Executive summary (GP-safe algorithm)
- Confirm neuropathic features (burning, shooting, electric shocks, allodynia, dysaesthesia) and treat reversible causes where possible.
- Initial drug choice (most adults): offer one of amitriptyline, duloxetine, gabapentin, or pregabalin.
- If ineffective/not tolerated: switch to one of the remaining options; do not persist indefinitely with “half-working” doses.
- If still inadequate: consider combination treatment (specialist advice often wise) and/or refer for complex pain.
- Trigeminal neuralgia is different (specialist-first; carbamazepine/oxcarbazepine typically used).
Practical dosing (typical adult starting points)
- Amitriptyline (off-label for pain): start 10 mg nocte (older/frail: 5 mg), increase by 10 mg every 5–7 days to 25–50 mg nocte (some benefit up to 75 mg; side effects often limit).
- Duloxetine: start 30 mg od for 1 week, then 60 mg od. (Avoid in severe hepatic disease; consider interactions.)
- Gabapentin: start 300 mg nocte → 300 mg bd → 300 mg tds over 3 days; titrate every 3–7 days to effect (often 900–1800 mg/day; max commonly 3600 mg/day). Renal adjustment required.
- Pregabalin: start 75 mg bd (or 50 mg bd if risk), titrate after 3–7 days to 150 mg bd; max 300 mg bd (600 mg/day). Renal adjustment required.
Controlled-drug reality (UK): gabapentin/pregabalin require cautious prescribing, clear indications, and dependence/abuse risk screening.
Red flags / urgent pathways
Escalate urgently if new/progressive neurological deficit, suspected cauda equina, spinal cord compression, rapidly progressive weakness, new saddle anaesthesia, or systemic red flags (malignancy, infection, immunosuppression). Neuropathic pain with “electric shocks” + unilateral facial triggers may suggest trigeminal neuralgia (specialist pathway).
Switching rules (to reduce “polypharmacy drift”)
- Define a trial: aim for a therapeutic dose for ~2–4 weeks (longer for antidepressants if titrating slowly), with a clear outcome measure (sleep, function, pain score).
- If no meaningful benefit: taper/stop and switch to an alternative first-line option.
- If partial benefit but limited by side effects: reduce dose or switch class (e.g., TCA → SNRI or gabapentinoid → SNRI).
- Combination therapy: consider only after sequential monotherapy trials, and document why (functional impairment + partial response).
Common prescribing pitfalls (high-yield)
- Neuropathic ≠ nociceptive: avoid defaulting to opioids/NSAIDs when the phenotype is neuropathic.
- Renal function: gabapentin/pregabalin dose must reflect eGFR (toxicity looks like sedation, dizziness, confusion, ataxia).
- Anticholinergic load: amitriptyline in older adults can worsen falls, constipation, urinary retention, and delirium risk.
- Review and stop rules: if no function gain, stop; do not keep “because they’ve been on it for years”.
Frequently asked questions
Which first-line option is best?
NICE allows choice among amitriptyline, duloxetine, gabapentin, or pregabalin. In practice: consider duloxetine if comorbid low mood/diabetic neuropathy features; avoid amitriptyline in frail/anticholinergic risk; prefer gabapentin/pregabalin only with clear indication + monitoring.
How quickly should I expect effect?
Gabapentinoids can show benefit within days at effective doses; TCAs/SNRIs often need a slower titration and 2–4 weeks at a useful dose to judge benefit.
When should I refer?
Refer for diagnostic uncertainty, severe functional impairment despite sequential first-line trials, complex comorbidity (substance use, severe mental illness), or where combination/advanced therapies are being considered.
Transparency
This page is an educational, clinician-written summary of publicly available NICE guidance intended for trained healthcare professionals. It uses original wording (not copied text) and should be used alongside the full NICE source, local pathways, and clinical judgement. Doses provided are for general reference; always check the BNF/SPC.