Drugs Used in Neuropathic Pain

Prescribing Notes:

• Amitriptyline is licensed for the treatment of neuropathic pain. Although imipramine is not licensed there is significant evidence and practice base to support the use.
• Co-prescribing tricyclic anti-depressants with tramadol, duloxetine or selective serotonin reuptake inhibitors increases the risk of serotonin syndrome.
• Tricyclic antidepressants have the potential to prolong the QT interval. Prescribers should be aware of the potential for interaction with other drugs associated with this effect (particularly citalopram). Where drug-drug combinations known to potentially cause QT prolongation are unavoidable, patients should be made aware of the risk and an ECG considered (this will depend on the risk of QT prolongation in individual patients). Further information can be found at Specialist Pharmacy Service - 'Identifying risk factors for developing a long QT interval'.
• Although imipramine may be better tolerated than amitriptyline, there is no evidence that one tricyclic antidepressant is more effective than another in the treatment of neuropathic pain. Therefore, if amitriptyline is deemed to be ineffective, following a suitable trial period at an optimised dose, Step 2 treatment should be trialled next.

Prescribing Notes:

• Less than 20% of patients prescribed gabapentin or pregabalin will obtain a significant reduction in pain.
• Both gabapentin and pregabalin have the potential to be misused due to the euphoric effects they can produce when taken in high (normally supratherapeutic) doses. Prescribers should be aware of the potential for misuse. Public Health England has produced advice for prescribers on managing the risk of the misuse associated with pregabalin and gabapentin.
• The SMC has restricted the use of pregabalin within NHS Scotland under certain circumstances. Further information can be found at SMC.

Gabapentin

Gabapentin is reserved for use within NHS Lanarkshire where tricyclic antidepressants are:

• Contraindicated
• Not tolerated
• Ineffective despite dose optimisation and a suitable trial period (i.e. 4-6 weeks)
• Unsuitable for individual patients (e.g. due to risk of QT prolongation)

It may be prescribed in combination with a tricyclic antidepressant where neuropathic pain is not adequately controlled by a tricyclic antidepressant alone, but has had a significant benefit (i.e. 30% reduction in pain score, significant improvement in functional ability or sleep pattern).

If response is sub-optimal after 8 weeks at the maximum tolerated dose then gabapentin should be gradually tapered and withdrawn.

In October 2017, the MHRA issued a Drug Safety Update for gabapentin. It highlighted that gabapentin is associated with a rare risk of severe respiratory depression and the dose may need to be adjusted in high risk patients.

Pregabalin

As with gabapentin, pregabalin may be used in conjunction with a tricyclic antidepressant - provided the tricyclic antidepressant is deemed effective.

If gabapentin is ineffective following an 8 week trial of the maximum tolerated dose, a trial of pregabalin may be initiated. Gabapentin should be gradually tapered and withdrawn before commencing pregabalin.

Once an optimised dose of pregabalin has been prescribed for 8 weeks, the patient should be reviewed and efficacy of treatment assessed. Patients experiencing a reduction in pain score less than 30% of baseline or limited improvement in functional ability should have their pregabalin dose gradually tapered and withdrawn.

In April 2022, the MHRA issued a Drug Safety Update for pregabalin- a new study has suggested pregabalin may slightly increase the risk of major congenital malformations if used in pregnancy. Patients should continue to use effective contraception during treatment and avoid use in pregnancy unless clearly necessary.

Tramadol

In 2014 tramadol was reclassified as a Schedule 3 Controlled Drug following an increase in the number of deaths related to its use.

Use of tramadol is restricted to patients who fail to obtain adequate benefit from Step 1 and 2 drugs whilst awaiting referral to the Pain Clinic.

Duloxetine

Is only licensed for the treatment of diabetic peripheral neuropathic pain. Its use is further restricted within NHS Scotland (as per SMC guidance) to specialist initiation in patients with peripheral diabetic neuropathy that has not adequately responded to other treatments (i.e. Step 1 and 2 treatments at an optimised dose for an appropriate trial period).

Should be discontinued after a trial period of 2 months if response is inadequate (i.e. less than 30% reduction in pain score or insignificant improvement in functional ability). Discontinuation should be gradual to avoid occurrence of withdrawal adverse effects.

Where duloxetine is effective, this should be reviewed at least every 3 months and a trial reduction considered to assess ongoing need.