Jason W Busse1,2,3,4, Li Wang1,2,5, Mostafa Kamaleldin6, Samantha Craigie3, John J Riva3,7, Luis Montoya8, Sohail M Mulla3,9, Luciane C Lopes10, Nicole Vogel11, Eric Chen12, Karin Kirmayr13, Kyle De Oliveira14, Lori Olivieri15, Alka Kaushal1,3,16, Luis E Chaparro17, Inna Oyberman17, Arnav Agarwal3,18, Rachel Couban1, Ludwig Tsoi19, Tommy Lam20, Per Olav Vandvik21, Sandy Hsu3, Malgorzata M Bala22, Stefan Schandelmaier3,23,24, Anne Scheidecker2,25, Shanil Ebrahim3, Vahid Ashoorion1,26, Yasir Rehman1,27, Patrick J Hong28, Stephanie Ross3, Bradley C Johnston3,29, Regina Kunz24, Xin Sun3,5, Norman Buckley1,2, Daniel I Sessler30, Gordon H Guyatt3. 1. Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada. 2. Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada. 3. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. 4. Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada. 5. Chinese Cochrane Centre, West China Hospital, Sichuan University, Chengdu. 6. Faculty of Medicine, Ain Shams University, Cairo, Egypt. 7. Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada. 8. Krembil Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada. 9. Now with the Canadian Agency for Drugs and Technologies in Health (CADTH), Toronto, Ontario, Canada. 10. Pharmaceutical Science, University of Sorocaba, Sao Paulo, Brazil. 11. Leonardo Hirslanden Klinik Birshof, Münchenstein, Switzerland. 12. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada. 13. Department of Internal Medicine, Hospital Alemán de Buenos Aires, Buenos Aires, Argentina. 14. Department of Anesthesiology and Pain Medicine, University of Ottawa, Ottawa, Ontario, Canada. 15. Department of Anesthesiology, Perioperative and Pain Medicine, University of Calgary, Calgary, Alberta, Canada. 16. Department of Family Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada. 17. Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada. 18. Department of Medicine, University of Toronto, Toronto, Ontario, Canada. 19. Accident and Emergency Department, Queen Mary Hospital, Pokfulam, Hong Kong, China. 20. Accident and Emergency Department, Tuen Mun Hospital, Hong Kong, China. 21. Department of Medicine, Gjøvik, Innlandet Hospital Trust, Norway. 22. Department of Hygiene and Dietetics, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland. 23. Institute for Clinical Epidemiology and Biostatistics, University of Basel Hospital, Basel, Switzerland. 24. Department of Clinical Research, University of Basel Hospital, Basel, Switzerland. 25. Department of Anesthesiology, Operative Intensive Care, Preclinical Emergency Medicine and Pain Management, University of Basel Hospital, Basel, Switzerland. 26. Isfahan Medical Education Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran. 27. Canadian Academy of Osteopathy, Hamilton, Ontario, Canada. 28. Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. 29. Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada. 30. Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio.
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.
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.
Authors: Amanda M Brandow; C Patrick Carroll; Susan Creary; Ronisha Edwards-Elliott; Jeffrey Glassberg; Robert W Hurley; Abdullah Kutlar; Mohamed Seisa; Jennifer Stinson; John J Strouse; Fouza Yusuf; William Zempsky; Eddy Lang Journal: Blood Adv Date: 2020-06-23
Authors: Cristina Miliano; E Reilly Scott; Laura B Murdaugh; Emma R Gnatowski; Christine L Faunce; Megan S Anderson; Malissa M Reyes; Ann M Gregus; Matthew W Buczynski Journal: J Neurosci Methods Date: 2019-10-12 Impact factor: 2.390
Authors: Nathan P Coussens; G Sitta Sittampalam; Samantha G Jonson; Matthew D Hall; Heather E Gorby; Amir P Tamiz; Owen B McManus; Christian C Felder; Kurt Rasmussen Journal: J Pharmacol Exp Ther Date: 2019-09-03 Impact factor: 4.030
Authors: Scott G Weiner; Shih-Chuan Chou; Cindy Y Chang; Chad Garner; Sanae El Ibrahimi; Sara Hallvik; Michelle Hendricks; Olesya Baker Journal: Pain Med Date: 2020-12-25 Impact factor: 3.750