Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study

Background: Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies. Aim: To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia. Design: Randomized double-blind placebo-controlled trial. Methods: We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study. Results: After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 ± 2.29 to 11.90 ± 6.52 (p < 0.0001); PPI 4.0 ± 0.52 to 1.95 ± 1.29 (p < 0.0001); VAS 70.17 ± 9.21 to 31.27 ± 29.74 (p < 0.0001) and 11 PLS 6.97 ± 0.73 to 3.63 ± 2.34 (p < 0.0001) in comparison to placebo (means ± SEM). The ‘global impression of change’ questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment. Discussion: Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients.