BACKGROUND: Valproic acid and its sodium salt (sodium valproate) are 
antiepileptic drugs that are sometimes used to treat chronic neuropathic pain 
and fibromyalgia, although they are not licensed for this use.
OBJECTIVES: To evaluate the analgesic efficacy and adverse effects of valproic 
acid and sodium valproate in the management of chronic neuropathic pain and 
fibromyalgia.
SEARCH STRATEGY: We identified randomised controlled trials (RCTs) of valproic 
acid and sodium valproate in acute, and chronic pain by searching MEDLINE, 
EMBASE and Cochrane CENTRAL to June 2011, together with reference lists of 
retrieved papers and reviews.
SELECTION CRITERIA: RCTs that were double blind and of eight-weeks duration or 
longer, reporting on analgesic effects and adverse events with valproic acid and 
sodium valproate in the treatment of chronic neuropathic pain and fibromyalgia.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted results 
and scored for quality. We extracted efficacy and adverse event data, and 
examined issues of study quality.
MAIN RESULTS: We included three studies, two in diabetic neuropathy (42 
participants treated with valproate, 42 with placebo), and one in post-herpetic 
neuralgia (23 treated with divalproex sodium, 22 with placebo). Study duration 
was eight or 12 weeks. No studies were found in fibromyalgia.Only one study 
reported one of our primary outcomes (≥ 50% pain relief), while all three 
reported group means for pain reduction from baseline to endpoint. In all three 
studies; efficacy results were given only for participants who completed the 
study. One study in diabetic neuropathy and the study in post-herpetic neuralgia 
reported significant differences between active and placebo groups, but there 
were insufficient data for reliable pooled analysis.More adverse events were 
reported with active treatment than placebo, and included nausea, drowsiness and 
abnormal liver function tests. One participant taking sodium valproate withdrew 
due to serious derangement of liver enzymes.
AUTHORS' CONCLUSIONS: These three studies no more than hint that sodium 
valproate may reduce pain in diabetic neuropathy, and divalproex sodium in 
post-herpetic neuralgia, but the use of 'completer' analysis may overestimate 
efficacy, and there were too few data for pooled analysis of efficacy or harm, 
or to have confidence in the results of the individual studies. There is 
insufficient evidence to support the use of valproic acid or sodium valproate as 
a first-line treatment for neuropathic pain. There is more robust evidence of 
greater efficacy for a small number of other drugs.