Despite empirical evidence bolstering the belief that newer
second-generation antipsychotic medications can increase patients' risk of
experiencing a potentially fatal cardiac arrhythmia, new clinical research has
found that these drugs are not associated with an increased rate of
hospitalization for ventricular arrhythmias or cardiac arrest.
The report in the April Archives of Internal Medicine describes a
case-control study of nursing-home residents in six U.S. states, using data
from the Centers for Medicare and Medicaid Services' Minimum Data Set.
Rosa Liperoti, M.D., M.P.H., a professor of gerontological sciences at
Catholic University of the Sacred Heart in Rome, teamed with colleagues at
Brown University School of Medicine to study Medicare claims data to estimate
the effect of first- and second-generation antipsychotic use on the risk of
hospitalization for cardiac rhythm disturbances. The work was funded by the
U.S. National Institute on Aging.
Liperoti and her colleagues examined claims data for the 18-month period
from July 4, 1998, to December 30, 1999, looking for nursing-home residents
who were admitted to a hospital for ventricular arrhythmias or cardiac arrest
during that time period. They identified 649 cases.
For the control group, which consisted of 2,962 subjects, the researchers
identified up to five patients living in the same nursing home in the same
period who were admitted to inpatient hospitalization and who were discharged
with a diagnosis of septicemia, gastrointestinal bleeding, or influenza with
no record of cardiac arrhythmia or arrest.
The researchers then identified for all subjects the most proximal
assessment of medication usage immediately prior to hospitalization, and from
those records identified all participants who were "exposed" to an
Patients exposed to antipsychotics were further divided into those exposed
to second-generation agents, those exposed to first-generation agents, and
those exposed to both. The two most commonly prescribed first-generation
medications were haloperidol and thioridazine, and the two most common
second-generation medications were risperidone and olanzapine.
Liperoti and her team found that those admitted for a cardiac arrhythmia or
arrest were more likely to be younger and to be male than were controls.
Patients in the cardiac-case group were more likely to have significant
functional impairment and cognitive deficits, but less likely to have cardiac
diseases than were controls. Overall, there was no difference in the
prevalence of antipsychotic use between cardiac cases and controls; however,
subjects with the cardiac disorders were more likely to use conventional
After controlling for potential confounding variables, such as age, sex,
race/ethnicity, body mass index, concurrent drug use, and comorbid conditions,
patients who were taking a conventional antipsychotic were 1.86 times more
likely than those taking no antipsychotic to be hospitalized for cardiac
arrhythmias or arrest. Patients taking second-generation antipsychotics,
however, showed a slight trend toward decreased risk of hospitalization for
cardiac arrhythmias or arrest compared with those with no antipsychotic use
(odds ratio 0.87); however, the difference was not statistically
When the researchers looked at patients' cardiac status, they found that
among residents receiving conventional antipsychotics, those with cardiac
disease were 3.27 times more likely to be admitted for an arrhythmia or arrest
than were controls with no cardiac disease.
Liperoti and her colleagues noted that "the daily doses in our study
were generally low (e.g., thioridazine daily dose mode was 50 mg) and were
within the recommended range for this population. Thus our findings may
indicate a particular sensitivity of the elderly population to the cardiotoxic
effect of conventional antipsychotics."
The team concluded that "physicians should use these drugs cautiously
among elderly patients" and that "therapeutic choice should be
based on a careful evaluation of the patient's individual needs and risk
profile, along with the beneficial and harmful effects of both classes of
An abstract of "Conventional and Atypical Antipsychotics and
the Risk of Hospitalization for Ventricular Arrhythmias and Cardiac
Arrest" is posted online at<http://archinte.ama-assn.org/cgi/content/abstract/165/6/696>.▪
Arch Intern Med2005165696