CLOBAZAM IN LONG-TERM EPILEPSY TREATMENT - SUSTAINED RESPONDERS VERSUS THOSE DEVELOPING TOLERANCE

Clobazam(CLB) is a structurally unique benzodiazepine (BZD) that has a nticonvulsant activity in all types of refractory seizures. The main d rawback to CLB, as to other BZDs, is the occurrence of tolerance. To d ate, there has been no way to predict which patients will develop tole rance. We compared clinical features and treatment variables between t wo groups of patients whose seizures were initially well controlled wi th CLB: patients with a sustained response and patients who developed tolerance. We retrospectively identified a group of 50 very good respo nders from among 173 consecutive patients with uncontrolled epilepsy t reated with CLB. Very good responders were defined as patients with >7 5% reduction in seizures after the addition of CLB who continued CLB t reatment for at least 1 month. At a mean follow-up of 37.5 +/- 12.8 mo nths, 25 patients continued to respond and 25 developed tolerance (mea n follow-up 17.0 15.7 months). Tolerance was defined as a relapse to a level greater than or equal to 50% of pre-CLB seizure frequency after an initial very good response for a minimum period of 1 month, despit e constant CLB dose and, when available, serum levels. There was no ch ange in concomitant medication. Significant differences were noted bet ween the two groups. The sustained response group had a shorter durati on of epilepsy (mean 16.5 vs. 24.5 years, p = 0.015), a greater propor tion of individuals with a known etiology for their epilepsy (48 vs. 1 6%, p = 0.006), and higher CLB levels (0.50 vs. 0.22 mu M, p = 0.017), but no significant difference in N-desmethyl-CLB levels. Certain fact ors apparently may influence the likelihood of developing tolerance to the antiepileptic effects of clobazam.