Abstracts

There is growing evidence that lamotrigine has a positive side effects profile in the treatment of epilepsy and may even provide a brightening effect on mood. Also, some older AEDs are known for contributing to adverse events. This study explores the relationship of lamotrigine (LTG) monotherapy on adverse events and quality of life after withdrawal from monotherapy therapy with valproate (VPA).
This was an open label conversion trial from VPA monotherapy to LTG monotherapy in patients with epilepsy. The study[rsquo]s duration was 19 weeks divided into four Phases: a screen phase ([le] 1 week), a LTG escalation phase (8 weeks), a VPA withdrawal phase ([le] 6 weeks) and a LTG monotherapy phase (4 weeks). All subjects were withdrawn from a stable dose of VPA, either due to inadequate seizure control or intolerable side effects, and converted to open label LTG. Two patient-reported health outcome questionnaires were given; the Adverse Events Profile (AEP) and the Quality of Life in Epilepsy 10-item version (QOLIE-10). The AEP was collected three times; at screen, end of VPA withdrawal phase, and end of LTG monotherapy. The QOLIE-10 was collected two times, at screen and end of LTG monotherapy. The AEP is composed of 19 item-questions. Each item represents an adverse event (i.e., tiredness, sleepiness, depression, etc.) that may be attributed to antiepileptic therapy. Each patient rated the extent to which each AE was a problem over the past four weeks on a four point scale from 1 [lsquo]never a problem[rsquo] to 4 [lsquo]always a problem[rsquo]. An overall adverse event score was computed for each patient and each time point. The QOLIE-10 is composed of 10 items, each asking the patient to rate their quality of life with respect to epilepsy and their current treatment for epilepsy. Each item was rated on a five point Likert scale (good/better to bad/worse). A single overall quality of life score was computed across all 10 items for each patient at each time point.
77 patients enrolled and 48 completed the study. The AEP revealed a statistical difference on the overall, and on most individual event items, when comparing scores collected at screening and the end of LTG monotherapy treatment. The overall score showed a mean decrease of 9.2 points in favor of LTG (p.[lt]0.0001, N=45). Further, all 19 individual items showed mean decreases with 13 achieving statistical significance with mean reductions ranging from 0.4 to 0.9 in favor of LTG (p[lt]0.05). The QOLIE-10 overall score also showed a statistically significant reduction in mean scores from screening to the end of monotherapy treatment of 6.5 in favor of LTG (p.[lt]0.0001, N=45).
These data, from a multi-site clinical trial, revealed significant and favorable outcomes for LTG monotherapy for persons switched from VPA monotherapy. These results were consistent on both the adverse events scale as well as quality-of-life instrument.
[Supported by: GlaxoSmithKline Inc.]