Background: Antipsychotics are frequently used in the hospital setting for managing both acute and chronic psychiatric disorders. However, antipsychotics have been associated with higher rates of mortality due to their cardiovascular risk factors, such as QT prolongation. This study aimed to determine the association between cumulative dose of antipsychotics (first and second-generation) and QT prolongation, as well as adverse cardiovascular events.

Methods: A multi-site, retrospective chart review (1/1/2010 – 1/1/2016) of patients >18 years who received antipsychotics during hospitalization. Those with baseline and follow up EKGs (before and after first antipsychotic dose) were included. Patients with EKGs with ventricular rate >120 bpm, LOS < 2 days, or > 26 days were excluded. Variables included: age, sex, race, marital status, dementia, and other QT prolonging medications. QT prolongation was considered to be an increase of 60ms or greater from baseline to follow-up EKGs. EHR were reviewed to determine the cumulative dose of the five antipsychotics (haloperidol, quetiapine, olanzapine, risperidone, aripiprazole) administered between the baseline and follow-up EKGs. The primary outcome was to assess the association between cumulative dose and change in QTc using a multiple linear regression. Secondary outcomes included QT prolongation (dichotomous), incidence of adverse cardiac events and inpatient mortality, using a GEE model with logit link.

Results: Of 39,939 inpatients who received antipsychotics, 1,682 had an initial and at least one follow-up EKG. Of those, 147 had a QT prolongation of greater than 60ms. Those patients were compared to a random sample of 147 patients without QT prolongation. Of the overall cohort (N=294), average age was 74.5, 45.6% were female, 75.9% were white, and 30% had dementia. The average number of other QT prolonging medications was 5.1. After controlling for patient demographic variables and other QT prolonging medications, cumulative dose of any antipsychotics was not associated with a significant increase in QT prolongation. There were no associations between cumulative dose and adverse cardiac events or mortality. Receipt of olanzapine was significantly associated with incident adverse cardiac events (22.6% vs. 8.4% for olanzapine vs. no olanzapine, OR=3.82). Adverse cardiac events were more common among patients with QT prolongation compared to those without QT prolongation (12.3% vs. 7.5%; OR=2.18, p=0.10). Patients with QT prolongation had slightly higher inpatient mortality (10.2% vs. 8.2%; OR=1.63, p=0.29).

Conclusions: This study demonstrated that amongst first and second-generation antipsychotics, cumulative doses of five commonly used agents did not significantly prolong QT. However, QT prolongation did have a tendency towards increased cardiac events and higher inpatient mortality. Larger studies are needed to understand the association between antipsychotics and adverse events.