Treatment resistant schizophrenia: Clinical, biological, and therapeutic perspectives

Treatment resistant schizophrenia (TRS) refers to the significant proportion of schizophrenia patients who continue to have symptoms and poor outcomes despite treatment. While many definitions of TRS include failure of two different antipsychotics as a minimum criterion, the wide variability in incl...

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Published inNeurobiology of disease Vol. 131; p. 104257
Main Authors Nucifora, Frederick C., Woznica, Edgar, Lee, Brian J., Cascella, Nicola, Sawa, Akira
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.11.2019
Elsevier
Subjects
Brain Imaging
CBT
Clozapine
DBS
Dopamine
Drug Resistance
ECT
Genetics
Glutamate
Humans
Neurobiology
rTMS
Schizophrenia
Schizophrenia - physiopathology
Schizophrenia - therapy
Treatment-Resistant
FDA
RCT
GWAS
Neurobiology
UTRS
Schizophrenia
Brain Imaging
HR
leTPC
BPRS
PRS
Glu
Treatment-Resistant
DBS
CBT
SNP
TRS
MD
Genetics
PANSS
CATIE
Dopamine
NMA
DLPFC
MR
CI
AH
Clozapine
Glutamate
PGC
non-TRS
CR
ECT
SAPS
HC
rTMS
DA
TRRIP
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Summary:Treatment resistant schizophrenia (TRS) refers to the significant proportion of schizophrenia patients who continue to have symptoms and poor outcomes despite treatment. While many definitions of TRS include failure of two different antipsychotics as a minimum criterion, the wide variability in inclusion criteria has challenged the consistency and reproducibility of results from studies of TRS. We begin by reviewing the clinical, neuroimaging, and neurobiological characteristics of TRS. We further review the current treatment strategies available, addressing clozapine, the first-line pharmacological agent for TRS, as well as pharmacological and non-pharmacological augmentation of clozapine including medication combinations, electroconvulsive therapy, repetitive transcranial magnetic stimulation, deep brain stimulation, and psychotherapies. We conclude by highlighting the most recent consensus for defining TRS proposed by the Treatment Response and Resistance in Psychosis Working Group, and provide our overview of future perspectives and directions that could help advance the field of TRS research, including the concept of TRS as a potential subtype of schizophrenia.
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ISSN:0969-9961
1095-953X
1095-953X
DOI:10.1016/j.nbd.2018.08.016