Clozapine for Management of Childhood and Adolescent-Onset Schizophrenia: A Systematic Review and Meta-Analysis

Clozapine for Management of Childhood and Adolescent-Onset Schizophrenia: A Systematic Review and Meta-Analysis

Adnan, M. Motiwala, F. Trivedi, C. Sultana, T. Mansuri, Z. Jain, S.
Journal of Child & Adolescent Psychopharmacology
Background Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term "childhood and adolescent-onset schizophrenia (CAOS)" for either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS. Methods We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the title, abstract, and full article review, 18 studies qualified (double-blind RCTs n = 4; OLS n = 4; observational studies n = 7; case reports n = 3). Results Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks) and long term (2-9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and hypersalivation were commonly reported (90%), constipation was next in frequency (13%-50%). Neutropenia was seen in 6%-15% of cases and agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8%-22%), treatment-onset diabetes was less frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen. Conclusions Limited studies indicate that clozapine is a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of CAOS.

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Type of intervention

Treatment and Child Welfare Interventions


Mental Health Problems and Disorders

Other Problems



Pharmacological Treatment


Age group

School Aged Children (6-12 years)

Adolescents (13-18 years)

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