Amitriptyline × Quetiapine

Both drugs prolong the QT interval. The amitriptyline SmPC lists QT-prolonging drugs, including some antipsychotics, among combinations that are not recommended because of the risk of ventricular arrhythmias (amitriptyline SmPC), and QT prolongation has been reported with quetiapine at therapeutic doses (quetiapine SmPC). A second mechanism is the combined anticholinergic effect: in quetiapine it comes from its metabolite norquetiapine (quetiapine SmPC), and amitriptyline has its own (amitriptyline label of the US Food and Drug Administration, FDA). Tricyclic antidepressants and neuroleptics inhibit each other's metabolism, which can lower the seizure threshold (amitriptyline SmPC). The quetiapine SmPC also warns about serotonin syndrome with tricyclic antidepressants.

Palpitations, dizziness, fainting; QT prolongation on the electrocardiogram (ECG) and, in severe cases, torsades de pointes. Dry mouth, constipation, urinary retention, blurred vision, fast heart rate; in older people, confusion, slowed thinking, delirium and falls. Drowsiness and dizziness on standing. Raised body temperature has been reported when amitriptyline is combined with anticholinergic or neuroleptic drugs, especially in hot weather.

The amitriptyline SmPC lists QT-prolonging drugs among combinations that are not recommended (amitriptyline SmPC), and the US Food and Drug Administration (FDA) says quetiapine should be avoided with other drugs known to prolong the QT interval (quetiapine FDA label). Avoid the combination where possible. If it is still needed, take into account the situations in which the quetiapine SmPC asks for particular caution: older age, congenital long QT, heart failure, cardiac hypertrophy, low potassium or magnesium (quetiapine SmPC). In older patients, start amitriptyline at low doses and observe them closely (amitriptyline FDA label). Because of the combined anticholinergic effect, use quetiapine with caution in patients with urinary retention, enlarged prostate, bowel obstruction, raised intraocular pressure or narrow-angle glaucoma (quetiapine SmPC). The dose of either drug may need adjustment because each inhibits the metabolism of the other (amitriptyline SmPC).