A pilot study of the beneficial effects of amantadine in the treatment of painful diabetic peripheral neuropathy

Background Current symptomatic treatments for painful peripheral neuropathy in diabetes have variable efficacy in individual patients. Amongst other chemical transmitters involved in pain reception, the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor is involved in nociception. Amantadine was recently shown to act as a non-competitive antagonist of NMDA and may be effective in the treatment of neuropathic pain in patients with cancer. We have looked at the benefit of amantadine infusion in diabetic patients with painful peripheral neuropathy. Methods Seventeen patients with diabetes (nine men) completed this double-blind randomized crossover placebo-controlled trial of intravenous amantadine. The average age was 58.4 (sd 11) years, with duration of diabetes of 21.1 (8.7) years and duration of painful peripheral neuropathy symptoms of 29.1 (24) months. All analgesics except paracetamol were stopped for 4 weeks prior to the study. Infusions were carried out on a weekly basis with amantadine being administered intravenously as a single 200-mg infusion. The Neuropathy Symptom Score (NSS), together with visual analogue scales, were used to assess current pain intensity (VAS-P) pre-therapy and 1 week later VAS-P was repeated together with a visual analogue scale used to assess relief in pain (VAS-R) and the Physicians Global Evaluation (PGE) score used to assess response to therapy. Results Pre-therapy, the NSS was 6.8 (6.3-7.4) at baseline, remaining unchanged at 6.6 (5.8-7.4) after placebo (P = 0.33), but fell to 4.6 (3.4-5.8) after amantadine (P = 0.003 vs. baseline and P = 0.02 vs. placebo). The baseline perception of pain was scored as 7.8 cm (7.3-8.3), with no difference following placebo, at 8.2 cm (7.7-8.6) (P = 0.34), but following amantadine it fell to 6.2 cm (4.9-7.8) (P = 0.01 compared with pre-therapy, P = 0.003 compared with placebo). The perception of relief from pain following placebo was only 0.2 (-0.2 to +0.6) but following amantadine was 10-fold better at 1.9 (0.8-3.1) (P = 0.016). The PGE assessment of pain relief was -0.3 (-0.5 to 0) for placebo and following amantadine was 0.8 (0.1-1.5) (P = 0.006). Conclusions Our study has shown that intravenous amantadine is beneficial in reducing the pain of painful peripheral neuropathy, with an effect sustained for at least 1 week after an infusion.