Association of Antipsychotic Dose With Survival of Advanced Cancer Patients With Delirium

Abstract

Context: Delirium is common in patients with advanced cancer, and antipsychotics are widely used for its management.

Objectives: We aimed to explore the association of the antipsychotic dose with survival of terminally ill cancer patients with delirium.

Methods: A secondary analysis of a multicenter prospective observational study was conducted. We enrolled adult advanced cancer patients who developed delirium and received antipsychotics at 14 palliative care units in Japan between September 2015 and May 2016. Hazard ratios of survival after starting antipsychotics between groups with different oral chlorpromazine equivalent doses: low: <100 mg, moderate: 100-200 mg, high: ≥200 mg, were calculated with adjustment for potential confounders using Cox regression. The antipsychotic dose-specific mortality risk was estimated with smooth splines.

Results: Of 453 patients enrolled, 422 patients were analyzed. The median antipsychotic dose was 92.6 mg: low-dose (N = 231), moderate-dose (122), and high-dose (69). The median survival of all patients was 11 days. Compared with the low-dose group, the high-dose group showed a significantly shorter survival (HR: 1.46, 95%CI: 1.08-1.98). Smooth splines demonstrated that HR continuously increased as the antipsychotic dose increased. In patients treated with atypical antipsychotics, the high-dose group showed a significantly shorter survival than the low-dose group (HR: 2.86), while in patients treated with typical antipsychotics, survival was not significantly different (0.99).

Conclusions: Higher doses of antipsychotics were associated with increased mortality in terminally ill cancer patients with delirium. To minimize the potential mortality risk, antipsychotics should be started at low doses and titrated carefully.

Keywords: Advanced cancer; antipsychotics; delirium; end of life; survival; terminal delirium.