Zonisamide for neuropathic pain in adults



Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of zonisamide for the relief of neuropathic pain has not previously been reviewed.


To assess the analgesic efficacy and associated adverse events of zonisamide for chronic neuropathic pain in adults.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (via CRSO), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 1 August 2014, together with reference lists of retrieved papers and reviews.

Selection criteria

We included randomised, double‐blind studies of at least two weeks' duration comparing zonisamide with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 and over. We included only full journal publication articles and clinical trial summaries.

Data collection and analysis

Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We considered the evidence using three tiers. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention‐to‐treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier evidence derived from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier evidence derived from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both.

We planned to calculate risk ratio (RR) and numbers needed to treat (NNT) and harm (NNH) for one additional event using standard methods expected by The Cochrane Collaboration.

Main results

We included a single study treating 25 participants (13 zonisamide, 12 placebo) with painful diabetic neuropathy over 12 weeks. No first or second tier evidence was available for any outcome. The small size of the study and potential major bias due to a high proportion of early study withdrawals with zonisamide precluded any conclusions being drawn. There were two serious adverse events (one death) in zonisamide‐treated participants, which were apparently not related to treatment.

Authors' conclusions

The review found a lack of evidence suggesting that zonisamide provides pain relief in any neuropathic pain condition. Effective medicines with much greater supportive evidence are available.


R Andrew Moore, Philip J Wiffen, Sheena Derry, Michael PT Lunn


Plain language summary

Zonisamide for neuropathic pain in adults

Neuropathic pain can arise from damage to nerves and injury to the central nervous system. It is different from pain messages carried along healthy nerves from damaged tissue (a fall, or cut, or arthritic knee). Neuropathic pain is treated by different medicines than those used for pain from damaged tissue. Medicines like paracetamol or ibuprofen are not usually effective in neuropathic pain, while medicines that are sometimes used to treat depression or epilepsy can be very effective in some people with neuropathic pain.

Zonisamide is one of a type of medicine normally used to treat epilepsy. Some of these medicines are also useful for treating neuropathic pain. We looked for clinical trials that used zonisamide to treat neuropathic pain. We found a single study with 25 participants treated either with zonisamide or placebo. Study reporting may have led to major over‐estimation of any treatment effects because most (8/13) participants treated with zonisamide withdrew before the end of 12 weeks of treatment for a variety of reasons, mostly adverse events (side effects).

There was too little information, which was of inadequate quality, to give any guidance as to whether zonisamide works as a pain medicine in any neuropathic pain condition. Other medicines have been shown to be effective in some types of neuropathic pain.


R Andrew Moore, Philip J Wiffen, Sheena Derry, Michael PT Lunn

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

This review found no evidence to suggest that zonisamide provides pain relief in any neuropathic pain condition. The single available study was small and potentially subject to major bias. There are more effective medicines available for the more common neuropathic pain conditions (Lunn 2014; Kalso 2013; Moore 2013b; Wiffen 2013).

Implications for research 

Reasonable levels of evidence exist for the benefit of other antiepileptic and antidepressant drugs in the treatment of chronic neuropathic pain (for example, 14 studies of pregabalin in 3680 participants (Moore 2009); 9 studies of duloxetine in 2776 participants (Lunn 2014)).

For zonisamide, the single study we have is so small and so open to bias and error as to be uninterpretable. While this does not appear to justify continued research with zonisamide, neither can it rule out any possible beneficial effects.

Get full text at The Cochrane Library