Withdrawal of antiepileptic medication in children. Correlation of cognitive function and plasma concentration--the multicentre 'Holmfrid' study.
Eighty-three patients with epilepsy and 83 matched controls completed 12 computerized cognitive tests while on antiepileptic drugs and six months later when they had been medication-free for three to four months. All patients had been seizure-free for more than one year and were on monotherapy with carbamazepine (CBZ, n = 56), valproate (VPA, n = 17), or phenytoin (PHT, n = 10). The tests and plasma concentration collection were done at noon. The mean peak plasma concentrations in the CBZ patients were as follows: 31% below 30 mumol/l, 48% between 30 and 42 mumol/l and 21% above 42 mumol/l. No difference in performance could be detected between the groups. One significant correlation between plasma concentration and test results was found. The mean VPA concentration was 625 mumol/l (S.D. 189). A tendency towards a weak negative correlation between test results and plasma concentration was present. The PHT patients' therapeutic range had a mean concentration of 32.0 mumol/l (S.D. 18.5). One significant correlation between a memory test and plasma concentration could be detected. Overall, the patients in the different antiepileptic groups performed less good than the control group and in a few cases the differences were statistically significant when compared either before or after withdrawal. A comparison of the changes after withdrawal showed improvement in the majority of tests, but these changes were also present in the matched control group.
Dept. of Paediatrics, County Hospital, Halmstad, Sweden.
B
B
Tonnby
H L
HL
Nilsson
A P
AP
Aldenkamp
W C
WC
Alpherts
G
G
Blennow
D
D
Elmqvist
J
J
Heijbel
P
P
Sandstedt
L
L
Wåhlander
E
E
Wosse
D000293:Adolescent; D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000097:blood / Q000627:therapeutic use; D002648:Child; D003071:Cognition; D006801:Humans; D010672:Phenytoin / Q000097:blood / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000097:blood* / Q000523:psychology*; D014635:Valproic Acid / Q000097:blood / Q000627:therapeutic use
D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin