Even though clozapine is the only drug with evidence-based efficacy in schizophrenia symptoms not responding to other agents, it is still under-prescribed in most countries around the world. The barriers for initiating clozapine are evident in both clinicians and patients. Prescribers mainly report delaying clozapine because of fear of severe side effects and lack of knowledge regarding management of side effects driven by stigmatic rather evidence-based views. Patients report reservations toward the need for safety regulation and blood tests.Enduring psychotic illness is often associated with high level of burden of symptoms, which does not allow progress into recovery process in the community. It is often the case that treatment with clozapine has a dramatic effect on symptoms, otherwise refractory. However, there cases in which there is only minor or no effect of the drug. In these cases, sometimes referred to as ultra-resistant schizophrenia, it is advised to optimise clozapine treatment using pharmacokinetic considerations and confirm sufficient clozapine serum levels using therapeutic drug monitoring. Further steps include precise diagnosis and management of other physical or psychiatric comorbidities, offering targeted psychotherapy such as CBT and family interventions and eventually to wait, as sometimes there are cases of late response.In this book we aimed at providing clinicians with practical, up-do-date knowledge to support their decision-making and safety management when prescribing clozapine. It is our hope that using the information in this book would encourage both prescribers and patients to consider clozapine treatment when it is needed, in a timely fashion. We believe that accurate and systematic information is a key for reducing anxiety and relieving stigma associated with clozapine treatment.

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