Non-opioid, then weak opioid, then strong opioid, with adjuvants at every step
Mnemonic
Three steps, climbing as pain persists or increases:
- Step 1 - non-opioid: paracetamol, NSAID
- Step 2 - weak opioid: codeine, dihydrocodeine, tramadol
- Step 3 - strong opioid: morphine, oxycodone, fentanyl
“Plus an adjuvant at every step”: amitriptyline, gabapentin or pregabalin for neuropathic pain, steroids for compression or raised pressure, bisphosphonates for bone pain, and antiemetics and laxatives alongside every opioid.
Non-opioids are continued as you climb, not replaced, since they are opioid sparing.
For cancer pain the ladder is climbed; for acute severe pain it is entered at the top and descended.
Every strong opioid prescription needs a laxative, since tolerance develops to almost every opioid effect except constipation, and an as required breakthrough dose of one sixth of the total daily dose.
Expansion
- Step 1: non-opioid. Paracetamol, NSAIDs
- Step 2: weak opioid plus non-opioid. Codeine, dihydrocodeine, tramadol
- Step 3: strong opioid plus non-opioid. Morphine, oxycodone, fentanyl
- Adjuvants at every step: gabapentinoids, tricyclics, SNRIs, steroids, antispasmodics, bisphosphonates for bone pain, and non-pharmacological measures
The ladder was designed for cancer pain and is climbed upward; in acute severe pain it is entered at the appropriate rung directly, or descended.
Practical principles
- Give analgesia regularly for continuous pain, with breakthrough doses of about one sixth of the total daily dose
- Always co-prescribe a laxative with an opioid, since tolerance to constipation never develops
- Codeine requires CYP2D6 conversion to morphine, so it is ineffective in poor metabolisers and dangerous in ultrarapid ones; it is avoided in children and in breastfeeding
- In renal impairment, morphine metabolites accumulate; oxycodone or alfentanil are preferred
- Neuropathic pain responds poorly to opioids; first line is amitriptyline, duloxetine, gabapentin or pregabalin