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Evaluation of the Effects of Duloxetine and Escitalopram on 24-Hour Heart Rate Variability: A Mechanistic Study Using Heart Rate Variability as a Pharmacodynamic Measure

Chappell, Jill C. PharmD*; Kovacs, Richard MD†‡; Haber, Harry MPH§; Wright, Ryan PhD*; Mitchell, Malcolm I. MD*; Detke, Michael MD†∥; Pangallo, Beth RN, MSM*

Journal of Clinical Psychopharmacology: April 2013 - Volume 33 - Issue 2 - p 236–239
doi: 10.1097/JCP.0b013e31828567b6
Brief Reports

A decrease in heart rate variability (HRV) can indicate increased sympathetic nervous system activity and possibly increased norepinephrine levels. In this randomized, placebo- and escitalopram (ESC)-controlled, subject-blind, 2-period, crossover study, 26 healthy subjects 50 to 65 years old received duloxetine (DLX) 60 mg once daily or ESC 20 mg once daily for 11 days, each in sequential study periods separated by a 10-day or more washout period. Continuous electrocardiogram recordings were obtained by Holter monitoring (baseline, day 9, and day 10 of treatment). Duloxetine and ESC did not produce any clinically significant effects on standard measures of HRV, which included SD of normal R-R intervals and the root mean square difference among successive R-R normal intervals index values, mean change in SD of normal R-R intervals, and frequency domain analysis. However, treatment with DLX was associated with significantly less change from baseline in total beats per 24 hours than ESC, which was an unexpected finding compared with previous observations in which vital signs were measured at a specific time point while awake. In conclusion, in healthy adults exposed to DLX or ESC, no clinically significant effects on HRV were observed.

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From *Eli Lilly and Company; †School of Medicine, Indiana University; ‡Krannert Institute of Cardiology, Indianapolis, IN; §i3 Statprobe, Ann Arbor, MI; and ∥MedAvante, Inc, Hamilton, NJ.

Received December 7, 2010; accepted after revision July 13, 2012.

This study was supported by Eli Lilly and Company.

Reprints: Jill C. Chappell, PharmD, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285 (e-mail:

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© 2013 by Lippincott Williams & Wilkins.