Next Article in Journal
Motor Imagery for Post-Stroke Upper Limb Recovery: A Meta-Analysis of RCTs on Fugl-Meyer Upper Extremity Scores
Next Article in Special Issue
Immersive, Open-World Virtual Reality for Dementia Care: NeuroVRX Pilot Study
Previous Article in Journal
Bone-Preserving Robotic Conversion of Medial UKA to TKA: A Step-by-Step Technique
Previous Article in Special Issue
Bridging Dementia Care in Japan: The Emerging Role of General Medicine Physicians
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JCM
Volume 14
Issue 21
10.3390/jcm14217892
jcm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia

by
Tatsuo Nakahara
1,
Yukiko Harada
1,
Naho Nakayama
1,
Kijiro Hashimoto
1,
Naoya Kida
2,
Toshiaki Onitsuka
3,
Hiroo Noda
4,
Kenji Murasugi
5,
Yoshihiro Takimoto
6,
Wataru Omori
7,
Tsuruhei Sukegawa
8,
Jun Shiraishi
9,
Kouji Tanaka
10,
Hitoshi Maesato
2,11 and
Takefumi Ueno
1,*
1
National Hospital Organization, Hizen Psychiatric Center, Saga 842-0192, Japan
2
National Hospital Organization, Ryukyu Hospital, Okinawa 904-1201, Japan
3
National Hospital Organization, Sakakibara Hospital, Mie 514-1292, Japan
4
National Hospital Organization, Saigata Medical Center, Niigata 949-3193, Japan
5
National Hospital Organization, Komoro Kogen Hospital, Nagano 384-8540, Japan
6
National Hospital Organization, Yamato Psychiatric Center, Nara 639-1042, Japan
7
National Hospital Organization, Department of Psychiatry, Kure Medical Center and Chugoku Cancer Center, Hiroshima 737-0023, Japan
8
National Hospital Organization, Tottori Medical Center, Tottori 689-0203, Japan
9
National Hospital Organization, Hokuriku Hospital, Toyama 939-1893, Japan
10
National Hospital Organization, Kikuchi National Hospital, Kumamoto 861-1116, Japan
11
National Hospital Organization, Kurihama Medical and Addiction Center, Kanagawa 239-0841, Japan
 
add Show full affiliation list
 
remove Hide full affiliation list
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2025, 14(21), 7892; https://doi.org/10.3390/jcm14217892
Submission received: 24 September 2025 / Revised: 23 October 2025 / Accepted: 29 October 2025 / Published: 6 November 2025
(This article belongs to the Special Issue Clinical Therapy in Dementia and Related Diseases)
Browse Figures
Versions Notes

Abstract

Background: Clozapine is the only antipsychotic medication proven effective in patients with treatment-resistant schizophrenia (TRS). However, many patients have serum concentrations outside the recommended therapeutic window, and clozapine exhibits substantial interindividual variability. This study aimed to (1) examine clozapine dosage and blood concentrations in patients with TRS; (2) investigate the effects of sex and age on dosage and blood concentrations; (3) assess clinical response to clozapine treatment; and (4) develop a random forest (RF) model to predict therapeutic response using clinical and therapeutic drug monitoring (TDM) data. Methods: Dried blood spots were used to measure concentrations of clozapine, norclozapine, and clozapine N-oxide. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). The RF algorithm was applied to analyze the relationships between biochemical and demographic factors and clinical response to clozapine. Results: A total of 754 blood samples from 167 patients were analyzed. Men received higher doses than women, and glucose levels were elevated in both sexes. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was 0.986 for the training set and 0.852 for the testing set. Accuracy, precision, recall, and F1-score (training/testing) were 0.938/0.786, 0.936/0.736, 0.934/0.780, and 0.935/0.757, respectively. The SHapley Additive exPlanations (SHAP) analysis indicated that baseline BPRS score, treatment duration, age, and clozapine concentration were important variables contributing to the output of the model. Conclusions: Our model achieved satisfactory predictive performance for clinical response and provides valuable insights into personalized prediction of clozapine efficacy.
Keywords: clozapine; norclozapine; clozapine N-oxide; therapeutic drug monitoring (TDM); random forest (RF); personalized medicine; treatment-resistant schizophrenia (TRS) clozapine; norclozapine; clozapine N-oxide; therapeutic drug monitoring (TDM); random forest (RF); personalized medicine; treatment-resistant schizophrenia (TRS)

Share and Cite

MDPI and ACS Style

Nakahara, T.; Harada, Y.; Nakayama, N.; Hashimoto, K.; Kida, N.; Onitsuka, T.; Noda, H.; Murasugi, K.; Takimoto, Y.; Omori, W.; et al. Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia. J. Clin. Med. 2025, 14, 7892. https://doi.org/10.3390/jcm14217892

AMA Style

Nakahara T, Harada Y, Nakayama N, Hashimoto K, Kida N, Onitsuka T, Noda H, Murasugi K, Takimoto Y, Omori W, et al. Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia. Journal of Clinical Medicine. 2025; 14(21):7892. https://doi.org/10.3390/jcm14217892

Chicago/Turabian Style

Nakahara, Tatsuo, Yukiko Harada, Naho Nakayama, Kijiro Hashimoto, Naoya Kida, Toshiaki Onitsuka, Hiroo Noda, Kenji Murasugi, Yoshihiro Takimoto, Wataru Omori, and et al. 2025. "Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia" Journal of Clinical Medicine 14, no. 21: 7892. https://doi.org/10.3390/jcm14217892

APA Style

Nakahara, T., Harada, Y., Nakayama, N., Hashimoto, K., Kida, N., Onitsuka, T., Noda, H., Murasugi, K., Takimoto, Y., Omori, W., Sukegawa, T., Shiraishi, J., Tanaka, K., Maesato, H., & Ueno, T. (2025). Personalized Prediction of Clozapine Treatment Response Using Therapeutic Drug Monitoring Data in Japanese Patients with Treatment-Resistant Schizophrenia. Journal of Clinical Medicine, 14(21), 7892. https://doi.org/10.3390/jcm14217892

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop