Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P< 2.0 × 10⁻¹⁶) and the ND-TRS without clozapine group (54.7%; P< 2.0 × 10⁻¹⁶). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P= 1.1 × 10⁻⁶) and the ND-TRS without clozapine group (17.0%; P= 5.9 × 10⁻⁶). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.