Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia: a chart review study

Parita Shah, Yusuke Iwata, Eric E. Brown, Julia Kim, Marcos Sanches, Hiroyoshi Takeuchi, Shinichiro Nakajima, Margaret Hahn, Gary Remington, Philip Gerretsen, Ariel Graff-Guerrero

Research output: Contribution to journalArticle

Abstract

Although clozapine is the main antipsychotic medication for treatment-resistant schizophrenia, 40–70% of patients on clozapine have persistent psychotic symptoms (i.e. ultra-treatment-resistant schizophrenia, UTRS). We aimed to examine clozapine response/non-response patterns in patients with treatment-resistant schizophrenia, as well as determine patient clinico-demographic factors associated with long-term clozapine non-response. Clinico-demographic characteristics of 241 patients on clozapine were collected through a retrospective chart review. The median (interquartile range, IQR) follow-up from illness onset was 25.0 (IQR = 24.0) years. Clozapine response was assessed at median 10.8 (IQR = 14.0) months (Time 1, T1) and 7.2 (IQR = 13.5) years (Time 2, T2) after its initiation. It was evaluated by chart reviewers based on the information provided in clinical notes. Binomial logistic regression was used to determine clinico-demographic factors associated with clozapine non-response at both T1 and T2 (i.e. stable UTRS, S-UTRS) compared to clozapine response at both times (i.e. stable clozapine responders, S-ClozResp). Among clozapine responders (n = 122) at T1, 83.6% remained clozapine responsive and 16.4% became non-responsive at T2. In the UTRS group (n = 119) at T1, 87.4% remained clozapine non-responsive and 12.6% became responsive at T2. Duration of delay in clozapine initiation (OR = 0.94, Wald χ2 = 5.33, p = 0.021) and number of pre-clozapine hospitalizations (OR = 0.95, Wald χ2 = 5.20, p = 0.023) were associated with S-UTRS. Most UTRS patients were non-responsive to clozapine from the start of treatment. Preventing delay in initiating clozapine and relapses could help promote long-term clozapine response in patients with treatment-resistant schizophrenia. Future longitudinal studies are required to explore the neuropathological correlates of relapses and delay in clozapine initiation.

Original languageEnglish
JournalEuropean Archives of Psychiatry and Clinical Neuroscience
DOIs
Publication statusAccepted/In press - 2019 Jan 1

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Clozapine
Schizophrenia
Therapeutics
Demography
Recurrence

Keywords

  • Clozaril
  • Outcome
  • Psychosis
  • Response
  • Schizophrenia
  • Treatment

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia : a chart review study. / Shah, Parita; Iwata, Yusuke; Brown, Eric E.; Kim, Julia; Sanches, Marcos; Takeuchi, Hiroyoshi; Nakajima, Shinichiro; Hahn, Margaret; Remington, Gary; Gerretsen, Philip; Graff-Guerrero, Ariel.

In: European Archives of Psychiatry and Clinical Neuroscience, 01.01.2019.

Research output: Contribution to journalArticle

Shah, Parita ; Iwata, Yusuke ; Brown, Eric E. ; Kim, Julia ; Sanches, Marcos ; Takeuchi, Hiroyoshi ; Nakajima, Shinichiro ; Hahn, Margaret ; Remington, Gary ; Gerretsen, Philip ; Graff-Guerrero, Ariel. / Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia : a chart review study. In: European Archives of Psychiatry and Clinical Neuroscience. 2019.
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