Clozapine Management in Schizophrenia Inpatients: A 5-Year Prospective Observational Study of Its Safety and Tolerability Profile

Background: Clozapine is well known for its efficacy and clinical superiority compared to other antipsychotics in treatment-resistant schizophrenia (TRS). However, it is frequently underutilized worldwide because of its acute adverse events, as well as for its long-term cardiometabolic and hematological consequences.

Objective: The aim of the study was to evaluate 5-year safety in chronic TRS inpatients with continuous clozapine use.

Methods: Patients with TRS and clozapine treatment were evaluated for 5 years. All participants were assessed using the Brief Psychiatric Rating Scale (BPRS), Glasgow Antipsychotic Side-effect Scale for Clozapine (GASS-C), Social Performance Scale (PSP) and Short Portable Mental Status Questionnaire (SPMSQ). Clinical, cardiometabolic and hematological data were collected periodically. General linear models (GLM) repeated measures controlling for CLZ dose were utilized to determine differences in variables across the time.

Results: Overall, 189 inpatients were screened for study participation. The final sample included twenty-one TRS patients (16 males, 76%) with an average age of 57.6 years, all with 5-year continuous use of clozapine (mean dose 266 mg/day). There was not a significant effect of time on BPRS (p=0.774), PSP (p=0.855) and SPMSQ (p=0.066); differences remained not significant after controlling for CLZ dose (p=0.585, p=0.467 and p=0.105, respectively). No changes were found in blood and clinical parameters except for red blood cell count, which decreased over time (p=0.024; η²= 0.952). Patients reported a significant BMI decrease (-8.98 kg, p=0.008) between baseline and 5 years last observation.

Conclusion: The findings show how the application of a structured dietary, clinical and therapeutic monitoring program in psychiatric care facilities could allow the safe and effective long-term cardiometabolic and hematological management of clozapine. The unique role that clozapine plays in the current treatment of patients with TRS requires greater clinical awareness. Although its acute and chronic side effects are notorious, its safety management is feasible and broadens its potential practical application.