[Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of different doses of folic acid].
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.


METHODS
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.
Fernández-Miranda
Consuelo
C
Servicio de Medicina Interna, Hospital Universitario 12 de Octubre, Madrid, Spain. cfmiranda@inicia.es
de la Peña
Pilar
P
Penas
Marta
M
Saiz
Rosana
R
Gómez
Pilar
P
Gómez de la Cámara
Agustín
A
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged
D000927:Anticonvulsants; D006710:Homocysteine; D005492:Folic Acid