Srinivasan 2021: low-dose naltrexone vs amitriptyline for diabetic nerve pain

What they tested

Sixty-seven people with painful diabetic neuropathy, nerve pain caused by diabetes, were randomly assigned after a 2-week run-in to naltrexone 2 mg a day or amitriptyline 10 mg a day as the comparison drug. Doses were raised, to naltrexone 4 mg or amitriptyline 25 or 50 mg, if pain fell by less than 20% on a visual analog scale, a line people mark to rate their pain.

After 6 weeks and a 2-week washout, people switched to the other drug for 6 more weeks. In this crossover design, each person tries both drugs. The main outcome was the change in pain score after 6 weeks.

What they found

The difference between the drugs in pain change was 1.64 (confidence interval -0.92 to 4.20) in the per-protocol analysis and 1.5 (-1.11 to 4.13) in the intention-to-treat analysis. Both ranges include zero, so neither drug was shown to ease pain better.

Eight adverse events were reported on naltrexone and 52 on amitriptyline (P < .001). The most common were mild diarrhea on naltrexone and sleepiness on amitriptyline.

Limits

• There was no placebo group, so the trial compares the two drugs with each other and can't show how much either helped beyond a dummy pill.
• Each treatment period lasted only 6 weeks, and the trial had 67 people.

What it means if you're considering naltrexone

This trial is about low-dose naltrexone for nerve pain, a different use from the 50 mg dose for alcohol or opioids. It suggests low-dose naltrexone may ease diabetic nerve pain about as well as amitriptyline with fewer side effects, but without a placebo group and with short treatment periods, it isn't strong proof.