Abstract

Treatment resistance to what is often deemed the last line of schizophrenia treatment, clozapine, is a burgeoning problem in psychiatric practice, with estimates of clozapine resistance standing at 40–70% of the treated population. This paper, a comprehensive review of available literature, looks at augmentation strategies to clozapine for such patients, with pharmacological and nonpharmacological modalities considered and reviewed. With a preponderance of open-label trials and case reports, our conclusion is that more research in this field via randomized clinical trials is crucial. Every case of clozapine resistance should be managed in an evidence-based and multidisciplinary manner, with augmentation only used once optimal dosage and duration of clozapine monotherapy is reached, and the psychosocial environment is optimized.

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