What do we know about treatment-resistant schizophrenia? A systematic review

Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia with high prevalence and human impact. Our aim was to perform a systematic review to find out the extent of published research on TRS and to determine the current knowledge of TRS. Studies were systematically collected using the databases of PubMed, Scopus and CINAHL. English language original studies and reviews on TRS with most of the sample including adults were included. The search located 449 studies. After abstract and title review, 285 studies were included regarding definitions of TRS (N=11), genetics (18), brain structure and functioning (18), cognition (8), other neurobiological studies (16), medication (158), psychotherapy and cognitive rehabilitation (12), electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) (15), prognosis (21), and other miscellaneous studies (8) on TRS. Definitions of TRS varied notably, and in most of the non-pharmacological studies the samples were small. Based on limited evidence of genetics, brain structure and functioning and cognition, TRS may present as a different disorder with different aetiology compared to non-TRS. Regarding treatments, clozapine, olanzapine, risperidone, ECT and cognitive-behavioural therapy have shown effectiveness, although the number of studies and quality of research on interventions is limited. Very little is known about risk factors, long-term course of illness and predictors of outcome in TRS, especially in naturalistic samples. Our findings suggest that TRS is a poorly defined, studied and understood condition considering its high prevalence, clinical and economic importance and poor prognosis. To create a framework of knowledge for TRS, as a basis to develop innovative studies on treatment, there is a need for a consensus on the definition of TRS. In addition, prospective long-term studies and prognostic studies are needed.