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Despite a growing understanding of opioid-related harms, there is a lack of published protocols for structured deprescribing of hospital-initiated opioids in Europe. Opioid stewardship initiatives, which encompass coordinated approaches to optimize prescribing practices and reduce long-term use, require deprescribing frameworks that extend beyond medication discontinuation to include patient communication and systematic care coordination. We aimed to develop an actionable opioid deprescribing framework that builds on trialed reduction protocols with patient-centered determinants for systematic implementation in tertiary care. We conducted a multi-level consensus study to bridge evidence, clinician expertise, and patient perspectives. Initial framework development included focus group discussions with multidisciplinary clinicians (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095). The framework was validated for our institution via a two-round Delphi survey across six medical specialties (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911). An opioid reduction calculator was developed in Python, incorporating clinical parameters to determine reduction trajectories for prespecified starting and end doses. Final refinement included interviews with patients receiving opioid therapy (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911) to optimize understandability of the reduction plan as a patient handout and for developing a patient pamphlet on opioids with patients (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200913). The framework identified four critical domains for successful deprescribing of hospital-initiated opioids: interventional reduction strategies, patient-specific physiological variables, environmental enablers, and procedural elements. Reduction strategies categorized patients into chronic and new users, incorporating grace periods for dose stabilization, with particular attention given to patients exhibiting pain catastrophizing behavior and frailty. Environmental and procedural factors included shared responsibility and interdisciplinarity, ensuring that follow-up is facilitated by a coordinated care team. These findings were operationalized into the reduction calculator, proposing initial individualized reduction plans (10\u201325%) based on key patient-specific variables with built-in stabilization periods. Delphi validation achieved full consensus (87.8% first-round agreement; 100% final consensus) on all framework components. Patient involvement refined the handout to improve understandability and actionability, and yielded comprehensive information on opioids. We developed an actionable opioid deprescribing framework that bridges published evidence with patient-centered care for our institution, providing other healthcare institutions with a practical blueprint for their own implementation. Our multi-level consensus identified critical patient-specific and environmental determinants, and established individualized reduction protocols, addressing a critical gap in transitional care while facilitating safe opioid deprescribing practices.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-19823-9","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:52:09Z","timestamp":1760453529000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimizing deprescribing of hospital-initiated opioids: a multi-level consensus study bridging evidence, expertise, and patient perspectives"],"prefix":"10.1038","volume":"15","author":[{"given":"Marcel","family":"Rainer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elin","family":"Sebesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Monika","family":"Wertli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Michelle","family":"Burden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"St\u00e4mpfli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"19823_CR1","doi-asserted-by":"crossref","unstructured":"Donohue, J. 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