Quetiapine × Trazodone

Trazodone prolongs the QT interval, and postmarketing reports include torsade de pointes at doses of 100 mg or less (trazodone label, US Food and Drug Administration, FDA). QT prolongation has been reported with quetiapine at therapeutic doses and in overdose (quetiapine summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). The trazodone label warns that other QT-prolonging drugs may add to its QT effect (trazodone FDA label). Both drugs act on the central nervous system. Trazodone can intensify the sedative effect of antipsychotics, and both drugs cause somnolence and orthostatic hypotension (SmPCs of both drugs, AEMPS). Trazodone is a serotonergic agent, and quetiapine raises the risk of serotonin syndrome when combined with serotonergic drugs. Neuroleptic malignant syndrome, including fatal cases, has been reported when trazodone was given with neuroleptics (SmPCs of both drugs, AEMPS). Quetiapine and its metabolites do not inhibit the major cytochrome P450 (CYP) enzymes, and the labels give no pharmacokinetic study of this pair (quetiapine FDA label).

QT interval prolongation itself causes no symptoms and shows only on the electrocardiogram (ECG). A ventricular arrhythmia causes palpitations, dizziness and fainting. The added sedative and blood pressure-lowering effects cause somnolence, dizziness on standing, fainting and falls, more often in older people (summaries of product characteristics of both drugs). Serotonin syndrome presents with agitation, hallucinations, tremor, muscle jerks, fever and a fast pulse (trazodone label). Neuroleptic malignant syndrome presents with high fever, muscle rigidity, confusion and unstable pulse and blood pressure (quetiapine summary of product characteristics).

The labels of both drugs from the US Food and Drug Administration (FDA) say to avoid combining them with drugs that prolong the QT interval. Each of the two prolongs QT according to its own documents (quetiapine and trazodone FDA labels; quetiapine summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). The Spanish SmPCs of both drugs are softer and ask for caution with this combination (quetiapine and trazodone SmPCs, AEMPS). Avoid both drugs in bradycardia, low potassium or magnesium, congenital QT prolongation or a history of arrhythmias (quetiapine and trazodone FDA labels). Use quetiapine with caution in older people and in heart failure or cardiac hypertrophy (quetiapine SmPC, AEMPS). Trazodone can intensify the sedative effect of antipsychotics, and its SmPC recommends a dose reduction in that case (trazodone SmPC, AEMPS). If orthostatic hypotension occurs, consider a lower quetiapine dose or a slower titration (quetiapine SmPC, AEMPS). Monitor somnolence and blood pressure closely after the start and before and after each dose increase. Tell the patient not to drive until they know how the drugs affect them (trazodone SmPC, AEMPS; FDA labels of both drugs). If serotonin syndrome or neuroleptic malignant syndrome is suspected, stop trazodone at once and start supportive treatment (trazodone SmPC, AEMPS). In neuroleptic malignant syndrome, stop quetiapine as well (quetiapine SmPC, AEMPS).