Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution

Gorz, Ana Maria; Silvado, Carlos E. S.; Bittencourt, Paulo Rogério M.

doi:10.1590/S0004-282X1986000300002

Abstracts

Barbiturates are considered first line antiepileptic drugs in third world countries due to traditional and economic reasons. This prospective uncontrolled study of 52 patients aged 15 to 64 years (mean 24) demonstrates that patients who become refractory to barbiturates are mainly those with partial seizures with or without generalization or with a focal EEG abnormality (71%). Seizures tend to become refractory approximately 6 years after barbiturates were started. Progressive barbiturate withdrawal over a period of two to 8 months (mean 5) with institution of treatment with carbamazepine, phenytoin or sodium valproate allowed complete barbiturate withdrawal in 42 of the 52 patients (81%). Furthermore monthly seizure frequency in those in whom barbiturates were withdrawn decreased from 7.1 to 1.7 per patient. An improvement in mental status was observed but not measured. These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal Which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations.

Barbitúricos são considerados tratamento anti-epiléptico de primeira escolha em países do terceiro mundo devido a razões econômicas e tradicionais. Este estudo prospectivo e não-controlado de 52 pacientes com idades entre 15 e 64 anos (média de 24) demonstra que pacientes que se tornam refratários a barbitúricos são principalmente aqueles com crises parciais com ou sem generalização secundária ou com uma anormalidade focal no eletrencefalograma (71%). As crises parecem se tornar retratarias aproximadamente 6 anos após o início do tratamento com barbitúricos. Retirada progressiva em um período de dois a 8 meses (média de 5) com início de tratamento com carbamazepina, difenil-hidantoína ou valproato de sódio permitiu retirada completa dos barbitúricos em 42 dos 52 pacientes (81%). Além disso a frequência mensal de crises naqueles de quem barbitúricos foram retirados diminuiu de 7,1 para 1,7 por paciente. Melhora no estado mental foi observada, porém não medida. Estes resultados indicam que barbitúricos não deveriam ser drogas de primeira escolha em pacientes com doença crônica tal como epilepsia, e indicam uma forma de retirada de barbitúricos que é segura e independente de hospitalização ou de monitorização de níveis séricos de drogas anti-epilépticas.

Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution

Epilepsia refrataria a barbitúricos: esquema seguro para substituição de terapêutica

Ana Maria Gorz^I; Carlos E. S. Silvado^II; Paulo Rogério M. Bittencourt^I

^Ie Departamento de Clínica Médica, Hospital de Clínicas da Universidade Federal do Paraná - Unidade de Neurologia Clínica, Hospital Nossa Senhora das Graças

^IICuritiba, Paraná, Brasil - Unidade de Neurologia Clínica, Hospital Nossa Senhora das Graças

SUMMARY

Barbiturates are considered first line antiepileptic drugs in third world countries due to traditional and economic reasons. This prospective uncontrolled study of 52 patients aged 15 to 64 years (mean 24) demonstrates that patients who become refractory to barbiturates are mainly those with partial seizures with or without generalization or with a focal EEG abnormality (71%). Seizures tend to become refractory approximately 6 years after barbiturates were started. Progressive barbiturate withdrawal over a period of two to 8 months (mean 5) with institution of treatment with carbamazepine, phenytoin or sodium valproate allowed complete barbiturate withdrawal in 42 of the 52 patients (81%). Furthermore monthly seizure frequency in those in whom barbiturates were withdrawn decreased from 7.1 to 1.7 per patient. An improvement in mental status was observed but not measured. These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal Which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations.

RESUMO

Barbitúricos são considerados tratamento anti-epiléptico de primeira escolha em países do terceiro mundo devido a razões econômicas e tradicionais. Este estudo prospectivo e não-controlado de 52 pacientes com idades entre 15 e 64 anos (média de 24) demonstra que pacientes que se tornam refratários a barbitúricos são principalmente aqueles com crises parciais com ou sem generalização secundária ou com uma anormalidade focal no eletrencefalograma (71%). As crises parecem se tornar retratarias aproximadamente 6 anos após o início do tratamento com barbitúricos. Retirada progressiva em um período de dois a 8 meses (média de 5) com início de tratamento com carbamazepina, difenil-hidantoína ou valproato de sódio permitiu retirada completa dos barbitúricos em 42 dos 52 pacientes (81%). Além disso a frequência mensal de crises naqueles de quem barbitúricos foram retirados diminuiu de 7,1 para 1,7 por paciente. Melhora no estado mental foi observada, porém não medida. Estes resultados indicam que barbitúricos não deveriam ser drogas de primeira escolha em pacientes com doença crônica tal como epilepsia, e indicam uma forma de retirada de barbitúricos que é segura e independente de hospitalização ou de monitorização de níveis séricos de drogas anti-epilépticas.

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1. BITTENCOURT, P.R.M.; CAROPRESO, V. & SILVADO, C.E.S. - Frequency of epileptic seizures and their etiology. Epilepsy International Symposium, Abstracts, 1983, pg. 392.
2. BITTENCOURT, P.R.M.; GABARDO, A.C. & SILVADO, C.E.S. - Monotherapy without serum levels for epilepsy. Epilepsy International Symposium, Abstracts, 1983, pg. 131.
3. BOOKER, H.E. - Phenobarbital: relation of plasma concentration to seizure control. In D.M. Woodbury, J.K. Penry & C.E. Pippinger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 241.
4. BUCHTAL, F.; SVENSMARK, O. & SIMONSEN, H. - Relation of EEG and seizures to phenobarbital in serum. Arch. Neurol. 19:567, 1968.
5. GALLAGHER, B.B.; BAUMEL, LP.; MATTSON, R.H. & WOODBURY, S.G. - Primidone, diphenylhidantoin and phenobarbital: aspects of acute and chronic toxicity. Neurology 23:145, 1973.
6. HUTT, S.J.; JACKSON, P.M.; BELSHAM, A. & HIGGINS, G. - Perceptual motor behaviour in relation to blood phenobarbitone level: a preliminary report. Dev. Med. Child Neurol. 10:626, 1968.
7. MACLEOD, CM.; DEKABAN, A.S. & HUNT, E. - Memory impairment in epileptic patients: selective effects of phénobarbital concentration. Science 202:1102, 1978.
8. MATTSON, R.H. & CRAMER, J.A. - Phénobarbital: toxicity. In D.M. Woodbury, J.K. Penry & CE. Pippinger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 351.
9. OUNSTED, C. - The hyperkinetic syndrome in epileptic children. Lancet 1:303, 1955.
10. OXLEY, J. ; RICHENS, A. & WADSWORTH, J. - Improvement in memory function in epileptic subjects following a reduction in serum phenobarbitone level. Epilepsy International Symposium, Abstracts, 1979, pg. 52.
11. REYNOLDS, E.H. & TRAVERS, R.D. - Serum anticonvulsant concentrations in epileptic patients with mental symptoms: a preliminary report. Brit. J. Psychiat. 124:440, 1974.
12. THEODORE, W.H. & PORTER, R.J. - Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy. Ann. Neurol. 13:320, 1983.
13. WOLF, P. & FORSYTHE, A. - Behaviour disturbance, phenobarbital and febrile seizures. In H. Meinardi & A.J. Rowan (eds.): Advances in Epileptology, 1977. Swets & Zeitlinger, Amsterdam, 1978, pg. 124.

Publication Dates

Publication in this collection
29 June 2011
Date of issue
Sept 1986

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. BITTENCOURT, P.R.M.; CAROPRESO, V. & SILVADO, C.E.S. - Frequency of epileptic seizures and their etiology. Epilepsy International Symposium, Abstracts, 1983, pg. 392.

[2] 2. BITTENCOURT, P.R.M.; GABARDO, A.C. & SILVADO, C.E.S. - Monotherapy without serum levels for epilepsy. Epilepsy International Symposium, Abstracts, 1983, pg. 131.

[3] 3. BOOKER, H.E. - Phenobarbital: relation of plasma concentration to seizure control. In D.M. Woodbury, J.K. Penry & C.E. Pippinger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 241.

[4] 4. BUCHTAL, F.; SVENSMARK, O. & SIMONSEN, H. - Relation of EEG and seizures to phenobarbital in serum. Arch. Neurol. 19:567, 1968.

[5] 5. GALLAGHER, B.B.; BAUMEL, LP.; MATTSON, R.H. & WOODBURY, S.G. - Primidone, diphenylhidantoin and phenobarbital: aspects of acute and chronic toxicity. Neurology 23:145, 1973.

[6] 6. HUTT, S.J.; JACKSON, P.M.; BELSHAM, A. & HIGGINS, G. - Perceptual motor behaviour in relation to blood phenobarbitone level: a preliminary report. Dev. Med. Child Neurol. 10:626, 1968.

[7] 7. MACLEOD, CM.; DEKABAN, A.S. & HUNT, E. - Memory impairment in epileptic patients: selective effects of phénobarbital concentration. Science 202:1102, 1978.

[8] 8. MATTSON, R.H. & CRAMER, J.A. - Phénobarbital: toxicity. In D.M. Woodbury, J.K. Penry & CE. Pippinger (eds.): Antiepileptic Drugs. Raven Press, New York, 1982, pg. 351.

[9] 9. OUNSTED, C. - The hyperkinetic syndrome in epileptic children. Lancet 1:303, 1955.

[10] 10. OXLEY, J. ; RICHENS, A. & WADSWORTH, J. - Improvement in memory function in epileptic subjects following a reduction in serum phenobarbitone level. Epilepsy International Symposium, Abstracts, 1979, pg. 52.

[11] 11. REYNOLDS, E.H. & TRAVERS, R.D. - Serum anticonvulsant concentrations in epileptic patients with mental symptoms: a preliminary report. Brit. J. Psychiat. 124:440, 1974.

[12] 12. THEODORE, W.H. & PORTER, R.J. - Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy. Ann. Neurol. 13:320, 1983.

[13] 13. WOLF, P. & FORSYTHE, A. - Behaviour disturbance, phenobarbital and febrile seizures. In H. Meinardi & A.J. Rowan (eds.): Advances in Epileptology, 1977. Swets & Zeitlinger, Amsterdam, 1978, pg. 124.