First-generation antipsychotics and QTc: any role for mediating variables?

Area of Science:

• Psychiatry
• Cardiology
• Pharmacology

Background:

• Corrected QT (QTc) interval prolongation is a known risk associated with first-generation antipsychotics (FGAs).
• Other factors like age, gender, concomitant medications, and alcohol use disorders may influence QTc prolongation.
• The potential mediating roles of these variables require further investigation.

Purpose of the Study:

• To investigate the impact of FGAs on QTc interval.
• To examine the mediating roles of age, gender, alcohol use disorders, and concurrent risky drug use on QTc prolongation.
• To confirm the direct effect of FGAs on QTc interval.

Main Methods:

• Utilized data from the STAR Network QTc study, a large (N=2366), cross-sectional national survey.
• Included a representative sample of patients taking FGAs, recruited from Italian mental health services.
• Analyzed data to assess the effects of FGAs, age, gender, alcohol misuse, and concurrent risky drugs on QTc.

Main Results:

• FGAs, age, gender, alcohol misuse, and concurrent risky drugs were found to impact QTc interval.
• Approximately one-third of the sample used FGAs, and nearly one-tenth used additional QTc-prolonging drugs.
• Comorbid alcohol abuse/dependence and concurrent risky drugs did not mediate the effect of FGAs on QTc.

Conclusions:

• First-generation antipsychotics (FGAs), concurrent risky drugs, and alcohol use disorders are confirmed to prolong the QTc interval.
• FGAs exert a direct effect on QTc prolongation.
• Clinicians must monitor QTc interval in patients using FGAs due to the risk of sudden unexplained death.