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Background  Clozapine is generally considered as the treatment of choice for patients with treatment-resistant schizophrenia (TRS). However, its superiority has recently been questioned because olanzapine has been suggested as non-inferior to clozapine in its effectiveness.    Aims  We aimed to investigate the current status of clozapine prescriptions to identify any disparity between clinical guidelines and real-world practices.    Method  In this study, we utilised the Health Insurance Review Agency database in the Republic of Korea to investigate the real-world effectiveness of clozapine for patients with TRS. We compared differences in patient variables before and after clozapine administration, and we also performed survival analyses for both psychiatric admissions and emergency room visits among patients who used clozapine or olanzapine.    Results  This study investigated an incident cohort of 64 442 patients, and 2338 patients have been prescribed clozapine. Of these, 998 patients had TRS. In survival analysis, clozapine showed a worse survival rate for psychiatric admissions than olanzapine (hazard ratio 0.615). We also identified that clinicians tended to try a number of antipsychotics, as recommended, before starting patients on clozapine.    Conclusions  In conclusion, we found that olanzapine led to higher survival rates for psychiatric admissions than clozapine. Thus, considering the risk of serious adverse effects, clozapine may be used conservatively. Considering several studies advocating superior efficacy of clozapine, further studies with extensive data are recommended.

Use of olanzapine compared with clozapine for treatment-resistant schizophrenia in a real-world setting: nationwide register-based study