Pharmacological Management of Anxiety in End‐of‐Life Care: A Systematic Review of Benzodiazepines, Opioids, and Psilocybin
Human Psychopharmacology Clinical and Experimental – January 01, 2026
Source: OpenAlex
Summary
A systematic review shows psilocybin, a hallucinogen, offers rapid, sustained anxiety relief for end-of-life patients. Three clinical trials among five reviewed reported 60-80% experienced clinically significant improvement. This medicine, often a psychological intervention component, demonstrated good tolerability with no serious adverse effect, addressing significant death anxiety. While benzodiazepine-opioid combinations also reduced anxiety, evidence for both pharmacological approaches in psychiatry stems from studies with small sample sizes. Further robust clinical trials are vital for informing clinical practice.
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.