Saturday, August 21, 2010

Pharmacotherapies for Neuropathic Pain Reviewed

Research UpdateChronic neuropathic pain can be caused by a variety of disorders and pharmacologic management is an important option; however, results are often unsatisfactory. An updated review of the research literature examines efficacy and safety data on currently available agents, finding that tricyclic antidepressants and opioids may be first-line therapies for a number of neuropathic conditions.

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.
COMMENTARY: It is interesting that, despite the extensive range of studies and a recent two-thirds increase in published trials, the authors conclude that only a limited improvement of neuropathic pain treatment has been obtained through the years. From the data analyses it appears that TCAs and opioids are generally efficacious and well-tolerated; with opioids being somewhat of a surprise because some of the literature disparages opioids as a first-line choice for neuropathies. In this Danish review, a second tier of agents (NNTs 3-6) include SNRIs, tramadol, and lidocaine patch. Cannabinoids (eg, marijuana and related agents) were considered in some of the research trials; however, while there was a favorable level of safety compared with placebo, moderate efficacy was only evident for central pain (NNT 3.4) and mixed neuropathies (NNT 8.3).

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].