High doses of carbamazepine for refractory partial epilepsy

Pereira, Cristiana Borges; Heise, Carlos Otto; Cukiert, Arthur

doi:10.1590/S0004-282X1996000100007

Abstracts

Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ). Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1). Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6). Seizure's control was observed in 7 (14.48%) patients taking 1200 mg/day and in 2 (4.16%) patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%). Ten patients (20.81%) had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.

epilepsy; carbamazepine; effectiveness; side effects

Foram analisados 48 pacientes epilépticos com crises parciais que faziam uso de carbamazepina (CBZ) em doses iguais ou superiores a 1200 mg por dia. Trinta e três estavam em monoterapia e 15 em politerapia. As outras medicações foram mantidas constantes durante a manipulação da dose de CBZ nos pacientes em politerapia. O critério utilizado para o aumento da dose de CBZ foi a falta de controle clínico e a ausência de efeitos colaterais (independente da dosagem sérica). A dose máxima variou de 1200 a 1900 mg/dia (1200 mg, n=18; 1300 mg/dia, n=1; 1400 mg/dia, n=7; 1600 mg/dia, n=9; 1700 mg/dia, n=4; 1800 mg/dia, n=8 ; 1900 mg/dia, n=1). Dosagens séricas de anticonvulsivantes eram utilizadas no sentido de confirmar a aderência ao tratamento. A média das dosagens disponíveis foi de 9,6 ug/mL. O tempo de seguimento variou de 3 a 96 meses (M=25,6). Houve controle das crises em 7 (14,48 %) pacientes com 1200 mg/dia e em 2 (4, 16 %) pacientes com 1400 mg/dia. Trinta e nove pacientes nao obtiveram controle (81,21%). Dez pacientes (20,81 %) mostraram sinais de intoxicação. Quando doses de CBZ até 1400 mg não são eficazes, doses mais altas da droga são frequentemente incapazes de controlar as crises epilépticas. Nesta situação, a chance de intoxicação aumenta significativamente sem que haja beneficios para o paciente.

epilepsia; carbamazepina; efeitos colaterais; eficacia

High doses of carbamazepine for refractory partial epilepsy

Altas doses de carbamazepina para epilepsia parcial refratária

Cristiana Borges Pereira; Carlos Otto Heise; Arthur Cukiert

Department of Neurology and Neurosurgery of the University of São Paulo School of Medicine

ABSTRACT

Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ). Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1). Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6). Seizure's control was observed in 7 (14.48%) patients taking 1200 mg/day and in 2 (4.16%) patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%). Ten patients (20.81%) had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.

Key-words: epilepsy, carbamazepine, effectiveness, side effects.

RESUMO

Foram analisados 48 pacientes epilépticos com crises parciais que faziam uso de carbamazepina (CBZ) em doses iguais ou superiores a 1200 mg por dia. Trinta e três estavam em monoterapia e 15 em politerapia. As outras medicações foram mantidas constantes durante a manipulação da dose de CBZ nos pacientes em politerapia. O critério utilizado para o aumento da dose de CBZ foi a falta de controle clínico e a ausência de efeitos colaterais (independente da dosagem sérica). A dose máxima variou de 1200 a 1900 mg/dia (1200 mg, n=18; 1300 mg/dia, n=1; 1400 mg/dia, n=7; 1600 mg/dia, n=9; 1700 mg/dia, n=4; 1800 mg/dia, n=8 ; 1900 mg/dia, n=1). Dosagens séricas de anticonvulsivantes eram utilizadas no sentido de confirmar a aderência ao tratamento. A média das dosagens disponíveis foi de 9,6 ug/mL. O tempo de seguimento variou de 3 a 96 meses (M=25,6). Houve controle das crises em 7 (14,48 %) pacientes com 1200 mg/dia e em 2 (4, 16 %) pacientes com 1400 mg/dia. Trinta e nove pacientes nao obtiveram controle (81,21%). Dez pacientes (20,81 %) mostraram sinais de intoxicação. Quando doses de CBZ até 1400 mg não são eficazes, doses mais altas da droga são frequentemente incapazes de controlar as crises epilépticas. Nesta situação, a chance de intoxicação aumenta significativamente sem que haja beneficios para o paciente.

Palavras-chaves: epilepsia, carbamazepina, efeitos colaterais, eficacia.

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Full text available only in PDF format.

Aceite: 9-outubro-1995.

Dr. Arthur Cukiert - Rua Nova York 744 apto 131 - 04560-001 São Paulo SP - Brasil.

1. Cabrini GP, Sironi VA, Marossero F, Baruzzi A. Indications of anticonvulsant plasma levels monitoring in medical and surgical treatment of epilepsy. J Neurosurg Sci 1979; 23:29-36.
2. Callaghan N, Kenny RA, O'Neill B, Crowley M, Goggin T. A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy. J Neurol Neurosurg Psychiatry 1985; 48:639-644.
3. Callaghan N, O'Callaghan M, Duggan B., Feely M. Carbamazepine as a single drug in the treatment of epilepsy. J Neurol Neurosurg Psychiatry 1978; 41:907-912.
4. Cascino GD. Epilepsy: contemporary perspectives on evaluation and treatment. Mayo Clin Proc 1994; 69:1199-1211.
5. Chadwick D, Turnbill DM. The comparative efficacy of antiepileptic drugs for partial and tonic-clonic seizures. J Neurol Neurosurg Psychiatry 1985; 48:1073-1077.
6. Cornaggia CM, Cattabeni G, Cerisola N, Leozappa C, Mascetti PL, Massioni R, Porro G, Manghi E. Intractable epilepsies: an open trial with clobazam Acta Neurol 1989; 11:1-9.
7. Defazio G, Lepore V, Specchio LM, Pisani F, Livrea P. The infuence of eletroencephalographic focus laterality on efficacy of carbamazepine in complex partial and secondarily generalized tonic-clonic seizures. Epilepsia 1991; 32:706-711.
8. Dooley JM, Camfield PR, Camfield CS, Gordon KE, Fraser AD. The use of antiepileptic drug levels in children: a survey of Canadian pediatric neurologists. Can J Neurol Sci 1993; 20:217-221.
9. Elwes RDC, Jonhson AL, Shorvon SD, Reynolds EH. The prognosis for seizure in newly diagnosed epilepsy. N Engl J Med 1984; 311:944-947.
10. Gilman JT, Duchowny M, Jayakar P, Resnick TJ. Medical intractability in children evaluated for epilepsy surgery. Neurology 1994; 44:1341-1343.
11. Guerreiro CAM, Ramos MC, Annes M. Dosagens séricas repetidas de anticonvulsivantes em pacientes epilépticas. Arq Neuropsiquiatr 1993; 51:36-40.
12. Heller AJ, Chesterman P, Elwes RDC, Reynolds EH, Crawford P, Chadwick D, Johnson AL. Monotherapy for newly diagnosed adult epilepsy: comparative trial and prognostic evaluation. Epilepsia 1989; 30: 648.
13. Jain KK. Investigation and management of loss of efficacy of an antiepileptic medication using carbamazepine as an example. J R Soc Med 1993; 86:133-136.
14. Kutt H, Penry K. Usefulness of blood levels of antiepileptic drugs. Arch Neurol 1974; 31:283-288.
15. Larkin JG, Herrick AL, McGuire GM, Percy-Robb IW, Brodie MJ. Antiepileptic drug monitoring at the epilepsy clinic: a prospective evaluation. Epilepsia 1991; 32:89-95.
16. Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 1992; 327:765-771.
17. Mattson RH, Cramer JA, Collins JF. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313:145-151.
18. Neufeld MY. Exacerbation of focal seizures due to carbamazepine treatment in an adult patient. Clin Neuropharmacol 1993; 16:359-361.
19. Pellock JM, Willmore LJ. A rational guide to routine blood monitoring in patients receiving antiepileptic drugs. Neurology 1991; 41:961-964.
20. Pryse-Phillips W, Jardine F, Bursey F. Compliance with drug therapy by epileptic patients. Epilepsia 1982; 23:269-274.
21. Rodin EA. Medical and social prognosis in epilepsy. Epilepsia 1972; 13:121-131.
22. Shorvon SD, Chadwick D, Galbraith AW, Reynolds EH. One drug for epilepsy. Br Med J 1978; 1:474-476.
23. Sillanpäa M. Carbamazepine: pharmacology and clinical uses. Acta Neurol Scand 1981; 64:69-76.
24. Strandjord RE, Johannessen SI. Single-drug therapy with carbamazepine in patients with epilepsy: serum levels and clinical effect. Epilepsia 1980; 21:655-662.
25. Van der Kleijn E, Schobben F, Termond E, Jansen W, Vree TB. Continuous monitoring of plasma antiepileptic drug levels. Acta Neurol Scand 1983; Suppl 97:91-114.

Publication Dates

Publication in this collection
07 Dec 2010
Date of issue
Mar 1996

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

[1] 1. Cabrini GP, Sironi VA, Marossero F, Baruzzi A. Indications of anticonvulsant plasma levels monitoring in medical and surgical treatment of epilepsy. J Neurosurg Sci 1979; 23:29-36.

[2] 2. Callaghan N, Kenny RA, O'Neill B, Crowley M, Goggin T. A prospective study between carbamazepine, phenytoin and sodium valproate as monotherapy in previously untreated and recently diagnosed patients with epilepsy. J Neurol Neurosurg Psychiatry 1985; 48:639-644.

[3] 3. Callaghan N, O'Callaghan M, Duggan B., Feely M. Carbamazepine as a single drug in the treatment of epilepsy. J Neurol Neurosurg Psychiatry 1978; 41:907-912.

[4] 4. Cascino GD. Epilepsy: contemporary perspectives on evaluation and treatment. Mayo Clin Proc 1994; 69:1199-1211.

[5] 5. Chadwick D, Turnbill DM. The comparative efficacy of antiepileptic drugs for partial and tonic-clonic seizures. J Neurol Neurosurg Psychiatry 1985; 48:1073-1077.

[6] 6. Cornaggia CM, Cattabeni G, Cerisola N, Leozappa C, Mascetti PL, Massioni R, Porro G, Manghi E. Intractable epilepsies: an open trial with clobazam Acta Neurol 1989; 11:1-9.

[7] 7. Defazio G, Lepore V, Specchio LM, Pisani F, Livrea P. The infuence of eletroencephalographic focus laterality on efficacy of carbamazepine in complex partial and secondarily generalized tonic-clonic seizures. Epilepsia 1991; 32:706-711.

[8] 8. Dooley JM, Camfield PR, Camfield CS, Gordon KE, Fraser AD. The use of antiepileptic drug levels in children: a survey of Canadian pediatric neurologists. Can J Neurol Sci 1993; 20:217-221.

[9] 9. Elwes RDC, Jonhson AL, Shorvon SD, Reynolds EH. The prognosis for seizure in newly diagnosed epilepsy. N Engl J Med 1984; 311:944-947.

[10] 10. Gilman JT, Duchowny M, Jayakar P, Resnick TJ. Medical intractability in children evaluated for epilepsy surgery. Neurology 1994; 44:1341-1343.

[11] 11. Guerreiro CAM, Ramos MC, Annes M. Dosagens séricas repetidas de anticonvulsivantes em pacientes epilépticas. Arq Neuropsiquiatr 1993; 51:36-40.

[12] 12. Heller AJ, Chesterman P, Elwes RDC, Reynolds EH, Crawford P, Chadwick D, Johnson AL. Monotherapy for newly diagnosed adult epilepsy: comparative trial and prognostic evaluation. Epilepsia 1989; 30: 648.

[13] 13. Jain KK. Investigation and management of loss of efficacy of an antiepileptic medication using carbamazepine as an example. J R Soc Med 1993; 86:133-136.

[14] 14. Kutt H, Penry K. Usefulness of blood levels of antiepileptic drugs. Arch Neurol 1974; 31:283-288.

[15] 15. Larkin JG, Herrick AL, McGuire GM, Percy-Robb IW, Brodie MJ. Antiepileptic drug monitoring at the epilepsy clinic: a prospective evaluation. Epilepsia 1991; 32:89-95.

[16] 16. Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 1992; 327:765-771.

[17] 17. Mattson RH, Cramer JA, Collins JF. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313:145-151.

[18] 18. Neufeld MY. Exacerbation of focal seizures due to carbamazepine treatment in an adult patient. Clin Neuropharmacol 1993; 16:359-361.

[19] 19. Pellock JM, Willmore LJ. A rational guide to routine blood monitoring in patients receiving antiepileptic drugs. Neurology 1991; 41:961-964.

[20] 20. Pryse-Phillips W, Jardine F, Bursey F. Compliance with drug therapy by epileptic patients. Epilepsia 1982; 23:269-274.

[21] 21. Rodin EA. Medical and social prognosis in epilepsy. Epilepsia 1972; 13:121-131.

[22] 22. Shorvon SD, Chadwick D, Galbraith AW, Reynolds EH. One drug for epilepsy. Br Med J 1978; 1:474-476.

[23] 23. Sillanpäa M. Carbamazepine: pharmacology and clinical uses. Acta Neurol Scand 1981; 64:69-76.

[24] 24. Strandjord RE, Johannessen SI. Single-drug therapy with carbamazepine in patients with epilepsy: serum levels and clinical effect. Epilepsia 1980; 21:655-662.

[25] 25. Van der Kleijn E, Schobben F, Termond E, Jansen W, Vree TB. Continuous monitoring of plasma antiepileptic drug levels. Acta Neurol Scand 1983; Suppl 97:91-114.