Impact of treatment duration on the effectiveness of opioid analgesia: a systematic review and meta-analysis

Opioid use can heighten pain perception over time.

To determine whether the effectiveness of opioid analgesia diminishes with treatment duration in those with chronic low back pain or osteoarthritis.

Systematic review of randomised trials comparing opioids with placebo/opioid-minimised pain management strategies in those with chronic low back pain or osteoarthritis.

A random-effects meta-analysis using MEDLINE, Embase, CENTRAL, and Scopus databases was undertaken in January 2025. The primary outcome was attainment of clinically important pain relief ('moderate' or ≥30% improvement). The secondary outcome was on-treatment pain (100-point scale). The primary analysis was difference in primary/secondary outcomes across short-term (≤4 weeks), intermediate-term (4-12 weeks), and long-term (≥12 weeks) duration subgroups.

In total, 27 trials were eligible for inclusion. Clinically important pain relief differed significantly between short-, intermediate-, and long-term treatment durations (P = 0.05). Opioid recipients were more likely to be responders in short-term trials (eight trials, risk ratio [RR] 1.42, 95% confidence interval [CI] = 1.08 to 1.89, moderate-certainty evidence), but not in intermediate-term trials (three trials, RR 1.04, 95% CI = 0.84 to 1.30, low-certainty evidence), or long-term trials (nine trials, RR 0.91, 95% CI = 0.73 to 1.14, moderate-certainty evidence), which trended in favour of controls. The mean difference in pain scores failed to reach this review's definition of clinical significance (≥10 points) for any timepoint, but was statistically significant in the short and intermediate term.

Although opioids likely provide meaningful pain relief over short durations (≤4 weeks), they appear to provide little or no benefit beyond placebo over longer periods, and may worsen pain control beyond 12 weeks.