December 2007

High Doses of Venlafaxine
Higher doses of venlafaxine (Effexor and others) likely increase the chance of antidepressant response, but also increase the risk of side effects.

SSRIs and Bleeding Risk in Patients with Hepatitis C
The risk of selective serotonin reuptake inhibitors causing bleeding in patients with hepatitis C is modest.

Bupropion versus SSRIs for Anxiety in MDD
According to Papakostas and colleagues, bupropion (Wellbutrin and others) appears to work as well as selective serotonin reuptake inhibitors to treat anxiety in patients with major depressive disorder.

Torsades de Pointes with Haloperidol
Intravenous administration of haloperidol (Haldol and others), especially at high doses, can cause QT prolongation and torsades de pointes.

In Brief
Ziprasidone for borderline personality disorder: A negative trial; Adjunctive medications for weight loss in patients with schizophrenia or bipolar disorder

High-Dose Ziprasidone
Patients with treatment-resistant psychosis may benefit from higher-than-recommended doses of ziprasidone (Geodon).

Baby Steps
Our clinical knowledge in psychiatry has increased over the past year, but scientific understanding and intervention technology still leaves much to be desired.

Index, Volume 30, 2007

Torsades de Pointes with Haloperidol

December 2007

A warning issued by the U.S. Food and Drug Administration (FDA) on September 17, 2007, caught the attention of the lay press.1 The FDA cautioned that haloperidol (Haldol and others), especially when administered intravenously or at higher-than-recommended doses, can prolong the cardiac QT interval and place patients at risk for torsades de pointes, a potentially lethal ventricular arrhythmia.

Haloperidol is available in parenteral form, but it is approved by the FDA only for intramuscular (IM), not intravenous (IV), administration. At least 28 cases of QT prolongation and torsades de pointes—some fatal—have been associated with IV haloperidol. The danger appears to increase with higher doses.

As the QT interval lengthens, the risk of life-threatening arrhythmias increases. Some patients are genetically prone to QT prolongation. Other factors that can prolong the QT interval are hyperkalemia, hypomagnesemia, hyperthyroidism, structural cardiac anomalies, and some medications. Antipsychotics that can increase the QT interval include thioridazine (Mellaril), pimozide (Orap), and ziprasidone (Geodon).

Over the past several decades, off-label use of IV haloperidol has become common in many hospitals. If a patient's agitation appears to warrant IV haloperidol, the rationale should be clearly documented, alternatives weighed, informed consent (usually via proxy) documented, and the electrocardiogram monitored.

We thank Dr. Chittaranjan Andrade, whose article in his newsletter, Synergy Times, inspired this piece.

1Information for Healthcare Professionals. Haloperidol (marketed as Haldol, Haldol Decanoate and Haldol Lactate). U.S. Food and Drug Administration website. Available at Accessed on October 10, 2007.