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• Arq. Neuro-Psiquiatr. 55 (4) • 1997 • https://doi.org/10.1590/S0004-282X1997000500012   copy

Treatment of febrile seizures with intermittent clobazam

Tratamento de convuslsões febris com clobazam intermitente

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstracts

Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean=23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, symptomatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range=l to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean=16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 °C, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20%) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9%), a difference highly significant (p<0.0001). Adverse effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting, somnolence and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily occurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to diazepam in the intermittent treatment of FS recurrence.

febrile seizures; clobazam; antiepileptic drugs

Avaliamos prospectivamente o uso intermitente do clobazam na profilaxia de convulsão febril em 50 crianças, 24 do sexo feminino e 26 do masculino, com idades entre 6 e 72 meses (média = 23,7 meses) que haviam apresentado pelo menos um episódio de convulsão febril. Foram excluídas crianças com anormalidades neurológicas severas, doença neurológica progressiva, crises durante infecção do SNC e crises epilépticas sintomáticas outras. As convulsões febris foram classificadas como simples em 25 crianças, complicadas em 20 e em 5 crianças não foi possível a classificação. O tempo médio de seguimento foi 7,9 meses (1-23 meses) e a idade, na primeira crise, variou de 5 a 42 meses (média = 16,8 meses). O clobazam foi administrado por via oral, durante os episódios febris, na dose de 5 mg/dia, em crianças até 5 kg; 10 mg/dia, de 5-10 kg; 15 mg/dia, de 11 -15 kg, e 20 mg/dia, acima de 20 kg. Quarenta crianças apresentaram febre (T > 37,8 °C), num total de 219 episódios febris. Doze crianças não chegaram a receber clobazam e 28 receberam pelo menos uma vez. A eficácia do tratamento foi avaliada comparando a recorrência de convulsão febril entre os episódios febris tratados com clobazam e aqueles tratados apenas com medicação anti-pirética. Dez crianças (20%) apresentaram recorrência de convulsão febril, durante o período de estudo. Dos 171 episódios febris tratados com clobazam, houve apenas 3 (1,7%) recorrências, enquanto dos 48 episódios tratados apenas com anti-térmicos houve 11 (22,9%) recorrências, uma diferença altamente significativa (p < 0,0001) Efeitos colaterais foram observados em 10/28 (35,7%), principalmente vômito, sonolência e hiperatividade. A interrupção da medicação devido a efeitos colaterais foi necessária em um paciente, com vômitos recorrentes. Concluímos que o clobazam é droga eficaz e segura na prevenção de recorrência de convulsão febril na infância, podendo ser uma alternativa ao tratamento com diazepam intermitente.

convulsão febril; clobazam; drogas anti-epilépticas

Treatment of febrile seizures with intermittent clobazam

Tratamento de convuslsões febris com clobazam intermitente

Maria Luiza G. Manreza; José Luiz D. Gherpelli; Lúcia R. Machado-Haertel; Cristiane C. Costas Pedreira; Carlos O. Heise; Aron Diament

Serviço de Neurologia Infantil, Divisão de Clínica Neurológica, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (FMUSP). São Paulo SP, Brasil

ABSTRACT

Fifty children, 24 female and 26 male, with ages varying from 6 to 72 months (mean=23.7 m.) that experienced at least one febrile seizure (FS) entered a prospective study of intermittent therapy with clobazam. Cases with severe neurological abnormalities, progressive neurological disease, afebrile seizures, symptomatic seizures of other nature, or seizures during a central nervous system infection were excluded. Seizures were of the simple type in 25 patients, complex in 20 and unclassified in 5. The mean follow-up period was 7.9 months (range=l to 23 m.), and the age at the first seizure varied from 5 to 42 months (mean=16.8 m.). Clobazam was administered orally during the febrile episode according to the child's weight: up to 5 kg, 5 mg/day; from 5 to 10 kg, 10 mg/day; from 11 to 15 kg, 15 mg/day, and over 15 kg, 20 mg/day. There were 219 febrile episodes, with temperature above 37.8 °C, in 40 children during the study period. Twelve children never received clobazam and 28 received the drug at least once. Drug efficacy was measured by comparing FS recurrence in the febrile episodes that were treated with clobazam with those in which only antipyretic measures were taken. Ten children (20%) experienced a FS during the study period. Of the 171 febrile episodes treated with clobazam there were only 3 recurrences (1.7%), while of the 48 episodes treated only with antipyretic measures there were 11 recurrences (22.9%), a difference highly significant (p<0.0001). Adverse effects occurred in 10/28 patients (35.7%), consisting mainly in vomiting, somnolence and hyperactivity. Only one patient had recurrent vomiting which lead to drug interruption. These effects did not necessarily occurred in every instance the drug was administered, being present in one febrile episode and not in the others. We conclude that clonazepam is safe and efficacious in preventing FS recurrence. It may be an alternative to diazepam in the intermittent treatment of FS recurrence.

Key words: febrile seizures, clobazam, antiepileptic drugs.

RESUMO

Avaliamos prospectivamente o uso intermitente do clobazam na profilaxia de convulsão febril em 50 crianças, 24 do sexo feminino e 26 do masculino, com idades entre 6 e 72 meses (média = 23,7 meses) que haviam apresentado pelo menos um episódio de convulsão febril. Foram excluídas crianças com anormalidades neurológicas severas, doença neurológica progressiva, crises durante infecção do SNC e crises epilépticas sintomáticas outras. As convulsões febris foram classificadas como simples em 25 crianças, complicadas em 20 e em 5 crianças não foi possível a classificação. O tempo médio de seguimento foi 7,9 meses (1-23 meses) e a idade, na primeira crise, variou de 5 a 42 meses (média = 16,8 meses). O clobazam foi administrado por via oral, durante os episódios febris, na dose de 5 mg/dia, em crianças até 5 kg; 10 mg/dia, de 5-10 kg; 15 mg/dia, de 11 -15 kg, e 20 mg/dia, acima de 20 kg. Quarenta crianças apresentaram febre (T > 37,8 °C), num total de 219 episódios febris. Doze crianças não chegaram a receber clobazam e 28 receberam pelo menos uma vez. A eficácia do tratamento foi avaliada comparando a recorrência de convulsão febril entre os episódios febris tratados com clobazam e aqueles tratados apenas com medicação anti-pirética. Dez crianças (20%) apresentaram recorrência de convulsão febril, durante o período de estudo. Dos 171 episódios febris tratados com clobazam, houve apenas 3 (1,7%) recorrências, enquanto dos 48 episódios tratados apenas com anti-térmicos houve 11 (22,9%) recorrências, uma diferença altamente significativa (p < 0,0001) Efeitos colaterais foram observados em 10/28 (35,7%), principalmente vômito, sonolência e hiperatividade. A interrupção da medicação devido a efeitos colaterais foi necessária em um paciente, com vômitos recorrentes. Concluímos que o clobazam é droga eficaz e segura na prevenção de recorrência de convulsão febril na infância, podendo ser uma alternativa ao tratamento com diazepam intermitente.

Palavras-chave: convulsão febril, clobazam, drogas anti-epilépticas.

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REFERENCES

1. Aicardi J. Febrile convulsions. In Aicardi J (ed). Epilepsy in children. New York: Raven Press, 1994:253-275.

2. Andermann E, Andermann F, Oliver A, Quesney LF. Temporal lobe epilepsy after prolonged febrile convulsions: excellent outcome after surgical treatment. Epilepsia 1993;34: 878-883.

3. Annegers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Med 1987;316:493-498.

4. Berg AT. Diazepam to prevent febrile seizures (Letter). N Engl J Med 1993;329:2033.

5. Berg AT, Shinnar S, Hauser WA, et al. A prospective study of recurrent febrile seizures. N Engl J Med 1992;327:1122-127.

6. Calandre EP, Domingues-Granados R, Gomez-Rubio M, Molina-Font JA. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand 1990;81:504-506.

7. Camfield P, Camfield C. Diazepam to prevent seizures (Letter). N Engl J Med 1993;329:2034.

8. Chevrie JJ. Epileptic seizures and epilepsies in children. In Dam M (ed). A practical approach to epilepsy. New York: Pergamon Press, 1991:17-39.

9. Consensus Development Panel. Febrile seizures: long term management of children with fever-associated seizures. Pediatrics 1980;66:1009-1012.

10. Darkins A, Polkey CE. The relationship of transient hemiparesis following febrile convulsions in infancy to subsequent temporal lobectomy for intractable seizures. J Neurol Neurosurg Psychiatry 1985;48:551-555.

11. Daugbjerg D, Brems M, Mai J, Ankerhus J, Kudsen FU. Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid? Acta Neurol Scand 1990;82:17-20.

12. Farwell JR, Lee YJ, Hirtz DG, Sulbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures-effects on intelligence and on seizure recurrence. N Engl J Med 1990;322:364-369.

13. Fejerman N. Introduction: febrile convulsions. In Fukuyama Y, Kamosseita S, Ohtsuka, C, Suzuki Y, (eds). Modern perspectives of child neurology, Japanese Society of Child Neurology, 1991:161-162.

14. Freeman JM. What have we learned from febrile seizures. Pediatr Ann 1992;21:355-361.

15. Guerreiro MM, Costa M, Bellomo MA, Sabino SH, Silva EA. Profilaxia intermitente na convulsão febril com diazepam via oral. Arq Neuropsiquiatr 1992;50:163-167.

16. Harvey AS, Grattan-S.nith JD, Desmond PM, Chow CW, Berkovic SF. Febrile seizures and hippocampal sclerosis: frequent and related findings in intractable temporal lobe epilepsy of childhood. Pediatr Neurol 1995;12:201-206.

17. Hashimoto K, Fujita T, Furuya M. Absences seizures following febrile seizures. Brain Dev 1989; 11:268-270.

18. Holthausen H. Febrile convulsions, mesial temporal sclerosis and temporal lobe epilepsy. In Wolf P (ed). Epileptic seizures and syndromes. London: John Libbey, 1994:449-467.

19. Kishi K, Ito M, Sejima H, Shirashi H. A clinical study on the effectiveness of intermittent oral diazepam powder for the prevention of recurrent febrile convulsions. Brain Dev 1994; 16:342.

20. Knudsen FU. Febrile convulsions. In Sillanpãa M, Johannessen SI, Blennow G, Dam M (eds). Paediatric epilepsy. Petersfield: Wrightson Biomedical Publ., 1990:65-72.

21. Knudsen FU. Intermittent prophylaxis with benzodiazepines-clinical trials. Acta Neurol Scand 1991;Suppl 1358:12-13.

22. Maytal J, Shinnar S. Febrile status epilepticus. Pediatrics 1990; 86:611-616.

23. McKinlay I, Newton R. Intention to treat febrile convulsions with rectal diazepam, valproate or phenobarbitone. Dev Med Child Neurol 1989;31:617-625.

24. Nelson KB. Febrile seizures update: natural history. In Fukuyama Y, Kamosseita S, Ohtsuka, C, Suzuki Y (eds). Modern perspectives of child neurology. Japanese Society of Child Neurology, 1991:169-173.

25. Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures. Pediatrics 1978;61:720-727.

26. Nelson KB, Ellenberg JH. Febrile seizures. In Dreifuss FE (ed). Pediatric epileptology Boston: John Wright, 1983:173-198.

27. Nelson KB, Ellenberg JH. Prenatal and perinatal antecedents of febrile seizures. Ann Neurol 1990;27:127-131.

28. O'Donohue NV. Febrile convulsions. In Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P (eds). Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey, 1992:45-52.

29. Rantala H, Uhari M. Risk factors for recurrences of febrile convulsions. Acta Neurol Scand 1994;90:207-210.

30. Rocca WA, Sharbrough FW, Hauser A, Annegers JF, Schoenberg BS. Risk factors for complex partial seizures: a population-based case-control study. Ann Neurol 1987;21:22-31.

31. Rosman NP, Colton T, Labazzo J, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med 1993;329:79-84.

32. Schmidt D, Tsai J J, Janz D. Febrile seizures in patients with complex partial seizures. Acta Neurol Scand 1985;72:68-71.

33. Shorvon SD. Clobazam. In Levy RH, Mattson RH, Meldrun BS (eds). Antiepileptic drugs. New York: Raven Press, 1995:763-778.

34. Tondi M, Carboni F, Deriu A, Manca S, Mastropaolo C. Intermitent therapy with clobazam for simple febrile seizures (Letter). Dev Med Child Neurol 1987;29:830-831.

35. Wallace SJ. Epileptic syndromes linked with previous history of febrile seizures. In Fukuyama Y, Kamosseita S, Ohtsuka, C, Suzuki Y (eds). Modern perspectives of child neurology. Japanese Society of Child Neurology, 1991:175-181.

36. Wyllie E. Children with seizures: when can treatment be deferred? J Child Neurol 1994;9(Suppl):2S8-2S13.

Aceite: 1-agosto-1997.

Dr. Maria Luiza Giraldes de Manreza M.D. - Serviço de Neurologia Infantil, Divisão de Clínica Neurológica do Hospital das Clínicas da FMUSP - P.O. Box 8091 - 05403-970 São Paulo SP - Brasil. FAX: 55-11-852 0063.

  • 1. Aicardi J. Febrile convulsions. In Aicardi J (ed). Epilepsy in children. New York: Raven Press, 1994:253-275.
  • 2. Andermann E, Andermann F, Oliver A, Quesney LF. Temporal lobe epilepsy after prolonged febrile convulsions: excellent outcome after surgical treatment. Epilepsia 1993;34: 878-883.
  • 3. Annegers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Med 1987;316:493-498.
  • 4. Berg AT. Diazepam to prevent febrile seizures (Letter). N Engl J Med 1993;329:2033.
  • 5. Berg AT, Shinnar S, Hauser WA, et al. A prospective study of recurrent febrile seizures. N Engl J Med 1992;327:1122-127.
  • 6. Calandre EP, Domingues-Granados R, Gomez-Rubio M, Molina-Font JA. Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand 1990;81:504-506.
  • 7. Camfield P, Camfield C. Diazepam to prevent seizures (Letter). N Engl J Med 1993;329:2034.
  • 8. Chevrie JJ. Epileptic seizures and epilepsies in children. In Dam M (ed). A practical approach to epilepsy. New York: Pergamon Press, 1991:17-39.
  • 9. Consensus Development Panel. Febrile seizures: long term management of children with fever-associated seizures. Pediatrics 1980;66:1009-1012.
  • 10. Darkins A, Polkey CE. The relationship of transient hemiparesis following febrile convulsions in infancy to subsequent temporal lobectomy for intractable seizures. J Neurol Neurosurg Psychiatry 1985;48:551-555.
  • 11. Daugbjerg D, Brems M, Mai J, Ankerhus J, Kudsen FU. Intermittent prophylaxis in febrile convulsions: diazepam or valproic acid? Acta Neurol Scand 1990;82:17-20.
  • 12. Farwell JR, Lee YJ, Hirtz DG, Sulbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures-effects on intelligence and on seizure recurrence. N Engl J Med 1990;322:364-369.
  • 13. Fejerman N. Introduction: febrile convulsions. In Fukuyama Y, Kamosseita S, Ohtsuka, C, Suzuki Y, (eds). Modern perspectives of child neurology, Japanese Society of Child Neurology, 1991:161-162.
  • 14. Freeman JM. What have we learned from febrile seizures. Pediatr Ann 1992;21:355-361.
  • 15. Guerreiro MM, Costa M, Bellomo MA, Sabino SH, Silva EA. Profilaxia intermitente na convulsão febril com diazepam via oral. Arq Neuropsiquiatr 1992;50:163-167.
  • 17. Hashimoto K, Fujita T, Furuya M. Absences seizures following febrile seizures. Brain Dev 1989; 11:268-270.
  • 18. Holthausen H. Febrile convulsions, mesial temporal sclerosis and temporal lobe epilepsy. In Wolf P (ed). Epileptic seizures and syndromes. London: John Libbey, 1994:449-467.
  • 19. Kishi K, Ito M, Sejima H, Shirashi H. A clinical study on the effectiveness of intermittent oral diazepam powder for the prevention of recurrent febrile convulsions. Brain Dev 1994; 16:342.
  • 20. Knudsen FU. Febrile convulsions. In Sillanpãa M, Johannessen SI, Blennow G, Dam M (eds). Paediatric epilepsy. Petersfield: Wrightson Biomedical Publ., 1990:65-72.
  • 21. Knudsen FU. Intermittent prophylaxis with benzodiazepines-clinical trials. Acta Neurol Scand 1991;Suppl 1358:12-13.
  • 22. Maytal J, Shinnar S. Febrile status epilepticus. Pediatrics 1990; 86:611-616.
  • 23. McKinlay I, Newton R. Intention to treat febrile convulsions with rectal diazepam, valproate or phenobarbitone. Dev Med Child Neurol 1989;31:617-625.
  • 24. Nelson KB. Febrile seizures update: natural history. In Fukuyama Y, Kamosseita S, Ohtsuka, C, Suzuki Y (eds). Modern perspectives of child neurology. Japanese Society of Child Neurology, 1991:169-173.
  • 25. Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures. Pediatrics 1978;61:720-727.
  • 26. Nelson KB, Ellenberg JH. Febrile seizures. In Dreifuss FE (ed). Pediatric epileptology Boston: John Wright, 1983:173-198.
  • 27. Nelson KB, Ellenberg JH. Prenatal and perinatal antecedents of febrile seizures. Ann Neurol 1990;27:127-131.
  • 28. O'Donohue NV. Febrile convulsions. In Roger J, Bureau M, Dravet C, Dreifuss FE, Perret A, Wolf P (eds). Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey, 1992:45-52.
  • 29. Rantala H, Uhari M. Risk factors for recurrences of febrile convulsions. Acta Neurol Scand 1994;90:207-210.
  • 30. Rocca WA, Sharbrough FW, Hauser A, Annegers JF, Schoenberg BS. Risk factors for complex partial seizures: a population-based case-control study. Ann Neurol 1987;21:22-31.
  • 31. Rosman NP, Colton T, Labazzo J, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med 1993;329:79-84.
  • 32. Schmidt D, Tsai J J, Janz D. Febrile seizures in patients with complex partial seizures. Acta Neurol Scand 1985;72:68-71.
  • 33. Shorvon SD. Clobazam. In Levy RH, Mattson RH, Meldrun BS (eds). Antiepileptic drugs. New York: Raven Press, 1995:763-778.
  • 34. Tondi M, Carboni F, Deriu A, Manca S, Mastropaolo C. Intermitent therapy with clobazam for simple febrile seizures (Letter). Dev Med Child Neurol 1987;29:830-831.
  • 35. Wallace SJ. Epileptic syndromes linked with previous history of febrile seizures. In Fukuyama Y, Kamosseita S, Ohtsuka, C, Suzuki Y (eds). Modern perspectives of child neurology. Japanese Society of Child Neurology, 1991:175-181.
  • 36. Wyllie E. Children with seizures: when can treatment be deferred? J Child Neurol 1994;9(Suppl):2S8-2S13.

Publication Dates

  • Publication in this collection
    07 Oct 2010
  • Date of issue
    1997
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