Feasibility of myelosuppressive chemotherapy in psychiatric patients on clozapine: A systematic review of the literature

Clozapine is the standard of care for treatment-refractory schizophrenia, yet it carries a small but clinically significant risk of agranulocytosis. When patients on clozapine require myelosuppressive chemotherapy for a new malignancy, clinicians face a dilemma: maintain the antipsychotic and risk cumulative bone marrow suppression, or discontinue it and risk a severe psychiatric relapse. This systematic review aimed to evaluate the clinical outcomes and feasibility of maintaining clozapine during chemotherapy.

Researchers conducted a systematic review following PRISMA guidelines, searching Ovid MEDLINE, EMBASE, and Cochrane databases for reports describing the use of clozapine concurrent with myelosuppressive chemotherapy. The review identified 27 eligible cases published up to March 31, 2019. The study extracted data on psychiatric stability, oncologic outcomes, neutropenic nadirs, and the use of supportive agents like granulocyte-colony stimulating factor (G-CSF).

The review found that in 14 of the 27 cases, clozapine was continued, whereas in 13 cases it was discontinued. Of those where clozapine was stopped, 12 patients experienced marked psychiatric deterioration, frequently necessitating the re-introduction of the medication. Conversely, patients who remained on clozapine generally maintained psychiatric stability. Regarding hematologic safety, the study reported that neutropenia-related complications were rare even when clozapine was continued. The authors suggest that discontinuing clozapine in these patients often results in more harm—via psychiatric crisis—than benefit, advocating for a multidisciplinary approach that includes close hematologic monitoring (including weekly blood counts) and collaboration between psychiatric and oncology teams.