To extend their earlier evidence review conducted in 2005, researchers in Denmark searched MEDLINE and EMBASE for randomized, double-blind, placebo-controlled trials (RCTs) examining pharmacotherapies for 6 different neuropathic pain conditions. They identified 174 studies for inclusion, representing a 66% increase in published RCTs on this subject in just the past 5 years. Painful polyneuropathy (most often due to diabetes) was examined in 69 studies and postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and mixed neuropathic pain were less often studied.
To the extent possible from the data, researchers calculated NNT (numbers needed to treat) and NNH (numbers needed to harm) values to compare the efficacy and safety of the different treatments investigated. NNT represents the number of patients requiring treatment with a particular agent for at least one of the patients to experience a clinically significant 50% reduction in pain intensity (the lower the number the better). NNH is the number of patients that needed to be treated in the trials for one patient to drop out due to adverse effects (higher numbers are better). Among the 22 agents considered in the various research trials, tricyclic antidepressants (TCAs), serotonin noradrenaline reuptake inhibitors (SNRIs), the anticonvulsants gabapentin and pregabalin, and opioids appeared to be the drug classes for which there is the best evidence for clinically relevant effects. However, using a stringently low NNT of ≤3.0 as a cut-off point, the following observations may be made:
- For polyneuropathy, TCAs (NNT 2.1), Botox type A (NNT 2.3), and opioids (NNT 2.6) were the most efficacious.
- For postherpetic neuralgia, valproate (NNT 2.1), opioids (NNT 2.6), and TCAs (NNT 2.8) appeared best.
- For central pain, only TCAs (NNT 2.7) demonstrated strong efficacy in available trials.
- Opioids (NNT 2.1) were found most efficacious in mixed neuropathic pain syndromes.
- None of the agents for treating HIV neuropathy or neuropathy associated with peripheral nerve injury had NNTs ≤3.0.
- In terms of safety as indicated by NNH values, both opioids (NNH 17.1) and TCAs (NNH 15.9) exhibited reasonably favorable profiles.
An important caveat is that most of the individual NNT and NNH values were determined by relatively few trials for each pharmacologic agent in each category; often the trials were short-term, in small numbers of patients, and categorizations of the involved neuropathic conditions were sometimes unclear. We agree with the review authors that further, large-scale drug trials are needed to determine the best treatments for individual patients with the different types of neuropathy.
REFERENCE: Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010(Sep);150(3):573-581 [abstract here].