Clinical Question: Does the anticonvulsant sodium valproate reduce symptoms of painful diabetic neuropathy?
Setting: Outpatient (any)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: For painful diabetic neuropathy, previous studies have shown that carbamazepine and gabapentin are potentially useful. However, the former is limited by toxicity and the latter by cost. In this study, 43 patients with diabetic neuropathy, an A1C level of less than 11 percent, and a pain score of more than 4 on a 10-point visual scale were randomized (allocation concealment uncertain) to treatment with sodium valproate, in a dosage of 500 mg once daily, or placebo. Analysis appears to have been per protocol rather than intention to treat, but this is a minor point because only one patient withdrew from the three-month study. After one week, if patients had no nystagmus or ataxia, and normal hepatic transaminase levels, the dosage was increased to 500 mg twice daily.
The primary outcome measures were the McGill Pain Questionnaire (MPQ), a visual analog scale (VAS) from zero to 10, and a pain intensity score. At the end of the three months, the MPQ decreased from 19.5 to 9.7, the VAS from 6.0 to 3.0, and the pain intensity score from 2.7 to 1.3 (all P < .001). The authors did not give exact numbers but showed graphically that the scores did not change significantly in the placebo group. One patient withdrew from the study because of elevated hepatic transaminase levels, and two patients complained of nausea.
Bottom Line: This small study provides preliminary evidence that sodium valproate in a dosage of 500 mg twice daily reduces the pain of diabetic neuropathy. Larger and longer studies are needed to confirm this finding, and to compare sodium valproate with other therapies. Valproic acid is more commonly available and is dosed in a 1:1 ratio with sodium valproate. (Level of Evidence: 1b–)