Clozapine and anti-cancer agents: A systematic literature review of case reports

Abstract

Clozapine is the gold standard for treatment-resistant schizophrenia. In the setting of malignancy with concurrent anti-cancer agent use, clozapine use may be of increased concern. Clozapine cessation holds its own risks. This study aims to systematically review all cases of concurrent pharmacotherapy with clozapine and anti-cancer agents and analyze the psychiatric and physical health outcomes. PubMed, EMBASE, CINAHL, and PsycINFO databases were searched from inception to February 2025. Descriptive statistics and narrative analysis of the included cases occurred. There were 53 cases of clozapine use with anti-cancer agents, with a male to female ratio of 1.7:1 and a mean age of 45.0 years. In 30 cases, clozapine was continued without interruption, and in additional 16 cases, clozapine was recommenced after a period of interruption. In cases with clozapine interruption or discontinuation, 90% noted significant deterioration in mental state despite alternative antipsychotic treatments. There were 34 cases of neutropenia, mostly (94%) in the setting of cytotoxic chemotherapy, with low rates of neutropenic complications. The successful continuation of clozapine with anti-cancer agents can occur, although risk-benefit analysis taking into account individual, clozapine, psychiatric, and physical health factors is required. Consideration of prophylactic neutropenia protective measures should form part of the discussion with the individual and their family.