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

摘要

Antiepileptic agents, particularly those with mood-stabilizing properties, are increasingly used in the managementof psychiatric disorders and may be prescribed in combination with antipsychotics. Aim of the present study was toevaluate 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 ofquetiapine were compared in patients treated with quetiapine alone (controls, n=35) and in patients comedicated with valproicacid (n=19), lamotrigine (n=16), carbamazepine (n=6), topiramate (n=6) and oxcarbazepine (n=5). The six groupswere matched for sex, age and daily dose of quetiapine. Dose-normalized plasma concentrations of quetiapine were significantlylower in the carbamazepine group than in the control group (p<0.001), while there were no differences inplasma quetiapine concentrations between the valproic acid, lamotrigine, topiramate or oxcarbazepine groups and the controlgroup. In 5 patients assessed on and off carbamazepine comedication, dose-normalized plasma concentrations ofquetiapine were significantly lower during combination therapy than on quetiapine alone (p<0.01). By contrast, no appreciablechanges in plasma levels of quetiapine were found in the 8 and 6 patients assessed on and off valproic acid or lamotriginecomedication, respectively. These findings confirm that carbamazepine decreases markedly steady-state plasmaconcentrations of quetiapine, presumably by inducing its CYP3A4-mediated biotransformation. Conversely, concomitantadministration of therapeutic doses of valproic acid, lamotrigine, topiramate or oxcarbazepine does not appear to affectsignificantly plasma levels of quetiapine.