Nortriptyline and Duloxetine Better Tolerated in Neuropathic Pain of Cryptogenic Sensory Polyneuropathy

According to a study published by JAMA Neurology, nortriptyline is most tolerable and effective at reducing neuropathic pain for individuals with cryptogenic sensory polyneuropathy (CSPN). The study was the first-of-its-kind prospective comparative effectiveness study to guide a physician’s drug choices between nortriptyline, duloxetine, pregabalin, and mexiletene to treat CSPN.

Participant who reported at least a 50% reduction in pain were deemed as having an efficacious result. The number of participants who discontinued the treatment drug because of adverse effects was also measured. Nortriptyline had the highest efficacious percentage (25%), and the second-lowest quit rate (38%), giving it the highest level of overall utility. Duloxetine had the second-highest efficacious rate (23%), and second-lowest drop-out rate (37%). Pregabalin had the lowest efficacy rate (15%), and mexiletene had the highest quit rate (58%).

The study involved 40 sites and enrolled 402 participants with diagnosed CSPN age 30 or more who reported a pain score of 4 or more on a 10-point scale. Participants were randomly assigned to receive 1 of 4 medications commonly used to treat CSPN: nortriptyline, a tricyclic antidepressant; duloxetine, a serotonin-norepinephrine reuptake inhibitor; pregabalin, an anti-seizure drug; or mexiletine, an antiarrhythmic medication. Participants took treatment for 12 weeks and were evaluated at 4, 8, and 12 weeks. 

“There was no clearly superior performing drug in the study,” Richard Barohn, MD, lead researcher and executive vice chancellor for health affairs at the University of Missouri, said. “However, of the 4 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.”

There are other nonnarcotic drugs used to treat painful peripheral neuropathy, including gabapentin, venlafaxine, and other sodium channel inhibitors. Barohn said additional comparative effectiveness research studies can be performed on those drugs, so providers can further build a library of data for the treatment of CSPN.