Although the anticonvulsants, including carbamazepine, phenytoin, and gabapentin, have been effective in treating painful diabetic neuropathy (see Chapter 21), newer classes of anticonvulsants have shown surprising promise in treating both the symptomatic pain of diabetic neuropathy and the neuronal deficits.
Topiramate is a fructose analog that was initially examined because of its antidiabetic possibilities. Although it is an anticonvulsant used in complex partial seizures, topira-mate was recently shown to be efficacious in the management of neuropathic pain (116). Unfortunately, it was first examined only in normal animals and had no hypo-glycemic properties. It has now undergone extensive testing for epilepsy, migraine, involuntary movements, central nervous system injury, and neuropathic pain. The first two studies used a titration to 400 mg/day, which was associated with fairly severe central nervous system side effects, which were prohibitive. The studies failed to establish an effect in diabetic neuropathic pain. A third study using different end points, with specificity for the nature and site of the pain and recognizing that a side effect of the drug paresthesia, might be mistaken for pain was successful (117). What has emerged from all the studies is that the drug lowers blood pressure, improves lipid profiles, decreases insulin resistance, and increases nerve fiber regeneration in the skin (118).
Topiramate has the potential to relieve pain by altering the biology of the disease and has now been shown to increase intraepidermal nerve fiber length and density (118). Further, trials are being done. One must start with no more than 15 mg/day, preferably at night and then increase the dose only after the patient can tolerate the drug. A maximum of 200 mg was sufficient to induce nerve fiber recovery.
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