Clobazam in long-term epilepsy treatment: sustained responders versus those developing tolerance

Clobazam (CLB) is a structurally unique benzodiazepine (BZD) that has anticonvulsant activity in all types of refractory seizures. The main drawback to CLB, as to other BZDs, is the occurrence of tolerance. To date, there has been no way to predict which patients will develop tolerance. We compared clinical features and treatment variables between two groups of patients whose seizures were initially well controlled with CLB: patients with a sustained response and patients who developed tolerance. We retrospectively identified a group of 50 very good responders from among 173 consecutive patients with uncontrolled epilepsy treated with CLB. Very good responders were defined as patients with > 75% reduction in seizures after the addition of CLB who continued CLB treatment for at least 1 month. At a mean follow-up of 37.5 +/- 12.8 months, 25 patients continued to respond and 25 developed tolerance (mean follow-up 17.0 +/- 15.7 months). Tolerance was defined as a relapse to a level > or = 50% of pre-CLB seizure frequency after an initial very good response for a minimum period of 1 month, despite constant CLB dose and, when available, serum levels. There was no change in concomitant medication. Significant differences were noted between the two groups. The sustained response group had a shorter duration of epilepsy (mean 16.5 vs. 24.5 years, p = 0.015), a greater proportion of individuals with a known etiology for their epilepsy (48 vs. 16%, p = 0.006), and higher CLB levels (0.50 vs. 0.22 microM, p = 0.017), but no significant difference in N-desmethyl-CLB levels.(ABSTRACT TRUNCATED AT 250 WORDS)