Opioids for Chronic Noncancer Pain A Systematic Review and Meta-analysis

Abstract

IMPORTANCE Harms and benefits of opioids for chronic noncancer pain remain unclear. OBJECTIVE To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. DATA SOURCES AND STUDY SELECTION The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. DATA EXTRACTION AND SYNTHESIS Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. MAIN OUTCOMES AND MEASURES The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference MID is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score SF-36 PCS; higher is better and the MID is 5 points), and incidence of vomiting. RESULTS Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years interquartile range, 51-61 years) were included. Of the included studies, therewere 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference WMD, -0.69 cm 95% CI, -0.82 to -0.56 cm on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9%95% CI, 9.7% to 14.1%), improved physical functioning (WMD, 2.04 points 95% CI, 1.41 to 2.68 points on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5%95% CI, 5.9% to 11.2%), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low-to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm95% CI, -1.54 to 0.34 cm; physical functioning: WMD, -0.90 points 95% CI, -2.69 to 0.89 points), tricyclic antidepressants (pain: WMD, -0.13 cm 95% CI, -0.99 to 0.74 cm; physical functioning: WMD, -5.31 points 95% CI, -13.77 to 3.14 points), and anticonvulsants (pain: WMD, -0.90 cm95% CI, -1.65 to -0.14 cm; physical functioning: WMD, 0.45 points 95% CI, -5.77 to 6.66 points). CONCLUSIONS AND RELEVANCE In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioningmay be similar, although the evidence was from studies of only low to moderate quality.