[Safety aspects during treatment with clozapine. : Monitoring and rechallenge - a narrative review]. / Sicherheitsaspekte bei der Behandlung mit Clozapin : Monitoring und Rechallenge ­ eine narrative Übersicht.

BACKGROUND: Due to its unique efficacy in treatment-resistant schizophrenia, discontinuation of treatment with clozapine is frequently associated with a significant worsening of symptoms, but also with an increased risk of suicide. Based on the literature, this review aims at summarizing different monitoring recommendations in order to be able to continue this therapy despite the occurrence of side effects. In addition, we provide recommendations when rechallenge of a previously stopped treatment with clozapine can be considered and when a definite discontinuation must take place. 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 of Psychiatry, Psychotherapy and Psychosomatics were searched for relevant literature, the last query dating from April 28th, 2023. RESULTS: If agranulocytosis or cardiomyopathy develops, treatment with clozapine must be discontinued and should not be resumed thereafter. In contrast, treatment with clozapine which had to be discontinued due to myocarditis or prolongation of the QTc interval may be continued if left ventricular function is normal or after normalization of the QTc interval. Other side effects are usually not absolute contraindications for rechallenge but often require the adjunctive use of additional pharmacologic and non-pharmacologic measures. CONCLUSION: Taking into consideration various monitoring recommendations, cessation of treatment with clozapine can often be prevented or treatment with clozapine that has been discontinued due to side effects can be resumed.

[Safety aspects during treatment with clozapine: : Adverse effects, titration, and therapeutic drug monitoring - a narrative review]. / Sicherheitsaspekte bei der Behandlung mit Clozapin: : Unerwünschte Arzneimittelwirkungen, Titration und Therapeutisches Drug Monitoring ­ eine narrative Übersicht.

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.