Prevalence of Treatment-Resistant Schizophrenia: A Nationwide Multicenter Study

Schizophrenia is characterized by positive symptoms, negative symptoms, and cognitive impairment and is primarily treated with antipsychotic medications. However, a subset of patients responds inadequately to treatment and is classified as having treatment-resistant schizophrenia (TRS). The prevalence of TRS among patients with schizophrenia remains insufficiently characterized. This study aimed to determine the prevalence of TRS using nationwide data and standardized diagnostic criteria.

This study included patients with schizophrenia who were discharged between 2016 and 2024 from 205 institutions participating in the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project and authorized to prescribe clozapine. TRS was defined according to standardized diagnostic criteria used in Japan. The prevalence of TRS was calculated among patients who underwent a TRS examination by their treating psychiatrist.

Among 18 914 patients, 9870 (52.2%) underwent a TRS examination. Among these 9870 patients, 2819 were classified as having TRS, corresponding to a prevalence of 28.6%. Among the 2819 patients with TRS, 1307 were prescribed clozapine at discharge, corresponding to a clozapine treatment rate of 46.4%.

This study had the largest sample size among single-cohort studies investigating the prevalence of TRS. The prevalence of TRS was 28.6% among patients with schizophrenia who underwent a TRS examination and was nearly identical to the pooled prevalence reported in studies at low risk of bias in a previous meta-analysis. These findings may provide important evidence regarding the prevalence of TRS in routine clinical practice.