Updated guidance from NICE recommends the following drug treatment for neuropathic pain (excluding trigeminal neuralgia):
• Offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment• If the initial treatment is not effective or not tolerated, offer one of the remaining 3 drugs, and consider switching again if the second or third drugs tried are also not effective or not tolerated• Consider tramadol only if acute rescue therapy is needed• Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments
For the treatment of trigeminal neuralgia, the guideline recommends that carbamazepine be offered for initial treatment. If this is not effective or not tolerated, or is contra-indicated, expert advice and early referral to a specialist pain service or a condition-specific service should be considered.
The guideline does not recommend the use of cannabis sativa extract, capsaicin patch, lacosamide, lamotrigine, levetiracetam, morphine, oxcarbazepine, topiramate, tramadol (long-term use) or venlafaxine for the treatment of neuropathic pain in non-specialist settings.
The current meta-analysis included 229 randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain. Combined NNTs for 50% pain relief were 6.4 for serotonin-noradrenaline reuptake inhibitors (mainly duloxetine), 7.7 for pregabalin; 7.2 for gabapentin (including extended release and enacarbil) and 10.6 (7·4–19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A.
It was not possible to determine NNTs for lidocaine patches. There were only three studies meeting the inclusion criteria (duration of at least 3 weeks) - one small (negative) study in post-surgical neuropathic pain and two enriched-enrolment studies (one positive; the other negative in the intention-to-treat population, but positive in the per-protocol population) in post-herpetic neuralgia. Studies of shorter duration were however positive, and safety and tolerability were good in all cases. It was therefore given a weak recommendation for second-line use.
The authors note that inadequate response to drug therapy signifies a substantial unmet need in patients with neuropathic pain; the results may also however be due to insufficient assay sensitivity in clinical trials. Placebo response is a major issue, as it the heterogeneous diagnostic criteria in several trials.