High‐dose opioids for chronic non‐cancer pain: an overview of Cochrane Reviews New search for studies and content updated (no change to conclusions)



This overview was originally published in 2017, and is being updated in 2022. 

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, for which opioids are prescribed by some physicians for pain management. There are concerns that the use of high doses of opioids for CNCP lacks evidence of effectiveness, and may increase the risk of adverse events.


To describe the evidence from Cochrane Reviews and overviews regarding the efficacy and safety of high‐dose opioids (defined as 200 mg morphine equivalent or more per day) for CNCP.


We identified Cochrane Reviews and overviews by searching the Cochrane Database of Systematic Reviews in The Cochrane Library. The date of the last search was 21 July 2022. Two overview authors independently assessed the search results. We planned to analyse data on any opioid agent used at a high dose for two weeks or more for the treatment of CNCP in adults.

Main results

We did not identify any reviews or overviews that met the inclusion criteria. The excluded reviews largely reflected low doses or titrated doses, where all doses were analysed as a single group; we were unable to extract any data for high‐dose use only.

Authors' conclusions

There is a critical lack of high‐quality evidence, in the form of Cochrane Reviews, about how well high‐dose opioids work for the management of CNCP 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. Considering that high‐dose opioids have been, and are still being used in clinical practice to treat CNCP, knowing about the efficacy and safety of these higher doses is imperative.


Charl Els, Tanya D Jackson, Reidar Hagtvedt, Diane Kunyk, Barend Sonnenberg, Vernon G Lappi, Sebastian Straube


Plain language summary

High doses of opioid medicines for the management of chronic non‐cancer pain

Bottom line

There is no high‐quality evidence to show how well high doses of opioids work, or what side effects they cause, when they are used for adults with chronic pain that is not due to cancer. 

Studies usually used doses below our cutoff. We need to know how well high‐dose opioid medicine works for chronic non‐cancer pain, and what side effects there may be.


Opioids are a type of pain medicine related to morphine. Opioids have been used for many years as painkillers for moderate or severe chronic pain, which is pain that lasts for a long time (usually longer than three months).

Study characteristics

In this updated overview, we aimed to summarise the knowledge from Cochrane Reviews and overviews about opioid medicine for pain relief in adults who had chronic pain not due to cancer. We wanted to know how well opioid medicines worked when they were used at high doses (equal to 200 mg of morphine per day or more), and what side effects there might be.

Key results

Despite systematic searches, most recently conducted in July 2022, we did not find any information about this. Studies on opioids rarely reported on high‐dose use. When they included them as part of a study of people using all levels of doses, they did not report separate information for people who used high‐dose opioids.


Charl Els, Tanya D Jackson, Reidar Hagtvedt, Diane Kunyk, Barend Sonnenberg, Vernon G Lappi, Sebastian Straube

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

There is an absence of high‐quality evidence to support or refute the use of high‐dose opioids for CNCP. Opioids are associated with increased risks for adverse events, including addiction, overdose, and death (Dowell 2016). 

For persons suffering from chronic non‐cancer pain

When selecting a treatment modality and dosage, risks and benefits must be considered. People should be made aware of the potential risks, and the absence of evidence for benefit of high‐dose opioids for CNCP. Physicians should have frank and open conversations with people in this regard, supplemented with a discussion on other, evidence‐based, strategies.

For policymakers

In the absence of evidence to support or refute the efficacy of high‐dose opioids, and in view of the established risks, the use of high‐dose opioids for treating CNCP should not be recommended.

For funders

In the absence of evidence to support or refute the efficacy of high‐dose opioids, they should not be recommended.

Implications for research 


Although we know that opioids are commonly prescribed to people, including at high doses, for the treatment of CNCP, there is no evidence to refute or support the efficacy of this clinical practice. However, the risks associated with high‐dose opioid use are well established. We do not at present have dependable information about how well high‐dose opioids work, or what adverse effects may accompany their use when they are used on a long‐term basis for CNCP.


On the one hand, the absence of high‐quality evidence for high‐dose opioid use would typically call for more randomised controlled trials to be conducted, specifically addressing this question. On the other hand, the potential for significant adverse events with high‐dose opioids provides an argument against conducting these studies. The ethics of conducting studies on high‐dose opioids needs to be considered carefully.

Where possible, data from people receiving high‐dose opioids in existing datasets should be re‐analysed separately.


Many of the outcomes of interest for high‐dose opioids are the same as for opioids studied at a lower dose range. Dworkin 2005 outlined six domains that should be considered for chronic pain clinical trials, including pain, physical functioning, emotional functioning, treatment satisfaction, symptoms, and adverse events, and participant disposition.

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