A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF VIGABATRIN 3 G DAY IN PATIENTS WITH UNCONTROLLED COMPLEX PARTIAL SEIZURES/

This study compared the efficacy and tolerability of vigabatrin 3 g/da y as add-on therapy with that of placebo in patients with focal epilep sy whose complex partial seizures were difficult to control with estab lished antiepilepsy drug therapy. We enrolled 203 patients; 182 (90 pl acebo; 92 vigabatrin) received drug therapy under double-blind conditi ons, We increased the daily dosage to 2.5 g/day during a 4-week titrat ion segment and maintained it at 3 g/day during the 12-week maintenanc e segment. By analyses we found a statistically significant lower freq uency of seizures (complex seizures plus partial seizures secondarily generalized) at the end of the study for patients receiving vigabatrin than for those receiving placebo, The median monthly frequency was re duced by three seizures per 28 days in the vigabatrin group (baseline, 8.3; end of study, 5.3) versus 0.8 seizures per 28 days in the placeb o group (baseline, 8.3; end of study, 7.5) (p = 0.0002). Therapeutic s uccess (a 50% reduction from baseline in mean monthly seizure frequenc y) was attained in 40 of the vigabatrin patients (43%) compared with 1 7 of those treated with placebo (19%) (p < 0.001). Vigabatrin signific antly increased the mean number of seizure-free days per 28 days (2.2 days) compared with placebo (0.5 days) (p = 0.0024). Mean trough serum vigabatrin concentration during therapy was 8.6 +/- 7.7 mu g/ml. The oral clearance of vigabatrin was determined to be 7.8 L/hr, and the el imination half-life was 8.4 hours. No clinically important changes in MRI, evoked potential, or other laboratory tests were noted during vig abatrin treatment. The results of this study indicate that 3 g/day vig abatrin is more effective than placebo as add-on therapy. Vigabatrin w as well tolerated, compliance was high with twice-daily administration , and therapy did not result in clinically relevant drug interactions.