Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults Stable (no update expected for reasons given in 'What's new')

Abstract

Abstract 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.

Author(s)

Dipender Gill, Sheena Derry, Philip J Wiffen, R Andrew Moore

Abstract

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.

Author(s)

Dipender Gill, Sheena Derry, Philip J Wiffen, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions

Implications for practice

There is some evidence that sodium valproate and divalproex sodium may be effective in the treatment of chronic pain associated with diabetic neuropathy and post‐herpetic neuralgia, respectively. However, based on the quantity and limitations of the available evidence, the use of these medications should be reserved for cases where other proven treatment options (e.g. Moore 2009, Moore 2011, Lunn 2009) have failed, are not available, or are not tolerated.

Implications for research

This review highlights the limited availability of high standard, randomised, double‐blinded placebo‐controlled trials investigating the use of sodium valproate and valproic acid in the treatment of chronic neuropathic pain and fibromyalgia. Evidenced‐based decisions require further study, but since these drugs are associated with known serious adverse effects, and alternative therapies are available, it is unlikely that any large trials will be conducted. In these circumstances a registry of their use in this context would be desirable.

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