Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

doi:10.1002/npr2.12218

. 2022 Mar;42(1):3-9.

doi: 10.1002/npr2.12218. Epub 2021 Dec 2.

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

Norio Yasui-Furukori¹, Hiroyuki Muraoka², Naomi Hasegawa³, Shinichiro Ochi⁴, Shusuke Numata⁵, Hikaru Hori⁶, Akitoyo Hishimoto⁷, Toshiaki Onitsuka⁸, Kazutaka Ohi⁹, Naoki Hashimoto¹⁰, Tatsuya Nagasawa¹¹, Yoshikazu Takaesu¹², Takahiko Inagaki¹³, Hiromi Tagata¹⁴, Takashi Tsuboi¹⁵, Chika Kubota¹⁶, Ryuji Furihata¹⁷, Jun-Ichi Iga⁴, Hitoshi Iida⁵, Kenichiro Miura³, Junya Matsumoto³, Hisashi Yamada¹⁸, Koichiro Watanabe¹⁵, Ken Inada², Kazutaka Shimoda¹, Ryota Hashimoto³

Affiliations

¹ Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan.
² Department of Psychiatry, Tokyo Women's Medical University, Tokyo, Japan.
³ Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁴ Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
⁵ Department of Psychiatry, Graduate School of Biomedical Science, Tokushima University, Tokushima, Japan.
⁶ Department of Psychiatry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁷ Department of Psychiatry, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
⁸ Department of Neuroimaging Psychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁹ Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan.
¹⁰ Department of Psychiatry, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
¹¹ Department of Neuro-Psychiatry, Kanazawa Medical University, Kanazawa, Japan.
¹² Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
¹³ Adolescent Mental Health Service, Biwako Hospital, Shiga, Japan.
¹⁴ Department of Neuropsychiatry, Toho University Graduate School of Medicine, Tokyo, Japan.
¹⁵ Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.
¹⁶ National Center of Neurology and Psychiatry Hospital, Tokyo, Japan.
¹⁷ Kyoto University Health Services, Kyoto, Japan.
¹⁸ Department of Neuropsychiatry, Hyogo College of Medicine, Hyogo, Japan.

PMID: 34854260
PMCID: PMC8919118
DOI: 10.1002/npr2.12218

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

Norio Yasui-Furukori et al. Neuropsychopharmacol Rep. 2022 Mar.

. 2022 Mar;42(1):3-9.

doi: 10.1002/npr2.12218. Epub 2021 Dec 2.

Authors

Affiliations

¹ Department of Psychiatry, Dokkyo Medical University School of Medicine, Tochigi, Japan.
² Department of Psychiatry, Tokyo Women's Medical University, Tokyo, Japan.
³ Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
⁴ Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Ehime, Japan.
⁵ Department of Psychiatry, Graduate School of Biomedical Science, Tokushima University, Tokushima, Japan.
⁶ Department of Psychiatry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
⁷ Department of Psychiatry, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
⁸ Department of Neuroimaging Psychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁹ Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan.
¹⁰ Department of Psychiatry, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.
¹¹ Department of Neuro-Psychiatry, Kanazawa Medical University, Kanazawa, Japan.
¹² Department of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
¹³ Adolescent Mental Health Service, Biwako Hospital, Shiga, Japan.
¹⁴ Department of Neuropsychiatry, Toho University Graduate School of Medicine, Tokyo, Japan.
¹⁵ Department of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.
¹⁶ National Center of Neurology and Psychiatry Hospital, Tokyo, Japan.
¹⁷ Kyoto University Health Services, Kyoto, Japan.
¹⁸ Department of Neuropsychiatry, Hyogo College of Medicine, Hyogo, Japan.

PMID: 34854260
PMCID: PMC8919118
DOI: 10.1002/npr2.12218

Abstract

Background: The decision to initiate clozapine treatment should be made on an individual basis and may be closely related to the early detection of treatment-resistant schizophrenia (TRS), although there is evidence that the early use of clozapine results in a better response to treatment. Therefore, we investigated the relationship between the examination rate of TRS and the prescription rate of clozapine.

Methods: After attending a 1-day educational program on schizophrenia based on the "Guidelines for the Pharmacological Treatment of Schizophrenia," we asked the participating facilities to submit records of whether or not TRS was evaluated for each patient. We calculated the clozapine prescription rate from the schizophrenic patients prescribed clozapine and all of the schizophrenic patients. Forty-nine facilities in 2017 were included in the study.

Results: There were dichotomous distributions in the examination rate of TRS and a non-normal distribution in the prescription rate of clozapine. There was a significant correlation between the prescription rate of clozapine and the examination rate of TRS (r _s = 0.531, P = 1.032 × 10^-4 ). A significant difference was found in the prescription rate of clozapine between the three groups of facilities according to the examination rate of TRS.

Conclusion: As a preliminary problem for the use of clozapine, in Japan, the examination rate of TRS varies, and there are many facilities that typically do not consider the possibility of TRS; this trend leads to a low rate of clozapine use. Clearly, further clinician training is needed for the early detection and appropriate management of TRS that includes an explanation of TRS and how to introduce clozapine therapy to patients and their families.

Keywords: clozapine; examination rate; prescription rate; treatment-resistant schizophrenia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**FIGURE 1**
Proportion of patients with schizophrenia who had examinations for treatment‐resistant schizophrenia in 49 facilities. This figure shows that the distribution is dichotomous

**FIGURE 3**
Clozapine prescription rates among the 3 facility groups, classified based on treatment‐resistant schizophrenia examination rates. This box‐and‐whisker plot shows the distribution of clozapine prescription rates. The centerline of the box shows the median, and the top and bottom sides of the box show the quartile ranges. Error bars indicate the maximum and minimum values. Outliers are plotted as points because the beard length only extends to 1.5 times the quartile range

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References

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1. Barch DM, Bustillo J, Gaebel W, Gur R, Heckers S, Malaspina D, et al. Logic and justification for dimensional assessment of symptoms and related clinical phenomena in psychosis: relevance to DSM‐5. Schizophr Res. 2013;150:15–20. - PubMed
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1. Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJM, Birnbaum ML, et al. Treatment‐resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174:216–29. - PMC - PubMed

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[1] Wyatt RJ, Alexander RC, Egan MF, Kirch DG. Schizophrenia, just the facts. What do we know, how well do we know it? Schizophr Res. 1988;1:3–18. - PubMed

[2] Wyatt RJ, Alexander RC, Egan MF, Kirch DG. Schizophrenia, just the facts. What do we know, how well do we know it? Schizophr Res. 1988;1:3–18. - PubMed

[3] Barch DM, Bustillo J, Gaebel W, Gur R, Heckers S, Malaspina D, et al. Logic and justification for dimensional assessment of symptoms and related clinical phenomena in psychosis: relevance to DSM‐5. Schizophr Res. 2013;150:15–20. - PubMed

[4] Barch DM, Bustillo J, Gaebel W, Gur R, Heckers S, Malaspina D, et al. Logic and justification for dimensional assessment of symptoms and related clinical phenomena in psychosis: relevance to DSM‐5. Schizophr Res. 2013;150:15–20. - PubMed

[5] Gaebel W, Weinmann S, Sartorius N, Rutz W, McIntyre JS. Schizophrenia practice guidelines: international survey and comparison. Br J Psychiatry. 2005;187:248–55. - PubMed

[6] Gaebel W, Weinmann S, Sartorius N, Rutz W, McIntyre JS. Schizophrenia practice guidelines: international survey and comparison. Br J Psychiatry. 2005;187:248–55. - PubMed

[7] Remington G, Addington D, Honer W, Ismail Z, Raedler T, Teehan M. Guidelines for the pharmacotherapy of schizophrenia in adults. Can J Psychiatry. 2017;62:604–16. - PMC - PubMed

[8] Remington G, Addington D, Honer W, Ismail Z, Raedler T, Teehan M. Guidelines for the pharmacotherapy of schizophrenia in adults. Can J Psychiatry. 2017;62:604–16. - PMC - PubMed

[9] Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJM, Birnbaum ML, et al. Treatment‐resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174:216–29. - PMC - PubMed

[10] Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJM, Birnbaum ML, et al. Treatment‐resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. Am J Psychiatry. 2017;174:216–29. - PMC - PubMed

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Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

Affiliations

Association between the examination rate of treatment-resistant schizophrenia and the clozapine prescription rate in a nationwide dissemination and implementation study

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Abstract

Conflict of interest statement

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