Article August 15, 2005

Schizophrenia, Antipsychotic Drugs, and Cardiovascular Disease

Alexander H. Glassman, MD

J Clin Psychiatry 2005;66(suppl 6):5-10

Article Abstract

Since the early 1980s, concern within the psychiatric community about whether antipsychotics areassociated with adverse cardiovascular events has grown. In the early 1990s, it became clear thatmesoridazine could cause torsades de pointes. More recently, concern has focused on the propensitythat some atypical antipsychotics have to prolong corrected QT (QTc) interval and whether this canresult in torsades de pointes and sudden death. Unfortunately, it has been difficult to accurately determinewhat role, if any, that atypical antipsychotics may have in contributing to these events, in partbecause of the rarity of the events and the lack of a sound, predictable marker. The best currentlyavailable markers, QTc interval and binding to the rapid delayed rectifier potassium current, are impreciseand cannot be relied upon to accurately predict torsades de pointes. Current evidence suggeststhat although atypical antipsychotics may increase the QTc interval, prolongation does not result intorsades de pointes, as observed with many conventional antipsychotics. Among the marketed atypicaldrugs, there was considerable concern about QTc prolongation with ziprasidone, but currentlyavailable data do not support the occurrence of torsades de pointes with any of the available atypicalantipsychotic drugs. However, identifying when QTc prolongation carries a risk of torsades de pointesremains a problem in developing new drugs. Psychiatric populations are at high risk for cardiovasculardisease, and emerging data indicate that some atypical antipsychotics may be associated withcardiovascular adverse events unrelated to QT prolongation. Thus, it is prudent for the psychiatriccommunity to be aware of psychiatric patients’ baseline medical condition and their risk status forcardiovascular disease.