Falah et al. A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis. Eur J Pain. 2011 j.1532-2149.2011.00073.x. [Epub ahead of print]
Levetiracetam is an anti-convulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple sclerosis.
This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well as pain intensity of more than 4 on a 0 to 10-point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Eighty-nine patients were screened for participation and 30 patients entered the study. Twenty-seven patients were included in the data analysis.
RESULTS: There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating (stabbing pain) or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anti-convulsant levetiracetam in non-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.
Levetiracetam is drug used to treat epilepsy and works by blocking nerve signalling. Central pain is thought to be caused by the misfiring of nerve impulse in damaged nerve pathways. As you know neuropathic pain is a really difficult to deal with and whilst there is logic to the approach unfortunately this study has to be considered a failure because the original hypothesis was not about subgroup analysis. Trying to spin poisitives out of the negative of no significant effect should be viewed with extreme caution. This is why in clinical trials a primary outcome measure has to be picked before the trial takes place. If there is not effect on the primary outcome it is a failure even if the other secondary outcomes are affected. Then another trial needs to be done now using the secondary outcomes in the first trial as primary outcome in the second trial. This is to stop the people who do the trial from "cherry-picking" the positives, which could be false positives.
With only 30 people in the whole study and then to try and subgroup analysis on smaller groups is asking for trouble as the power to really detect effects are deminished. Therefore, the study will really need to be done again