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Treatment-Resistant Schizophrenia

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Psychotic Disorders

Part of the book series: Current Clinical Psychiatry ((CCPSY))

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Abstract

A significant minority of patients (about one quarter to one third) will have a poor response to first-line antipsychotics and be considered treatment-resistant. In this chapter, I outline a sequential approach to treatment-resistant schizophrenia. An important first step is to rule out “pseudo-refractoriness,” most commonly due to insufficient adherence. Therapeutic drug monitoring and a long-acting injectable trial are key tools to correctly establishing treatment resistance. The gold standard for treatment resistance is clozapine, and every treatment-resistant patient deserves a time-limited trial of clozapine in order to determine if he or she is a good clozapine responder. The chapter concludes with a discussion of clozapine augmentation and non-pharmacological interventions for patients who remain ill despite clozapine.

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Additional Resources

    Book

    • Buckley PF, Gaughran F, editors. Treatment-refractory schizophrenia : a clinical conundrum. Heidelberg: Springer; 2014. – A whole book about TRS, with international authors from Australia, Europe, and the Americas.

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    Articles

    • Kane J, Honigfeld G, Singer J, Meltzer H. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry. 1988;45:789–96. – Read this one, as it is one of only a handful of truly seminal articles on the treatment of schizophrenia. Note the excellent clinical trials methodology, with a prospective treatment period to establish non-response.

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    • Kane JM, Agid O, Baldwin ML, Howes O, Lindenmayer JP, Marder S, et al. Clinical guidance on the identification and management of treatment-resistant schizophrenia. J Clin Psychiatry. 2019;80:pii: 18com12123. – Excellent review of treatment-resistant schizophrenia by John Kane who conducted the Kane trial over 20 years ago (see above).

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    • Sisti DA, Segal AG, Emanuel EJ. Improving long-term psychiatric care: bring back the asylum. JAMA. 2015;313:243–4. – An important viewpoint that argues for the ethical imperative to provide the whole continuum of psychiatric care, including caring for those with serious illness that have been hurt the most from deinstitutionalization (or rather, transinstitutionalization). While the title is provocative, the authors do not argue for a return to the state of hospitals of late but simply to provide humane and safe spaces for those who cannot help themselves.

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    Authors and Affiliations

    1. Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

      Oliver Freudenreich

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    1. Oliver Freudenreich
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    Freudenreich, O. (2020). Treatment-Resistant Schizophrenia. In: Psychotic Disorders. Current Clinical Psychiatry. Humana, Cham. https://doi.org/10.1007/978-3-030-29450-2_12

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    • DOI: https://doi.org/10.1007/978-3-030-29450-2_12

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    • Publisher Name: Humana, Cham

    • Print ISBN: 978-3-030-29449-6

    • Online ISBN: 978-3-030-29450-2

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