Fluoxetine Suggested Cause of Long QT Syndrome
To the Editor: I read with interest the case report “Long QT Syndrome after a Motor Vehicle Incident” by Dr Crown and colleagues (February 2006). It raises several questions and comments. First, did their patient undergo genetic testing? Second, what consideration was given to the patient’s therapeutic use of fluoxetine in contributing to her condition, and was this medication discontinued? Based on the patient’s family history, her long QT syndrome appears to be congenital; however, fluoxetine, like other selective serotonin reuptake inhibitors (SSRIs), is known to cause prolongation of the corrected QT (QTc) interval and dysrhythmias with therapeutic use and in the overdose setting.1-4 Fluoxetine has a very long half-life (24-144 hours), and its pharmacologically active metabolite, norfluoxetine, has a half-life of 4 to 16 days.5 Therefore, the patient’s clinical condition, even several days after her motor vehicle incident, could have been related to fluoxetine.

On an academic note, sertraline and venlafaxine have been misclassified in Table 1 as tricyclic antidepressants. Both medications lack the classic “cyclic” chemical structure of the cyclic antidepressants. Rather, sertraline should be categorized as an SSRI, whereas venlafaxine should be classified as an atypical antidepressant that inhibits the reuptake of serotonin, dopamine, and norepinephrine.

Bryan S. Judge, MD
Grand Rapids Medical Education and Research Center
Michigan State University Program in Emergency Medicine
DeVos Children’s Hospital Regional Poison Center
Grand Rapids, Mich

1. Wilting I, Smals OM, Holwerda NJ, et al. QTc prolongation and torsades de pointes in an elderly woman taking fluoxetine. Am J Psychiatry. 2006;163:325.

2. Varriale P. Fluoxetine (Prozac) as a cause of QT prolongation. Arch Intern Med. 2001;161:612.

3. Appleby M, Mbewu A, Clarke B. Fluoxetine and ventricular torsade-is there a link? Int J Cardiol. 1995;49:178-180.

4. Hofman M, Liu JK. Conduction abnormality and ventricular tachyarrhythmia associated with fluoxetine overdose [abstract]. Vet Human Toxicol. 1994;36:371.

5. Stork CM. Serotonin reuptake inhibitors and atypical antidepressants. In: Goldfrank LG, Flomenbaum NE, Lewin NA, et al, eds. Goldfrank’s Toxicologic Emergencies. 7th ed. New York, NY: McGraw-Hill; 2002:865-874.

The Authors Reply: We appreciate Dr Judge’s input about our patient. To answer his questions, first the visit took place several years ago in Memphis, Tennessee. At that time, genetic counseling was not considered. The patient and her family were, however, eventually tested at the Sudden Arrhythmia Death Syndrome Foundation in Salt Lake City, Utah (www.sads.org/Genetics/genetictesting.htm), and we understand that the entire family was screened. Previously a research center, testing is now available commercially at this institute.

Second, it was our understanding that since the patient’s condition was well controlled with her pacemaker, there would be no compelling need to withdraw the patient from needed medication (ie, the fluoxetine).

Finally, we agree with the categorization of sertraline and venlafaxine; we should have titled the antidepressant category in our table “tricyclic antidepressants/ serotonin and norepinephrine reuptake inhibitors.” Because of space requirements, this was not done. We appreciate the clarification.

Loren A. Crown, MD
University of Tennessee
Covington, Tenn

Joseph J. Flagge, MD
Palmetto General Hospital
Hialeah, Fla

Dale Criner, MD
University of Tennessee
Jackson, Tenn