Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis

Avery, Nicholas; McNeilage, Amy G; Stanaway, Fiona; Ashton-James, Claire E; Blyth, Fiona M; Martin, Rebecca; Gholamrezaei, Ali; Glare, Paul

doi:10.1136/bmj-2021-066375

Cited by 57Opioid Use Disorder TreatmentPain Management and Opioid UseMusculoskeletal pain and rehabilitation

Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis

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Avery, Nicholas, McNeilage, Amy G, Stanaway, Fiona, Ashton-James, Claire E, Blyth, Fiona M, Martin, Rebecca, Gholamrezaei, Ali, Glare, Paul·2022·BMJ

DOI 10.1136/bmj-2021-066375PMC PMC8977989

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Abstract

Abstract Objective To review interventions to reduce long term opioid treatment in people with chronic non-cancer pain, considering efficacy on dose reduction and discontinuation, pain, function, quality of life, withdrawal symptoms, substance use, and adverse events. Design Systematic review and meta-analysis of randomised controlled trials and non-randomised studies of interventions. Data sources Medline, Embase, PsycINFO, CINAHL, and the Cochrane Library searched from inception to July 2021. Reference lists and previous reviews were also searched and experts were contacted. Eligibility criteria for study selection Original research in English. Case reports and cross sectional studies were excluded. Data extraction and synthesis Two authors independently selected studies, extracted data, and used the Cochrane risk-of-bias tools for randomised and non-randomised studies (RoB 2 and ROBINS-I). Authors grouped interventions into five categories (pain self-management, complementary and alternative medicine, pharmacological and biomedical devices and interventions, opioid replacement treatment, and deprescription methods), estimated pooled effects using random effects meta-analytical models, and appraised the certainty of evidence using GRADE (grading of recommendations, assessment, development, and evaluation). Results Of 166 studies meeting inclusion criteria, 130 (78%) were considered at critical risk of bias and were excluded from the evidence synthesis. Of the 36 included studies, few had comparable treatment arms and sample sizes were generally small. Consequently, the certainty of the evidence was low or very low for more than 90% (41/44) of GRADE outcomes, including for all non-opioid patient outcomes. Despite these limitations, evidence of moderate certainty indicated that interventions to support prescribers’ adherence to guidelines increased the likelihood of patients discontinuing opioid treatment (adjusted odds ratio 1.5, 95% confidence interval 1.0 to 2.1), and that these prescriber interventions as well as pain self-management programmes reduced opioid dose more than controls (intervention v control, mean difference –6.8 mg (standard error 1.6) daily oral morphine equivalent, P<0.001; pain programme v control, −14.31 mg daily oral morphine equivalent, 95% confidence interval −21.57 to −7.05). Conclusions Evidence on the reduction of long term opioid treatment for chronic pain continues to be constrained by poor study methodology. Of particular concern is the lack of evidence relating to possible harms. Agreed standards for designing and reporting studies on the reduction of opioid treatment are urgently needed. Review registration PROSPERO CRD42020140943.

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Most longitudinal studies have found that patients on opioid agonists are not able to successfully complete tapering attempts.
“Nevertheless, most longitudinal studies have found that patients on opioid agonists are not able to successfully complete tapering attempts.6–8”
From Tapering and withdrawing opioids: guidance informed by fundamental principles to minimise withdrawal symptoms (2025) · cites this paper as [8]
The Results (Narrative synthesis; page unavailable) report that a buprenorphine/naloxone tapering trial failed to retain any of its six tapering participants. That supports difficulty completing a taper in one trial, but the review does not establish that most longitudinal studies found patients on opioid agonists unable to complete tapering. (LLM, conf=0.84)
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Authors: Avery, N., McNeilage, A. G., Stanaway, F., Ashton-James, C. E., Blyth, F. M., Martin, R., Gholamrezaei, A., & Glare, P.
Affiliations: The University of Sydney (AU)
Royal North Shore Hospital (AU)
Corresponding author: Glare, Paul
ORCID: Avery, Nicholas
McNeilage, Amy G
Stanaway, Fiona
Ashton-James, Claire E
Blyth, Fiona M
Martin, Rebecca
Gholamrezaei, Ali
Glare, Paul
Venue: BMJ
Publisher: BMJ
Published: 2022-04-04
Volume: 377
Pages: e066375
ISSN: 1756-1833 (ISSN-L)
DOI: 10.1136/bmj-2021-066375
PMC: PMC8977989
OpenAlex: W4224236297
Cited by: 56
References: 218
Citations by year: 2026: 12 · 2025: 17 · 2024: 11 · 2023: 10 · 2022: 6
FWCI: 2.19
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/4.0/ (unspecified)
Locations: BMJ (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: Ernest Heine Family Foundation
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
Keywords: chronic non-cancer pain, opioid dose reduction, opioid discontinuation, opioid substitution therapy, complementary and alternative medicine, guideline adherence, withdrawal symptoms, quality of life, morphine milligram equivalents, patient-reported outcomes, substance use, adverse events
MeSH terms: Analgesics, Opioid, Cross-Sectional Studies, Humans, Quality of Life, Chronic Pain, Pain Management

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Efficacy of interventions to reduce long term opioid treatment for chronic non-cancer pain: systematic review and meta-analysis

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