related findings remain exploratory. Changes in SPDs were not significantly associated with changes in OCD severity or global functioning, and the clinical value of direct assessment of sensory difficulties requires further study.

Real-world ADHD pharmacological treatment patterns and their association with negative clinical outcomes in youth with comorbid autism: a Swedish population-based study

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) medications can reduce ADHD symptom severity in individuals with comorbid autism spectrum disorder (ASD). However, clinical guidance on pharmacological treatment of ADHD in this clinical population remains limited and inconsistent. Characterising real-world treatment patterns (ie, initiation timing, medication choices, switching, discontinuation) and the impact of alternative medication choices on clinical outcomes is critical for informing evidence-based management strategies. Objective To (1) characterise ADHD pharmacological treatment patterns in youth with ADHD+ASD versus ADHD alone and (2) assess whether using alternative ADHD medications versus methylphenidate is associated with differential changes in negative clinical outcomes among youth with ADHD+ASD. Methods This is a population-based cohort study using Swedish national registers. The study included children (<13 years) and adolescents (13–17 years) with an incident ADHD diagnosis between 2007 and 2018 and followed-up until 2021, comparing youth with co-occurring ASD (n=24 117) and ADHD alone (n=79 830). Descriptive outcomes included time to pharmacological treatment initiation, medication type, number of medication switches and discontinuations. The primary outcome was changes in rates of inpatient psychiatric hospitalisations, accidental injuries and specialist care visits for substance use, depressive or anxiety disorders in the 1 year after versus the 1 year before medication initiation. Findings Individuals with ADHD+ASD experienced longer delays to treatment initiation (12–14% initiated >12 months after diagnosis vs 7–8% in ADHD alone). Children with ADHD+ASD were slightly more likely to discontinue treatment within 3 months (16% vs 12%) and had the highest average number of medication switches within 3 years (2.6; IQR 0.0–2.0). In within-individual analyses, comparisons of alternative ADHD medications versus methylphenidate did not yield statistically significant differences after correcting for multiple comparisons. Conclusions Children with ADHD+ASD experienced longer delays to treatment initiation and more frequent medication switching compared with those with ADHD only. The effects of alternative ADHD medication options on key negative clinical outcomes appeared similar to those of methylphenidate. Clinical implications These findings suggest that, rather than recommending fixed first-line and second-line treatments for individuals with ADHD-ASD, clinical guidelines should emphasise appropriate training as well as prompt and individualised treatment based on a shared decision-making process.