High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews

Cochrane Database Syst Rev. 2017 Oct 30;10(10):CD012299. doi: 10.1002/14651858.CD012299.pub2.


Background: Chronic pain is typically described as pain on most days for at least three months. Chronic non-cancer pain (CNCP) is any chronic pain that is not due to a malignancy. Chronic non-cancer pain in adults is a common and complex clinical issue where opioids are routinely used for pain management. There are concerns that the use of high doses of opioids for chronic non-cancer pain lacks evidence of effectiveness and may increase the risk of adverse events.

Objectives: To describe the evidence from Cochrane Reviews and Overviews regarding the efficacy and safety of high-dose opioids (here defined as 200 mg morphine equivalent or more per day) for chronic non-cancer pain.

Methods: We identified Cochrane Reviews and Overviews through a search of the Cochrane Database of Systematic Reviews (The Cochrane Library). The date of the last search was 18 April 2017. Two review authors independently assessed the search results. We planned to analyse data on any opioid agent used at high dose for two weeks or more for the treatment of chronic non-cancer pain in adults.

Main results: We did not identify any reviews or overviews meeting the inclusion criteria. The excluded reviews largely reflected low doses or titrated doses where all doses were analysed as a single group; no data for high dose only could be extracted.

Authors' conclusions: There is a critical lack of high-quality evidence regarding how well high-dose opioids work for the management of chronic non-cancer pain in adults, and regarding the presence and severity of adverse events. No evidence-based argument can be made on the use of high-dose opioids, i.e. 200 mg morphine equivalent or more daily, in clinical practice. Trials typically used doses below our cut-off; we need to know the efficacy and harm of higher doses, which are often used in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Chronic Pain / drug therapy*
  • Humans
  • Review Literature as Topic


  • Analgesics, Opioid