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There is increasing interest in new atypical neuroleptics, such as olanzapine and risperidone, as substitutes for haloperidol in the management of delirium and nausea in palliative care. This interest stems from their large spectrum of action on numerous receptors that are clearly involved in the mechanisms of both delirium and nausea. In the psychiatric treatment of schizophrenia and psychosis, it has been demonstrated that these molecules induce significantly less extra-pyramidal side effects such as akathisia, acute dystonia, and parkinsonism. However, no superiority of these molecules over traditional neuroleptics such as haloperidol, has been demonstrated. In palliative care, haloperidol is prescribed at much lower doses, and for shorter durations, thereby potentially reducing the risk of extrapyramidal side effects, which is usually linked to dose and duration of treatment. The level of evidence supporting the use of atypical neuroleptics in palliative medicine, both for delirium and nausea, is limited to case reports and one open-label study. Larger controlled trials are required. The absence of parenteral formulations of atypical neuroleptics is another limiting factor to their use in palliative care. This article explores the existing level of evidence for the management of delirium and nausea in palliative care and psychiatry. We present a summary of extrapyramidal side-effects. We identify situations where atypical neuroleptics could be prescribed instead of haloperidol in the management of delirium in the palliative patient. These situations include treatment duration of over 2 or 3 weeks, and patients with extrapyramidal side effects.