Short, Intermediate, and Long-Term Effects of Opioids on Pain Intensity in Patients with Osteoarthritis or Low Back Pain: A Systematic Review and Meta-Analysis

Abstract

Chronic opioid use is associated with the development of hyperalgesia, which may end up attenuating any analgesic benefits over long-term therapy. We wanted to determine whether the analgesic efficacy of opioids compared to control therapy for osteoarthritis and chronic lower back pain differed over short, intermediate, and long-term treatment duration. After publishing our review protocol, we conducted a systematic electronic search in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and Scopus, and extracted relevant papers on September 5, 2019. After dual title/abstract and full text screenings, we were left with 25 eligible randomized controlled trials that enrolled patients with either osteoarthritis and/or chronic lower back pain and compared opioid therapy to placebo/opioid-minimized pain management. Of these, 9 studies employed an “enriched-enrolment randomized-withdrawal design” where opioids were introduced in all participants and then withdrawn in those randomized to the placebo arm. These studies were excluded from the main analysis. Studies were categorized as short (≤4 week), intermediate (4-12 week), or long-term (≥12 week) and our primary outcome was the number of people obtaining a 30% or better reduction in pain, which we analysed using Forest plots of the three duration subgroups. The analgesic efficacy of opioids compared to control differed significantly between the three subgroups (Chi² = 6.64, df = 2, P = 0.04). The only significant difference in analgesia was observed in short-term studies, where 53% more patients experienced clinically significant analgesia in the opioid arm compared to the control arm (RR 1.53, 95% CI 1.09 to 2.14). There was no statistically significant difference in analgesic efficacy of opioids compared to control in intermediate-term studies (RR 1.01, 95% CI 0.72 to 1.43), nor in long-term studies (RR 0.86, 95% CI 0.69 to 1.08), which trended towards harm. This review provides evidence that the analgesic efficacy of opioids in comparison to control in patients with osteoarthritis and chronic lower back pain diminishes over treatment duration. Although we see an analgesic benefit of opioids in the short-term, this benefit is not observed in therapy that lasts over 4 weeks, which supports the hypothesis that opioids may induce hyperalgesia which attenuates their analgesic benefit over time. Medical practitioners should consider prescribing only short courses of opioids for patients with chronic non-cancer pain.