Clozapine for Severe Irritability in Children and Adolescents With Autism Spectrum Disorder: A Retrospective Case Series and Brief Literature Review.

BACKGROUND

Severe irritability in children and adolescents with autism spectrum disorder (ASD), including aggression toward others, self-injury, and object destruction, is a significant source of distress for individuals and may persist despite behavioral and psychosocial interventions. Although treatment with FDA-approved antipsychotics such as risperidone and aripiprazole is available, clozapine has been considered a potential option for the refractory cases. This study retrospectively examined the clinical response, tolerability, and safety of clozapine in children and adolescents with ASD and severe treatment-resistant irritability.

METHODS

This retrospective case series included 13 patients under 18 years old with ASD who were treated with clozapine for irritability at a tertiary child and adolescent psychiatry department. Clinical outcomes were assessed using the Clinical Global Impression (CGI) scales, alongside documented emergency visits, hospitalizations, and adverse events.

FINDINGS: The mean age at clozapine initiation was 12.6 ± 3.1 years, and 12 patients were male. The most common psychiatric comorbidity in our sample was attention-deficit/hyperactivity disorder (ADHD; n = 6), while 7 patients had comorbid intellectual disability. The mean clozapine dose was 138.4 ± 62.8 mg/d. At the last available follow-up, 8 patients were classified as treatment responders based on CGI-I ratings (CGI-I = 1 or 2), while 5 patients were classified as nonresponders (CGI-I ≥ 3). Sialorrhea, sedation, and increased appetite were the most frequent adverse events; one patient developed transient neutropenia.

CONCLUSIONS

Clozapine may be an effective and generally well-tolerated option for children and adolescents with ASD and severe treatment-resistant irritability.