Intervention Review

Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults

  1. Dipender Gill1,
  2. Sheena Derry2,*,
  3. Philip J Wiffen2,
  4. R Andrew Moore2

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 5 OCT 2011

Assessed as up-to-date: 9 AUG 2011

DOI: 10.1002/14651858.CD009183.pub2


How to Cite

Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD009183. DOI: 10.1002/14651858.CD009183.pub2.

Author Information

  1. 1

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK

  2. 2

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

*Sheena Derry, Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. sheena.derry@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 5 OCT 2011

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

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 methods

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.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Valproic acid and sodium valproate for neuropathic pain and fibromyalgia

Neuropathic pain is caused by nerve damage, often accompanied by changes in the central nervous sytem, and fibromyalgia is a related complex pain syndrome. Many people with these conditions are disabled with moderate or severe pain for many years. Conventional analgesics are usually not effective treatment options. In light of the fact that there are similarities between the pathophysiologic and biochemical mechanisms observed in epilepsy and in neuropathic pain, it is not surprising that antiepileptic agents can be used to treat neuropathic pain. The aim of this review was to investigate the efficacy and adverse events associated with use of sodium valproate and valproic acid for the treatment of chronic neuropathic pain and fibromyalgia. We identified three relevant studies, two in diabetic neuropathy and a third in post-herpetic neuralgia. Two of the three studies report significantly greater reduction in pain for valproate than placebo, but studies were small (≤ 45 participants) and provided insufficient data for pooled analysis, and the methods of analysis used may have overestimated treatment effect. Adverse events such as nausea, sedation, drowsiness, vertigo, and abnormal liver function are more common with valproate than placebo, but these studies were unsuitable to allow for a comprehensive assessment of harm.

There is insufficient evidence to support the use of valproic acid or sodium valproate as a first-line treatment for neuropathic pain.