Safety aspects during treatment with clozapine. : Monitoring and rechallenge - a narrative review

Abstract

Due to its unique efficacy in treatment-resistant schizophrenia, discontinuation of treatment with clozapine is frequently associated with asignificant 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 apreviously stopped treatment with clozapine can be considered and when adefinite discontinuation must take place. Medline, the Guideline for the use of clozapine 2013 of the Netherlands Clozapine Collaboration Group, and the S3Guideline for Schizophrenia of the German Association of Psychiatry, Psychotherapy and Psychosomatics were searched for relevant literature, the last query dating from April28th, 2023. 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. 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.