Amitriptyline

• Start with 10mg at 7-8 pm with upward titration to an effective dose or the person's maximum tolerated dose of no higher than 75mg as a single evening dose.
• If anticholinergic side effects are excessive but tricyclic is efficacious then consider imipramine as a secondary option. Imipramine has a similar anticholinergic profile to nortriptyline but is significantly cheaper.
• See notes above for tricyclic drugs, caution in the elderly.
• Cost (28 days): 75mg daily = £2.37

Imipramine

• Use the same regime as amitriptyline (see above). Ensure the patient takes their dose in the early evening to reduce the risk of next morning sedation.
• Imipramine can be used as a second line agent if amitriptyline is efficacious but its anticholinergic side effects limit its use. See notes above for tricyclic drugs, caution in the elderly.
• Nortriptyline remains an option as a tertiary tricyclic drug if imipramine is still not tolerable for the patient but is considerably more expensive, 75mg daily = £26.64 (28 days)
• Cost (28 days): 75mg daily = £3.03

Gabapentin

• Start at 300mg at night, with upward titration to an effective dose or the person's maximum tolerated dose of no higher than 3600mg per day (divided into three doses). Some patients, particularly the elderly, may need significantly lower doses.
• Review all patients after 6 months. Try slow downward dose titration to see if lower maintenance dose or stopping is possible. Always stop slowly.
• Cost (28 days): 3600mg daily = £14.65

Notes

1. If initial first-line drug is ineffective or not tolerated consider switching to the other first-line drug.
2. Patients who have gained some benefit from either amitriptyline or gabapentin but have not tolerated dose titrations may be trialled on a combination of amitriptyline plus gabapentin before considering the second-line treatment options below. The combination may allow lower doses to be used and the side-effect profile may be less.
3. Pregabalin is not recommended locally for first-line treatment
4. Tricyclic antidepressants (TCAs) are widely used and have a well-established evidence base, although unlicensed. They are contraindicated in recent MI or history of arrhythmias and in severe liver disease. They should not be used when there is a risk of overdose.
5. Patients already on SSRI antidepressants are more usually treated with gabapentin. For full list of cautions and side effects see current edition of BNF.
6. Gabapentin should be the second choice, unless amitriptyline is contraindicated or not tolerated. It is as effective as amitriptyline with fewer side effects in some patients. It is primarily excreted by the kidneys, therefore, reduce dose in renal impairment; it may also aggravate sedative effects of other drugs in such patients.
7. Gabapentin may cause dizziness and sedation in the first few days of use.
8. See section 4.8.1 Control of the Epilepsies for MHRA Drug Safety Updates for gabapentin

Switch to:

Pregabalin

• Start at 150mg per day (divided into two doses; a lower starting dose such as 25mg 12 hourly is often appropriate), with upward titration to an effective dose or the person's maximum tolerated dose of no higher than 600mg per day (divided into two doses)
• Prescribe twice daily: pregabalin capsules have a flat pricing structure so it is most cost-effective to prescribe the least number of capsules to form the required dose and to prescribe twice daily instead of three times daily
• Public Health England: Practitioners should prescribe pregabalin and gabapentin appropriately to minimise the risks of misuse and dependence, and should be able to identify and manage problems of misuse if they arise. Most patients who are given these drugs will use their medicines appropriately without misuse. Further information see here
• Pregabalin may be combined with either tricyclic antidepressants or duloxetine
• Cost (28 days): 600mg daily (300mg 12 hourly) = £64.40
• See section 4.8.1 Control of the Epilepsies for MHRA Drug Safety Updates

Consider:

Duloxetine

• Start at 60mg per day (a lower starting dose may be appropriate for some people), with upward titration to an effective dose or the person's maximum tolerated dose of no higher than 120mg per day
• Cost (28 days): 120mg daily = £4.74

For painful diabetic neuropathy

If the first-line treatment detailed above is ineffective, after a trial of at least one month, duloxetine should be considered. Start duloxetine at 60mg per day (a lower starting dose may be appropriate for some people), with upward titration to an effective dose or the person's maximum tolerated dose of no higher than 120mg per day. Stop duloxetine if pain is not reduced by 30% at one month and consider pregabalin.

If second line treatment not effective, refer to specialist pain service and/or condition specific service e.g. oncology, neurology, diabetology.

While waiting for referral consider adding in:

Tramadol

• Acute rescue therapy
• 50mg four times daily, with upward titration to a maximum daily dose of 400mg in four divided doses. Tramadol may be used instead of or in combination with second-line treatment but do not combine tramadol with duloxetine (risk of serotonergic syndrome).

Usually initiated on advice from pain clinic

Capsaicin 0.075% cream

• Axsain® cream 0.075%

Notes

1. Apply sparingly three times daily
2. It can be helpful in post-herpetic neuralgia
3. Severe initial stinging may limit use
4. Needs careful patient instruction

Emla® cream

(Lidocaine with prilocaine 25mg + 25mg)

Notes

1. May be helpful on sensitive skin

Only initiated on advice from pain clinic

Lidocaine 700mg (5% w/w) medicated plaster

Notes

1. Only recommended for the treatment of post-herpetic neuralgia
2. Apply to the painful area once daily for up to 12 hours, followed by a 12-hour plaster-free period; plasters may be cut to size if necessary. Up to 3 plasters may be used to cover large areas. Review after 2-4 weeks, discontinue if ineffective
3. Not recommended for initiation in primary care (see national guidance from NHS England). Only for use following initiation by specialist pain team (this may include recommendation to prescribe following outpatient appointment or "advice and guidance" service)
4. Pain specialists may occasionally recommend a trial of lidocaine plasters in difficult to treat cases of other forms of neuropathic pain (off-license). If successful, GPs may continue prescribing with ongoing review from pain specialists
5. Lidocaine plasters can result in gradual desensitisation of the nerves, leading to improvement in symptoms; the plaster may be discontinued if this should occur. Prescribers should therefore consider a trial withdrawal of therapy to reassess ongoing need at appropriate intervals e.g. at 3-6 months, and then 6 monthly

The management of trigeminal neuralgia is distinct from other forms of neuropathic pain.

Carbamazepine

• Initially 100mg twice a day, increasing dose until pain is relieved.
• When pain is in remission, reduce the dose of carbamazepine and gradually withdraw drug if patient remains pain-free for one month.
• Appropriate for GP prescribing