[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.236.145.124. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Original Investigation
December 18, 2018

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

Author Affiliations
  • 1Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
  • 2Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
  • 3Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
  • 4Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada
  • 5Chinese Cochrane Centre, West China Hospital, Sichuan University, Chengdu
  • 6Faculty of Medicine, Ain Shams University, Cairo, Egypt
  • 7Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
  • 8Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • 9Now with the Canadian Agency for Drugs and Technologies in Health (CADTH), Toronto, Ontario, Canada
  • 10Pharmaceutical Science, University of Sorocaba, Sao Paulo, Brazil
  • 11Leonardo Hirslanden Klinik Birshof, Münchenstein, Switzerland
  • 12Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 13Department of Internal Medicine, Hospital Alemán de Buenos Aires, Buenos Aires, Argentina
  • 14Department of Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, Ontario, Canada
  • 15Department of Anesthesiology, Perioperative and Pain Medicine, University of Calgary, Calgary, Alberta, Canada
  • 16Department of Family Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada
  • 17Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada
  • 18Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 19Accident and Emergency Department, Queen Mary Hospital, Pokfulam, Hong Kong, China
  • 20Accident and Emergency Department, Tuen Mun Hospital, Hong Kong, China
  • 21Department of Medicine, Gjøvik, Innlandet Hospital Trust, Norway
  • 22Department of Hygiene and Dietetics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
  • 23Institute for Clinical Epidemiology and Biostatistics, University of Basel Hospital, Basel, Switzerland
  • 24Department of Clinical Research, University of Basel Hospital, Basel, Switzerland.
  • 25Department of Anesthesiology, Operative Intensive Care, Preclinical Emergency Medicine and Pain Management, University of Basel Hospital, Basel, Switzerland
  • 26Isfahan Medical Education Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
  • 27Canadian Academy of Osteopathy, Hamilton, Ontario, Canada
  • 28Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  • 29Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada
  • 30Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio
JAMA. 2018;320(23):2448-2460. doi:10.1001/jama.2018.18472
Key Points

Question  Is the use of opioids to treat chronic noncancer pain associated with greater benefits or harms compared with placebo and alternative analgesics?

Findings  In this meta-analysis that included 96 randomized clinical trials and 26 169 patients with chronic noncancer pain, the use of opioids compared with placebo was associated with significantly less pain (−0.69 cm on a 10-cm scale) and significantly improved physical functioning (2.04 of 100 points), but the magnitude of the association was small. Opioid use was significantly associated with increased risk of vomiting.

Meaning  Opioids may provide benefit for chronic noncancer pain, but the magnitude is likely to be small.

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, there were 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 cm [95% 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 cm [95% 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 functioning may be similar, although the evidence was from studies of only low to moderate quality.

×