Comparative effectiveness of antipsychotic monotherapy and polypharmacy in schizophrenia patients with clozapine treatment: A nationwide, health insurance data-based study.

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia (TRS). However, it remains uncertain whether antipsychotic augmentation to clozapine has the superior effectiveness over clozapine alone and the effect size of clozapine compared to other antipsychotic drugs in TRS. Therefore, we examined the comparative effectiveness of antipsychotic monotherapy and polypharmacy on the risk of psychiatric admission and treatment discontinuation in TRS. Data were collected from the Health Insurance Review Agency database between January 2010 and December 2019 in South Korea. Among prevalent patients with schizophrenia, we defined 22,327 patients with TRS as those who had been prescribed with clozapine at least once during the entire observation period. Stratified Cox proportional hazards regressions were performed using data on all antipsychotic prescriptions of patients with TRS to investigate the risk of psychiatric hospitalization and treatment discontinuation associated with antipsychotic treatment. In individual comparisons, clozapine monotherapy was the most effective for the risk of psychiatric hospitalization compared to no use (hazard ratio [HR] = 0.23, 95% confidence interval [CI] = 0.22-0.25). In group comparisons, clozapine with long-acting injectable (LAI) second-generation antipsychotics (SGA) was superior to clozapine monotherapy for the risk of psychiatric hospitalization (HR = 0.60, 95%CI = 0.41-0.88). Clozapine monotherapy was associated with the lowest risk of treatment discontinuation in the individual and group comparisons. This retrospective observational population-based study reports that clozapine with LAI SGA is more effective in lowering the risk of psychiatric hospitalization in antipsychotic group comparison with the reference of clozapine monotherapy.

Diagnostic conversion from unipolar to bipolar affective disorder-A population-based study.

OBJECTIVES: It is essential to clinically distinguish bipolar affective disorder from unipolar affective disorders. However, patients previously diagnosed with unipolar affective disorder are sometimes later diagnosed with bipolar affective disorder, known as diagnostic conversion. Here we investigated diagnostic conversion using data from a nationwide population-based register. METHODS: We obtained claims data from 2007 to 2020 in Korea's Health Insurance Review Agency database and identified a cohort of patients who were diagnosed with unipolar depression in 2009 without prior psychiatric diseases within the previous 2 years. We studied the rate of diagnostic conversion and risk factors, especially antidepressants. RESULTS: About 6.5% of patients underwent diagnostic conversion during the observation period. Younger age at disease onset and usage of antidepressants increased the relative risk for diagnostic conversion. Patients using serotonin-norepinephrine reuptake inhibitors (SNRI) showed more than twice the risk compared to no usage of antidepressant. LIMITATION: First, this study was based on the population-based register data. Thus, we defined the patient cohort diagnosed with unipolar depression with strict inclusion criteria. Second, the exposure time differed between different antidepressants. Third, we estimated the relative risk for diagnostic conversion compared to no use of antidepressants. Moreover, we could not rule out the potential influence of antidepressant polypharmacy. CONCLUSION: We confirmed diagnostic conversion in some patients and identified younger age or usage of antidepressants, especially SNRI, as risk factors. Because unipolar and bipolar affective disorders show different disease courses or prognoses and have different treatment strategies, clinicians should be mindful of diagnostic conversion.