Neuropathic pain is pain that arises from damage to the part of the nervous system that carries sensory information to the brain. It is difficult to treat because of its severity, duration and resistance to simple painkillers. Some studies have suggested that oxcarbazepine, when given on its own, can relieve pain from nerve damage. To investigate the benefits and harms of oxcarbazepine in different forms of neuropathic pain, we performed a comprehensive search for randomised controlled trials and found four trials, involving 634 participants with painful diabetic neuropathy and 145 with neuropathic pain due to radiculopathy. All were funded by the manufacturer. The results showed that oxcarbazepine produced pain relief and an improved global impression of change in pain at 16 weeks for people with diabetic neuropathy. This evidence, which was of moderate quality, only included data from the single positive trial, and did not take into account negative results from other diabetic peripheral neuropathy trials that could not be included in our analysis. For painful radiculopathy, data from the only included trial showed no significant efficacy of oxcarbazepine. Although trial reports stated that most side effects were mild to moderate in severity, the number of any kind of event and those leading to participants' dropping out of the trials were both higher in the oxcarbazepine group than in the placebo group, and serious events were not uncommon. In the radiculopathy trial, numbers with serious adverse events were similar with oxcarbazepine and placebo, but with oxcarbazepine more people experienced adverse events that led them to stop treatment. We did not find studies of oxcarbazepine for other types of neuropathic pain that met our inclusion criteria. More well designed randomised controlled trials of oxcarbazepine for various types of neuropathic pain are needed, with large numbers of participants spread over different centres. Such studies should also compare the effect of different dosages on pain relief.
On the basis of moderate quality evidence from one trial in diabetic peripheral neuropathy, oxcarbazepine is effective in reducing pain for this condition. However, this conclusion does not take into account negative results from other trials in diabetic peripheral neuropathy that could not be included in our meta-analysis. We did not find any evidence from randomised controlled trials to determine the efficacy or safety of oxcarbazepine for other kinds of neuropathic pain, other than one low quality trial in people with radiculopathy. Most adverse effects related to oxcarbazepine are rated as mild to moderate in severity, but adverse events leading to discontinuation of drug administration or serious adverse events are not uncommon. More well designed randomised controlled trials investigating oxcarbazepine for various types of neuropathic pain are needed.
Neuropathic pain is difficult to treat. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine and is reportedly better tolerated. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain.
To determine the benefits and harms of oxcarbazepine for different forms of neuropathic pain.
We searched the Cochrane Neuromuscular Disease Group Specialized Register (30 October 2012), CENTRAL (2012, Issue 10), MEDLINE (January 1966 to October 2012), EMBASE (January 1980 to October 2012) and the Chinese Biomedical Retrieval System (January 1978 to October 2012) for trials. We also searched the National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials, and wrote to the companies who make oxcarbazepine and to pain experts asking for additional information.
All randomised controlled trials and cross-over studies of oxcarbazepine for the treatment of people of any age or sex with any neuropathic pain were eligible. We planned to include trials of oxcarbazepine compared with placebo or any other intervention, regardless of administration route, dosage or length of treatment.
Two review authors independently selected the studies for inclusion, assessed their risk of bias, extracted data and typed the data onto forms. The authors resolved any disagreements through discussion.
Four multicentre, randomised, placebo-controlled, double-blind trials with a total of 779 participants were eligible for inclusion. These were from a series of studies funded by the manufacturer. Three of them investigated oxcarbazepine in people with painful diabetic neuropathy (634 participants) and one was a trial of oxcarbazepine for neuropathic pain due to radiculopathy (145 participants). Although these trials were well designed, the imbalanced and large amount of incomplete outcome data led to a risk of bias in the results. Results for painful diabetic neuropathy showed that compared to the baseline the proportion of participants who reported a 50% or 30% reduction of pain scores after 16 weeks of treatment was significantly higher in the oxcarbazepine group than the placebo group (50% reduction: risk ratio (RR) 1.91, 95% confidence interval (CI) 1.08 to 3.39, number of people needed to treat for an additional beneficial outcome (NNTB) 6.0, 95% CI 3.3 to 41.0; 30% reduction: RR 1.57, 95% CI 1.01 to 2.44, NNTB 6.1, 95% CI 3.1 to 113.6). However, both results were based on data from the single positive trial (146 participants) since the two negative trials did not provide data that could be included in a meta-analysis. For participants with neuropathic pain due to radiculopathy, the trial demonstrated no significant efficacy for oxcarbazepine. Although trial reports stated that most side effects were mild to moderate in severity, more people experienced serious adverse events with oxcarbazepine than with placebo (RR 3.65, 95% CI 1.45 to 9.20, number needed to treat for an additional harmful outcome (NNTH) 17.4, 95% CI 11.0 to 42.0) in the three painful diabetic neuropathy trials. The proportion of people with adverse events leading to withdrawals was statistically higher in the oxcarbazepine group than in the placebo group (RR 3.83, 95% CI 2.29 to 6.40). For radiculopathy the difference between oxcarbazepine and placebo did not reach significance for serious adverse events, but more people had adverse events leading to withdrawal with oxcarbazepine than with placebo (RR 2.84, 95% CI 1.55 to 5.23).