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

Anxiety is common and harmful for people receiving end-of-life care, but treating it with drugs is difficult. A systematic review of five studies found that both benzodiazepine-opioid combinations and psilocybin reduced anxiety symptoms. Psilocybin provided rapid and lasting relief, with about 60% to 80% of participants showing meaningful improvement. Both types of treatment were well tolerated and caused no serious side effects. However, the evidence is limited by small studies and narrow contexts, highlighting a need for more robust clinical trials.

Study at a glance

Abstract

ABSTRACT Objective 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. Design 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. Results 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. Conclusions 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.