Opioids

Opioids should not be considered routinely for people with chronic non-malignant pain. In carefully selected individuals, when other therapies have been fully explored, opioids can be considered for short-term treatment (up to three months), if it is considered that the potential benefits outweigh the risks of serious harms such as addiction, overdose and death.^{161,162,163,164,165,166,167,168,169,170}

Benefits:

The benefits of opioids in chronic pain are limited to lower doses for short to medium-term treatment (less than three months).

Risks:

All people on an opioid should have a review of their treatment, prioritising individuals prescribed more than 50mg morphine equivalent dose (MED), who should be reviewed at least annually to consider ongoing effectiveness and potential harms, due to lack of evidence to support long-term use.^170,171 See the table below for dose equivalence.

There are a variety of opioid dose conversion charts available. Currently the preferred version is the BNF which aligns with the Faculty of Pain Management and Scottish Palliative Care Guidelines.¹⁵⁸

If a different dose conversion is used this should be specified as should the date/version of the conversion used (due to regular updates).

If converting from one opioid to another, individuals should be monitored to assess effectiveness and adverse reactions.

• Note as with all opioid conversions, these are approximate doses
• Dose conversions should be conservative and doses rounded down
• Monitor the individual to assess effectiveness and adverse effects, so that the dose can be adjusted if necessary
• If there is opioid toxicity, reduce the dose by one third when changing opioid

Morphine sulfate 10mg daily dose equivalents

Individuals who require particular consideration include:

• history of substance abuse
• renal impairment
• recently discharged following surgery
• older and/or frail

Higher doses have a greater risk of serious harm (four times higher for 50-100mg MED, nine times higher for doses greater than 100mg MED). Such harms can include increased risk for falls and major trauma, and increased odds of road accident.^171,172 The risks of dependence are increased in individuals with current or history of problem substance use (including alcohol misuse) or mental health conditions (for example, major depression). Additional support and monitoring may be necessary when prescribing for individuals at risk of opioid misuse.¹⁵⁹

Risks can be categorised by the timescale on which they may be seen, although some can occur in any timeframe.

Evidence for effectiveness and risks

There are few trials of efficacy of long-term opioid use (≥3 months) in individuals with chronic non-malignant pain, and limited numbers of studies with variable quality which demonstrate long-term efficacy.157,173

Generally:

• Opioids should only be considered for short to medium-term treatment (less than three months) for carefully selected patients with chronic non-malignant pain, when other therapies have been insufficient, and the benefits are greater than the risks of serious harms such as addiction, overdose and death^161,162,170
• Individual review is recommended within four weeks of starting opioid treatment or sooner if required.¹⁷¹ The frequency of review once the opioid regimen is established depends on the factors mentioned, but should be at least annually¹⁵⁷ to identify possible harms and consider the effectiveness of treatment^{164,165,166,167,168,169,171}
• Prescribers should consider the risks and harms against the benefits of taking opioids^{163,170,172,177}
• Higher doses have a greater risk of serious harm (four times higher for 50-100mg MED, nine times higher for doses greater than 100mg MED). Such harms can include increased risk for falls and major trauma, and increased odds of road accident¹⁷¹
• Due to tolerance developing, the analgesic effect of opioids lessens over time and individuals require higher doses to maintain the same level of pain relief^154,171,187
• If a change from one opioid to another is required, the relative potency should be accounted for and dose equivalence charts used (see the table above ). Exercise caution when changing from one opioid to another, especially fentanyl due to its high potency (good practice point).

Morphine:

• Individuals should be considered as opioid non-responsive if 20mg of immediate-release morphine does not reduce pain intensity
• As there is no evidence of difference in pain control between opioids, morphine is the preferred cost-effective option¹⁵⁵
• As more evidence is available, the accepted upper dosage limits are being reviewed and reduced. Current recommendations indicate the upper dosage levels should be less than 50mg to minimise longer term risks and adverse effects, and previous upper limits of 90mg to 120mg should be reviewed
• It is good practice to not prescribe more than 90mg/day MED¹⁷⁷ without seeking advice from a prescriber specialising in pain^183,184
• It is good practice to use extreme caution when prescribing more than 120mg/day MED due to the risk of harm substantially increasing at these doses¹⁷¹
• Note palliative care and post-operative care are not included in chronic pain

Tramadol:

• Tramadol has high potential for drug interactions, due to opioid effect and an enhancement of serotonergic and adrenergic pathways
• It is good practice not to combine with other opioids for mild to moderate pain¹⁷⁷
• One study considered tramadol as suitable for neuropathic pain,¹⁸⁵ however another found no significant difference between it and placebo¹⁶²

Other opioids:

• Transdermal buprenorphine or fentanyl could be an option for treatment when there are reasons prohibiting oral administration.
• Fentanyl:
  • other analgesics and other opioids for non-malignant pain should be trialled before prescribing fentanyl patches
  • due to the potency of fentanyl the use of transdermal patches is contra-indicated in opioid-naive individuals
  • the use of immediate release fentanyl is not recommended as it is restricted for use for the management of breakthrough pain in adults using opioid therapy for chronic cancer pain, when other short-acting opioids are unsuitable
  • is suitable in renal impairment and use with caution186
• Buprenorphine:
  • is an alternative for those with renal dysfunction (even severe)187
  • patches are available in several brands. They are available in different strengths and are not all interchangeable therefore buprenorphine patches should be prescribed by brand name
  • patches are not appropriate for individuals with acute pain and those who need rapid dose escalation
  • 7-day transdermal patches (5 to 20 micrograms) should be prescribed in line with Scottish Medicines Consortium (SMC) restriction: For use in elderly individuals (over 65 years) for the treatment of non-malignant pain of moderate intensity when an opioid is necessary for obtaining adequate analgesia
• Oxycodone:
  • requires dose adjustment in renal impairment
  • oxycodone and naloxone combination prolonged released tablets are not recommended by SMC
• Tapentadol use is restricted by SMC. See local formularies.

Opioid use is receiving increasing attention, with opioid deaths in Scotland and the USA a major cause of public concern:

Media coverage may raise specific concern about drugs which are in everyday use, such as fentanyl

Individuals prescribed opioid medication should understand that many of these deaths are associated with unregulated products (with potentially very high doses of drug) and illicit drug use – and should understand their own situation in context

National Records of Scotland shows that there were 1,017 deaths due to drug misuse in Scotland in 2024.¹⁹⁶ Of these deaths, medication implicated included

• opiates/opioids (such as heroin/morphine and methadone): 810 deaths (80%)
• benzodiazepines (such as diazepam and bromazolam): 574 deaths (56%)
• gabapentin and/or pregabalin: 374 deaths (37%)

Generally:

• Potentially fatal interactions between medicines that cause CNS depression, particularly opioids, gabapentinoids and benzodiazepines

Common side effects of opioids

Prescribers should consider the adverse effects against the limited long-term benefits, as there are few trials examining the efficacy of long-term opioid use (≥3 months) in those with chronic pain. There are limited numbers of studies of variable quality which demonstrate long-term efficacy.^157,173

• Abrupt discontinuation should be avoided to prevent severe discontinuation/withdrawal symptoms
• The Clinical Opiate Withdrawal Scale (COWS) can be used in all settings to monitor opioid withdrawal
• Tools are available to form the basis for discussing the detail of a planned reduction/cessation, so that informed joint decisions can be made around the treatment plan (e.g. Pain Management Taper Calculator)
• Options for reduction include:
  • use of a single modified release opioid, and when the dose is stable, reduce
  • keep the modified-release dose stable and then wean down immediate-release as needed to the point of stability, then the modified-release dose can be reduced by 5%-10% per dose per week¹⁷²
  • if taking immediate release preparation, change to or add a modified-release preparation, and then withdraw the immediate-release opioid¹⁸⁸
• Due to the small number of studies (with varying heterogeneity) any specific opioid analgesic deprescribing strategy cannot currently be recommended¹⁹⁹