OBJECTIVE: To test the hypothesis that improved nerve function using the anti-epileptic/migraine drug topiramate would translate to better quality of life (QOL). METHODS: Twenty patients with diabetic peripheral neuropathy were consented and entered into a study on topiramate. The dosage for each patient was titrated over a six-week period from 25mg per day to 50mg twice a day. The patients remained on 100mg a day for 12 weeks and then were tapered off the medication over an additional 4-week period. Each patient received quantitative sensory testing, electromyography, skin blood flow, skin biopsies, and neurological examinations before and after treatment with topiramate. Each patient also answered the Norfolk Quality of Life questionnaire for diabetic neuropathy (QOL-DN) before and after treatment. The QOL-DN questionnaire was used to assess the patients' perception of the effects of diabetic peripheral neuropathy on their quality of life. RESULTS: Total QOL: before=27.76±5.40, after=17.29±4.66 (P=0.00028). Small fiber: before=2.35±0.77, after=1.59±.68 (p=0.149). ADLs: before=1.83± 0.74, after=1.22±0.69 (p=0.276). Symptom Score: before=8.28±1.24, after=3.39±.69 (p=.00004). Autonomic Function: before=1.06± 0.47, after=1.00± 0.47 (p=0.834). Large Fiber: before=15.06±3.30, after=10.01±2.79 (p=0.0044). Topiramate significantly improved 3 of the 5 domains of QOL-DN. There was a significant correlation between the changes in QOL symptom score and proximal leg cold sensation (r=0.459, p=0.0448). In addition, the correlation between changes in QOL large fiber neuropathy score and objective changes in Total Neuropathy Score approached significance (r=0.459, p=0.0637). Thus, topiramate improves objective indices of nerve function and QOL. CONCLUSIONS: Nerve Function improvement and enhanced QOL can be used as a measure of response to therapy in clinical trials.