Clozapine dosing patterns and clinical outcomes in patients with treatment resistant schizophrenia

Clozapine is the only medication found to be effective for patients with treatment resistant schizophrenia-spectrum disorders (TRS) and its prescription patterns may impact on their outcomes. The study aims to explore the impact of clozapine dosing frequency, dose level and presence of pharmacological augmentation on the clinical, social and cognitive outcomes in patients with TRS. Patients with TRS and on clozapine were interviewed. Daily defined dose (DDD) and anticholinergic burden were calculated. Patients were categorized in three ways: the single daily dose (SDD) and multiple daily dose (MDD), <= 300 mg/day (LD) and > 300 mg/day (HD) of clozapine, and clozapine monotherapy (MT) and augmentation therapy (AT). The impact of these clozapine prescription patterns and their interaction on patient outcomes were examined with ANOVA. Of 124 patients on clozapine, 98 patients (79%) had SDD, 59 patients (47.6%) received LD, and 58 patients (46.8%) had MT. Patients in the LD group had significantly better cognitive functions. Though no significant effect of clozapine dosing frequency on outcomes, among patients on LD, those on MDD had better processing speed, short-term and visual memory. Patients with MT had better motivation. Among patients on HD, those with MT had better motivation and vocational functioning. These results provide guidance to the clozapine prescription in a naturalistic setting to achieve optimizing outcomes for patients with TRS in social and cognitive functions. Further longitudinal studies are needed to verify the results. (c) 2023 Elsevier B.V. and ECNP. All rights reserved.

Automated summary

The study aims to explore the impact of clozapine dosing frequency, dose level, and pharmacological augmentation on the clinical, social, and cognitive outcomes in patients with treatment-resistant schizophrenia spectrum disorders (TRS). The results showed that among patients receiving low-dose clozapine, multiple daily doses were associated with better processing speed, short-term, and visual memory. Additionally, clozapine monotherapy was related to better motivation in TRS patients. These findings provide guidance for optimizing outcomes in TRS patients and further research is needed to confirm the results.