O12.2. CLOZAPINE RE-CHALLENGE OR CONTINUATION FOLLOWING A NEUTROPENIA: CASE-SERIES OF 22 CASES

There is an increasing number of case reports in which clozapine was re-initiated or maintained after an initial neutropenia. However, there are relatively few systematic case series that have been published, and their follow-up duration was relatively modest. The present report describes characteristics and trajectories of 22 clozapine treated SZ patients (15 men, 7 women) who have been rechallenged (n=16) or maintained (n=6) on clozapine following the occurrence of a significant neutropenia and who have been followed for an average of 7.2 years. This is a complete sample of patients who experienced such as a situation rom 1998 until 2017 while treated at the Institut de Santé Mentale de Québec, where the vast majority of clozapine patients in the Québec City Metropolitan area (population = 750,000) are treated. The following variables were collected from extensive medical records review: demographic information, detailed hematological information, medication and other active medical diagnoses that could have contributed to the neutropenia, clozapine regimen and use of GCS-F and lithium. The mean age at clozapine introduction was 35,9 yrs (range 16–56). The mean observation period following the index neutropenia lasted 7.2 years (range 4 months -19,4). The mean delay between the index neutropenia and the re-challenge was 2.4 months. Five out of these 22 patients experienced additional neutropenias, and 3 of these 5 patients experienced more than one additional neutropenias, one undergoing a total of 11 neutropenias. At the end of the observation period, 17/22 patients were still on Clozapine; among the five patients in whom clozapine was stopped, three had died, one from a paralytic ileus that was deemed clozapine-related, and 2 from non-clozapine related causes. One stopped Clozapine for a non-hematological side-effect, and only one stopped due to neutropenia, i.e., after an eleventh neutropenia despite concomitant GCS-F use. This study adds to available evidence that a clozapine re-challenge or continuation following a neutropenia can be reasonably considered once potential risks and benefits have been carefully analyzed and then discussed with the patient and his/her family in order to make a shared decision. Furthermore, the present results raise the possibility that continuing clozapine with stringent hematological monitoring may be considered in some cases of neutropenia that do not reach the agranulocytosis threshold. These results also support that conclusion that conditions other than hematological ones (e.g., severe constipation) should be closely monitored and rigorously addressed in order to ensure the safety of Clozapine use.

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