Abstracts

Pregabalin (PGB) is an alpha-2-delta ligand that in clinical trials has been shown to reduce the frequency of partial seizures with or without secondary generalizations. PGB has also been found to exert a positive effect on the sleep disturbances (SDs) often experienced by epileptic patients. In a study presented in detail elsewhere, we demonstrated that: a) SDs occur frequently; b) the magnitude of SDs appears independent of the number of AEDs received by patients; and c) the impact of SDs on the overall quality of life of epileptic patients is significant. We report findings from an investigation performed to quantify the effect of PGB on sleep disturbances using polysomnographic (PSG) and self-assessed sleep measurements in patients with well-controlled partial seizures. The effect of add-on PGB treatment on sleep was investigated in an exploratory, 4-week, double-blind study of patients receiving AED monotherapy and known to suffer epilepsy-related SDs (per the Sleep Diagnosis Questionnaire measuring the previous 6 months). Patients received add-on PGB 300mg/d (n=8) or placebo (n=7). Differences between PGB and placebo groups were ascertained by comparing mean changes in PSG and self-assessed sleep variables from baseline (BL) to endpoint (EP). The primary efficacy measure was the PSG-sleep efficiency. Secondary efficacy parameters included other PSG variables and MOS Sleep assessments. PSG measurements revealed that the patients experienced clinically relevant SDs caused by sleep fragmentation. PSG measurements at baseline and endpoint revealed that PGB treatment produced a significant improvement in sleep efficiency (from 73.7% at BL to 80.8% at EP; p[lt]0.05). Furthermore, PGB treatment was found to produce a significant reduction in the number of awakenings (p[lt]0.05) and appeared to produce improvement in waketime-after-sleep-onset (p=0.055). Unlike placebo, PGB yielded statistically significant improvements on sleep disturbance (MOS subscales; 16.9) and sleep duration (1.5h). The most common AEs were dizziness and somnolence. This exploratory study of epileptic patients indicates that PGB add-on treatment reduces sleep disturbances by improving sleep continuity. The improvements were statistically significant and clinically meaningful since patients reported noticing the improvements in their sleep. The improvements are not due to the AE, somnolence, and appear to be caused by effects on sleep architecture. These findings are important because sleep disturbances experienced by epileptic patients are frequent and have been found to significantly affect their quality of life. (Supported by Pfizer Inc.)