Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval

Area of Science:

• Pharmacology
• Cardiology
• Psychiatry

Background:

• Antipsychotic (AP) drugs can prolong the QT interval corrected for heart rate (QTc).
• This risk is dose-dependent and may be exacerbated by concurrent prescription of multiple AP drugs, leading to increased cumulative dosage.
• Understanding the relationship between AP polypharmacy, dosage, and QTc prolongation is crucial for patient safety.

Purpose of the Study:

• To investigate whether antipsychotic (AP) drug dose mediates the relationship between polypharmacy and QTc interval prolongation.
• To analyze the association between AP polypharmacy, cumulative AP dose, and QTc interval in psychiatric patients.

Main Methods:

• Utilized data from a cross-sectional survey of psychiatric patients in Italy.
• Employed the Baron and Kenny mediational model to assess the association between AP polypharmacy, AP dose, and QTc interval.
• Included 725 patients, with 186 (26%) receiving two or more AP drugs (polypharmacy).

Main Results:

• Patients on AP polypharmacy had significantly higher cumulative AP doses (PDD/DDD = 2.93) compared to monotherapy (PDD/DDD = 0.82).
• Mean QTc interval was significantly longer in patients on AP polypharmacy (420.86 ms) than monotherapy (413.42 ms).
• Mediation analysis confirmed that AP dose significantly mediates the association between polypharmacy and QTc interval.

Conclusions:

• Antipsychotic polypharmacy is associated with a longer QTc interval.
• The effect of AP polypharmacy on QTc interval is mediated by the cumulative antipsychotic drug dose.
• Clinicians must consider the increased risk of QTc prolongation when prescribing multiple antipsychotic drugs due to dose-related effects.