Levetiracetam for neuropathic pain in adults

  • Review
  • Intervention

Authors

  • Philip J Wiffen,

    1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK
    Search for more papers by this author
  • Sheena Derry,

    Corresponding author
    1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK
    • Sheena Derry, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. sheena.derry@ndcn.ox.ac.uk.

    Search for more papers by this author
  • R Andrew Moore,

    1. University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences (Nuffield Division of Anaesthetics), Oxford, Oxfordshire, UK
    Search for more papers by this author
  • Michael PT Lunn

    1. National Hospital for Neurology and Neurosurgery, Department of Neurology and MRC Centre for Neuromuscular Diseases, London, UK
    Search for more papers by this author

Abstract

Background

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

Objectives

To assess the analgesic efficacy and adverse events of levetiracetam in chronic neuropathic pain conditions in adults.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6) (via the Cochrane Library), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 3 July 2014, together with reference lists of retrieved papers and reviews.

Selection criteria

We included randomised, double-blind studies of two weeks duration or longer, comparing levetiracetam with placebo or another active treatment in adults with chronic neuropathic pain conditions. Studies had to have a minimum of 10 participants per treatments arm.

Data collection and analysis

Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. 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 from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with at least 200 participants in the comparison; and third tier evidence from data involving fewer than 200 participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both.

Main results

We included six studies: five small, cross-over studies with 174 participants, and one parallel group study with 170 participants. Participants were treated with levetiracetam (2000 mg to 3000 mg daily) or placebo for between four and 14 weeks. Each study included participants with a different type of neuropathic pain; central pain due to multiple sclerosis, pain following spinal cord injury, painful polyneuropathy, central post-stroke pain, postherpetic neuralgia, and post-mastectomy pain.

None of the included studies provided first or second tier evidence. The evidence was very low quality, downgraded because of the small size of the treatment arms, and because studies reported results using last observation carried forward (LOCF) imputation for withdrawals or using only participants who completed the study according to the protocol, where there were greater than 10% withdrawals. There were insufficient data for a pooled efficacy analysis in particular neuropathic pain conditions, but individual studies did not show any analgesic effect of levetiracetam compared with placebo. We did pool results for any outcome considered substantial pain relief (≥ 50% pain intensity reduction or ‘complete’ or ‘good’ responses on the verbal rating scale) for four studies with dichotomous data; response rates across different types of neuropathic pain was similar with levetiracetam (10%) and placebo (12%), with no statistical difference (risk ratio 0.9; 95% confidence interval (CI) 0.4 to1.7).

We pooled data across different conditions for adverse events and withdrawals. Based on very limited data, significantly more participants experienced an adverse event with levetiracetam than with placebo (number needed to treat for an additional harmful event (NNH) 8.0 (95% CI 4.6 to 32)). There were significantly more adverse event withdrawals with levetiracetam (NNH 9.7 (6.7 to 18)).

Authors' conclusions

The amount of evidence for levetiracetam in neuropathic pain conditions was very small and potentially biased because of the methods of analysis used in the studies. There was no indication that levetiracetam was effective in reducing neuropathic pain, but it was associated with an increase in participants who experienced adverse events and who withdrew due to adverse events.

Plain language summary

Levetiracetam 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 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.

Levetiracetam 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 in which levetiracetam was used to treat neuropathic pain. We found six studies in 344 adult participants with six different neuropathic pain conditions published up to July 2014. These studies were randomised and double blind, which usually means we can trust them. But all had one or more problems that could make the results look better than found in practice. There was no benefit from levetiracetam in any of the six conditions. More participants experienced adverse events with levetiracetam (67 in 100) than with placebo (54 in 100), and stopped taking levetiracetam because of adverse events (13 in 100) than stopped taking placebo (2 in 100). Adverse events included tiredness, dizziness, headache, constipation, and nausea.

There was too little information, which was of inadequate quality, to be sure that levetiracetam works as a pain medicine in any of the neuropathic pain conditions investigated. Other medicines have been shown to be effective in some of these conditions.

Laički sažetak

Levetiracetam za neuropatsku bol odraslih

Neuropatska bol može biti posljedica oštećenja živaca ili ozljede središnjeg živčanog sustava. Razlikuje se od boli koja se širi zdravim živcima i posljedica je oštećenja tkiva (primjerice, zbog pada, porezotine ili artritisa koljena). Neuropatska bol se liječi lijekovima koji se razlikuju od lijekova protiv boli koja nastaje zbog oštećenja tkiva. Lijekovi kao što su paracetamol ili ibuprofen obično nisu učinkoviti za ublažavanje neuropatske boli, dok nekad lijekovi koji se koriste za liječenje depresije ili epilepsije mogu biti vrlo učinkoviti kod nekih osoba koje pate od neuropatske boli.

Levetiracetam je vrsta lijeka koja se obično koristi za liječenje epilepsije. Neki od tih lijekova također su korisni za liječenje neuropatske boli. Pretražena je literatura kako bi se našli pokusi u kojima je levetiracetam ispitan za lječenje neuropatske boli. Pronađeno je 6 studija s ukupno 344 odraslih ispitanika, koji su patili od 6 različitih neuropatskih bolnih stanja. Te studije objavljene su do srpnja 2014. Studije su bile randomizirane i dvostruko-slijepe, što obično znači da će dati pouzdane rezultate. Međutim, sve su imale jedan ili više metodoloških problema, zbog čega njihovi rezultati mogu izgledati bolji nego što je stvarno djelovanje lijeka u praksi. Nije uočena korist od levetiracetama niti u jednom od 6 analiziranih bolnih stanja. Više ispitanika doživjelo je nuspojave u skupini koja je primala levetiracetam (67 od 100) u usporedbi s placebom (54 od 100) i prestalo je uzimati levetiracetam zbog nuspojava (13 od 100) nego što ih je prestalo uzimati terapiju u placebo skupini (2 od 100). Nuspojave su uključivale umor, vrtoglavicu, glavobolju, zatvor stolice i mučninu.

Sustavnim pregledom nađeno je premalo informacija, koje uz to nisu bile primjerene kvalitete, da bismo bili sigurni da levetiracetam ublažava bol u ispitanim neuropatskim bolnim stanjima. Drugi lijekovi su se pokazali učinkoviti u nekima od tih stanja.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Livia Puljak
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr