Safety aspects during treatment with clozapine: Adverse effects, titration, and therapeutic drug monitoring - a narrative review

Background According to current guidelines, clozapine should be used as a third step in treatment resistant schizophrenia (TRS). In everyday clinical practice, however, it is frequently used at a much later stage, which leads to a significant deterioration of prognosis. The first part of this narrative overview focuses on the most frequent side effects of clozapine, on the relevance of slow titration, and on specific aspects of therapeutic drug monitoring (TDM).Material and Methods Medline, the Guideline for the use of clozapine 2013 of the Netherlands Clozapine Collaboration Group, and the S3 Guideline for Schizophrenia of the German Association for Psychiatry, Psychotherapy and Psychosomatics were searched for relevant literature, the last query dating from April 28th, 2023.Results Despite its unique efficacy clozapine is underused in clinical practice and prescription varies between and within countries. Next to hematological, metabolic, and vegetative side effects, clozapine induced inflammation manifesting in the form of pneumonia or myocarditis, which is mainly associated with rapid titration, represents a major clinical challenge with CRP monitoring being of particular relevance. In this context, it also has to be noted that sex, smoking behavior, and ethnic origin impact clozapine metabolism, thus requiring personalized dosing.Conclusion Slow titration when possible, TDM, and CYP diagnostics when appropriate increase patient safety during treatment with clozapine and thus the likelihood of early prescription of this compound in TRS.