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Real-world and clinical trial data support that clozapine is the only effective antipsychotic for treatment resistant schizophrenia and other severe mental illnesses. Clozapine also reduces rates of suicidality, psychiatric hospitalization and all-cause mortality. However, clozapine is underutilized for two reasons: misunderstandings of its efficacy benefits and misapprehension of, limited knowledge or misinformation about the management of treatment related risks and adverse effects. In response to worldwide efforts to promote clozapine use, this user-friendly Handbook provides clinicians with evidence-based approaches for patient management, as well as logical approaches to the management of clinical situations and adverse effects. It outlines clearly the rationale for specific management decisions and prioritises the options based on this logic. This Handbook is designed for use by clinicians worldwide and is essential reading for all mental health care professionals.