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Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials

Authors Meske DS, Lawal OD, Elder H, Langberg V, Paillard F, Katz N

Received 19 December 2017

Accepted for publication 27 February 2018

Published 3 May 2018 Volume 2018:11 Pages 923—934


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Michael E Schatman

Diana S Meske,1 Oluwadolapo D Lawal,1 Harrison Elder,1 Valerie Langberg,2 Florence Paillard,1 Nathaniel Katz1,3

1Analgesic Solutions, Natick, MA, USA, 2The Center for Evidence Synthesis in Health, Brown University, Providence, RI, USA, 3Department of Anesthesiology and Perioperative Medicine, Tufts University School of Medicine, Boston, MA, USA

Introduction: Opioids have been used for millennia for the treatment of pain. However, the long-term efficacy of opioids to treat chronic non-cancer pain continues to be debated. To evaluate opioids’ efficacy in chronic non-cancer pain, we performed a meta-analysis of published clinical trials for μ-opioid receptor agonists performed for US Food and Drug Administration approval.
Methods: MEDLINE and Cochrane trial register were searched for enriched enrollment randomized withdrawal studies (before June 2016). Selection criteria included: adults, ≥10 subjects per arm, any chronic pain condition, double-blind treatment period lasting ≥12 weeks, and all μ-agonist opioids approved in the USA.
Results: Fifteen studies met criteria. Opioid efficacy was statistically significant (p<0.001) versus placebo for pain intensity (standardized mean difference: −0.416), ≥30% and ≥50% improvement in pain (risk difference: 0.166 and 0.137), patient global impression of change (0.163), and patient global assessment of study medication (0.194). There were minor benefits on physical function and no effect on mental function.
Conclusion: Opioids are efficacious in the treatment of chronic non-cancer pain for up to 3 months in randomized controlled trials. This should be considered, alongside data on opioid safety, in the use of opioids for the treatment of chronic pain.

Keywords: opioid analgesics, non-cancer pain, long-term efficacy, EERW trials, opioid efficacy; evidence-based medicine

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