Never Say Never: Successful Clozapine Rechallenge After Multiple Episodes of Neutropenia

Clozapine is a second-generation antipsychotic with a superior efficacy for the management of treatment-resistant schizophrenia but underutilized because of potential side effects. A 59-year-old Caucasian male veteran was transferred from the long-term care unit to the acute psychiatry unit because of suicidality. He was noted as having a long-standing history of psychosis with significant referential and paranoid delusions. He had experienced two previous trials of clozapine; although he had significant response in the past, both trials ended in neutropenia and an absolute neutrophil count <500 cells per microliter, despite the second trial also including supplemental "as-needed" doses of pegfilgrastim to manage decline in neutrophil counts. This particular strategy of filgrastim use was determined to be a weakness of the second trial. A PubMed search identified recent literature that discussed preemptive dosing of filgrastim to prevent neutropenia. Thus, a protocol was established to administer 300 μg filgrastim subcutaneously, three times weekly, concurrently with clozapine initiation. This plan was discussed on local and national levels to achieve consensus before its initiation. Using a revised, patient-specific protocol led to successful initiation of clozapine and the ability to maintain the regimen for over 24 months without interruption or any further suicidal ideation.