Oxcarbazepine for neuropathic pain

In 2013 a Chocrane review determined the efficacy of oxcarbazepine for neuropathic pain. But their results were based on moderate-quality evidence from only one RCT. Therefore this updated review considered new, potentially eligible studies to support the effectiveness of oxcarbazepine in painful diabetic neuropathy, neuropathic pain from radiculopathy and a mixture of neuropathies.

Several anticonvulsant drugs are used in the neuropathic pain management. Oxcarbazepine is one such anticonvulsant drug closely associated with carbamazepine. Oxcarbazepine has been described to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is contradictory. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of review to examine the benefits and harms of oxcarbazepine for different types of neuropathic pain.

On 21 November 2016, the database search of Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase was initiated.  The Chinese Biomedical Retrieval System (January 1978 - November 2016) was explored. The US National Institutes of Health (NIH) databases and WHO International Clinical Trials Registry Platform were investigated for ongoing trials in January 2017. The companies who make oxcarbazepine and pain experts were requested for further information about the drug.

Total 5 multicentre, randomised, placebo-controlled, double-blind trials with 862 participants were eligible for inclusion in this updated review. Three trials comprised of participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one comprised people with neuropathic pain because of radiculopathy (n = 145), and one was newly recognised at this update involving participants with peripheral neuropathic pain of mixed origin i.e. polyneuropathy, peripheral nerve injury or postherpetic neuralgia (n = 83). Some studies did not describe all the outcomes of interest. For painful DPN, as compared to the baseline, the percent of participants who described at least a 50% or 30% reduction of pain scores following 16 weeks of treatment in the oxcarbazepine group vs the placebo group were: at least 50% reduction: 34.8% with oxcarbazepine vs 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 vs 28.6% with placebo (RR 1.57, 95% CI 1.01 to 2.44; NNTB 6, 95% CI 3 to 114; n = 146). Both the findings were based on data from a single trial, since two trials that found little or, not significant did not provide data that could be considered in a meta-analysis. Although being well designed, incomplete outcome data and possible unblinding of participants because of obvious adverse effects makes the results at a high risk of bias.
 There was also serious imprecision and high risk of publication bias. The radiculopathy trial had no advantage for the outcome 'at least 50% pain relief' from oxcarbazepine. In a mixture of neuropathies, 19.3% of people receiving oxcarbazepine vs 4.8% receiving placebo had at least 50% pain relief. These small trials depicted low event rates and impact, at best, low-quality evidence for any outcome. The percent of people with 'improved' or 'very much improved' pain was 45.9% with oxcarbazepine vs 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 vs 14.9% with placebo in radiculopathy (RR 1.61, 95% CI 0.81 to 3.20; n = 145). The investigators found no trials in other types of neuropathic pain for example trigeminal neuralgia. According to the Trial reports, most adverse effects were mild to moderate in severity. Considering the moderate-quality evidence from the 3 DPN trials, serious adverse effects arised 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). Number needed to treat an additional serious adverse effect outcome (NNTH) was 17 (95% CI 11 to 42). The RR associated with serious adverse effects in the radiculopathy trial was 3.13 (95% CI 0.65 to 14.98, n = 145). Fifth trial did not provide data. More people withdrew due to adverse effects with oxcarbazepine than with the placebo (DPN: 25.6% with oxcarbazepine vs 6.8% with placebo; RR 3.83, 95% CI 2.29 to 6.40; radiculopathy: 42.3% with oxcarbazepine vs 14.9% with placebo; RR 2.84, 95% CI 1.55 to 5.23; mixed neuropathic pain: 13.5% with oxcarbazepine vs 1.2% with placebo; RR 11.51, 95% CI 1.54 to 86.15).

Not enough evidence was found to support the effectiveness of oxcarbazepine in PDN, neuropathic pain from radiculopathy and a mixture of neuropathies. Some very-low-quality evidence recommends efficacy, but in case of small trials, low event rates, heterogeneity in some measures and high risk of publication bias depicts that the investigators have very low confidence in the measures of effect. Adverse effects, serious adverse effects and adverse effects leading to discontinuation are probably more familiar with oxcarbazepine than placebo; but, the numbers of participants and event rates are low. For further analysis, more well-designed, multicentre RCTs investigating oxcarbazepine for various k types of neuropathic pain are required, and selective publication of studies or data should be ignored.