Evidence map›Paper›PMID 40521596›Full record

ArticleFrontiers in psychiatry2025

Higher clozapine concentration-to-dose ratios at week 1 after initiation are associated with increased risk of clozapine-associated fever in Japanese patients with schizophrenia.

Yuki Kikuchi, Hiroaki Tanifuji, Mutsumi Sakata, Kazuro Ikawa, Daisuke Kume, Naoki Horikawa, Sota Ueno, Yoshifumi Onuma, Masato Ishihara, Bunichiro Onodera and 6 more

Abstract read
In one paragraph

Article in Frontiers in psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Yuki KikuchiDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Hiroaki TanifujiDepartment of Pharmacy, Kodama Hospital, Ishinomaki, Japan.
Mutsumi SakataNozoe Hills Hospital, Fukuoka, Japan.
Kazuro IkawaDepartment of Clinical Pharmacotherapy, Hiroshima University, Hiroshima, Japan.
Daisuke KumeNozoe Hills Hospital, Fukuoka, Japan.
Naoki HorikawaNozoe Hills Hospital, Fukuoka, Japan.
Sota UenoDepartment of Psychiatry, Kodama Hospital, Ishinomaki, Japan.
Yoshifumi OnumaDepartment of Psychiatry, Kodama Hospital, Ishinomaki, Japan.
Masato IshiharaDepartment of Psychiatry, Kodama Hospital, Ishinomaki, Japan.
Bunichiro OnoderaDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Takeshi ToraiwaDepartment of Psychiatry, Kodama Hospital, Ishinomaki, Japan.
Hiroshi KomatsuDepartment of Psychiatry, Tohoku University Hospital, Sendai, Japan.
Toshihiro SatoDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Masamitsu MaekawaDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Nariyasu ManoDepartment of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Hiroaki TomitaDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The clinical use of clozapine in the treatment of schizophrenia is sometimes halted due to its inflammatory side effects. However, no method has been established for preemptively identifying patients who are at high risk for these events. Therefore, in this study, we assessed whether the blood clozapine concentration-to-dose ratio (C/D) on day 8 after initiation could predict the risk of clozapine-associated fever. Method: Patients whose blood levels of clozapine were measured on day 8 after initiation were retrospectively investigated. The C/D ratio on day 8 was compared between patients who had fever after day 8 and those who did not. Results: A total of 43 patients were included in the study. The range of C/D ratios on day 8 was from 0.35-4.0, with a median of 1.65. Patients with fever had significantly higher C/D ratios on day 8 than those without fever (2.33 vs. 1.47; P < 0.005). Conclusion: Measuring blood clozapine levels on day 8 may help to better estimate the risk of clozapine-associated fever in patients with schizophrenia.

Indexed as

adverse effectc-reactive proteininflammationmyocarditispneumonia

Identifiers

PMID40521596
PMCPMC12162642

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