The finding:
Advanced stage cancer patients with delirium who were treated with high dose (>200mg/day chlorpromazine equivalent) antipsychotics had significantly shorter survival than those treated with low dose (<100mg/day) with a hazard ratio of 1.46. The increase in mortality risk increased as antipsychotic dose increased. The mortality risk difference was seen in people with predicted survival in the range of weeks but not in those with predicted survival time of days. A second notable finding was that atypical antipsychotics showed a clear dose-response trend for shorter survival, whereas typical antipsychotics did not have a similar trend. While there are inadequate data around the clinical context and patient-level decision-making to draw firm conclusions about the mortality risk and dosing of typical antipsychotics, it does seem clear that higher doses of atypical antipsychotics carry higher mortality risk than lower doses. The authors suggest that both typical and atypical antipsychotics should be started at low doses and titrated carefully to minimize risk of mortality.

Strength and weaknesses:
The strengths of this study are that it was a multi-center prospective study that adjusted for confounders in age, sex, clinical survival prediction, co-treatments, etiologies, delirium subtypes and severity, and antipsychotic class used. Weaknesses include an observational design which cannot confirm causal relationships. There was not a standardized delirium treatment protocol employed. Severity of agitation and the condition of the patient could influence dosing but were not part of the adjustment scheme. The dose of antipsychotic was only collected once on day three and the data were analyzed under the assumption that mortality risk was comparable among different antipsychotics within a class which may be incorrect.

Relevance:
C-L psychiatrists are often called to assist in management of agitation and delirium in patients nearing the end of life with metastatic cancer. Awareness of the potential risks of antipsychotics in this population will allow us to provide the best-informed care for this vulnerable group.