Background Delirium is a neurocognitive syndrome common in palliative care. Although typical antipsychotics are the pharmacological management of choice for distressing symptoms of delirium, the atypical antipsychotic olanzapine may have a role.

Aim To evaluate the evidence for olanzapine, given orally or subcutaneously (sc), in the management of delirium in adults in the palliative care setting.

Methods Electronic databases (Embase, MEDLINE, and PsycINFO) were searched in March 2019 complemented by hand-searching using reference lists and review articles. All studies excluding case reports were included. The primary and secondary outcomes were reduction in delirium severity and toxicity respectively. Relevant studies were summarised and synthesised. Meta-analysis was not performed due to heterogeneity in the studies.

Results Five studies with 244 participants were included in the analysis - one randomised controlled trial, one non-randomised trial with a control arm, two prospective cohort studies, and one cross-sectional study. All studies were in cancer patients. Delirium severity reduced by an average of 6.93 on the Memorial Delirium Assessment Score at one week, with no statistical difference seen between olanzapine and alternative antipsychotics. Olanzapine did not cause extrapyramidal side effects (EPSE) in any study but did lead to sedation in three studies (10–30% of participants affected). One study assessed the safety and efficacy of sc olanzapine - no injection site toxicity was seen but the sample was small, attrition was high, and systemic toxicity was noted. The overall quality of the studies was graded as weak.

Conclusion Olanzapine has weak evidence of comparative effectiveness to other antipsychotics in reducing delirium severity in patients with cancer. A lack of EPSE suggests a potential role in the management of delirium in Parkinson’s disease and Lewy body dementia but further studies are required to evaluate this. There is insufficient evidence to support the use of olanzapine sc in this setting.