Alpha lipoic acid: a new treatment for neuropathic pain in patients with diabetes?

Background: Neuropathic pain is difficult to treat. We identified those studies in the literature in which the effectiveness of alpha lipoic acid as a treatment for neuropathic pain was evaluated. Methods: Systematic literature review. The databases MEDLINE and EMBASE were searched using the keywords "lipoic acid", "thioctic acid", "diabet*", and the medical subject headings (MeSH) "thioctic acid" and "diabetes mellitus". Randomised placebo-controlled trials (RCTs) and meta-analyses were selected and assessed for their methodological quality. Results: Five RCTs and one meta-analysis were found. The Total Symptom Score (TSS) was used as the primary outcome measure. A significant improvement in the TSS was reported in four of the RCTs. An oral or intravenous alpha lipoic dose of at least 600 mg per day resulted in a 50% reduction in the TSS. However, compared with the control group, the TSS reduction in most groups was less than 30%, which is the threshold presumed to be clinically relevant. Four RCTs were of good quality (level of evidence 1b), one RCT had methodological limitations (level 2b), and the methodological quality of the meta-analysis was insufficient for the purposes of this review. Conclusion: Based on the currently available evidence, when given intravenously at a dosage of 600 mg once daily over a period of three weeks, alpha lipoic acid leads to a significant and clinically relevant reduction in neuropathic pain (grade of recommendation A). It is unclear if the significant improvements seen after three to five weeks of oral administration at a dosage of >= 600 mg daily are clinically relevant.