Major adverse cardiac events with haloperidol: A meta-analysis

Area of Science:

• Cardiology
• Pharmacology
• Psychiatry

Background:

• Haloperidol is a widely used antipsychotic with known QT interval-prolonging risks.
• It is frequently flagged in medication safety alerts.
• This study investigates cardiac risks associated with haloperidol.

Purpose of the Study:

• To systematically review and summarize high-quality evidence on the frequency and nature of proarrhythmic major adverse cardiac events (MACE) linked to haloperidol.
• To assess the association between haloperidol use and cardiac safety outcomes.

Main Methods:

• Searched multiple databases (Medline, Embase, etc.) for randomized controlled trials (RCTs) comparing haloperidol to placebo in adults.
• Utilized an FDA-adapted MACE composite outcome (death, cardiac arrest, ventricular tachyarrhythmia, seizure, syncope).
• Performed random-effects meta-analyses, including corrections for zero-event studies.

Main Results:

• Analyzed 84 RCTs with 12,180 participants; 44% included patients with psychiatric diagnoses, and 59.5% collected ECG data.
• Over 1100 events were recorded, predominantly deaths (97.8%), with few ventricular arrhythmias or seizures/syncope.
• No significant difference in MACE was found between haloperidol and placebo groups (RR 0.93, 95% CI: 0.80-1.08), nor an increased risk of mortality with IV haloperidol.

Conclusions:

• Haloperidol was not found to be arrhythmogenic or increase mortality in the analyzed short-duration trials.
• Further research is essential to understand the real-world clinical outcomes associated with QT interval-prolonging medications (QTPmeds).
• Findings aim to inform safer prescribing practices for haloperidol.