Was Thioridazine (an antipsychotic medication) discontinued?

From the Guidelines

Thioridazine was discontinued from the global market due to serious cardiac safety concerns, specifically its potential to cause QT interval prolongation and torsades de pointes, a potentially fatal heart rhythm disturbance. The medication, which was an antipsychotic used to treat schizophrenia and other psychotic disorders, was found to have a cardiac risk that outweighed its benefits, especially with the availability of newer antipsychotic medications with better safety profiles 1. According to a study published in Circulation, thioridazine is one of the high-profile examples of drugs associated with torsades de pointes, along with methadone and haloperidol 1. The FDA had already placed a black box warning on thioridazine in 2000, restricting its use to patients who failed to respond to other antipsychotic medications 1.

Some key points to consider:

• Thioridazine's QT-prolonging effect is dose-dependent and can be increased by factors such as genetic variations in the CYP2D6 enzyme, which is responsible for its metabolism 1.
• The risk of torsades de pointes associated with thioridazine is difficult to establish, but it is generally believed to be less than that reported for antiarrhythmic agents 1.
• Newer antipsychotic medications, such as ziprasidone and olanzapine, have been found to have a lower risk of QT prolongation compared to thioridazine 1.
• The discontinuation of thioridazine was a precautionary measure to protect patients from the potential risk of cardiac arrhythmias, and patients who were previously taking thioridazine were transitioned to alternative antipsychotic medications under medical supervision 1.

In terms of management, it is essential to carefully evaluate the risk-benefit ratio of using QT-prolonging medications, including thioridazine, and to consider alternative treatments with better safety profiles 1. Patients who require antipsychotic medication should be closely monitored for signs of QT prolongation and torsades de pointes, and their treatment should be adjusted accordingly 1.

From the Research

Thioridazine Discontinuation

• Thioridazine was discontinued from the market worldwide in 2005 due to its association with QT interval prolongation and the risk of cardiac arrhythmias 2.
• The discontinuation of thioridazine led to an increase in hospitalization rates for schizophrenia patients who were previously stable on the medication 2.
• Studies have shown that thioridazine has a high potential for QT interval prolongation, which can lead to torsade de pointes and sudden death 3, 4.
• The mechanisms underlying thioridazine-induced cardiotoxicity have been explored, and it has been found that the drug induces hERG channel deficiency and L-type calcium channel activation via reactive oxygen species production 5.

Risks Associated with Thioridazine

• Thioridazine has been associated with a higher risk of QT interval prolongation and torsade de pointes compared to other antipsychotic drugs 3, 4.
• The risk of sudden death is increased with thioridazine use, particularly at higher doses and in combination with other medications that prolong the QT interval 4.
• The discontinuation of thioridazine highlights the importance of monitoring patients for QT interval prolongation and other cardiac risks when prescribing antipsychotic medications 2.

Comparison with Other Antipsychotic Drugs

• Other antipsychotic drugs, such as olanzapine, quetiapine, and risperidone, have not been associated with the same level of QT interval prolongation and cardiac risk as thioridazine 4.
• Ziprasidone has been found to prolong the QT interval, but the risk of torsade de pointes and sudden death is unclear 6, 4.
• Aripiprazole, brexpiprazole, and olanzapine have been recommended as alternative treatments for patients with mental disorders due to their lower risk of QT interval prolongation 6.