A Guideline Review on Treatment-Resistant Schizophrenia: A Focus on Clozapine and other Pharmacotherapeutic Strategies

Background: Treatment-Resistant Schizophrenia (TRS) represents a significant challenge in mental health provision. Although underused in clinical practice, clozapine remains the treatment of first choice for TRS. This review aims at reviewing clozapine and other treatment options for TRS as recommended in the most recent schizophrenia Clinical Practice Guidelines (CPGs). Methods: A literature search for CPGs was undertaken in four electronic databases, using the terms: ‘schizophrenia’, ‘clozapine’ and ‘guidelines’. Results: Seven schizophrenia CPGs published by national or professional institutions were identified from the period of 2010-2020. The CPGs varied in the scope of the information provided about clozapine’s role in the management of schizophrenia. However, they provided strong supporting evidence on its efficacy in the management of TRS. Main differences in recommendations provided in the schizophrenia CPGs were in relation to the definition of TRS, on the management of patients with TRS who do not respond to clozapine treatment, and on the breath of information in relation to clozapine’s safety profile and monitoring recommendations. Conclusions and Recommendations: Future iteration of schizophrenia CPGs should address these important gaps in information, including strategies to support the safe use of clozapine to decrease treatment delays and reluctance in the use of this effective medication.