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A 52-year-old woman and a 56-year-old man who were receiving carbamazepine experienced markedly elevated levels of its active metabolite, carbamazepine-10,11-epoxide (CBZ-E), after starting quetiapine therapy. The CBZ-E:carbamazepine ratio increased 3-4-fold in each patient. Levels of CBZ-E returned to baseline after discontinuing this drug combination. The metabolite can accumulate and cause neurotoxicity. The woman experienced ataxia and agitation while receiving quetiapine, which resolved after carbamazepine was switched to oxcarbazepine. The man was asymptomatic. To our knowledge, these are the first two case reports describing this interaction. Quetiapine may inhibit epoxide hydrolase and/or glucuronidation of carbamazepine-10,11-trans-diol in the same way as valproate and possibly lamotrigine do. If carbamazepine and quetiapine are administered concurrently, clinicians should consider monitoring CBZ-E concentrations.
Quetiapine, an atypical antipsychotic in the dibenzothiazepine chemical class, was approved in 1997 by the United States Food and Drug Administration. Carbamazepine is widely administered for the treatment of epilepsy, psychiatric conditions, and pain. Concurrent administration of carbamazepine can reduce quetiapine blood concentrations by inducing cytochrome P450 3A4 and thereby accelerating its clearance from the body. However, there is no known effect of quetiapine on carbamazepine or its active metabolite carbamazepine-10,11-epoxide (CBZ-E). The metabolite contributes to both seizure control and toxicity, including drowsiness, confusion, dizziness, ataxia, and exacerbation of seizures.
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