4.7.3 Neuropathic pain

Neuropathic pain (except trigeminal neuralgia*)

ChoiceDrugDosage
1st choicesAmitriptyline tablets 10mg, 25mg, 50mg; oral solution 10mg/5ml, 25mg/5ml, 50mg/5mlDose:
Start at 10mg and titrate by 10mg a week until 70-75mg daily is reached (as a single dose in the evening)
[Unlicensed]
Or
Gabapentin capsules 100mg, 300mg, 400mg Dose:
Start at 300mg at night (100mg [unlicensed] if the patient very frail or susceptible to sedative medications). Titrate up in steps of 300mg daily (with total given in 3 divided doses) according to side effects/response, to a usual max of 1.8mg daily (note licensed max 3.6g daily but if no substantial improvement at 2.4mg, increasing the dose further is unlikely to be of benefit)
2nd choicesDuloxetine capsules 30mg, 60mgDose:
Start at 30mg daily and titrate up to a maximum of 60mg twice daily.
A lower starting dose may be appropriate in some people.
Nausea is common on initiation but may resolve on continued treatment
Or
Pregabalin capsules 25mg, 50mg, 75mg, 100mg, 150mg, 200mg, 225mg, 300mg Start at 75mg at night. This can then be titrated according to side effects to a maximum of 600mg daily in two divided doses. A more conservative dose schedule may be considered in the elderly (e.g. initially 25mg twice daily [unlicensed]).

*Carbamazepine is first choice for trigeminal neuralgia

Prescribing Notes

  • See Regional Guidance ‘Management of Neuropathic Pain’.
  • See NICE CG173 Neuropathic pain- pharmacological management Nov 2013.
  • See NICE NG59 Low back pain and sciatica
  • Do not offer gabapentinoids, other antiepileptics, oral corticosteroids or benzodiazepines for managing sciatica as there is no overall evidence of benefit and there is evidence of harm (NICE NG59)
  • On 1st April 2019, gabapentin and pregabalin were reclassified as schedule 3 controlled drugs, the letter sent out to primary care can be found here.  Prescribers should be aware of the risks of overuse and can refer to clinical resources on gabapentinoids for tapering plans, posters and prescribing review support.
  • Patients should be warned of likely side-effects and that, unlike conventional analgesics, medication may have to be taken regularly for 4–6 weeks before the full analgesic effect is realised.
  • Current evidence suggests that tricyclic antidepressants and anticonvulsants are similarly effective at reducing pain, and have similar rates of adverse events.
  • If amitriptyline gives satisfactory pain reduction but is not tolerated due to adverse effects, consider oral nortriptyline as an alternative at the same dose (as amitriptyline).
  • Patients should be advised that maximum tolerated doses of amitriptyline should be used for 4 weeks before benefits can be judged.
  • Gabapentin tablets are substantially more expensive than the capsules. If decision to prescribe has been made use the most cost effective strength and formulation.
  • Once the patient is on maximum tolerated dose of gabapentin, wait for 2-4 weeks to assess if there is a worthwhile benefit. Titrate dose down slowly and STOP if no benefit.
  • A “worthwhile benefit” could be considered to be an improvement in pain, function, quality of life or a decrease in sleep disturbance (rather than 100% pain resolution).
  • If switching between gabapentin and pregabalin, there is no washout period necessary. Advice is based on local expert opinion and is outside product license.
  • Weight gain can occur with both gabapentin and pregabalin and is not a reason to switch between these therapeutic options.
  • All strengths of pregabalin capsules are the same cost, therefore ensure the correct strength of capsule is prescribed i.e. 300mg rather than 2 x 150mg.
  • Lidocaine medicated plasters are not recommended for routine use, they are only licensed in post-herpetic neuralgia and are listed on the HSC Deprescring: Limited Evidence List and Stop List.  An SOP for review of this product in primary care is available here.
  • If treatment with regular assessment is unsuccessful then referral for specialist advice is recommended.
  • Tapentadol MR may be recommended as a sole agent for mixed (neuropathic/nociceptive) pain in a specialist setting.

Cautions

  • Amitriptyline should be used with caution in the elderly and patients with glaucoma or prostatic hypertrophy. In the older patient, higher doses of amitriptyline are particularly likely to cause anticholinergic effects such as postural hypotension, sedation, confusion, dry mouth, urinary retention and constipation and should therefore be avoided. Full details of amitriptyline cautions are available in the BNF.
  • Caution on concurrent use of amitriptyline with other antidepressants. This is sometimes prescribed inadvertently (e.g. in patients with neuropathic pain and depression).
  • In patients with a reduced eGFR, see BNF for dosing directions for initiating and titration of both gabapentin and pregabalin.
  • Be aware of the risk of CNS depression, including severe respiratory depression, with gabapentin and consider whether dose adjustments might be necessary in patients at higher risk of respiratory depression. For further details see MHRA.