Drug interference can completely extinguish quetiapine blood levels

The metabolic pathways of quetiapine include sulfoxidation and oxidation. Both products are pharmacologically inactive. The metabolism involves the cytochrome P450 3A4 isoenzyme which can be induced by carbamazepine and other substances.

A 45 year old female patient was repeatedly treated in our hospital for a schizoaffective disorder. Although she had received carbamazepine (600mg), risperidone (8mg), quetiapine (700mg) and zolpidem (10mg), she was obliged to return to hospital due to hypomanic symptoms soon after being discharged. Despite good compliance and rigorous surveillance of the drug administration on the ward, the level of quetiapine in the blood was twice found to be negative (sensitivity of the test 25 ug/l). This led us to discontinue carbamazepine, risperidone and zolpidem. Instead, lithium was added, while the quetiapine dosage remained unchanged. During the following two weeks, quetiapine levels were measured at 53.9, 34.6 and 52.4 ug/l. Compared to the dosage level, these values are still low.

Our hypothesis suggests that the induction of the 3A4 isoenzyme by carbamazepine may be responsible for the suppression of the quetiapine level in the blood. This might partly be effective even after two weeks now. We expect a further increase with continued dosages. Although an accelerated metabolism of quetiapine is not surprising, the extent might be unknown to doctors.