# Managing Symptoms in Adolescent-Onset Schizophrenia: A Narrative Review of Therapeutic Interventions

## TL;DR

This review explores treatments for adolescent-onset schizophrenia, emphasizing drug and therapy combinations for better outcomes.

## Contribution

The paper provides a narrative review of therapeutic interventions specifically for adolescent-onset schizophrenia.

## Key findings

- Aripiprazole and brexpiprazole are well-tolerated first-line treatments for positive symptoms in AOS.
- Clozapine is most effective for treatment-resistant AOS, though with higher metabolic risks.
- CBT and MET improve adherence and functional recovery when combined with medication.

## Abstract

Adolescent-onset schizophrenia (AOS; onset between ages 13 and 18) represents a rare but severe subtype of schizophrenia that disrupts crucial neurodevelopmental and psychosocial milestones. Marked by prominent cognitive deficits, negative symptoms, and poor long-term outcomes, AOS poses unique diagnostic and therapeutic challenges distinct from adult-onset cases. A comprehensive search of PubMed/MEDLINE (January 2003–February 2025) and reference lists of prior reviews identified twenty-four primary studies addressing pharmacological, psychosocial, and neurobiological aspects of AOS. Synthesis of this evidence highlights atypical antipsychotics such as aripiprazole and brexpiprazole as well-tolerated first-line options for positive symptom reduction, while clozapine remains the most effective treatment for resistant AOS. High-dose olanzapine offers comparable efficacy but carries greater metabolic risk. Psychosocial approaches—including cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET)—enhance adherence, insight, and functional recovery when integrated with pharmacotherapy. Converging neuroimaging and biomarker data reveal persistent neuroinflammatory and glutamatergic dysregulation, characterized by elevated interleukin-6 (IL-6), C-C motif chemokine ligand 11 (CCL11), and dorsomedial prefrontal hypoglutamatergia, suggesting immune-mediated and developmental mechanisms underlying symptom persistence. Emerging research on neuromodulation and N-methyl-D-aspartate (NMDA)-targeted strategies further broadens the therapeutic landscape. Collectively, these findings highlight the importance of early, developmentally informed, and multidisciplinary interventions tailored to adolescents. Strengthening longitudinal, biomarker-guided, and neuromodulation-inclusive studies will be critical for refining precision treatment models and informing future clinical and policy frameworks for adolescent psychosis care.