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Clinical Utility and Safety of Slower-than-Recommended Titration of Clozapine for Treatment-Resistant Schizophrenia: a Retrospective Cohort Study

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Abstract

Slow titration of clozapine is recommended given the risk of serious adverse effects. However, the utility and safety of slower-than-recommended titration of clozapine remain unclear. Consequently, we aimed to investigate the clinical utility and safety of slower-than-recommended titration of clozapine for treatment-resistant schizophrenia. We conducted a retrospective chart review of 152 inpatients with treatment-resistant schizophrenia who had been newly started on clozapine in a tertiary psychiatric public hospital between April 2012 and March 2018. The primary outcome was clozapine continuation for the first 18 weeks. We performed multivariate logistic regression to identify the association between the rate of clozapine dose titration and clozapine continuation for the first 18 weeks. Among the 152 inpatients, 122 (80%) could continue clozapine for the first 18 weeks. There was no significant association between the rate of clozapine dose titration and clozapine continuation for the first 18 weeks (adjusted odds ratio 1.23; 95% CI 0.29–5.26; p = 0.78). Our findings indicate that slower-than-recommended titration of clozapine may not improve toward clozapine continuation for the first 18 weeks. Therefore, it may not be a beneficial option in terms of safe clozapine continuation when starting clozapine for treatment-resistant schizophrenia.

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Availability of Data and Material

The datasets acquired and analyzed in this study are not publicly available because the Institutional Review Board of the Okayama Psychiatric Medical Center has not approved it.

Abbreviations

BMI:

Body mass index

TRS:

Treatment-resistant schizophrenia

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Acknowledgements

The authors are very grateful to Mr. Kohei Kitagawa for his significant help with data collection. The authors also thank the physicians and medical staff at the Okayama Psychiatric Medical Center for facilitating data collection.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Psychiatry, Okayama Psychiatric Medical Center, 3-16 Shikatahon-machi, Kita-ku, Okayama, 700-0915, Japan

    Masaru Tsukahara, Ryuhei So, Yuji Yada, Masafumi Kodama & Yoshiki Kishi

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  1. Masaru Tsukahara
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  2. Ryuhei So
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  3. Yuji Yada
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  4. Masafumi Kodama
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  5. Yoshiki Kishi
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Contributions

MT and RS contributed in concept and designing of this study. MT, RS and YY collected the data. MT and RS performed the statistical analysis. MT and RS drafted the manuscript. All authors contributed in interpretation of the results. All authors read and approved the content of the manuscript.

Corresponding author

Correspondence to Ryuhei So.

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Conflict of Interest

RS has received personal fees from Igaku-shoin Co., Ltd., Kagaku- hyoronsha Co., Ltd., Medical Review Co., Ltd., Otsuka Pharmaceutical Co., Ltd., and CureApp Inc. outside the submitted work. YY has received honoraria for his participation as a speaker at educational events sponsored by Novartis and Dainippon Sumitomo. YK has received personal fees from Otsuka Pharmaceutical Co., Ltd., and Janssen Pharmaceutical K.K., outside the submitted work. MT and MK declared no conflict of interest.

Ethics Approval

This study protocol was approved by the Institutional Review Board of the Okayama Psychiatric Medical Center, which also permitted the inclusion of participants who did not actively reject the use their data in this study.

Consent to Participate

This study protocol was approved by the Institutional Review Board of the Okayama Psychiatric Medical Center, which also permitted the inclusion of participants who did not actively reject the use their data in this study.

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Not applicable.

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Tsukahara, M., So, R., Yada, Y. et al. Clinical Utility and Safety of Slower-than-Recommended Titration of Clozapine for Treatment-Resistant Schizophrenia: a Retrospective Cohort Study. Psychiatr Q 92, 703–713 (2021). https://doi.org/10.1007/s11126-020-09841-3

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  • DOI: https://doi.org/10.1007/s11126-020-09841-3

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