Efficacy and Safety of Oral and Transdermal Opioid Analgesics for Musculoskeletal Pain in Older Adults: A Systematic Review of Randomized, Placebo-Controlled Trials

J Pain. 2018 May;19(5):475.e1-475.e24. doi: 10.1016/j.jpain.2017.12.001. Epub 2017 Dec 11.


This systematic review with meta-analysis was performed to evaluate the efficacy and safety of using opioid analgesics in older adults with musculoskeletal pain. We searched Cochrane Library, MEDLINE, EMBASE, Web of Science, AMED, CINAHL, and LILACS for randomized controlled trials with mean population age of 60 years or older, comparing the efficacy and safety of opioid analgesics with placebo for musculoskeletal pain conditions. Reviewers extracted data, assessed risk of bias, and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Random effects models were used to calculate standardized mean differences (when different scales were used across trials), mean differences and odds ratios with respective 95% confidence intervals (CIs). Meta-regressions were carried out to assess the influence of opioid analgesic daily dose and treatment duration on our main outcomes. We included 23 randomized placebo-controlled trials in the meta-analysis. Opioid analgesics had a small effect on decreasing pain intensity (standardized mean difference = -.27; 95% CI = -.33 to -.20) and improving function (standardized mean difference = -.27, 95% CI = -.36 to -.18), which was not associated with daily dose or treatment duration. The odds of adverse events were 3 times higher (odds ratio = 2.94; 95% CI = 2.33-3.72) and the odds of treatment discontinuation due to adverse events 4 times higher (odds ratio = 4.04; 95% CI = 3.10-5.25) in patients treated with opioid analgesics. The results show that in older adults suffering from musculoskeletal pain, using opioid analgesics had only a small effect on pain and function at the cost of a higher odds of adverse events and treatment discontinuation. For this specific population, the opioid-related risks may outweigh the benefits.

Perspective: The systematic review shows that, in older adults suffering from musculoskeletal conditions, opioid analgesics have only a small effect on pain and disability. Conversely, this population is at higher risk of adverse events. The results may reflect age-related physiological changes in pain processing, pharmacokinetics, and pharmacodynamics.

Keywords: Ageing; opioid; osteoarthritis; pain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Constipation / chemically induced
  • Headache / chemically induced
  • Humans
  • Middle Aged
  • Musculoskeletal Pain / diagnosis
  • Musculoskeletal Pain / drug therapy*
  • Musculoskeletal Pain / epidemiology
  • Nausea / chemically induced
  • Pain Measurement / drug effects*
  • Pain Measurement / methods
  • Randomized Controlled Trials as Topic / methods*
  • Treatment Outcome


  • Analgesics, Opioid

Associated data

  • ANZCTR/ACTRN 12609000966291
  • ANZCTR/ACTRN 12613000530729
  • ANZCTR/ACTRN 12615000775516