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

Abstract

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; η 2 = 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.

Effectiveness of SGA-LAIs on Clinical, Cognitive, and Social Domains in Schizophrenia: Results from a Prospective Naturalistic Study

“…This finding is in line with similar evidence suggesting that switching from an oral AP to LAI formulation may lead to improvements in cholesterol and prolactin levels in individuals with SCZ [ 11 , 40 ]. This effect is particularly evident considering both the greater therapeutic adherence and the feasible general improvement in lifestyle, diet, and physical activity consequent to functional recovery [ 41 , 42 , 43 ], as well as the potential disease-modifying effect on symptoms, functional outcome, and mortality [ 44 , 45 ]. However, considering that the results of studies in this area have been mixed, more research is needed to fully understand the effects of such a switch on metabolic parameters [ 11 ].…”

Clozapine once- versus multiple-daily dosing: a two-center cross-sectional study, systematic review and meta-analysis

“…The primary outcome was defined as standardized mean difference (SMD) of clinical symptom severity assessment scales ratings between patients treated with clozapine once- vs. multiple-daily dosing. Further, we estimated a pooled odds ratio (OR) for ADRs; ADRs were defined on the basis of description (binary) [ 26 ], or, in cases of standardized scales, such as the Glasgow Antipsychotic Side-Effect Scale for Clozapine well-established thresholds were used [ 14 , 27 ]. Meta-analyses also included differences for age, percentage males, percentage smokers, clozapine daily dose, co-medication with other antipsychotics, benzodiazepines, antidepressants, mood stabilizers, anticholinergics, and laxatives between patients receiving clozapine once- vs. multiple-daily dosing.…”

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

“… 333 , 346 Regular physical exercise, a Mediterranean diet, and smoking cessation to decrease cardiovascular risk are the primary recommendations to counteract weight gain. 226 , 347 Among pharmacological interventions, adjunctive metformin shows a good safety profile and the best efficacy for stabilizing weight gain. 177 , 178 , 348 , 349 Consequently, the first guideline for metformin use during antipsychotic treatment advocates a routine early initiation in addition to behavioral interventions to most effectively minimize weight gain and cardiometabolic risk.…”

“…Regular physical exercise, a mediterranean diet and smoking cessation to decrease cardiovascular risk, are the primary recommendations to counteract weight gain 236,237 .…”