TY - JOUR
T1 - Clozapine response trajectories and predictors of non-response in treatment-resistant schizophrenia
T2 - a chart review study
AU - Shah, Parita
AU - Iwata, Yusuke
AU - Brown, Eric E.
AU - Kim, Julia
AU - Sanches, Marcos
AU - Takeuchi, Hiroyoshi
AU - Nakajima, Shinichiro
AU - Hahn, Margaret
AU - Remington, Gary
AU - Gerretsen, Philip
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
Funding for this study was provided by the Ontario Mental Health Foundation (Type A grant) and the Canadian Institutes of Health Research (MOP-142493 and MOP-141968). We are grateful to Wanna Mar, Research Coordinator, for providing administrative support. We also thank research volunteers Danielle Uy, Katharine Constable, Kathryn Kalahani-Bargis, and Kristy Orser for their assistance with organizing the study data for analysis.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
KW - Clozaril
KW - Outcome
KW - Psychosis
KW - Response
KW - Schizophrenia
KW - Treatment
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UR - http://www.scopus.com/inward/citedby.url?scp=85070807654&partnerID=8YFLogxK
U2 - 10.1007/s00406-019-01053-6
DO - 10.1007/s00406-019-01053-6
M3 - Article
C2 - 31428862
AN - SCOPUS:85070807654
SN - 0003-9373
VL - 270
SP - 11
EP - 22
JO - Archiv fur Psychiatrie und Nervenkrankheiten
JF - Archiv fur Psychiatrie und Nervenkrankheiten
IS - 1
ER -
