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

Abstract

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. Electronic supplementary material The online version of this article (10.1007/s40266-019-00666-9) contains supplementary material, which is available to authorized users.

Opioids for chronic osteoarthritis pain: An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks double‐blind duration

“…Fuggle et al analysed 17 RCTs with opioids for OA of which 14 RCTs were included in our review too. They found an increased risk of AEs with opioids compared with placebo (RR 1.70, 95% CI 1.37 to 2.12) (Fuggle et al, ).…”

“…A recent Cochrane review analysed tramadol with and without acetaminophen for OA pain (Toupin et al, ). Another recent systematic review analysed the harms, but not the efficacy of all opioids for OA pain (Fuggel et al, ).…”

Associations between pre-surgical daily opioid use and short-term outcomes following knee or hip arthroplasty: a prospective, exploratory cohort study

“…Whilst the Royal Australian College of General Practitioners consider opioids an important part of the armoury for managing pain, their use is cautioned for their association with dose-dependent harm including dependence, withdrawal, falls, and cognitive effects, and rather should be administered as a last resort [7]. It is well-recognised that people suffering from chronic knee or hip arthritis are prescribed strong opioid therapy [8][9][10], and this is despite i) an absence of strong evidence of clinically relevant benefit over active or inactive control therapies [11,12], and ii) concern over their safety [13]. Moreover, many peopleup to 24% as estimated by a recent systematic review [14] with end-stage arthritis and awaiting total knee or hip arthroplasty (TKA, THA) are taking opioids prior to surgery and this appears to have implications for recovery.…”

Expert Opinion on the Extensive Use of Prescription Crystalline Glucosamine Sulfate in the Multimodal Treatment of Osteoarthritis in Ukraine, Kazakhstan, Uzbekistan, and Armenia

“…Opioids are associated with significant morbidity, respiratory depression, and may result in dependence and drug abuse. 36 Generally, opioids utilization depends on safety, consent, and cost-effectiveness and their availability in the markets of certain countries. 5,29 Duloxetine, a selective inhibitor of serotonin and norepinephrine reuptake increasing the inhibitory descendent pathway reduces the neuronal pain transmission.…”