RATIONALE: 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. OBJECTIVES: 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.
RCT Entities:
RATIONALE: 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. OBJECTIVES: 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: Emily Karanges; Kong M Li; Craig Motbey; Paul D Callaghan; Andrew Katsifis; Iain S McGregor Journal: Int J Neuropsychopharmacol Date: 2011-02-18 Impact factor: 5.176
Authors: Zhibin Li; Harold Snieder; Shaoyong Su; Xiuhua Ding; Julian F Thayer; Frank A Treiber; Xiaoling Wang Journal: Int J Psychophysiol Date: 2009-03-10 Impact factor: 2.997
Authors: Agorastos Agorastos; Michael Kellner; Oliver Stiedl; Christoph Muhtz; Klaus Wiedemann; Cüneyt Demiralay Journal: Int J Neuropsychopharmacol Date: 2014-12-11 Impact factor: 5.176