Haloperidol and QTc Prolongation in Adults With Psychiatric or Behavioral Indications: A Systematic Review and...

Haloperidol is widely used for agitation, psychosis, and delirium, but concerns remain regarding QTc prolongation and ventricular arrhythmias. We evaluated the association between haloperidol and QTc prolongation in adults with psychiatric or behavioral indications and secondarily summarized clinically relevant proarrhythmic events.

We conducted a systematic review registered in PROSPERO (CRD420261306215) following PRISMA 2020. Randomized controlled trials and comparative observational studies enrolling adults receiving haloperidol versus placebo, no antipsychotic, or another antipsychotic were included. The primary outcome was QTc prolongation as defined by study authors. A sensitivity analysis assessed QTc ≥500 ms when explicitly reported by study arm. Meta-analyses were performed using odds ratios when appropriate. Risk of bias was assessed with RoB 2 and the Newcastle-Ottawa Scale; certainty was rated with GRADE.

Sixteen unique studies (17 publications; 16,189 participants) were included. In placebo- or no-antipsychotic comparisons (k=3 randomized controlled trials), haloperidol was not associated with a clear difference in QTc prolongation by author-defined thresholds (random-effects OR=1.18, 95%CI 0.83-1.69; I²=0%). In the sensitivity analysis restricted to QTc ≥500 ms (k=2 randomized controlled trials), evidence was imprecise due to the small number of studies, low event frequency, and wide confidence interval (OR=1.00, 95%CI 0.38-2.65). Clinically relevant proarrhythmic events were infrequent and usually not reported by study arm or yielded double-zero data, precluding quantitative synthesis.

: In placebo-controlled trials conducted in intensive care settings, haloperidol did not show an increase in QTc prolongation by author-defined criteria. Evidence for QTc ≥500 ms remains limited by imprecision, and clinically relevant proarrhythmic events were rare and inconsistently reported.