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Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis

Fuggle, Nicholas; Curtis, Elizabeth; Shaw, Sarah; Spooner, Laura; Bruyère, Olivier; Ntani, Georgia; Parsons, Camille; Conaghan, Philip G.; Corp, Nadia; Honvo, Germain; Uebelhart, Daniel; Baird, Janis; Dennison, Elaine; Reginster, Jean-Yves; Cooper, Cyrus

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Nicholas Fuggle

Elizabeth Curtis

Sarah Shaw

Laura Spooner

Olivier Bruyère

Georgia Ntani

Camille Parsons

Philip G. Conaghan

Germain Honvo

Daniel Uebelhart

Janis Baird

Elaine Dennison

Jean-Yves Reginster

Cyrus Cooper


OBJECTIVE: We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS: A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). RESULTS: Database searches identified 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42-7.89); ER opioids (RR 4.22, 95% CI 3.44-5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87-18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22-5.18); ER opioids (RR 4.03, 95% CI 3.37-4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74-7.43; ER opioids: RR 7.87, 95% CI 5.20-11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90-4.02; ER opioids: RR 2.76, 95% CI 2.19-3.47) was found with all opioid formulations versus placebo. CONCLUSIONS: Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.

Journal Article Type Review
Acceptance Date Apr 1, 2019
Publication Date 2019-04
Publicly Available Date May 26, 2023
Journal Drugs & Aging
Print ISSN 1170-229X
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 36
Pages 129 - 143
Keywords osteoarthritis
Publisher URL


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