Although there have previously been no reported cases of an interaction between trazodone and omeprazole, a new report is believed to be the first instance of reversible second-degree Mobitz type 1 atrioventricular (AV) block with concomitant use of trazodone and omeprazole.

A 54-year-old male former smoker with dyslipidemia, coronary artery disease, and anxiety disorder presented to emergency department after an episode of lightheadedness and syncope; he reported an episode of lightheadedness a week before presentation. He was being treated with trazodone 50mg, omeprazole 20mg, and simvastatin 20mg daily but had doubled his trazodone dose the previous evening to calm his anxiety. His pulse was 65/minute (irregular) and blood pressure was 163/116mmHg with no orthostatic hypotension on admission. An electrocardiogram showed a sinus rhythm at 60 beats per minutes, second-degree Mobitz type 1 AV block with 5:4 AV conduction, ventricular rate of 52/minute, narrow QRS, and a normal QTc of 434 milliseconds; telemetry indicated frequent 8:7, 7:6, 5:4, 4:3 AV conductions recurring after every few beats of normal AV conduction. Due to the probability of omeprazole potentiating trazodone accumulation these medications were discontinued in the patient and by day 3 after stopping treatment, all symptoms had resolved and the frequency of Mobitz type 1 AV block was reduced to once per hour.

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Trazodone is a serotonin receptor antagonist and reuptake inhibitor (SARI) that has been linked to cases of first-degree AV block and complete heart block despite minimal anticholinergic muscarinic receptor blocking action. It is metabolized by liver microsome-based cytochrome P450 enzyme CYP3A4  into m-chlorophenylpiperazine (m-CPP); the trazodone toxicity in this patient was attributed to long-term concomitant use of the CYP3A4 inhibitor omeprazole that led to trazodone accumulation. With the popularity of omeprazole as a therapy for gastroesophageal reflux disease (GERD), this interaction merits additional research and case studies.

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