Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 May 3:11:923-934.
doi: 10.2147/JPR.S160255. eCollection 2018.

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

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

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

Diana S Meske et al. J Pain Res. .

Abstract

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

PubMed Disclaimer

Conflict of interest statement

Disclosure Nathaniel Katz has acted as a consultant for Allergan, Plc, Collegium Pharmaceuticals, Inc., Depomed, Inc., Egalet Corporation, Endo Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc., Mallinckrodt, Inc., Pfizer Inc., and Purdue Pharma, L. P. Diana S Meske was employed by Analagesic Solutions when the work was completed for this manuscript, however at the time of publication she was employed by Collegium Pharmaceutical Inc. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Change in PI from randomization baseline to week 12 with active study opioid drug versus placebo. Notes: The standardized mean difference effect size was −0.416 and p<0.001, with a lower bound estimate of −0.521 and an upper bound −0.312. Abbreviation: PI, pain intensity.
Figure 3
Figure 3
Percentage of patients with ≥30% or ≥50% improvement with active study drug versus placebo. Notes: The graph shows the mean (SD) percent of patients with improvement, from each study that reported these data. A binary random-effects meta-analysis using the restricted maximum likelihood method was performed showing a statistically significant difference between active study drug and placebo for both ≥30% and ≥50%.
See this image and copyright information in PMC

References

    1. The use of opioids for the treatment of chronic pain: A consensus statement from the American Academy of Pain Medicine and the American Pain Society [press release] Glenview, IL, USA: 1997. - PubMed
    1. The use of opioids for the treatment of chronic pain: a consensus statement from the American Academy of Pain Medicine and the American Pain Society [press release] Dallas, TX, USA: 1998. - PubMed
    1. US Centers for Disease Control and Prevention (CDC) CDC Guideline for Prescribing Opioids for Chronic Pain. 2016. - PubMed
    1. Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a national institutes of health pathways to prevention workshop. Ann Intern Med. 2015;162(4):276–286. - PubMed
    1. Frieden TR, Houry D. Reducing the risks of relief – The CDC opioid-prescribing guideline. N Engl J Med. 2016;374(16):1501–1504. - PMC - PubMed