Based on a systematic review on TRS 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). Definitions of TRS varied notably. TRS was associated with 3 to 11-fold higher healthcare costs than schizophrenia in general. One-fifth to one-third of all patients with schizophrenia were considered to be resistant to treatment. Based on limited evidence of genetics, brain structure and functioning and cognition, TRS may present as a different disorder with different etiology compared to non-TRS. Clozapine, olanzapine, risperidone, ECT and cognitive-behavioral therapy have shown effectiveness, although the number of studies and quality of research on interventions is limited. About 40% to 70% of TRS patients had an unfavorable prognosis. Younger age, living in a rural or less urban area, primary education level, more psychiatric hospital treatment days in the year before first schizophrenia diagnosis, inpatient at first schizophrenia diagnosis, paranoid subtype, comorbid personality disorder and previous suicide attempt may be risk factors associated with TRS.

TRS is a poorly defined, studied and understood condition. 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. Prospective long-term prognostic and novel treatment intervention studies are needed [1].