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.
Tonnby
B
B
Dept. of Paediatrics, County Hospital, Halmstad, Sweden.
Nilsson
H L
HL
Aldenkamp
A P
AP
Alpherts
W C
WC
Blennow
G
G
Elmqvist
D
D
Heijbel
J
J
Sandstedt
P
P
Wåhlander
L
L
Wosse
E
E
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