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Add-on Trial of Clobazam in Intractable Adult Epilepsy with Plasma Level Correlations

Published online by Cambridge University Press:  18 September 2015

A. Guberman ,
M. Couture ,
K. Blaschuk  and
A. Sherwin
A. Guberman*
Affiliation:
Division of Neurology, Montreal
M. Couture
Affiliation:
Division of Neurology, Montreal
K. Blaschuk
Affiliation:
Ottawa General Hospital, Ottawa and the Montreal Neurological Institute, Montreal
A. Sherwin
Affiliation:
Ottawa General Hospital, Ottawa and the Montreal Neurological Institute, Montreal
*
Division of Neurology, Ottawa General Hospital, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6
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Abstract:

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Clobazam, a novel benzodiazepine, was used as an add-on agent in 47 adult patients with intractable epilepsy and a variety of seizure types. A >75% reduction in seizure frequency was observed in 42% (18) of the patients and a >50% reduction in 65% (29) of the patients which was sustained over a mean follow-up period of 13.3 (±5.6) months. Nine patients had to discontinue the drug due to minor adverse effects or increased seizures. Possible tolerance developed in 6 patients. Plasma levels of the active metabolite N-desmethylclobazam were linearly related to dosage and appeared to correlate with both therapeutic and toxic responses. Clobazam appears to be a safe and effective add-on antiepileptic for a wide variety of seizure types in intractable epilepsy.

Résumé:

RÉSUMÉ:

Le clobazam, une nouvelle benzodiazépine, a été utilisé comme traitement d'appoint chez 47 adultes présentant une épilepsie réfractaire et des crises de types variés. Une diminution de plus de 75% de la fréquence des crises a été observée chez 42% (18) des patients et une diminution de plus de 50% chez 65% (29), diminution maintenue sur une période de suivi moyenne de 13.3 (±5.6) mois. Neuf patients ont dû cesser la médication à cause d'effets secondaires mineurs ou d'une augmentation des crises. Il est possible qu'une tolérance se soit développée chez 6 patients. Les niveaux plasmatiques du métabolite actif, le N-desmethylclobazam, étaient en relation linéaire avec la dose et semblaient corréler avec la réponse thérapeutique et la toxicité. Le clobazam semble être un agent antiépileptique d'appoint sécuritaire et efficace dans une grande variété de types de convulsions dans l'épilepsie réfractaire.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 17 , Issue 3 , August 1990 , pp. 311 - 316
Copyright
Copyright © Canadian Neurological Sciences Federation 1990

References

REFERENCES

1. Gastaut, H. Propriètès antiSpileptiques exceptionelles et mèonnues d’un anxiolytique du commerce, le clobazam. Concours Med 1978; 100: 3697–9701.Google Scholar
2. Koeppen, D. A review of clobazam studies in epilepsy. In: Hindmarch, I, Stonier, PD, Trimble, MR, (editor). Human Psychopharmacology and Clinical Applications. International Congress and Symposium Series, No 74. London: Royal Society of Medicine, 1985; 207–215.Google Scholar
3. Robertson, MM. Current status of the 1,4– and 1,5–benzodiazepines in the treatment of epilepsy: the place of clobazam. Epilepsia 1986; 27(1): S3697–S41.Google Scholar
4. Koeppen, D, Baruzzi, A, Copozza, M, et al. Clobazam in therapyresistant patients with partial epilepsy: a double-blind placebocontrolled crossover study. Epilepsia 1987; 28: 495–506.Google Scholar
5. Heazlewood, RL and Lemass, RWJ. Simple high-performance liquid chromatographic assay for the routine monitoring of clonazepam in plasma. J Chromatogr 1984; 336–229–233.CrossRefGoogle ScholarPubMed
6. Schmidt, D, Rohde, M, Wolf, P, et al. Clobazam for refractory focal epilepsy. A controlled trial. Arch Neurol 1986; 43: 824–826.Google Scholar
7. Franceschi, M, Ferini-Strambi, L, Mastrangelo, M, et al. Clobazam in drug-resistant and alcoholic withdrawal seizures. Clin Trials J 1983; 20: 119–125.Google Scholar
8. Feely, M, Gibson, J, Mastrangelo, M, et al. Intermittent clobazam for catamenial epilepsy: avoid tolerance. J Neurol Neurosurg Psychiatry 1984; 47: 1279–1282.CrossRefGoogle ScholarPubMed
9. Aguglia, U, Tinuper, P. Eating seizures. Eur Neurol 1984; 22: 227–231.Google Scholar
10. Gastaut, H Aguglia, U et al. Traitement de certains ètats de mal par ingestion d’une dose unique de clobazam.Rev EEG Neurophysiol 1984; 14: 203–206.Google Scholar
11. Tinuper, P, Aguglia, U, Gestaut, H, et al. Use of clobazam in certain forms of status epilepticus and in startle-induced epileptic seizures.Epilepsia 1986; 27 (1): S203–S206.Google Scholar
12. Scott, DF, Moffett, A. On the anticonvulsant and psychotropic properties of clobazam - a preliminary study. Epilepsia 1986; 27 (1): S42–S44.CrossRefGoogle ScholarPubMed
13. Dulac, D, Figueroa, D, Rey, E, et al. Monotheiapie par le clobazam dans les Epilepsies de l’enfant. Presse Med 1983; 21: 1067–1069.Google Scholar
14. Plouin, P, Jalin, C. EEG changes in epileptic children treated with clobazam as monotherapy. In: Hindmarch, I, Stonier, PD, Trimble, MR, (editor). Human Psychopharmacology and Clinical Applications. International Congress and Symposium Series, No 74. London: Royal Society of Medicine, 1985; 191–197.Google Scholar
15. Cull, CA, Trimble, MR. Anticonvulsant benzodiazepines and performance. In: Hindmarch, I, Stonier, PD, Trimble, MR, (editor). Human Psychopharmacology and Clinical Applications. International Congress and Symposium Series, No. 74, London: Royal Society of Medicine, 1985; 121–128.Google Scholar
16. Simon, P. Comparative study in mice often 1,4-benzodiazepines and of clobazam: anticonvulsant, anxiolytic, sedative, and myorelaxant effects. Epilepsia 1986; 27 (1): S14–S17.Google Scholar
17. Martin, AA. The antiepileptic effects of clobazam: a long-term study in resistant epilepsy. In: Hindmarch, I, Stonier, PD, (editor). Clobazam. International Congress and Symposium Series, No. 43, London: Royal Society of Medicine, 1981; 151–157.Google Scholar
18. Callaghan, N, Goggin, T. Adjunctive therapy in resistant epilepsy. Epilepsia 1988; 29 (1): S29–S35.Google Scholar
19. Shorvon, SD. Benzodiazepines. Clobazam. In: Levy, R, Mattson, R, Meldrum, B, Penry, B, Dreifuss, FB, (editor). Antiepileptic Drugs, 3rd ed, New York: Raven Press, 1989; chapter 59.Google Scholar
20. Gastaut, H, Low, MD. Antiepileptic properties of clobazam, a 1,5 benzodiazepine, in man. Epilepsia 1979; 20:S29–S35.Google Scholar
21. Callaghan, N, Goggin, T. Tolerance to anticonvulsant effects of diazepam, clonazepam, and clobazam in amygdalakindled rats. Epilepsia 1988; 30: 276–285.Google Scholar