# Pharmacological Management of Anxiety in End‐of‐Life Care: A Systematic Review of Benzodiazepines, Opioids, and Psilocybin

## TL;DR

This study reviews how benzodiazepines, opioids, and psilocybin can help manage anxiety in end-of-life care, finding both effective and safe options but noting a lack of strong evidence.

## Contribution

Systematically evaluates the efficacy and safety of benzodiazepines, opioids, and psilocybin for anxiety in end-of-life care.

## Key findings

- Benzodiazepine-opioid combinations and psilocybin both reduced anxiety symptoms in end-of-life patients.
- Psilocybin provided rapid and sustained anxiety relief in 60%-80% of participants.
- Small sample sizes and limited study contexts highlight a need for more high-quality research.

## Abstract

Anxiety is common in patients receiving end‐of‐life care and significantly impacts their quality of life. However, pharmacological management remains challenging due to complex clinical presentations and potential side effects, emphasizing the need for systematically reviewing existing treatments. Here we aim to systematically evaluate the efficacy and safety of pharmacological treatments for anxiety in end‐of‐life care.

Systematic review following PRISMA guidelines, prospectively registered in PROSPERO (CRD42024556913). Comprehensive searches were performed in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. Eligible studies included adults receiving end‐of‐life care and evaluated pharmacological interventions targeting anxiety.

Five studies met inclusion criteria: two assessing benzodiazepines combined with opioids and three evaluating psilocybin. Both benzodiazepine‐opioid combinations and psilocybin reduced anxiety symptoms. Psilocybin studies reported rapid and sustained anxiety relief, with approximately 60%–80% of participants experiencing clinically significant improvements. Both treatment categories showed good tolerability without serious adverse events. However, the evidence base was limited by small sample sizes and narrow study contexts.

Benzodiazepine‐opioid combinations and psilocybin show promise for anxiety relief in end‐of‐life patients. Nevertheless, limited high‐quality evidence highlights an important research gap. Further robust clinical trials are needed to confirm these findings and guide clinical practice in palliative care.