Clinical Question: Is divalproex sodium (valproic acid and sodium valproate in a 1:1 ratio) an effective treatment for post-herpetic neuralgia?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Uncertain

Synopsis: A number of treatment options are available for patients with post-herpetic neuralgia, including antidepressants and anticonvulsants such as gabapentin, carbamazepine, and phenytoin. This small study identified 48 consecutive outpatients in India who had pain for at least six months after the onset of herpes zoster rash of at least 40 on a 100-point visual analog scale. Patients were randomized to treatment with divalproex sodium in a dosage of 1,000 mg per day or placebo.

After eight weeks, 22 of the 24 patients in the divalproex group completed the study; one was excluded because his pain score was less than 40, and one left because of vertigo during treatment. More dropouts occurred in the placebo group: one patient withdrew consent, one had insufficient pain, two failed to comply with the treatment regimen, and two dropped out because of ineffective therapy, leaving 18 patients who completed the study. Analysis was provided only for those who completed the study rather than by intention to treat.

Divalproex sodium was well tolerated in everyone except the patient with vertigo. At the end of eight weeks, 58 percent of patients in the active treatment group reported “much or moderate improvement” on the Global Impression of Change question compared with 15 percent in the placebo group (number needed to treat = two, statistical significance not reported). Active treatment also reduced pain more than placebo as measured by several validated scales in a statistically and clinically significant manner. However, this study has a number of important limitations, including small sample size, per-protocol analysis, poor reporting of results, and uncertain generalizability to non–South Asian populations.

Bottom Line: This small study provides limited support for divalproex sodium as an option for patients with post-herpetic neuralgia. (Level of Evidence: 2b)