Zonisamide in the Treatment of Painful Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

ABSTRACT Background. Painful diabetic neuropathy is a form of neuropathic pain frequently encountered as a complication of diabetes mellitus types I and II. Pharmacotherapy is one modality of treatment for this distressing and often disabling condition, but there is no medication available that consistently provides adequate pain relief with acceptable safety and tolerability. Tricyclic antidepressants, certain antiepileptic drugs, and opioids have been shown in randomized, controlled trials to be of benefit in painful diabetic neuropathy, although none has Food and Drug Administration (FDA)‐approved labeling for this indication. Study Objective. To analyze the safety and efficacy of zonisamide in the treatment of painful diabetic neuropathy. This pilot study is the first randomized, controlled trial of zonisamide for the treatment of any neuropathic pain disorder. Study Design. Forty‐two patients 18–80 years of age with type I or type II diabetes mellitus and at least a 3‐month history of painful diabetic neuropathy were screened in the study, and 25 were randomized to zonisamide (N = 13) or placebo (N = 12). The study drug was titrated over a 6‐week period and continued at a fixed dosage for a 6‐week maintenance period. The mean dosage of zonisamide for the maintenance phase was 540 mg/day. Outcome Measures. Patients kept a daily log of their pain using both a 0–100 mm visual analog scale and a 0–10 Likert scale. Result. Pain scores on both the visual analog scale and the Likert scale decreased more for the zonisamide group compared with the placebo group, regardless of whether the comparison was made for the intent‐to‐treat population, the population that entered the maintenance phase, or the completer population, but these differences did not reach statistical significance. Tolerability of zonisamide was only fair in this study, which had a high number of dropouts from the zonisamide group. Conclusion. A larger randomized, controlled trial is needed to establish the efficacy and tolerability of zonisamide for painful diabetic neuropathy.