Gabapentin for Chronic Neuropathic Pain.

Narrative: Neuropathic pain, when the pain generator is the nerve itself, occurs in a variety of conditions including diabetes mellitus and postherpetic neuropathy. The exact mechanism of action for these conditions is unclear. Some speculate that aberrant nerve signal modulation may be a culprit, which would explain why neuropathic pain rarely responds adequately to traditional analgesics, and why an effective treatment has proven elusive. Further complicating matters for patients, neuropathic pain typically is chronic in nature. Given the chronic nature and the poorly understood etiology, neuropathic pain is a challenge to treat and to study. Patients generally consider a 50% reduction in their chronic pain a useful outcome because it has been associated with important beneficial effects on sleep interference and depression.1 Physicians have tried a variety of medicines off-label including opiates, antidepressants, and antiepileptics to relieve patients’ neuropathic pain. One such drug, gabapentin (Neurontin), received approval by the U.S. Food and Drug Administration (FDA) in 1993 as an adjunct medicine for partial seizures and additional FDA approval in 2002 for the treatment of postherpetic neuralgia.2 Gabapentin remains off-label when used to treat diabetic neuropathy. This summary uses a Cochrane review, updated in 2014, to address the efficacy of gabapentin compared with placebo to palliate neuropathic pain.3 The Cochrane review includes 37 trials enrolling more than 5,600 patients. Overall, there were limited quality data to permit analysis of other neuropathic indications other than postherpetic neuralgia and diabetic neuropathy. Oral gabapentin dosed at 1,200 mg or more daily demonstrated a 50% reduction in pain intensity, with a number needed to treat (NNT) of eight for postherpetic neuralgia and an NNT of six for diabetic neuropathy. Gabapentin treatment was associated with several adverse effects including dizziness (number needed to harm [NNH] = 8), somnolence (NNH = 11), ataxia (NNH = 13), and edema (NNH = 21). There were no obvious differences in patient response with doses greater than 1,200 mg. The NNT for gabapentin is similar to a recent meta-analysis that demonstrated an NNT of seven.4