Opioid-induced neurotoxicity in palliative medicine: a rapid review

BACKGROUND: Opioid-induced neurotoxicity (OIN) is a significant complication in palliative care, presenting with symptoms of hypersomnolence, hallucinations, cognitive dysfunction (including delirium), myoclonus and hyperalgesia. Due to limited research studies, a consensus on recognising these clinical manifestations is yet to be reached, complicating both early diagnosis and management. OBJECTIVES: This rapid review aims to synthesise current evidence on the prevalence, clinical manifestations, risk factors and management strategies of OIN in the palliative care setting to enhance clinical practice. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search of Medline, Embase and the Cochrane Central Database, complemented by supplementary searches in ten palliative care journals. Studies with five or more palliative care patients were included, excluding those involving minors, animal models or substance misuse. Data were extracted, cross-checked and synthesised narratively. RESULTS: A total of 21 studies met the inclusion criteria. Prevalence of OIN varied widely from 6.4% to 38%, with common symptoms including delirium, myoclonus and hyperalgesia. Identified risk factors included age, renal and liver dysfunction, high opioid doses and concurrent use of specific medications. Opioid rotation and dose reduction emerged as potential management strategies, though patient responses varied significantly. CONCLUSIONS: OIN is under-diagnosed due to symptom overlap with other conditions. While opioid rotation and dose reduction show promise in managing OIN, further research is needed to establish standardised diagnostic criteria and effective treatment protocols. Enhanced clinical awareness and an individualised approach to opioid prescribing are crucial for improving patient outcomes in palliative care. PROSPERO REGISTRATION NUMBER: CRD42024543988.