Hyperhomocysteinemia in epileptic patients on new antiepileptic drugs.
OBJECTIVE
Older enzyme-inducing antiepileptic drugs (AEDs) may induce supraphysiologic plasma concentrations of total (t) homocysteine (Hcy). The aim of the present study was to investigate the effect of new AEDs on plasma tHcy levels.


METHODS
Patients 18-50 years of age, on AEDs monotherapy, with no other known cause of hyper-tHcy were enrolled. Plasma tHcy, folate, vitamin B(12), and AEDs levels were determined by standard high-performance liquid chromatography (HPLC) methods. Methylenetetrahydrofolate-reductase (MTHFR) polymorphisms were checked using Puregene genomic DNA purification system (Gentra, Celbio, Italy). A group of healthy volunteers matched for age and sex was taken as control.


RESULTS
Two hundred fifty-nine patients (151 on newer and 108 on older AEDs) and 231 controls were enrolled. Plasma tHcy levels were significantly higher [mean values, standard error (SE) 16.8, 0.4 vs. 9.1, 0.2 microm; physiologic range 5-13 microm] and folate lower (6.3, 0.1 vs. 9.3, 0.1 nm; normal > 6.8 nm) in patients compared to controls. Patients treated with oxcarbazepine, topiramate, carbamazepine, and phenobarbital exhibited mean plasma tHcy levels above the physiologic range [mean values (SE) 16 (0.8), 19.1 (0.8), 20.5 (1.0), and 18.5 (1.5) microm, respectively]. Conversely, normal tHcy concentrations were observed in the lamotrigine and levetiracetam groups [both 11.1 (0.5) microm].


CONCLUSIONS
Oxcarbazepine and topiramate might cause hyper-tHcy, most likely because of the capacity of these agents to induce the hepatic enzymes. Because literature data suggest that hyper-tHcy may contribute to the development of cerebrovascular diseases and brain atrophy, a supplement of folate can be considered in these patients to normalize plasma tHcy.
Neurology Clinic, University of Perugia, Perugia and Fondazione Santa Lucia - IRCCS, Roma, Italy. vincenzobelcastro@libero.it
Vincenzo
V
Belcastro
Pasquale
P
Striano
Gaetano
G
Gorgone
Cinzia
C
Costa
Clotilde
C
Ciampa
Daniela
D
Caccamo
Laura R
LR
Pisani
Giancarla
G
Oteri
Maria G
MG
Marciani
Umberto
U
Aguglia
Salvatore
S
Striano
Riccardo
R
Ientile
Paolo
P
Calabresi
Francesco
F
Pisani
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000097:blood; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D000077213:Lamotrigine; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000009:adverse effects / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D000077236:Topiramate; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000097:blood
D000927:Anticonvulsants; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D010634:Phenobarbital