Abstract
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.
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Acknowledgments
The authors would like to acknowledge the support of the following people throughout the project: Kristi Griffiths, Sasha Saunders, Kristy-Lee Feilds, Mimi Leith, Marijke Braeken, Julie Ji, Daniel Quintana, James Heathers, Caroline Fields, Jonathan Kreiger, Sara Shahrestani, Camilla Hanson, and Matthew Beauregard. This research was supported by an Australian Research Council Discovery project grant (DP0987332), a National Health and Medical Research Council (NHMRC) project grant (464863) and a NHMRC Career Development Award (571101) awarded to AHK. The authors AHK and TO are currently supported by an International Research Professorship from the Universidade de São Paulo and an Australian Postgraduate Award, respectively.
Conflict of interest
PJN is an employee at GlaxoSmithKline Pharmaceuticals and holds shares in the company. GSM has received research support from AstraZeneca, Eli Lilly, Organon, Pfizer, Servier, and Wyeth. He has been a speaker for AstraZeneca, Eli Lilly, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth. He has been a consultant for AstraZeneca, Eli Lilly, Janssen Cilag, Lundbeck, and Servier. No other authors declare no potential conflict of interest.
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Kemp, A.H., Outhred, T., Saunders, S. et al. Impact of escitalopram on vagally mediated cardiovascular function in healthy participants: implications for understanding differential age-related, treatment emergent effects. Psychopharmacology 231, 2281–2290 (2014). https://doi.org/10.1007/s00213-013-3374-4
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DOI: https://doi.org/10.1007/s00213-013-3374-4