To the Editor: Ziprasidone, an atypical antipsychotic, has a unique receptor and side effect profile. It has a high ratio of serotonin 5-HT_2A to dopamine D₂ receptor affinity, moderate α₁ and histamine H₁ affinity, and low α₂ and muscarinic M₁ affinity and inhibits 5-HT and norepinephrine reuptake (1). While not associated with weight gain, it can prolong the QTc interval (2). While uncommon, prolongation of the QTc interval can cause torsade de pointes, a potentially fatal arrhythmia (2). I know of only one report in the literature of a ziprasidone overdose: ingestion of 3120 mg with minimal side effects (3). The current report details a ziprasidone overdose with a disparate clinical course.

To my knowledge, this is the second reported case of ziprasidone overdose in the literature. As in the previous case (3), only minimal QTc change was noted. In addition, this patient experienced borderline intraventricular conduction delay, delirium, hemodynamic instability, diarrhea, and urinary retention. It is difficult to know to what extent the ziprasidone overdose was related to her clinical course. She sought medical help quickly, perhaps influencing the amount of ziprasidone that was absorbed. Multiple medical conditions were present that could have influenced her clinical course. These included her altered physical and mental status, concomitant medication use, obesity, diabetes, and hypercholesterolemia.

These data support the cardiac safety of ziprasidone, even in the face of substantial overdose. While there were multiple health and drug reasons that might have contributed to—or caused—the patient’s clinical course, the amount of ziprasidone ingested was significant. The data suggest that patients who take an overdose of ziprasidone should be carefully monitored for ECG changes as well as delirium, hemodynamic instability, and anticholinergic side effects.