{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:32:01Z","timestamp":1787585521251,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Research Council (NWO)","award":["NWA. 1160.18.300"],"award-info":[{"award-number":["NWA. 1160.18.300"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: As long-term prescription opioid use is associated with increased morbidity and mortality, timely dose reduction of prescription opioids should be considered. However, most research has been conducted on patients using heroin. Given the differences between prescription and illicit opioid use, the aim of this review was to provide an overview of pharmacological strategies to reduce prescription opioid use or improve clinical outcomes for people who experience long-term prescription opioid use, including those with opioid use disorder. Methods: We conducted a systematic database search of PubMed, Embase, CINAHL, and the Cochrane Library. Outcomes included dose reduction, treatment dropout, pain, addiction, and outcomes relating to quality of life (depression, functioning, quality of life). Results: We identified thirteen studies (eight randomized controlled trials and five observational studies). Pharmacological strategies were categorized into two categories: (1) deprescribing (tapering) opioids or (2) opioid agonist treatment (OAT) with long-acting opioids. Tapering strategies decreased opioid dosage and had mixed effects on pain and addiction. OAT with buprenorphine or methadone led to improvements in pain relief and quality of life, with a slight (non-significant) preference for methadone in terms of treatment retention (RR = 1.10 [CI: 0.89\u20131.37]) but not for other outcomes. Most studies had high dropout rates and a serious risk of bias. Conclusions: Tapering reduced prescription opioid doses had mixed effects on pain. OAT improved clinical outcomes without dose reduction. Based on our review findings, there is no clear preference for either tapering or OAT. Tapering may be considered first as it reduces dependency, tolerance, and side effects, but is associated with adverse events and not always feasible. OAT can be a suitable alternative. Non-pharmacological interventions may facilitate tapering. Further research is needed to identify novel pharmacological strategies to facilitate opioid tapering. Registration: PROSPERO 2022 CRD42022323468.<\/jats:p>","DOI":"10.3390\/jcm13247770","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T10:54:20Z","timestamp":1734605660000},"page":"7770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological Strategies to Decrease Long-Term Prescription Opioid Use: A Systematic Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9471-6779","authenticated-orcid":false,"given":"Hannah","family":"Ellerbroek","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), 6525 HR Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7858-7153","authenticated-orcid":false,"given":"Gerard A.","family":"Kalkman","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5398-6414","authenticated-orcid":false,"given":"Cornelis","family":"Kramers","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Canisius-Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands"},{"name":"Department of Pharmacy, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7715-5209","authenticated-orcid":false,"given":"Arnt F. A.","family":"Schellekens","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Nijmegen Institute for Scientist-Practitioners in Addiction (NISPA), 6525 HR Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8560-9514","authenticated-orcid":false,"given":"Bart J. F.","family":"van den Bemt","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Department of Pharmacy, Sint Maartenskliniek, 6574 NA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1097\/j.pain.0000000000002423","article-title":"Efficacy and safety of strong opioids for chronic non-cancer pain and chronic low back pain: A systematic review and meta-analyses","volume":"163","author":"Nury","year":"2021","journal-title":"PAIN"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s40263-019-00660-0","article-title":"Opioid-induced tolerance and hyperalgesia","volume":"33","author":"Mercadante","year":"2019","journal-title":"CNS Drugs"},{"key":"ref_3","first-page":"Cd012509","article-title":"Adverse events associated with medium- and long-term use of opioids for chronic non-cancer pain: An overview of Cochrane Reviews","volume":"10","author":"Els","year":"2017","journal-title":"Cochrane Database Syst. 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