Abstracts

Rationale: In the treatment of people with epilepsy (PWE), an increased emphasis has been placed on quality of life issues as studies evaluating newer antiepileptic drugs (AEDs) address health outcome measures as well as seizure control. Both lamotrigine (LTG) and levetiracetam (LEV) are newer AEDs that have proven efficacy and tolerability as adjunctive therapy for partial seizures in PWE. For many patients, AED-related disturbances of mood can have a negative impact on quality of life. Retrospective case reviews and spontaneous adverse event reports document an incidence of behavioral abnormalities ranging from 3.9% to 30% with LEV; whereas, data from LTG clinical trials suggest improvement of mood in PWE. To date, however, no direct comparison has been made between the two agents in a prospective fashion. The results reported are from a randomized, double-blind trial comparing the mood effects of LTG and LEV in PWE.Methods: Eligible patients were at least 16 years old with an IQ estimate of at least 80 and had a diagnosis of partial epilepsy inadequately controlled by an AED regimen containing carbamazepine or phenytoin. Excluded were patients taking antidepressant or antipsychotic medications, or those with a comorbidity of an unstable or progressive nature (e.g., delirium, psychosis, brain tumor). Patients were randomized to initially receive either LTG 50mg per day or LEV 500mg per day and were escalated over eight weeks to LTG 400mg per day or LEV 2000mg per day for an additional 12 weeks. The primary endpoint was change in the Anger-Hostility subscale score of the Profile of Mood States (POMS) between baseline and the end of Week 20. Mood was measured by the change in the Total Mood Disturbance score of the POMS between baseline and each weekly assessment in the 20-week period. Statistical analysis was done using analysis of covariance.Results: A total of 268 PWE enrolled into the study, with 132 patients receiving LTG and 136 patients receiving LEV; 89 (67%) patients receiving LTG and 89 (65%) patients receiving LEV completed the study. Mean baseline Anger-Hostility scores were 10.6 for LTG and 9.1 for LEV; mean change from baseline to the end of Week 20 was -2.0 for LTG and -0.3 for LEV (p <0.05). Mean baseline Total Mood Disturbance scores were 39.0 for LTG and 35.6 for LEV; mean change from baseline to the end of Week 20 was -9.6 for LTG and -0.9 for LEV (p <0.05). Scores for LTG improved in all weeks, and were consistently improved more than with LEV at each weekly measurement. The percentage of patients seizure-free throughout the entire treatment period was similar at 29% for LTG and 28% for LEV (p=0.888). Conclusions: In PWE, LTG had a sustained improvement in mood scores relative to LEV with similar efficacy in seizure reduction. This study provides additional data which will assist physicians in making decisions of treatment in this patient population.