QTc Prolongation and Torsades de Pointes in an Elderly Woman Taking Fluoxetine

Transient unexplained loss of conscience in Ms. A led to her admission. Routine physical and laboratory examinations revealed no abnormalities (e.g., ischemia, electrolyte disturbances) besides a left bundle branch block and a prolonged QTc interval (478 msec, corrected for QRS interval widening because of the left bundle branch block; reference <450 msec). Her medications at admission were acetylsalicylic acid, 30 mg/day, and fluoxetine, 20 mg/day (serum levels at admission: fluoxetine, 204 μg/liter; norfluoxetine, 138 μg/liter); fluoxetine had been started 6 months earlier. During the night, continuous ECG recordings revealed recurrent short episodes of torsades de pointes. Multiple syncopal episodes occurred before admission, each time resolving spontaneously, which had never been observed before the initiation of fluoxetine.

Ms. A started having symptoms after the initiation of fluoxetine treatment and the documented pause-dependent polymorphic ventricular tachycardia characteristic of drug-induced QTc prolongation (1), which render fluoxetine use the most likely cause. Therefore, fluoxetine was discontinued. ECG recordings 2 and 8 months after fluoxetine discontinuation were normal apart from the left bundle branch block (QTc interval, 421 msec and 408 msec, respectively, corrected for the widening of the QRS interval). No further episodes of syncope or tachyarrhythmias were seen.