title: Impact of escitalopram on vagally mediated cardiovascular function in healthy participants: implications for understanding differential age-related, treatment emergent effects.
abstract: BACKGROUND
  Black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide. While underlying mechanisms for age-related treatment effects remain unclear, vagally mediated cardiovascular function may play a key role. Decreased heart rate (HR) and an increase in its variability (HRV) improve one's capacity to adapt to environmental stress and attenuate risk for suicide.
  
  
  OBJECTIVE
  Using a double blind, randomized, placebo-controlled, crossover, experimental study, we examine whether a single dose of escitalopram (20 mg) attenuates cardiovascular responses to stress under experimental conditions and determine whether age moderates these effects.
  
  
  METHODS
  Forty-four healthy females received a single dose of escitalopram (20 mg) and placebo treatment separated by a 1-week interval (>5 half-lives). HR and high frequency HRV (HF HRV normalized units; 0.15-0.40 Hz) were measured during resting state and stress.
  
  
  RESULTS
  While escitalopram attenuated the increase in HR and increased HF HRV, these moderate to large effects were only significant in participants over 25 years of age. No beneficial cardiovascular effects of escitalopram were observed in those under the age of 25.
  
  
  CONCLUSIONS
  Maturational differences in the development of the prefrontal cortex--a critical region in the central network of autonomic control--may underpin these differential findings. This study provides a theoretical framework on which future research on treatment-emergent suicidality in clinical populations could be based.
authors: SCAN Research and Teaching Unit, School of Psychology, University of Sydney, Darlington, NSW, 2006, Australia, andrew.kemp@sydney.edu.au.
authors: Andrew H
authors: AH
authors: Kemp
authors: Tim
authors: T
authors: Outhred
authors: Sasha
authors: S
authors: Saunders
authors: Andre R
authors: AR
authors: Brunoni
authors: Pradeep J
authors: PJ
authors: Nathan
authors: Gin S
authors: GS
authors: Malhi
mesh_terms: D000328:Adult; D000375:Aging / Q000187:drug effects* / Q000502:physiology; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D012146:Rest; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram