Clozapine treatment in adolescents with schizophrenia and autism spectrum disorder: Comparative clinical profiles and treatment outcomes from a retrospective study

Abstract

Objective:

Clozapine is a gold-standard antipsychotic for treatment-resistant schizophrenia, increasingly used off-label for severe autism spectrum disorder (ASD) with irritability or disruptive behaviors. This study evaluated clozapine’s efficacy and tolerability in children and adolescents with ASD or schizophrenia spectrum disorders (SSDs).

Methods:

A retrospective review of 26 inpatients (ASD: n = 8; SSD: n = 18) treated with clozapine included demographics, dosing, and hospitalization data. Symptom severity was assessed with the Clinical Global Impression-Severity Scale (CGI-S), Scale for the Assessment of Negative Symptoms (SANSs), Scale for the Assessment of Positive Symptoms (SAPSs), and Aberrant Behavior Checklist (ABC). Side effects were evaluated with the Ugvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. Hematological parameters—white blood cells, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR)—were compared pre-treatment and at 6 months.

Results:

Of the 26 patients, 50% had early-onset schizophrenia, 30.8% had ASD, and 19.2% had schizoaffective disorder. Clozapine was initiated at a mean age of 15.8 years, with a mean dose of 284.6 mg/day. Both SSD (p < 0.001) and ASD (p = 0.01) groups showed significant CGI improvement. SANS and SAPS improved in SSD (p = 0.001, p < 0.001); ABC improved in ASD (p = 0.012). UKU scores decreased in SSD (p < 0.001) and trended downward in ASD (p = 0.38). Hypersalivation (61.5%), increased appetite (53.8%), and sedation (34.6%) were common; no discontinuations occurred. Neutrophils increased (p = 0.007), and lymphocytes decreased (p = 0.037), with significant NLR elevation in SSD (p = 0.006).

Conclusion:

Clozapine demonstrated strong efficacy and improved tolerability, reducing side effects compared to prior polypharmacy in refractory pediatric ASD and SSD.