In two studies, the effects of the potentially interacting drugs mirtazapin
e and carbamazepine on their pharmacokinetics have been investigated. Subje
cts were treated with carbamazepine combined with placebo for 21 days and s
ubsequently with carbamazepine combined with mirtazapine for another 7 days
(Study A) or with mirtazapine combined with placebo for 7 days and subsequ
ently mirtazapine combined with carbamazepine for another 21 days (Study B)
. Pharmacokinetic results indicate that carbamazepine decreased significant
ly AUC and C-max values for mirtazapine and increased values for demethyl-m
irtazapine C-max. Mirtazapine had no effect on carbamazepine pharmacokineti
c parameters, but did lower carbamazepine-10,11-epoxide levels. Mirtazapine
did not affect the single dose kinetics or the enzyme inducing properties
of carbamazepine. VAMRS alertness scores reflected the somnolence-inducing
effects of carbamazepine and mirtazapine and psychometric test results reve
aled impairment of specific tasks. The combination was safe and routine lab
oratory testing did not reveal clinically relevant abnormalities. The dose
of mirtazapine in patients on carbamazepine may have to be increased for op
timal antidepressant efficacy.