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.
authors.affiliation: Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan; Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: hajime-greentea@hotmail.co.jp.
authors.forename: Bunta
authors.initials: B
authors.lastname: Yoshimura
authors.affiliation: Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan. Electronic address: navyflag1234@yahoo.co.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yada
authors.affiliation: Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan. Electronic address: nexttext@gmail.com.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: So
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: manabuta1971@hotmail.com.
authors.forename: Manabu
authors.initials: M
authors.lastname: Takaki
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: nyamada@okayama-u.ac.jp.
authors.forename: Norihito
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003024:Clozapine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012559:Schizophrenia / Q000188:drug therapy*; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine
keywords: Clozapine; Critical treatment window; Delay; Schizophrenia; Treatment-resistant