A. Singh et al., CLOBAZAM IN LONG-TERM EPILEPSY TREATMENT - SUSTAINED RESPONDERS VERSUS THOSE DEVELOPING TOLERANCE, Epilepsia, 36(8), 1995, pp. 798-803
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.