Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action

Pain. 1999 Dec;83(3):389-400. doi: 10.1016/S0304-3959(99)00154-2.


Tricyclic antidepressants and carbamazepine have become the mainstay in the treatment of neuropathic pain. Within the last decade, controlled trials have shown that numerous other drugs relieve such pain. We identified all placebo-controlled trials and calculated numbers needed to treat (NNT) to obtain one patient with more than 50% pain relief in order to compare the efficacy with the current treatments, and to search for relations between mechanism of pain and drug action. In diabetic neuropathy, NNT was 1.4 in a study with optimal doses of the tricyclic antidepressant imipramine as compared to 2.4 in other studies on tricyclics. The NNT was 6.7 for selective serotonin reuptake inhibitors, 3.3 for carbamazepine, 10.0 for mexiletine, 3.7 for gabapentin, 1.9 for dextromethorphan, 3.4 for tramadol and levodopa and 5.9 for capsaicin. In postherpetic neuralgia, the NNT was 2.3 for tricyclics, 3.2 for gabapentin, 2.5 for oxycodone and 5.3 for capsaicin, whereas dextromethorphan was inactive. In peripheral nerve injury, NNT was 2.5 for tricyclics and 3.5 for capsaicin. In central pain, NNT was 2.5 for tricyclics and 3. 4 for carbamazepine, whereas selective serotonin reuptake inhibitors, mexiletine and dextromethorphan were inactive. There were no clear relations between mechanism of action of the drugs and the effect in distinct pain conditions or for single drug classes and different pain conditions. It is concluded that tricyclic antidepressants in optimal doses appear to be the most efficient treatment of neuropathic pain, but some of the other treatments may be important due to their better tolerability. Relations between drug and pain mechanisms may be elucidated by studies focusing on specific neuropathic pain phenomena such as pain paroxysms and touch-evoked pain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Carbamazepine / therapeutic use
  • Diabetic Neuropathies / complications*
  • Humans
  • N-Methylaspartate / antagonists & inhibitors
  • N-Methylaspartate / therapeutic use
  • Narcotics / therapeutic use
  • Neuralgia / drug therapy
  • Pain / drug therapy*
  • Pain / etiology
  • Polyneuropathies / complications*
  • Randomized Controlled Trials as Topic
  • Serotonin Uptake Inhibitors / therapeutic use


  • Analgesics
  • Antidepressive Agents, Tricyclic
  • Narcotics
  • Serotonin Uptake Inhibitors
  • Carbamazepine
  • N-Methylaspartate