Which antipsychotic is most associated with significant QT interval prolongation?

Thioridazine is the antipsychotic most associated with significant QT interval prolongation due to its ability to block potassium channels, which can disrupt the normal cardiac repolarization process. This prolongation can lead to potentially serious cardiac arrhythmias, such as torsades de pointes, especially in patients with other risk factors or when combined with other medications that also prolong the QT interval.

While other antipsychotics, such as risperidone, asenapine, and lurasidone, may have some impact on the QT interval, thioridazine has a much stronger association and is known for this specific side effect. This makes it crucial for healthcare providers to monitor patients closely when prescribing thioridazine, particularly those who may already have underlying heart conditions or are taking multiple medications.