Use of opioids in persistent pain – the evidence

13 June 2018

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The media attention on the use of opioids in long-term pain management shows little sign of abating. However, health care professionals understand there is a place for some prescribing of strong opioids rather than avoid this option totally. If you need to or are considering prescribing strong opioids for someone, what are the considerations to make?

What does the evidence say about using opioids in persistent pain?

The weight of evidence to support the use of opioids is centred on extensive use in cancer pain, end of life care and acute pain as in trauma or pain after surgery. There is very little evidence that suggests the beneficial use of opioid medicines (‘strong’ opioids in particular – think of morphine >30-40mg daily dose equivalent) in non-cancer related persisting pain. The longest trials of opioids in persistent non-cancer pain have been up to 16 weeks only. The studies are often have fewer than 250 subjects and drop out rates of up to 65% have been reported. So there is very little good quality evidence to support the notion that longer-term opioid use is safe or efficacious.

What we know

1.    Doses above 120mg morphine or equivalent per day (roughly, 60mg oxycodone, 37mcg/hour fentanyl or buprenorphine 52.5mcg/hour) have been shown to markedly increase the risk of harm without providing superior analgesia. If a person has reached that level of dosing without noticeable or satisfactory improvement in function and change in pain levels, it is extremely unlikely that further increases are suddenly going to be effective. In fact, this demonstrates the opioids do not work. The best evidence would suggest reducing and stopping them, even if there isn’t another medicine to offer.

2.    Opioids do have limited evidence to support their use. This is in a relatively small proportion of people who use low doses, intermittently i.e. who use them only when required or who have regular breaks from use. For example, a significant pain setback where there is a clear self management plan and short term use of opioids would enable regain of function and life roles.

Clearly, when initiating opioids, the intention is never to have people remain on them for the next five years. Yet we now find ourselves with the difficulties of tapering people from opioids and some difficult or tricky reviews. This means more challenges and the need to act wisely and an answer that seems easy enough – it’s all about how you start and if necessary stop them. This will protect and support the patient better and ourselves, the prescribers.

When considering starting opioids

Make it clear to the person receiving the prescription that this is a trial; so agree a time duration e.g. initially two weeks and then review regularly; agree a dose – this will partly depend on whether their currently taking another opioid e.g. co-codamol 30/500.

If they were taking 8 tablets of co-codamol 30/500 a day, this would equate to 240mg codeine, which is roughly equivalent to 24mg morphine. When changing opioids it is advised to reduce the dose by 20-50% morphine equivalent dose. In this case then, it would be sensible to start with 2.5mg morphine up to four times a day which could be increased to 5mg four times a day using morphine sulphate oral solution (10mg/5mLs). Alternatively, morphine modified-release 5mg twice a day could be used if it was a more suitable formulation for the individual.

Which ‘strong’ opioid should be used?

The scientific literature does provide much evidence of any advantage of one opioid over another. For this reason, oral morphine should be the first line strong opioid of choice unless there is a known contraindication e.g. allergy, hallucinations from previous use. Use an immediate release preparation for the trial (e.g. Oramorph 10mg/5mLs or Sevredol 10mg tablets) and give limited quantities such as two weeks. Opioids Aware suggests that a failure to reduce pain intensity following a single 20mg morphine dose suggests pain that is not opioid sensitive.

Transdermal preparations are not suitable for initiating a trial and should be used as a second-line option for the vast majority of people. Check your local formularies / guidelines for more information.

What is a reasonable trial duration?

When someone reports constant pain, a 1-2 week trial should be enough time to determine if a difference has been made. Where there is intermittent pain or temporary increases in symptoms on the back of more manageable daily levels, then longer may be required. A study by the Center for Disease Control in the United States found that giving initial durations of longer than 2 weeks significantly increased the chance of a person remaining on the opioid a year later and even 5 years later. Small quantities and frequent initial review may prevent unhelpful, harmful long-term use.

The main reason for trial of opioids is to see if they enable the person to achieve personal key goals around physical activities, possibly sleep improvement, day-to-day life roles and work related activities. Pain reduction is possible but should not be regarded as the primary outcome to be achieved.

If the personal key goals are not seen within an agreed time frame, the opioids medicine will be tapered and stopped. A reasonable time frame might depend on the person’s goal but 12 – 16 weeks is a reasonable time frame to determine if people are able to make progress with their activity, day-to day-life goals.

The majority of people will know fairly quickly whether the opioid medicine has had some benefit. They may report initially an improvement in pain intensity. However, this is not the same as optimal benefit. The important outcome after all, is for people to start to see improvement in function and signs of this should be seen within agreed time trial.


  1. Agree it is a trial and its duration
  2. Agree outcomes, via SMART goals and tapering /stopping if no progress in goals + pain intensity reduction.
  3. Agree which opioid medicine is suitable and the starting dose
  4. Ensure patients clear about risks/harm and impact on things such as driving
  5. Ensure common side effects such as constipation are also addressed from the start.

How to assess success

How will the person know that the opioids are ‘working’?

People should be encouraged to keep a diary to record the outcome of their opioid trial. Helpful things to record are:

  • the opioid doses they have taken each day, the time, amount etc
  • their pain level e.g. out of 10, with 0 being pain free and 10 being the worst, debilitating pain
  • most importantly change in their 24 hour activity pattern and sleep
  • the effect the opioid has had on progressing their day to day role function / activities and other goals
  • any side-effects or changes due to the opioid use.

This is probably the only time that there is value in recording pain levels in persistent pain in this way. Recording twice daily is a sensible – too much focus on measuring pain can be detrimental.

If the person does not report any improvement in pain, function or sleep during the trial period, it is extremely unlikely they will benefit from opioids over a longer time.

Documentation is vital at all stages to assist with communication between you and your colleagues, as well as with the person receiving the opioid. It is recommended to include:

1) the agreed trial conditions:

  • medicine/formulation choice
  • duration of the trial and timing of reviews
  • patient focused activity goals

2) all reports of positive effects and side-effects:

  • include any perceived pain reduction
  • how side-effects are managed and if they are limiting the usefulness of the opioids
  • reasons for continuing or not continuing the opioids

Where people have reported good effect in terms of pain reduction but side-effects are limiting functional improvement –try to treat those side-effects in order to optimise potential use and so better patient functional outcomes. This may involve additional medicines to manage side-effects e.g. laxatives for constipation, or altering dosing regimens. As before, limit prescription quantities and review progress every two weeks.


  • Do not continue to increase opioid doses if the person is not reporting benefit.
  • Remember to reduce and stop them, as agreed at start of the trial should the agreed outcomes not be achieved.

Even when benefit is seen during the trial period, this is not a guarantee of long-term outcome.

  • People on stable opioid doses should be reviewed twice a year and when reporting any problems with the medicines or reducing effect, discussion and agree a trial taper. Opioids can always be re-trialed at another time.

For more help with the review process see our Opioid zone review resources.

More information and references are available at Opioids Aware.