Among four drugs commonly used to treat unexplained neuropathic pain in seniors, nortriptyline and duloxetine stand out as the most effective and least likely to be discontinued, physician researchers report.

Image of Richard Barohn, M.D.
Richard Barohn, M.D.

Chronic neuropathy, or pain caused by nerve damage, is estimated to affect about 20 million people in the United States. The cause is unknown in about 25% of these cases, which are diagnosed as cryptogenic sensory polyneuropathy, or CSPN. Diagnosis usually occurs in the sixth or seventh decade of life, and effective treatment guidance is lacking for these patients, investigators said. 

In an effort to build a library of treatment data for this condition, the researchers compared four drugs with different mechanisms of action in 402 adult patients across 40 sites. Participants were aged 30 or older, had diagnoses of CSPN, and reported a pain score of four or greater on a 10-point scale. 

The patients were treated with one of the drugs in a real-life clinic situation and evaluated at four, eight and 12 weeks. Drug efficacy was based on a 50% or greater reduction in reported pain. Investigators also tracked any drug discontinuation due to adverse effects.

They reported the following results:

  • Nortriptyline, a tricyclic antidepressant, had the highest efficacious percentage (25%) and the second-lowest quit rate (38%), giving it the highest level of overall utility.
  • Duloxetine, a serotonin-norepinephrine reuptake inhibitor, had the second-highest efficacious rate (23%) and lowest drop-out rate (37%).
  • Pregabalin, an anti-seizure drug, had the lowest efficacy rate (15%).
  • Mexiletine, an antiarrhythmic medication, had the highest quit rate (58%).

“There was no clearly superior performing drug in the study,” said study lead Richard Barohn, M.D., of the University of Missouri. “However, of the four medications, nortriptyline and duloxetine performed better when efficacy and dropouts were both considered. Therefore, we recommend that either nortriptyline or duloxetine be considered before the other medications we tested.”

Barohn’s laboratory plans to continue collecting effectiveness data on nearly a dozen drugs for CSPN, potentially including gabapentin, venlafaxine and other sodium channel inhibitors.

CSPN does not necessarily curtail physical functioning, so treatment is focused on pain management, physical therapy for balance training and, occasionally, assistive devices.

The study was published in JAMA Neurology.