Antipsychotics and Arrhythmias
Abstract & Commentary
Synopsis: Antipsychotic medications may prolong the QT interval, which, in turn, may result in arrhythmias. These data suggest that some of the newer agents, specifically olanzapine (Zyprexa), are less likely to produce this effect in an animal model.
Source: Drici M-D, et al. Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. J Clin Psychopharmacol 1998;18:477-481.
The fact that some antipsychotic medications prolong the QT interval has been known for quite some time, but is now the source of increased study because of the relatively recent development of the far superior "atypical antipsychotics." This study evaluated the effect of four atypical antipsychotics and haloperidol (Haldol) on the QT interval using a previously validated feline heart model. QT prolongation is of potential clinical significance because excessive prolongation may be a predisposing factor for ventricular arrhythmias, such as torsade de pointes. The drugs—haloperidol, risperidone (Risperdal), sertindole (unmarketed), clozapine (Clozaril), and olanzapine (Zyprexa)—were infused in increasing concentration. Four artifactual free beats were selected for analysis for each drug and concentration. The QT interval was defined as the duration of the interval from the earliest depolarization wave in any lead to the end of the longest T wave in any of the three recorder leads. The data were pooled and analyzed using analysis of variance with Bonferroni-Dunn correction for multiple comparisons. Differences were considered significant at P = 0.05. The QT interval remained stable during the control condition. All five drugs increased the QT interval in a dose-dependent manner (P < 0.01), with haloperidol having the greatest effect, followed by risperidone.
Comment by Lauren B. Marangell, MD
Antipsychotic medications are used to treat a variety of syndromes, including agitation in the medical setting. Haloperidol is the antipsychotic drug most commonly used for this purpose, and is in general safe for short-term use. However, the newer antipsychotic medications have recently become first-line agents in the treatment of chronic psychotic disorders because of both improved efficacy and a greatly reduced side-effect burden. One of the important advantages of the newer "atypical" drugs is a lower incidence of dystonia, drug-induced Parkinsonism, and tardive dyskinesia. All of the drugs tested in the current study are atypical antipsychotics, with the exception of haloperidol. Risperdal and olanzapine are the clinically relevant comparators because sertindole was withdrawn prior to FDA approval and clozapine requires weekly monitoring for agranulocytosis, making it an impractical first-line agent. Preliminary data, mostly in the form of case reports, suggest that both risperidone and olanzapine may also be effective in the treatment of acute agitation. The current data indicate that olanzapine may be less likely to produce QT prolongation, which may be a factor in drug selection. Although cardiovascular events are considered to be rare with these drugs, it is prudent to evaluate the patient for other disorders or concomitant medications that may also affect the QT interval, especially hypokalemia.
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