A systematic review of randomized trials of long-term opioid management for chronic non-cancer pain

Laxmaiah Manchikanti, Hary Ailinani, Dhanalakshmi Koyyalagunta, Sukdeb Datta, Vijay Singh, Ike Eriator, Nalini Sehgal, Rinoo Shah, Ramsin Benyamin, Ricardo Vallejo, Bert Fellows, Paul J. Christo

Research output: Contribution to journalReview articlepeer-review

129 Scopus citations


Background: Even though opioids have been used for pain for thousands of years, opioid therapy for chronic non-cancer pain is controversial due to concerns regarding the long-term effectiveness and safety, particularly the risk of tolerance, dependance, or abuse. While the debate continues, the use of chronic opioid therapy for chronic non-cancer pain has increased exponentially. Even though evidence is limited, multiple expert panels have concluded that chronic opioid therapy can be effective therapy for carefully selected and monitored patients with chronic non-cancer pain. Study Design: A systematic review of randomized trials of opioid management for chronic noncancer pain. Objective: The objective of this systematic review is to evaluate the clinical efficacy of opioids in the treatment of chronic non-cancer pain. Methods: A comprehensive evaluation of the literature relating to opioids in chronic non-cancer pain was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs) and Jadad criteria. A literature search was conducted by using PubMed, EMBASE, Cochrane library, ECRI Institute Library, U.S. Food and Drug Administration (FDA) website, U.S. National Guideline Clearinghouse (NGC), Database of Abstracts of Reviews of Effectiveness (DARE), clinical trials, systematic reviews and cross references from systematic reviews. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) and used by other systematic reviews and guidelines. Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, withdrawals, and adverse effects. Results: Based on the USPSTF criteria, the indicated level of evidence was fair for Tramadol in managing osteoarthritis. For all the drugs assessed, including Tramadol, for all other conditions, the evidence was poor based on either weak positive evidence, indeterminate evidence, or negative evidence. Limitations: A paucity of literature, specifically with follow-up beyond 12 weeks for all types of opioids with controlled trials for various chronic non-cancer pain conditions. Conclusions: This systematic review illustrated fair evidence for Tramadol in managing osteoarthritis with poor evidence for all other drugs and conditions. Thus, recommendations must be based on non-randomized studies.

Original languageEnglish (US)
Pages (from-to)91-121
Number of pages31
JournalPain physician
Issue number2
StatePublished - Mar 2011


  • Adverse effects
  • Buprenorphine
  • Chronic non-cancer pain
  • Fentanyl
  • Functional improvement
  • Hydrocodone
  • Hydromorphone
  • Methadone
  • Morphine
  • Opioid effectiveness
  • Opioid efficacy
  • Opioids
  • Oxycodone
  • Oxymorphone
  • Randomized trials
  • Significant pain relief
  • Systematic reviews
  • Tapentadol
  • Tramadol

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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