Saturday, 19 July 2014

Levetiracetam for pain... no evidence of it working

Levetiracetam is not effective in neuropathic pain. #MSBlog #MSResearch

"The meta-analysis below shows that the anti-convulsant, levetiracetam, is not effective in neuropathic pain. This mirrors my experience in clinical practice with the drug. The most effective drugs for neuropathic drugs are so called sodium channel blockers. To the best of my knowledge levetiracetam does not block sodium channels, it binds to a protein on synaptic vesicles and inhibits presynaptic calcium channels, which reduces neurotransmitter release. All this is very complex, but in short its mechanism of action is not targeting what we think is happening in MS-related neuropathic pain. The current evidence suggest that aberrant sodium channels inserted in demyelinated segments are firing spontaneously, hence the impact of sodium channel blockers. Other mechanisms that may be abnormal in MS is the central perception of pain and descending inhibitory pathways to the spinal cord, which is why we use anti-depressants to try and modulate these other mechanisms."

Epub: Wiffen et al. Levetiracetam for neuropathic pain in adults. Cochrane Database Syst Rev. 2014 Jul;7:CD010943.

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.

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)).

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.

1 comment:

  1. What drug are you finding works best for nerve pain? Daughter's Dr. is prescribing Lyrica. She is very active, on tysabri, loses legs and has much pain after spin class, needs cane to get to car.


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