Red Flags
- Cauda equina syndrome (saddle anaesthesia, urinary retention, bilateral leg pain) — emergency MRI same-day; surgical decompression[1]
- Suspected secondary cause (malignancy, infection, demyelination, vasculitis, diabetic plexopathy with sudden onset) — investigate before chronic neuropathic pain pathway[1]
- Suicidality, severe self-harm, or substance use disorder developing on neuropathic pain medication — same-day mental health support[1]
- Severe activation, mood change, or worsening depression on TCA / SNRI / gabapentinoid in early weeks — review medication and monitor closely[1]
First-line treatment
Interventions
- Treat underlying cause where possible[1]Glycaemic control in diabetic neuropathy; vitamin B12 replacement; antiretrovirals for HIV neuropathy; VZV vaccination history for post-herpetic; surgical decompression for compressive lesions; chemotherapy adjustment for chemo-induced
- Stepwise pharmacotherapy[1]First-line: amitriptyline, duloxetine, gabapentin, or pregabalin (any one). If first ineffective or not tolerated at adequate dose, switch to one of the others. Combine if partial response and tolerability allows
- Adjunctive non-pharmacological[1]Cognitive behavioural therapy for chronic pain, mindfulness, exercise, physiotherapy, TENS (selected); occupational therapy; address sleep and mood; pain management programmes for refractory cases
- Specialist pain medicine for refractory disease[1]Failure of three first-line agents at adequate dose and duration; consider cannabinoids (selected jurisdictions), interventional procedures (nerve blocks, neuromodulation, intrathecal therapy), botulinum toxin for selected pain types
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Amitriptyline[1] | Tricyclic antidepressant | 10–25 mg PO at night start, titrate by 10–25 mg every 1–2 weeks to 75 mg/day max in pain | — | Effective for neuropathic pain and comorbid insomnia; anticholinergic effects (dry mouth, urinary retention, constipation, glaucoma); ECG before higher doses in cardiac comorbidity |
| Duloxetine[1] | Serotonin-norepinephrine reuptake inhibitor (SNRI) | 30 mg PO daily start, titrate to 60–120 mg daily | — | First-line especially with comorbid depression or anxiety; nausea on initiation; hepatic caution; avoid with MAOI and severe renal impairment |
| Gabapentin[1] | Gabapentinoid (α2δ ligand) | 300 mg PO night × 3 days, then 300 mg BD × 3 days, then 300 mg TDS; usual 900–3600 mg/day in three divided doses | — | First-line; lower cost than pregabalin; renal dose adjustment; sedation, dizziness, peripheral oedema common |
| Pregabalin[1] | Gabapentinoid | 75 mg PO BD start, titrate to 150–300 mg BD as tolerated | — | First-line; weight gain, sedation, peripheral oedema; renal dose adjustment; misuse potential — controlled in some jurisdictions |
| Topical capsaicin 8% patch[1] | TRPV1 agonist (topical) | Single 30-min application to affected area; can repeat every 90 days | — | Localised peripheral neuropathic pain (post-herpetic, diabetic localised); transient burning at application site; pre-treat with topical anaesthetic; specialist application |
| Topical lidocaine 5% patch[1] | Sodium channel blocker (topical) | Up to 3 patches applied to most painful area for up to 12 h/24 h | — | Localised neuropathic pain (post-herpetic neuralgia); minimal systemic absorption; safer in elderly with comorbidities |
| Tramadol (selected, short-term)[1] | Atypical opioid / SNRI | 50–100 mg PO every 4–6 h, max 400 mg/day | — | Reserve for severe refractory pain; risk of serotonin syndrome with serotonergic agents; dependence; avoid long-term and in elderly with falls risk |
Amitriptyline[1]
Tricyclic antidepressant
- Adult
- 10–25 mg PO at night start, titrate by 10–25 mg every 1–2 weeks to 75 mg/day max in pain
- Paediatric
- —
Effective for neuropathic pain and comorbid insomnia; anticholinergic effects (dry mouth, urinary retention, constipation, glaucoma); ECG before higher doses in cardiac comorbidity
Duloxetine[1]
Serotonin-norepinephrine reuptake inhibitor (SNRI)
- Adult
- 30 mg PO daily start, titrate to 60–120 mg daily
- Paediatric
- —
First-line especially with comorbid depression or anxiety; nausea on initiation; hepatic caution; avoid with MAOI and severe renal impairment
Gabapentin[1]
Gabapentinoid (α2δ ligand)
- Adult
- 300 mg PO night × 3 days, then 300 mg BD × 3 days, then 300 mg TDS; usual 900–3600 mg/day in three divided doses
- Paediatric
- —
First-line; lower cost than pregabalin; renal dose adjustment; sedation, dizziness, peripheral oedema common
Pregabalin[1]
Gabapentinoid
- Adult
- 75 mg PO BD start, titrate to 150–300 mg BD as tolerated
- Paediatric
- —
First-line; weight gain, sedation, peripheral oedema; renal dose adjustment; misuse potential — controlled in some jurisdictions
Topical capsaicin 8% patch[1]
TRPV1 agonist (topical)
- Adult
- Single 30-min application to affected area; can repeat every 90 days
- Paediatric
- —
Localised peripheral neuropathic pain (post-herpetic, diabetic localised); transient burning at application site; pre-treat with topical anaesthetic; specialist application
Topical lidocaine 5% patch[1]
Sodium channel blocker (topical)
- Adult
- Up to 3 patches applied to most painful area for up to 12 h/24 h
- Paediatric
- —
Localised neuropathic pain (post-herpetic neuralgia); minimal systemic absorption; safer in elderly with comorbidities
Tramadol (selected, short-term)[1]
Atypical opioid / SNRI
- Adult
- 50–100 mg PO every 4–6 h, max 400 mg/day
- Paediatric
- —
Reserve for severe refractory pain; risk of serotonin syndrome with serotonergic agents; dependence; avoid long-term and in elderly with falls risk
Safety-net
- Allow at least 4–8 weeks of treatment at adequate dose before judging effectiveness; gradual titration reduces side effects[1]
- Avoid alcohol — worsens neuropathic pain and interacts with most neuropathic medications[1]
- Tell every healthcare worker about your neuropathic pain medications — interactions matter for analgesia, surgery, and other prescriptions[1]
Referral criteria
- Failure of two or three adequate first-line trials at maximum tolerated doseSpecialist pain medicine clinic[1]
- Severe disability, suicidality, or substance use complicating painMultidisciplinary pain service with psychology and psychiatry input[1]
- Suspected secondary cause requiring further workup or interventional managementNeurology / relevant subspecialty[1]
- Pregnancy or planning pregnancy on neuropathic pain medicationJoint pain medicine and obstetric clinic — many agents contraindicated[1]
Clinical summary
Stepwise pharmacological and non-pharmacological management of neuropathic pain in adults including diabetic, post-herpetic, and post-surgical aetiologies.