Pharmacotherapeutic Determinants for QTc Interval Prolongation in Japanese Patients with Mood Disorder.

Introduction: An increased incidence of sudden death has been observed among patients treated with antidepressants. A prolonged QTc interval is a known prognostic factor for fatal arrhythmia, and several studies have shown that the use of antidepressants can cause a prolonged QTc interval. However, few studies, especially in Japan, have compared the effects of multiple drugs on QTc interval or examined dose relationships in a clinical setting. Methods: We compared the effects of antidepressants on QT interval, corrected to QTc by Bazett's formula, in 729 Japanese patients who were diagnosed with mood disorder. Results: Using stepwise multiple linear regression analysis, we found that the use of tricyclic antidepressants (P < 0.01) and concomitant use of antipsychotics (P < 0.05), as well as advanced age and being female (known factors for prolonged QTc interval; both P < 0.01), significantly prolonged the QTc interval. Analysis of individual antidepressants also revealed that the use of clomipramine (P < 0.01) and amitriptyline (P < 0.05) significantly prolonged the QTc interval. Conclusion: Our results reveal that tricyclic antidepressants, especially clomipramine and amitriptyline, confer a risk of prolonged QTc interval in a dose-dependent manner. The selective serotonin reuptake inhibitors investigated (fluvoxamine, paroxetine, sertraline) were not indicated as risk factors for QTc prolongation. [ABSTRACT FROM AUTHOR]