Therapeutic Drug Monitoring of Quetiapine: Effect of Coadministration with Antiepileptic Drugs in Patients with Psychiatric Disorders

Abstract

Antiepileptic agents, particularly those with mood-stabilizing properties, are increasingly used in the manage- ment of psychiatric disorders and may be prescribed in combination with antipsychotics. Aim of the present study was to evaluate the pharmacokinetic interaction between various antiepileptics and quetiapine, a second-generation antipsychotic, in psychiatric patients, by using data from a therapeutic drug monitoring service. Steady-state plasma concentrations of quetiapine were compared in patients treated with quetiapine alone (controls, n=35) and in patients comedicated with val- proic acid (n=19), lamotrigine (n=16), carbamazepine (n=6), topiramate (n=6) and oxcarbazepine (n=5). The six groups were matched for sex, age and daily dose of quetiapine. Dose-normalized plasma concentrations of quetiapine were sig- nificantly lower in the carbamazepine group than in the control group (p<0.001), while there were no differences in plasma quetiapine concentrations between the valproic acid, lamotrigine, topiramate or oxcarbazepine groups and the con- trol group. In 5 patients assessed on and off carbamazepine comedication, dose-normalized plasma concentrations of quetiapine were significantly lower during combination therapy than on quetiapine alone (p<0.01). By contrast, no appre- ciable changes in plasma levels of quetiapine were found in the 8 and 6 patients assessed on and off valproic acid or lamo- trigine comedication, respectively. These findings confirm that carbamazepine decreases markedly steady-state plasma concentrations of quetiapine, presumably by inducing its CYP3A4-mediated biotransformation. Conversely, concomitant administration of therapeutic doses of valproic acid, lamotrigine, topiramate or oxcarbazepine does not appear to affect significantly plasma levels of quetiapine.