MANAGEMENT OF TREATMENT-RESISTANT SCHIZOPHRENIA: CURRENT EVIDENCE AND CLINICAL PERSPECTIVES

Abstract

This study aimed to analyze and critically synthesize the available evidence in the literature regarding the management of treatment-resistant schizophrenia, with emphasis on pharmacological and non-pharmacological strategies, challenges related to clozapine resistance, and emerging perspectives for clinical practice. This is a narrative literature review with a descriptive and analytical approach, conducted through a search of the PubMed/MEDLINE database using descriptors related to treatment-resistant schizophrenia, clozapine, therapeutic resistance, and management strategies. Studies published in English, without time restriction, were included, prioritizing systematic reviews, meta-analyses, randomized controlled trials, consensus statements, and clinical guidelines. The results showed that treatment-resistant schizophrenia affects approximately 20% to 30% of patients and is associated with greater clinical severity and worse functional prognosis. Clozapine remains the treatment of choice; however, a significant proportion of patients show resistance to its use, requiring additional strategies such as treatment optimization, pharmacological combinations, psychosocial interventions, and electroconvulsive therapy. Furthermore, advances in biomarkers and predictive tools point toward more individualized approaches in the future. It is concluded that the management of treatment-resistant schizophrenia requires an integrated, evidence-based approach, with a need for further research to improve the effectiveness and personalization of care.