TY - JOUR
T1 - Predictors of Treatment-Resistant and Clozapine-Resistant Schizophrenia
T2 - A 12-Year Follow-up Study of First-Episode Schizophrenia-Spectrum Disorders
AU - Chan, Sherry Kit Wa
AU - Chan, Hei Yan Veronica
AU - Honer, William G.
AU - Bastiampillai, Tarun
AU - Suen, Yi Nam
AU - Yeung, Wai Song
AU - Lam, Ming
AU - Lee, Wing King
AU - Ng, Roger Man King
AU - Hui, Christy Lai Ming
AU - Chang, Wing Chung
AU - Lee, Edwin Ho Ming
AU - Chen, Eric Yu Hai
PY - 2021/3
Y1 - 2021/3
N2 - Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.
AB - Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.
KW - clinical predictors
KW - clozapine-resistant schizophrenia
KW - early intervention service
KW - long-term outcomes
KW - treatment resistant schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85103227674&partnerID=8YFLogxK
U2 - 10.1093/schbul/sbaa145
DO - 10.1093/schbul/sbaa145
M3 - Article
C2 - 33043960
AN - SCOPUS:85103227674
SN - 0586-7614
VL - 47
SP - 485
EP - 494
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 2
ER -