Drug Interactions between carbamazepine and trazodone

MONITOR: Coadministration with carbamazepine may decrease the plasma concentrations of trazodone and its active metabolite, meta-chlorophenylpiperazine. The proposed mechanism is carbamazepine induction of trazodone metabolism via CYP450 3A4. In six depressed patients treated with trazodone 150 mg to 300 mg daily, plasma concentrations of trazodone and meta-chlorophenylpiperazine were reduced by 76% and 60%, respectively, following administration of carbamazepine 400 mg/day for four weeks. A pair of case reports also suggest that trazodone may inhibit the metabolism of carbamazepine, possibly by competitive inhibition of CYP450 3A4 metabolism. In the first report, a 53-year-old white male had an increased carbamazepine concentration-dose ratio from 0.89 to 1.12 two months after beginning trazodone treatment. The patient did not exhibit any signs or symptoms of carbamazepine toxicity. In the second report, a 77-year-old female experienced ataxia and severe tremor in association with increased carbamazepine serum levels from 8.4 to 11.6 mg/L three days after the addition of trazodone 100 mg/day and escitalopram 10 mg/day. Carbamazepine levels returned to normal a week after the discontinuation of trazodone while escitalopram was continued.

MANAGEMENT: Pharmacologic response to trazodone should be monitored more closely whenever carbamazepine is added to or withdrawn from stabilized therapy, and the trazodone dosage adjusted as necessary. Similarly, it may be appropriate to monitor carbamazepine levels and pharmacologic effects following initiation, change of dosage, or discontinuation of trazodone therapy. Patients should be advised to contact their physician if they experience potential signs and symptoms of carbamazepine toxicity such as nausea, visual disturbance, dizziness, or ataxia.

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