Oxcarbazepine for neuropathic pain

Muke Zhou, Ning Chen, Li He, Mi Yang, Cairong Zhu, Fengbo Wu

Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013. To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain. On 21 November 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese Biomedical Retrieval System (January 1978 to November 2016). We searched the US National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials in January 2017, and we wrote to the companies who make oxcarbazepine and to pain experts requesting additional information. All RCTs and randomised 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 with a treatment duration of at least six weeks, regardless of administration route and dose. We used standard methodological procedures expected by Cochrane. Five multicentre, randomised, placebo-controlled, double-blind trials with a total of 862 participants were eligible for inclusion in this updated review. Three trials involved participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain due to radiculopathy (n = 145), and one, which was newly identified at this update, involved participants with peripheral neuropathic pain of mixed origin (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83). Some studies did not report all outcomes of interest. For painful DPN, compared to the baseline, the proportion of participants who reported at least a 50% or 30% reduction of pain scores after 16 weeks of treatment in the oxcarbazepine group versus the placebo group were: at least 50% reduction: 34.8% with oxcarbazepine versus 18.2% with placebo (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, 95% CI 3 to 41); and at least 30% reduction: 44.9% with oxcarbazepine versus 28.6% with placebo (RR 1.57, 95% CI 1.01 to 2.44; NNTB 6, 95% CI 3 to 114; n = 146). Both results were based on data from a single trial, since two trials that found little or no benefit did not provide data that could be included in a meta-analysis. Although these trials were well designed, incomplete outcome data and possible unblinding of participants due to obvious adverse effects placed the results at a high risk of bias. There was also serious imprecision and a high risk of publication bias. The radiculopathy trial reported no benefit for the outcome 'at least 50% pain relief' from oxcarbazepine. In mixed neuropathies, 19.3% of people receiving oxcarbazepine versus 4.8% receiving placebo had at least 50% pain relief. These small trials had low event rates and provided, at best, low-quality evidence for any outcome. The proportion of people with 'improved' or 'very much improved' pain was 45.9% with oxcarbazepine versus 30.1% with placebo in DPN (RR 1.46, 95% CI 1.13 to 1.88; n = 493; 2 trials; very-low-quality evidence) and 23.9% with oxcarbazepine versus 14.9% with placebo in radiculopathy (RR 1.61, 95% CI 0.81 to 3.20; n = 145).We found no trials in other types of neuropathic pain such as trigeminal neuralgia.Trial reports stated that most adverse effects were mild to moderate in severity. Based on moderate-quality evidence from the three DPN trials, serious adverse effects occurred in 8.3% with oxcarbazepine and 2.5% with placebo (RR 3.65, 95% CI 1.45 to 9.20; n = 634; moderate-quality evidence). The number needed to treat for an additional harmful (serious adverse effect) outcome (NNTH) was 17 (95% CI 11 to 42). The RR for serious adverse effects in the radiculopathy trial was 3.13 (95% CI 0.65 to 14.98, n = 145). The fifth trial did not provide data.More people withdrew because of adverse effects with oxcarbazepine than with placebo (DPN: 25.6% with oxcarbazepine versus 6.8% with placebo; RR 3.83, 95% CI 2.29 to 6.40; radiculopathy: 42.3% with oxcarbazepine versus 14.9% with placebo; RR 2.84, 95% CI 1.55 to 5.23; mixed neuropathic pain: 13.5% with oxcarbazepine versus 1.2% with placebo; RR 11.51, 95% CI 1.54 to 86.15). This review found little evidence to support the effectiveness of oxcarbazepine in painful diabetic neuropathy, neuropathic pain from radiculopathy and a mixture of neuropathies. Some very-low-quality evidence suggests efficacy but small trials, low event rates, heterogeneity in some measures and a high risk of publication bias means that we have very low confidence in the measures of effect. Adverse effects, serious adverse effects and adverse effects leading to discontinuation are probably more common with oxcarbazepine than placebo; however, the numbers of participants and event rates are low. More well-designed, multicentre RCTs investigating oxcarbazepine for various types of neuropathic pain are needed, and selective publication of studies or data should be avoided.