Opioids for Neuropathic Pain: Evidence-Based Recommendation

Introduction to Neuropathic Pain Management

The American College of Physicians recommends that opioids should not be used as first-line therapy for neuropathic pain due to limited efficacy and significant risks of addiction, respiratory depression, and potential pronociception, reserving them for second- or third-line options for patients with moderate to severe pain who have failed first-line treatments 1, 2, 3

The National Comprehensive Cancer Network recommends gabapentin as a first-line treatment for diffuse neuropathic pain, starting with 100-300 mg at bedtime and titrating to 900-3600 mg/day in 2-3 divided doses, with a number needed to treat (NNT) of 4.39 for postherpetic neuralgia 2, 3
The American Academy of Neurology recommends pregabalin as a first-line treatment for diffuse neuropathic pain, starting with 150 mg/day in 2-3 divided doses and increasing to 300-600 mg/day, with an NNT of 4.93 2, 3
The American Diabetes Association recommends duloxetine as a first-line treatment for diabetic neuropathy, starting with 60 mg once daily and increasing to 120 mg/day, with an NNT of 5.2 3
The American College of Cardiology recommends tricyclic antidepressants, such as nortriptyline or desipramine, as a first-line treatment for neuropathic pain, starting with 10-25 mg at bedtime and titrating to 75-150 mg/day, with an NNT of 2.64 2, 3

The Clinical Infectious Diseases society recommends tramadol as a second-line treatment for neuropathic pain, starting with 50 mg once or twice daily and increasing to 400 mg/day, due to its dual mechanism of action as a weak μ-opioid agonist and SNRI, with lower abuse potential 9, 3
The Journal of the National Comprehensive Cancer Network recommends strong opioids, such as morphine or oxycodone, as a second-line treatment for neuropathic pain, only after failure of first-line treatments and with close monitoring, due to their high risk of addiction and side effects 1, 6

The Centers for Disease Control and Prevention recommends screening for aberrant use risk using the SOAPP-R or Opioid Risk Tool before prescribing opioids for neuropathic pain, and establishing a pain treatment agreement and regular monitoring for efficacy, side effects, and signs of misuse 4
The American Society of Addiction Medicine recommends reassessing the necessity of opioids at each visit and discontinuing them if ineffective, due to their high risk of addiction and side effects 4

The Cochrane Review found that the evidence supporting opioid use in neuropathic pain is weak, with a 2013 review of 14 trials showing 57% of opioid-treated patients achieving ≥33% pain reduction versus 34% with placebo, but with high dropout rates and limited study duration 6
The Clinical Infectious Diseases society found that systematic reviews show opioids provide modest pain reduction, but no improvement in physical or emotional functioning, with an NNT of 2.67 for oxycodone, extended-release morphine, and methadone in postherpetic neuralgia 1, 6