[Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid]. / Hiperhomocisteinemia en pacientes tratados con antiepilépticos. Efecto de diferentes dosis de ácido fólico.

BACKGROUND AND OBJECTIVE: An increase homocysteine values, which is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eighty six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or primidone and/or carbamazepine), 5 received non inductors (valproate) and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean [SD]12.2 [6.7] 95% confidence interval [CI],10.0-13.5 vs 8.8[2.2] 95% CI, 8.3-9.2 micromol/l; p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%; p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients.

Hiperhomocisteinemia en pacientes tratados con antiepilépticos. Efecto de diferentes dosis de ácido fólico / Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid

FUNDAMENTO Y OBJETIVO: La elevación de la homocisteína, que es un factor de riesgo de enfermedad aterotrombótica, puede producirse con la administración de antiepilépticos. Los objetivos de este estudio han sido: a) evaluar la frecuencia y los factores determinantes de hiperhomocisteinemia en pacientes adultos tratados con antiepilépticos, y b) conocer el efecto de diferentes dosis de ácido fólico sobre los valores de homocisteína plasmática. PACIENTES Y MÉTODO: Se estudió a 98 pacientes y a 100 controles sanos con edad y sexo similares. De los pacientes, 86 recibían tratamiento con inductores de enzimas hepáticas (difenilhidantoínay/o fenobarbital y/o primidona y/o carbamacepina), 5 con no inductores (valproato) y 7 con combinación de ambos. Treinta y ocho pacientes se trataron aleatoriamente de forma abierta y concurrente con 0,2 mg (n = 18) o 5,2 mg (n = 20) de ácido fólico diariamente durante 3 meses. RESULTADOS: Las concentraciones de homocisteína estaban aumentadas en los pacientes en relación con los controles (media [desviación estándar] 12,2 [6,7] µmol/l intervalo de confianza del 95%,10,0-13,5, frente a 8,8 [2,2] µmol/l; intervalo de confianza del 95%, 8,3-9,2 µmol/l;p < 0,001). En 28 pacientes y en 4 controles existía hiperhomocisteinemia (el 28,6 frente al4,0%; p < 0,001). En el análisis multivariante, la hiperhomocisteinemia se asoció positivamente al tratamiento con antiepilépticos inductores y negativamente a los valores de folato y al sexo femenino. La homocisteinemia descendió significativamente tras el tratamiento con ácido fólico, tanto en dosis altas como bajas (p < 0,001 para ambos grupos), y en este último grupo se obtuvieron concentraciones similares a las de los controles sanos. CONCLUSIONES: La hiperhomocisteinemia es frecuente en los pacientes tratados con antiepilépticos. El tratamiento con inductores de las enzimas hepáticas y los valores bajos de folato son predictores de hiperhomocisteinemia. El tratamiento con ácido fólico, incluso a dosis muy bajas, disminuye significativamente la homocisteinemia en estos pacientes

BACKGROUND AND OBJECTIVE: An increase homocysteine values, wich is an independent risk factor for atherotrombotic disease, can be produced with antiepileptic treatment. The aims of this study were: 1) to assess the frequency and determinant factors of hyperhomocysteinemia in adult patients receiving antiepileptic drugs, and 2) to know the effect of different doses of folic acid. PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in age and gender were studied. Eigthy six patients were treated with hepatic enzyme inductors (diphenylhydantoine and/or phenobarbital and/or prim done and/or carbamazepine), 5 received non inductors (valproate)and 7 were treated with both in combination. Thirty eight patients were randomized to receive in an open and concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months. RESULTS: Homocysteine values were increased in patients in relation with controls (mean[SD]12.2 [6.7] 95% confidence interval [CI],10,0-13,5 vs 8.8[2.2] 95% CI, 8,3-9,2 µmol/l;p < 0.001). Hyperhomocysteinemia was found in 28 patients and 4 controls (28.6% vs 4.0%;p < 0.001). In a multivariate analysis hyperhomocysteinemia was positively associated with treatment with antiepileptic inductors and negatively with folate values and female gender. Homocysteine values decreased after treatment with folic acid at high and low doses (p < 0.001 for both groups), and the values observed in the latter group were similar to those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients treated with antiepileptic drugs. Treatment with hepatic enzyme inductors and low folate values are predictors of hyperhomocysteinemia. Administration of folic acid, even at very low doses, produces a significant decrease of homocysteinemia in these patients