Cerebroventricular clozapine would be a viable treatment modality for clozapine-dependent schizophrenia patients with neutropenia

Abstract

The atypical antipsychotic clozapine is very effective for treatment of schizophrenia, but it causes agranulocytosis requiring drug cessation in up to 2% of cases. There has been some success rechallenging with clozapine at a later date or giving granulocyte colony stimulating factor or lithium while continuing clozapine. However, there are still some patients for whom these strategies do not work yet who cannot be controlled on other medications. This paper proposes that for such individuals, cerebroventricular administration of clozapine via Ommaya catheters could allow continued use of clozapine therapy. Direct infusion into cerebrospinal fluid means far smaller amounts of drug would be needed for efficacy, and clozapine concentrates in the central nervous system where it would not be exposed to bone marrow stem cells to cause agranulocytosis. This treatment paradigm would also provide a means for court-ordered clozapine therapy and a possible delivery system for future therapeutics based on trophic factors such as brain-derived neurotrophic factor.