| November 7, 2002
Schizophrenia Drugs Linked to Increased
Risk of Heart Attack
PA) - Patients with schizophrenia who take antipsychotic
drugs are more likely to have experienced cardiac arrest
or ventricular arrhythmia than non-schizophrenia patients,
according to researchers at the University of Pennsylvania
School of Medicine. While previous research has
linked several of these drugs to irregular electrocardiogram
results, the Penn researchers used billing data to uncover
a link between the drugs and cardiac arrest. Their findings
are presented in the November 9 issue of the British
The study's primary comparison was between thioridazine,
which has a marked effect on the electrocardiogram,
and haloperidol, which has less of an effect. "Overall,
the risk with thioridazine was no worse than that with
haloperidol. Thioridazine may, however, represent an
elevated risk at high doses," said Sean Hennessy,
PharmD, PhD, assistant professor in Penn's Department
of Biostatistics and Epidemiology. "To reduce cardiac
risk, thioridazine should be prescribed at the lowest
dose needed to obtain an optimal therapeutic effect."
Hennessy and his colleagues conducted a cohort study
of billing data collected between 1993 and 1996 from
three Medicaid programs. The researchers included patients
with more than one prescription for oral thioridazine
and haloperidol, as well as the antipsychotic drugs
risperidone and clozapine, plus at least two instances
of a schizophrenia diagnosis. They compared the records
of these patients with two control groups - one group
of glaucoma patients and one group of psoriasis patients
- since both patient types require periodic prescriptions
and are not associated with cardiovascular problems.
In all, they looked at data taken from over 120,000
"We compared the frequency of cardiac arrest and
ventricular arrhythmia associated with different antipsychotic
drugs versus the control groups," said Hennessy.
"Our findings clearly link patients with treated
schizophrenia to higher rates of cardiac arrest, ventricular
arrhythmia, and death." According to Hennessy,
the elevated risk could be a result of either the disease
or its treatment.
While haloperidol and thioridazine both presented a
similar overall risk in this study, the effect with
thioridazine seemed to be dose-related. "Therefore,
to minimize the risk of arrhythmia, it seems prudent
to suggest that physicians prescribe the lowest dose
of thioridazine possible," said Hennessy.
Separate data presented to FDA have suggested that thioridazine
may have a greater effect than haloperidol on the QT
interval as recorded on an electrocardiogram (ECG).
The QT interval is defined as the time between the Q
wave (when the heart's ventricles contract) and T wave
(when the ventricles relax again). While QT prolongation
is often used as a surrogate marker of a drug's cardiac
risk, the true relationship is unknown. This study helps
to clarify that relationship.
"If our findings are confirmed, they would support
the use of QT prolongation as a marker for a drug's
risk," said Hennessy, "There are still plenty
of questions to be asked. Is there a certain subset
of the population more at risk for developing a QT irregularity
with certain drugs? Is there a role for regular ECG
monitoring in individual patients? Obviously, we shouldn't
be keeping QT on the Q.T."
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