• Naosuke Yokomichi, Isseki Maeda, Tatsuya Morita, Kazuhiro Yoshiuchi, Asao Ogawa, Takayuki Hisanaga, Akihiro Sakashita, Rika Nakahara, Keisuke Kaneishi, and Satoru Iwase.
• Division of Palliative and Supportive Care (N.Y.), Seirei Mikatahara General Hospital, Hamamatsu, Japan; Department of Palliative Care (I.M.), Senri-Chuo Hospital, Osaka, Japan; Division of Palliative and Supportive Care (T.M.), Palliative Care Team, and Seirei Hospice, Seirei Mikatahara General Hospital, Hamamatsu, Japan; Department of Stress Sciences and Psychosomatic Medicine (K.Y.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Psycho-Oncology Service (A.O.), National Cancer Center Hospital East, Kashiwa, Japan; Department of Palliative Medicine (T.H.), Tsukuba Medical Center Hospital, Tsukuba, Japan; Department of Palliative Medicine (A.S.), Hyogo Brain and Heart Center, Himeji, Japan; Department of Psycho-Oncology (R.N.), National Cancer Center Hospital, Tokyo, Japan; Department of Palliative Care Unit (K.K.), JCHO Tokyo Shinjuku Medical Center, Tokyo, Japan; Department of Palliative Medicine (S.I.), Saitama Medical University, Saitama, Japan. Electronic address: n-yokomichi@sis.seirei.or.jp.
• J Pain Symptom Manage. 2022 Jul 1; 64 (1): 28-36.

ContextDelirium is common in patients with advanced cancer, and antipsychotics are widely used for its management.ObjectivesWe aimed to explore the association of the antipsychotic dose with survival of terminally ill cancer patients with delirium.MethodsA 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.ResultsOf 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).ConclusionsHigher 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.Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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