Ziprasidone Does Not Seem to Cause Arrhythmias, As Once Feared

September 26, 2011 · Posted in Current Treatments · Comment 


A comprehensive review of ziprasidone’s effect on the QTc interval, a measure of electrical activity in the heart, has been completed by John Kane of the Zucker Hillside Hospital in Glen Oaks, NY. He and his colleagues reviewed relevant data that had been published over the past decade. Ziprasidone can prolong the QTc interval, which theoretically puts a person at risk for cardiac arrhythmias. Kane and colleagues concluded that the effect of ziprasidone on the QTc interval is related to dose and to the patient’s baseline QTc interval.

The QTc prolongation appears to plateau at the higher end of the usual clinical dose range of ziprasidone. In their review, the researchers found no cases of a QTc interval greater than 480 milliseconds, which is thought to be the threshold for developing vulnerability to arrhythmias. Additionally, no deaths were attributed to ziprasidone in any of the studies reviewed.

Ziprasidone side effects differ in different mood states

Keming Gao from Case-Western Reserve University reviewed the adverse effects of ziprasidone monotherapy in the treatment of patients with bipolar depression, mania, or schizophrenia. Gao noted that akathisia (restless legs) and other extrapyramidal side effects (such as tremor or speech problems) during mania were more common among patients on ziprasidone than among those on placebo, and these effects were more often found in patients with mania than those with depression.

Editor’s note: The finding that these extrapyramidal side effects are more common during mania is interesting because it runs contrary to findings on another atypical antipsychotic, aripiprazole. Aripiprazole is a partial dopamine agonist, meaning it partially activates dopamine receptors, and bipolar depressed patients on aripiprazole experience more akathisia than patients taking aripiprazole for mania or schizophrenia do.

Ziprasidone fully blocks dopamine receptors, and this may explain why its effects on dopamine turnover may, in contrast to aripiprazole, convey greater risk for extrapyramidal side effects in mania than in depression. This is unusual since most side effects tend to be more prominent during the depressive phases than manic phases of the illness. The reasons for this reversal with ziprasidone deserve further investigation and clarification.