A nationwide study in Japan found that 28.6% of hospitalized patients with schizophrenia who received a formal assessment met the country’s criteria for treatment-resistant schizophrenia (TRS).
The analysis included discharge records for 18,914 inpatients from 205 hospitals licensed to prescribe clozapine. The patients were discharged between 2016 and 2024 and had stayed in hospital for at least four days.
Psychiatrists assessed 9,870 patients, or 52.2% of the overall group, for treatment resistance. Among those assessed, 2,819 met the standardized criteria. The researchers described the work as the largest single study of TRS prevalence to date.
What the study measured
TRS refers to schizophrenia that meets defined criteria for inadequate response to treatment. The Japanese criteria also include intolerance to other antipsychotic medicines, a feature not included in every international definition.
The study was conducted through EGUIDE, a nationwide program that trains psychiatrists to follow treatment guidelines for schizophrenia and depression. Its participating hospitals were all licensed to prescribe clozapine, the antipsychotic described in the report as having established efficacy for TRS.
The average inpatient age was about 46 years. The study did not follow patients over time. Instead, it used discharge records to describe how often treatment resistance was identified in this hospital-based group.
Clozapine use remained below half among those meeting criteria
Of the 2,819 patients who met the criteria for TRS, 1,307—46.4%—were prescribed clozapine at discharge. That means more than half left the hospital without the medicine, although the report did not provide reasons for the difference.
The report noted that clozapine use among people with TRS remains below 25% in many clinical settings and has been lower in Japan than in other countries. In a comparison using 2014 data from 17 countries, reported use was 0.6 per 100,000 people in the Japanese cohort, compared with 189.2 per 100,000 in Finland.
The researchers suggested that active screening for treatment resistance and increases over time in TRS assessments and clozapine prescribing may help explain the higher rate seen at EGUIDE hospitals. These were proposed explanations, not causes established by the study.
Why the 28.6% figure needs careful interpretation
The percentage applies only to patients who were formally assessed. Nearly half of the inpatients—47.8%—had no TRS assessment, so the assessed group was not a random sample of all hospitalized patients in the analysis.
Assessment was more common among patients in university and private hospitals and less common among those in public hospitals. Because the research involved EGUIDE hospitals licensed to prescribe clozapine, the result may not represent routine practice across every Japanese hospital.
The figure also may not apply to outpatients or to people receiving care outside the participating institutions. The report did not provide a confidence interval or results broken down by age, sex, year of discharge, or the reasons clozapine was not prescribed.
How the estimate compares with earlier research
The Japanese estimate was close to the 28.4% figure from a 2023 meta-analysis by Elton Diniz and colleagues when that analysis was limited to studies considered at lower risk of bias. Across all 50 studies in that review, involving 29,390 patients, the estimated prevalence was 36.7%.
A separate 2022 meta-analysis of 12 first-episode cohorts estimated that 22.8% of patients met TRS criteria. The estimate rose to 24.4% when the analysis was limited to first-episode schizophrenia cohorts.
These comparisons should not be treated as direct head-to-head measurements. The studies used different populations, settings and definitions, and Japan’s criteria include intolerance to other antipsychotics.
For readers and clinicians interpreting the findings, the central message is narrower than a national estimate: in this selected inpatient population, treatment resistance was identified frequently among those assessed, while clozapine prescribing did not extend to everyone who met the study criteria.
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