Gilron I, Robb S, Tu D, et al. Randomized, double-blind, controlled trial of a combination of alpha-lipoic acid and pregabalin for neuropathic pain: the PAIN-CARE trial. Pain. 2023 Sep 7. doi: 10.1097/j.pain.0000000000003038. (Original study)

We compared a combination of the nonsedating antioxidant, alpha-lipoic acid (ALA), with the sedating anticonvulsant, pregabalin, vs each monotherapy to treat neuropathic pain due to peripheral neuropathies. In this randomized, double-blind, 3-period crossover trial, participants received oral ALA, pregabalin, and their combination-each for 6 weeks. The primary outcome was mean daily pain intensity at maximal tolerated doses (MTD); secondary outcomes included quality of life (SF-36), sleep (Medical Outcomes Study-Sleep Scale), adverse effects, drug doses, and other measures. Of 55 participants randomized (20-diabetic neuropathy, 19-small fiber neuropathy, and 16-other neuropathies), 46 completed 2 periods, and 44 completed 3. At MTD, the primary outcome of mean pain intensity (0-10) was 5.32 (standard error, SE = 0.18), 3.96 (0.25), 3.25 (0.25), and 3.16 (0.25) at baseline, ALA, pregabalin, and combination, respectively (P < 0.01 for ALA vs combination and pregabalin). Treatment differences were similar in subgroups with diabetic neuropathy and with other neuropathies. SF-36 total scores (higher number indicates better quality of life) were 66.6 (1.88), 70.1 (1.88), and 69.4 (1.87) with ALA, pregabalin, and combination (P < 0.05 for ALA vs combination and pregabalin). At MTD, there were no statistically significant treatment differences in adverse effects or drug doses. This trial demonstrates superiority of pregabalin vs ALA but provides no evidence to suggest added benefit of combining ALA with pregabalin to treat neuropathic pain.

Discipline Area Score
Physician 5 / 7
Comments from MORE raters

Physician rater

Small trial of short duration that confirms the benefit of pregabalin for symptom control in peripheral neuropathy, but demonstrates a lack of efficacy with adding alpha lipoic acid.

Physician rater

This article looked at 54 patients randomized to pregabilin and alpha lipoic acid (ALA), each given alone and together. It showed that adding the antioxidant ALA to pregabalin did not increase the pain relief of pregabalin alone. They ended up with 44 patients who completed the trial and it took 5 years to complete.

Physician rater

Neuropathic pain is a very common problem in OPD medicine and produces lots of frustration for patients and physicians. Adding medicaments to manage chronic pain is a difficult decision and physicians must be cautious when deciding so. Adverse effects may overshadow the beneficial ones. When combining or adding medication, a very close follow-up must be warranted and monitoring effects is a good practice point.
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