Several anticonvulsant drugs are used in the neuropathic pain management.
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.
Cochrane Database Syst Rev. 2017 Dec 2;12:CD007963
Oxcarbazepine for neuropathic pain.
Zhou M et al.
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