Is the improvement in vitality independent of the improvements in sleep interference and pain in patients with diabetic peripheral neuropathic pain? Responses to treatment with duloxetine

A major issue in pain literature has been whether there is an etiological association between pain, sleep, and vitality.

Data from duloxetine clinical trials in patients with diabetic peripheral neuropathic pain (DPNP) were used to investigate associations between pain, sleep and vitality. Data were pooled from 3 double-blind, randomized, placebo-controlled, 12-week trials in which major mood disorders were excluded. Study 1 (N=457) compared duloxetine 20mg once daily (QD), 60mg QD, 60mg twice daily (BID), and placebo; Studies 2 (N=334) and 3 (N=348) compared duloxetine 60mg QD and 60mg BID with placebo. A subset of patients (n=804) with complete data across the 4 assessments was constructed by dropping patients 1) reporting maximum vitality at baseline, 2) experiencing treatment-emergent somnolence, asthenia or fatigue or 3) taking sedating concomitant medications or duloxetine 20 mg/day. Efficacy measures included daily and night pain severity collected via patient diaries, Brief Pain Inventory (BPI) sleep interference, and SF-36 vitality domain.

For duloxetine, mean improvements from baseline to endpoint in daily and night pain severity, BPI sleep interference, and vitality were significantly superior to placebo (£.002). Correlations between changes to endpoint in daily pain, night pain, and sleep interference with vitality changes were -.33, -.31, and -.28, respectively (p<.001). The direct effect of treatment on change in vitality was statistically significant (66%, p=.024) when assessed in an indirect manner through change in sleep interference alone but not when jointly assessed with average pain (32%, p=.283) or night pain (48%, p=.097).

Results suggest weak to moderate associations between changes in average pain, night pain, and sleep interference with changes in vitality. Improvement in vitality was independent of improvements in sleep interference alone but the treatment effect on vitality was mediated by sleep interference when jointly modeled with improvement in average or night pain.

Funding from Eli Lilly and Company