Moderate-to-severe chronic pain
Pain of moderate-to-severe intensity lasting more than 3 months and unresponsive to adequate doses of NSAIDs and paracetamol. NICE NG193 (2021) and WHO 2018 set out a step-wise approach with priority on non-opioid management and multidisciplinary rehabilitation; opioids are reserved for when alternatives fail, at minimum effective doses and with scheduled reassessment. Transdermal buprenorphine is considered in older adults and renal impairment given its lower accumulation risk.
ICD-10 R52.24 drugs
Also known as: Chronic refractory pain
Drugs used for this condition
- AFentanylSecond line · Opioid analgesic – synthetic μ-opioid receptor agonistTransdermal fentanyl is used in stable chronic pain in opioid-tolerant patients who do not manage on oral opioids or have intake problems. NCCN Adult Cancer Pain 2024 and WHO 2018 do not prescribe the patch to opioid-naive patients or for acute pain. Starting dose 25 mcg/h with patch change every 72 hours. Peak concentration is reached at 17–48 hours after the first patch – a short-acting opioid is needed in this window for breakthrough pain.
- BBuprenorphine (transdermal)Second line · Opioid analgesic – partial μ-opioid receptor agonistUsed in moderate-to-severe chronic pain with limited response to non-opioid agents. NICE NG193 (2021) and WHO 2018 do not place opioids as first-line for chronic non-cancer pain; they are considered only when alternatives fail. Starting dose: Transtec 35 mcg/h (patch changed every 96 hours); Norspan 5 mcg/h (weekly patch). Preferred in older patients and renal impairment due to lower accumulation. Long-term use with scheduled reassessment every 3 months and attempted gradual dose reduction.
- BMethadoneThird line · Synthetic opioid, full mu-receptor agonistFull μ-opioid agonist for moderate-to-severe chronic cancer and non-cancer pain. SED uses methadone for opioid rotation in morphine tolerance and when a neuropathic pain component is present.
- BTapentadolSecond line · Opioid analgesic with dual mechanismUsed in moderate-to-severe chronic pain, particularly with mixed nociceptive-neuropathic components. NICE NG193 (2021) does not place opioids as first-line in chronic non-cancer pain; they are considered when alternatives fail. Extended-release starting dose 50 mg twice daily, titrated to 250 mg twice daily. Compared with oxycodone, less constipation and nausea.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit