The critical treatment window of clozapine in treatment-resistant schizophrenia

Secondary analysis of an observational study

Bunta Yoshimura, Yuji Yada, Ryuhei So, Manabu Takaki, Norihito Yamada

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Previous studies have suggested that a delay in initiating clozapine is one of the predictors of outcomes in treatment-resistant schizophrenia (TRS). However, whether there is a critical treatment window of clozapine in TRS and the duration of that window remain unclear. We conducted a secondary analysis of a previously published observational study using a retrospective chart review of 105 patients with TRS who were treated with clozapine. We included 90 patients who remained on clozapine for at least 3 months. The delay in initiating clozapine was an independent contributor to symptomatic improvement based on treatment with clozapine by multiple linear regression analysis. A receiver operating characteristic curve analysis (area under the curve: 0.78) confirmed 2.8 years was the best predictive cut-off value of delay in initiating clozapine for responses in patients treated with clozapine (sensitivity: 0.66, specificity: 0.84). In patients with a delay in initiating clozapine of ≤2.8 years and a delay in initiating clozapine of >2.8 years, the response rates were 81.6% and 30.8% (risk ratio=2.65; 95% confidence interval, 1.80, 3.63), respectively. Clinicians should reduce the delay in initiating clozapine to less than 3 years to improve symptomatic outcomes in TRS and to prevent clozapine-resistant schizophrenia.

Original languageEnglish
Pages (from-to)65-70
Number of pages6
JournalPsychiatry Research
Volume250
DOIs
Publication statusPublished - Apr 1 2017

Fingerprint

Clozapine
Observational Studies
Schizophrenia
Therapeutics
ROC Curve
Area Under Curve
Linear Models
Odds Ratio
Regression Analysis
Confidence Intervals

Keywords

  • Clozapine
  • Critical treatment window
  • Delay
  • Schizophrenia
  • Treatment-resistant

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

The critical treatment window of clozapine in treatment-resistant schizophrenia : Secondary analysis of an observational study. / Yoshimura, Bunta; Yada, Yuji; So, Ryuhei; Takaki, Manabu; Yamada, Norihito.

In: Psychiatry Research, Vol. 250, 01.04.2017, p. 65-70.

Research output: Contribution to journalArticle

@article{4cb35cc54df2435e82aba721f704a3d5,
title = "The critical treatment window of clozapine in treatment-resistant schizophrenia: Secondary analysis of an observational study",
abstract = "Previous studies have suggested that a delay in initiating clozapine is one of the predictors of outcomes in treatment-resistant schizophrenia (TRS). However, whether there is a critical treatment window of clozapine in TRS and the duration of that window remain unclear. We conducted a secondary analysis of a previously published observational study using a retrospective chart review of 105 patients with TRS who were treated with clozapine. We included 90 patients who remained on clozapine for at least 3 months. The delay in initiating clozapine was an independent contributor to symptomatic improvement based on treatment with clozapine by multiple linear regression analysis. A receiver operating characteristic curve analysis (area under the curve: 0.78) confirmed 2.8 years was the best predictive cut-off value of delay in initiating clozapine for responses in patients treated with clozapine (sensitivity: 0.66, specificity: 0.84). In patients with a delay in initiating clozapine of ≤2.8 years and a delay in initiating clozapine of >2.8 years, the response rates were 81.6{\%} and 30.8{\%} (risk ratio=2.65; 95{\%} confidence interval, 1.80, 3.63), respectively. Clinicians should reduce the delay in initiating clozapine to less than 3 years to improve symptomatic outcomes in TRS and to prevent clozapine-resistant schizophrenia.",
keywords = "Clozapine, Critical treatment window, Delay, Schizophrenia, Treatment-resistant",
author = "Bunta Yoshimura and Yuji Yada and Ryuhei So and Manabu Takaki and Norihito Yamada",
year = "2017",
month = "4",
day = "1",
doi = "10.1016/j.psychres.2017.01.064",
language = "English",
volume = "250",
pages = "65--70",
journal = "Psychiatry Research",
issn = "0165-1781",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - The critical treatment window of clozapine in treatment-resistant schizophrenia

T2 - Secondary analysis of an observational study

AU - Yoshimura, Bunta

AU - Yada, Yuji

AU - So, Ryuhei

AU - Takaki, Manabu

AU - Yamada, Norihito

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Previous studies have suggested that a delay in initiating clozapine is one of the predictors of outcomes in treatment-resistant schizophrenia (TRS). However, whether there is a critical treatment window of clozapine in TRS and the duration of that window remain unclear. We conducted a secondary analysis of a previously published observational study using a retrospective chart review of 105 patients with TRS who were treated with clozapine. We included 90 patients who remained on clozapine for at least 3 months. The delay in initiating clozapine was an independent contributor to symptomatic improvement based on treatment with clozapine by multiple linear regression analysis. A receiver operating characteristic curve analysis (area under the curve: 0.78) confirmed 2.8 years was the best predictive cut-off value of delay in initiating clozapine for responses in patients treated with clozapine (sensitivity: 0.66, specificity: 0.84). In patients with a delay in initiating clozapine of ≤2.8 years and a delay in initiating clozapine of >2.8 years, the response rates were 81.6% and 30.8% (risk ratio=2.65; 95% confidence interval, 1.80, 3.63), respectively. Clinicians should reduce the delay in initiating clozapine to less than 3 years to improve symptomatic outcomes in TRS and to prevent clozapine-resistant schizophrenia.

AB - Previous studies have suggested that a delay in initiating clozapine is one of the predictors of outcomes in treatment-resistant schizophrenia (TRS). However, whether there is a critical treatment window of clozapine in TRS and the duration of that window remain unclear. We conducted a secondary analysis of a previously published observational study using a retrospective chart review of 105 patients with TRS who were treated with clozapine. We included 90 patients who remained on clozapine for at least 3 months. The delay in initiating clozapine was an independent contributor to symptomatic improvement based on treatment with clozapine by multiple linear regression analysis. A receiver operating characteristic curve analysis (area under the curve: 0.78) confirmed 2.8 years was the best predictive cut-off value of delay in initiating clozapine for responses in patients treated with clozapine (sensitivity: 0.66, specificity: 0.84). In patients with a delay in initiating clozapine of ≤2.8 years and a delay in initiating clozapine of >2.8 years, the response rates were 81.6% and 30.8% (risk ratio=2.65; 95% confidence interval, 1.80, 3.63), respectively. Clinicians should reduce the delay in initiating clozapine to less than 3 years to improve symptomatic outcomes in TRS and to prevent clozapine-resistant schizophrenia.

KW - Clozapine

KW - Critical treatment window

KW - Delay

KW - Schizophrenia

KW - Treatment-resistant

UR - http://www.scopus.com/inward/record.url?scp=85010662205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010662205&partnerID=8YFLogxK

U2 - 10.1016/j.psychres.2017.01.064

DO - 10.1016/j.psychres.2017.01.064

M3 - Article

VL - 250

SP - 65

EP - 70

JO - Psychiatry Research

JF - Psychiatry Research

SN - 0165-1781

ER -