Clozapine Rechallenge or Continuation Despite Neutropenia, an Extended Follow-up of a Consecutive Quebec Case Series

J Clin Psychopharmacol. 2022 May 12. doi: 10.1097/JCP.0000000000001556. Online ahead of print.


Background: Clozapine is the most efficacious antipsychotic for treatment-resistant schizophrenia. However, clozapine-induced neutropenia may warrant treatment discontinuation, hindering recovery. Several case reports describe clozapine rechallenge or continuation despite neutropenia, although many are subject to selective reporting, with incomplete information and short follow-up periods. Thus, consecutive case series, devoid of such bias, with long-term comprehensive follow-up are needed to better assess this practice. This study aimed to describe consecutively the evolution of every patient in the Québec City catchment area for whom clozapine was either reintroduced after neutropenia during a previous clozapine trial or was maintained despite a first neutropenia.

Methods: Patients were identified through clozapine's national hematological monitoring database and their medical records between January 1, 2000, and October 22, 2017.

Results: Twenty-three patients were identified, 8 continued clozapine despite neutropenia, while 15 discontinued clozapine and attempted rechallenge; among the latter, 4 patients were successfully rechallenged after agranulocytosis without the use of granulocyte colony-stimulating factors, which is the largest published consecutively. A total of 6 patients experienced further neutropenia episodes. Every patient who had a neutropenia recurrence also had a possible explanation for neutropenia other than exposure to clozapine. After a median follow-up of 4.8 years, 16 patients were still on clozapine and 3 cases discontinued because of a hematological event.

Conclusions: This study adds further data on the subject of clozapine rechallenge or continuation despite neutropenia. Clozapine rechallenge after agranulocytosis may be less perilous than first thought, but a systematic review on this specific subject is needed.