While nortriptyline is not FDA-approved for the treatment of neuropathic pain, it is commonly used for chronic pain conditions and is often used outside its approved indications to treat patients with neuropathic pain. In a recent review published in the Cochrane Library, researchers sought to investigate the safety and efficacy of nortriptyline in the treatment of chronic neuropathic pain in adults.

Six studies involving 310 patients with neuropathic pain were included in the analysis (272 were randomized to nortriptyline); treatment periods lasted between three and eight weeks. The primary outcomes of the study were  patient-reported pain relief of ≥30%, patient-reported pain relief of ≥50%, Patient Global Impression of Change (PGIC) much or very much improved, and PGIC very much improved. 

Because these studies for methodologically flawed (due to small size) and possibly subject to bias, not one study was able to provide first or second tier evidence for any outcome. For postherpetic neuralgia, there was little evidence to show that either nortriptyline or gabapentin was more efficacious. Among the individual studies, third tier evidence showed similar benefit for nortriptyline vs. gabapentin, morphineclomipramine, amitriptyline, and placebo.  Adverse events were reported more often in patients taking nortriptyline vs. those given placebo; however, compared to other active medications, the numbers were similar.

The authors conclude that little information exists to justify the use of nortriptyline to treat neuropathic pain. Medications such as duloxetine and pregabalin, which have greater supportive evidence, are available to treat these conditions.