Efficacy, Tolerability, and Dose-Dependent Effects of Opioid Analgesics for Low Back Pain: A Systematic Review and Meta-analysis

JAMA Intern Med. 2016 Jul 1;176(7):958-68. doi: 10.1001/jamainternmed.2016.1251.


Importance: Opioid analgesics are commonly used for low back pain, however, to our knowledge there has been no systematic evaluation of the effect of opioid dose and use of enrichment study design on estimates of treatment effect.

Objective: To evaluate efficacy and tolerability of opioids in the management of back pain; and investigate the effect of opioid dose and use of an enrichment study design on treatment effect.

Data sources: Medline, EMBASE, CENTRAL, CINAHL, and PsycINFO (inception to September 2015) with citation tracking from eligible randomized clinical trials (RCTs).

Study selection: Placebo-controlled RCTs in any language.

Data extraction and synthesis: Two authors independently extracted data and assessed risk of bias. Data were pooled using a random effects model with strength of evidence assessed using the grading of recommendations assessment, development, and evaluation (GRADE).

Main outcomes and measures: The primary outcome measure was pain. Pain and disability outcomes were converted to a common 0 to 100 scale, with effects greater than 20 points considered clinically important.

Results: Of 20 included RCTs of opioid analgesics (with a total of 7925 participants), 13 trials (3419 participants) evaluated short-term effects on chronic low back pain, and no placebo-controlled trials enrolled patients with acute low back pain. In half of these 13 trials, at least 50% of participants withdrew owing to adverse events or lack of efficacy. There was moderate-quality evidence that opioid analgesics reduce pain in the short term; mean difference (MD), -10.1 (95% CI, -12.8 to -7.4). Meta-regression revealed a 12.0 point greater pain relief for every 1 log unit increase in morphine equivalent dose (P = .046). Clinically important pain relief was not observed within the dose range evaluated (40.0-240.0-mg morphine equivalents per day). There was no significant effect of enrichment study design.

Conclusions and relevance: For people with chronic low back pain who tolerate the medicine, opioid analgesics provide modest short-term pain relief but the effect is not likely to be clinically important within guideline recommended doses. Evidence on long-term efficacy is lacking. The efficacy of opioid analgesics in acute low back pain is unknown.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Analgesics, Opioid* / administration & dosage
  • Analgesics, Opioid* / therapeutic use
  • Chronic Pain
  • Humans
  • Low Back Pain* / diagnosis
  • Low Back Pain* / drug therapy
  • Medication Therapy Management
  • Pain Management / methods*
  • Pain Measurement / methods
  • Treatment Outcome


  • Analgesics, Opioid