Therapeutic monitoring of antiepileptic drugs for epilepsy.
BACKGROUND
The aim of drug treatment for epilepsy is to prevent seizures without causing adverse effects. To achieve this, drug dosages need to be individualised. Measuring antiepileptic drug levels in body fluids (therapeutic drug monitoring) is frequently used to optimise drug dosage for individual patients.


OBJECTIVE
To review the evidence regarding the effects of therapeutic drug monitoring upon outcomes in epilepsy.


METHODS
We searched the Cochrane Epilepsy Group Specialised Register (September 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 4), MEDLINE (January 1966 to April 2005) and EMBASE (1974 to May 2005). No language restrictions were imposed. We checked the reference lists of retrieved articles for additional reports of relevant studies.


METHODS
Randomised controlled trials comparing the outcomes of antiepileptic drug monotherapy guided by therapeutic drug monitoring with drug treatment without the aid of therapeutic drug monitoring.


METHODS
We based this review on published aggregate data. The main outcomes measured were the proportions of patients achieving a 12-month remission from seizures, reporting adverse effects, and being withdrawn from the treatment they had been randomised to receive.


RESULTS
Only one study met the inclusion criteria for the review. In this open study, 180 patients with newly-diagnosed, untreated epilepsy were randomised to treatment with the antiepileptic drug selected by their physician either with or without therapeutic drug serum level monitoring as an aid to dosage adjustments. The antiepileptic drugs used were carbamazepine, valproate, phenytoin, phenobarbital and primidone. A 12-month remission from seizures was achieved by 60% of the patients randomised to therapeutic drug monitoring (intervention group) and by 61% in the control group. A total of 56% in the intervention group and 58% in the control group were seizure free during the last 12 months of follow up. Adverse effects were reported by 48% in the intervention group and 47% of the control group patients. Of those randomised to therapeutic drug monitoring, 62% completed the two-year follow up compared with 67% of the control group.


CONCLUSIONS
We found no clear evidence to support routine antiepileptic drug serum concentration measurement with the aim of reaching predefined target ranges for the optimisation of treatment of patients with newly-diagnosed epilepsy with antiepileptic drug monotherapy. However, this does not exclude the possible usefulness of therapeutic drug monitoring of specific antiepileptic drugs during polytherapy, in special situations or in selected patients, although evidence is lacking.
Tomson
T
T
Karolinska University Hospital, Department of Neurology, Stockholm, Sweden, S-171 76. torbjorn.tomson@karolinska.se
Dahl
M L
ML
Kimland
E
E
D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood; D002220:Carbamazepine / Q000008:administration & dosage / Q000097:blood; D016903:Drug Monitoring; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D010634:Phenobarbital / Q000008:administration & dosage / Q000097:blood; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood; D011324:Primidone / Q000008:administration & dosage / Q000097:blood; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood
D000927:Anticonvulsants; D011324:Primidone; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital