Impact of etiology and duration of pain on pharmacological treatment effects in painful polyneuropathy.

BACKGROUND: The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for. METHODS: We analysed data from four published, randomized, controlled trials of drugs in painful polyneuropathy to see if diabetic etiology and duration of neuropathic pain had an impact on drug efficacy. The studies had a cross-over design, and had nearly similar outcome recordings as well as a thorough baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed. RESULTS: Diabetes as etiology of polyneuropathy had no impact on the effect of antidepressants (imipramine, venlafaxine, escitalopram), but there was a significant interaction with treatment effect on anticonvulsants with better effects in diabetics (0.86 NRS points, p = 0.021) with most pronounced interaction for oxcarbazepine (1.47 NRS points, p = 0.032). There was an interaction between duration of neuropathic pain and treatment with antidepressants with better effect with duration less than 3 years (0.62 NRS points, p = 0.036), whereas anticonvulsants tended to work best with duration of pain for more than 3 years. CONCLUSION: Despite the small sample size and limited number of drugs included this study suggests that diabetic etiology of polyneuropathy may impact on the efficacy of anticonvulsants, and duration of neuropathic pain may impact on the efficacy of antidepressants. SIGNIFICANCE: This study found that duration of pain appears to have an impact on the effect of antidepressants in neuropathic pain and that diabetes as etiology for painful polyneuropathy appears to influence pain relief obtained with anticonvulsants.

A randomized, placebo-controlled trial of levetiracetam in central pain in multiple sclerosis.

Levetiracetam is an anticonvulsant 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. 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 or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.