Chakrabarti S. Clozapine resistant schizophrenia: Newer avenues of management. World J Psychiatr 2021; 11(8): 429-448 [PMID: 34513606 DOI: 10.5498/wjp.v11.i8.429]
Corresponding Author of This Article
Subho Chakrabarti, MD, Professor, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India. subhochd@yahoo.com
Research Domain of This Article
Psychiatry
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Psychiatr. Aug 19, 2021; 11(8): 429-448 Published online Aug 19, 2021. doi: 10.5498/wjp.v11.i8.429
Clozapine resistant schizophrenia: Newer avenues of management
Subho Chakrabarti
Subho Chakrabarti, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
Author contributions: Chakrabarti S is the sole author of this manuscript.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Subho Chakrabarti, MD, Professor, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh 160012, India. subhochd@yahoo.com
Received: February 23, 2021 Peer-review started: February 24, 2021 First decision: March 30, 2021 Revised: April 12, 2021 Accepted: July 13, 2021 Article in press: July 13, 2021 Published online: August 19, 2021
Abstract
About 40%-70% of the patients with treatment-resistant schizophrenia have a poor response to adequate treatment with clozapine. The impact of clozapine-resistant schizophrenia (CRS) is even greater than that of treatment resistance in terms of severe and persistent symptoms, relapses and hospitalizations, poorer quality of life, and healthcare costs. Such serious consequences often compel clinicians to try different augmentation strategies to enhance the inadequate clozapine response in CRS. Unfortunately, a large body of evidence has shown that antipsychotics, antidepressants, mood stabilizers, electroconvulsive therapy, and cognitive-behavioural therapy are mostly ineffective in augmenting clozapine response. When beneficial effects of augmentation have been found, they are usually small and of doubtful clinical significance or based on low-quality evidence. Therefore, newer treatment approaches that go beyond the evidence are needed. The options proposed include developing a clinical consensus about the augmentation strategies that are most likely to be effective and using them sequentially in patients with CRS. Secondly, newer approaches such as augmentation with long-acting antipsychotic injections or multi-component psychosocial interventions could be considered. Lastly, perhaps the most effective way to deal with CRS would be to optimize clozapine treatment, which might prevent clozapine resistance from developing. Personalized dosing, adequate treatment durations, management of side effects and non-adherence, collaboration with patients and caregivers, and addressing clinician barriers to clozapine use are the principal ways of ensuring optimal clozapine treatment. At present, these three options could the best way to manage CRS until research provides more firm directions about the effective options for augmenting clozapine response.
Core Tip: About 40%-70% of patients develop clozapine-resistant schizophrenia, which has serious health, economic, and social consequences. Research on clozapine-resistant schizophrenia has provided little support for the efficacy of psychotropics, electroconvulsive therapy, and cognitive-behavioural therapy in augmenting clozapine non-response. Therefore, newer approaches are needed including a clinical consensus about using the most effective of the currently available augmentation strategies. Augmentation with long-acting antipsychotic injections or multi-component psychosocial interventions could also be tried. Finally, the best option at present may be to prevent clozapine resistance from developing by optimizing clozapine treatment and collaborating with patients and caregivers to ensure its continuation.
