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Hydrocortisone in the emergency department: a prospective, double-blind, randomized, controlled posttraumatic stress disorder study. Hydrocortisone during golden hours

Published online by Cambridge University Press:  09 June 2022

Lior Carmi Open the ORCID record for Lior Carmi [Opens in a new window] ,
Joseph Zohar ,
Tal Weissman ,
Alzbeta Juven-Wetzler ,
Linda Bierer ,
Rachel Yehuda  and
Hagit Cohen
Lior Carmi
Affiliation:
Post Trauma Center, Chaim Sheba Medical Center, Ramat Gan, Israel The Data Science Institution, The Inter Disciplinary Center, Herzliya, Israel
Joseph Zohar*
Affiliation:
Post Trauma Center, Chaim Sheba Medical Center, Ramat Gan, Israel
Tal Weissman
Affiliation:
Post Trauma Center, Chaim Sheba Medical Center, Ramat Gan, Israel
Alzbeta Juven-Wetzler
Affiliation:
The Psychiatry Department, Chaim Sheba Medical Center, Tel Hashomer, Israel
Linda Bierer
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Rachel Yehuda
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA PTSD Clinical Research Program & Laboratory of Clinical Neuroendocrinology and Neurochemistry, James J. Peters Veterans Affairs Medical Center, New York, NY, USA
Hagit Cohen
Affiliation:
Anxiety and Stress Research Unit, Ben-Gurion University of the Negev, Beer Sheva, Israel
*
*Author for correspondence: Joseph Zohar, Email: Joseph.Zohar@sheba.health.gov.il
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Abstract

Objectives

A blunted response of the hypothalamic-pituitary-adrenal axis immediately after exposure to traumatic events has been proposed as a risk factor for posttraumatic stress disorder (PTSD). Accordingly, administration of hydrocortisone in the aftermath of a traumatic event is indicated. This study consisted of a randomized, placebo-controlled, double-blind trial investigating whether a single intravenous dose of hydrocortisone administered within 6 hours after exposure to trauma would reduce the incidence of PTSD at the 13-month follow-up.

Methods

A total of 118 consented patients with acute stress symptoms were administered a single intravenous bolus of hydrocortisone/placebo within 6 hours of the traumatic event. Blood samples were taken before hydrocortisone administration.

Results

At 13 months, the hydrocortisone group did not differ from the placebo group regarding PTSD prevalence or symptom severity. However, a significant interaction between time of the trauma (ie, night, when cortisol’s level is low) and treatment was found. Specifically, a lower prevalence of PTSD was found at the 13-month follow-up in the hydrocortisone night group.

Conclusions

Administration of hydrocortisone within 6 hours of the traumatic event was not effective in preventing PTSD compared to placebo. However, nocturnal administration (when cortisol levels are low) may suggest a new venue for research.

Keywords

Posttraumatic stress disorderhydrocortisonegolden hourshypothalamic-pituitary-adrenal axiscortisol
Type
Original Research
Information
CNS Spectrums , Volume 28 , Issue 4 , August 2023 , pp. 457 - 463
Copyright
© The Author(s), 2022. Published by Cambridge University Press

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References

Yehuda, R. Post-traumatic stress disorder . N Engl J Med. 2002;346:7.CrossRefGoogle ScholarPubMed
McFarlane, AC, Barton, CA, Yehuda, R, Wittert, G. Cortisol response to acute trauma and risk of posttraumatic stress disorder. Psychoneuroendocrinology. 2011;36(5):720–727.CrossRefGoogle Scholar
Galatzer-Levy, IR, Ma, S, Statnikov, A, Yehuda, R, Shalev, AY. Utilization of machine learning for prediction of post-traumatic stress: a re-examination of cortisol in the prediction and pathways to non-remitting PTSD. Transl Psychiatry. 2017;7(3):e1070.CrossRefGoogle Scholar
Yehuda, R, LeDoux, J. Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron. 2007;56(1):19–32. doi:10.1016/j.neuron.2007.09.006.CrossRefGoogle Scholar
Delahanty, DL, Raimonde, AJ, Spoonster, E. Initial posttraumatic urinary cortisol levels predict subsequent PTSD symptoms in motor vehicle accident victims. Biol Psychiatry. 2000;48(9):940–947.CrossRefGoogle Scholar
Yehuda, R, Bierer, LM, Schmeidler, J, Aferiat, DH, Breslau, I, Dolan, S. Low cortisol and risk for PTSD in adult offspring of holocaust survivors. Am J Psychiatry. 2000;157(8):1252–1259. doi:10.1176/appi.ajp.157.8.1252.CrossRefGoogle Scholar
Resnick, HS, Yehuda, R, Pitman, RK, Foy, DW. Effect of previous trauma on acute plasma cortisol level following rape. Am J Psychiatry. 1995;152(11):1675–1677. doi:10.1176/ajp.152.11.1675.Google Scholar
Cohen, H, Zohar, J, Gidron, Y, et al. Blunted HPA axis response to stress influences susceptibility to posttraumatic stress response in rats. Biol Psychiatry. 2006;59(12):1208–1218. doi:10.1016/j.biopsych.2005.12.003.CrossRefGoogle Scholar
Jeong, KH, Jacobson, L, Pacak, K, Widmaier, EP, Goldstein, DS, Majzoub, JA. Impaired basal and restraint-induced epinephrine secretion in corticotropin-releasing hormone-deficient mice. Endocrinology. 2000;141(3):1142–1150. doi:10.1210/endo.141.3.7370.CrossRefGoogle Scholar
Pacak, K, Palkovits, M, Kopin, IJ, Goldstein, DS. Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympathoadrenal activity: in vivo microdialysis studies. Front Neuroendocrinol. 1995;16(2):89–150. doi:10.1006/frne.1995.1004.CrossRefGoogle Scholar
Cahill, L, Prins, B, Weber, M, McGaugh, JL. Beta-adrenergic activation and memory for emotional events. Nature. 1994;371(6499):702–704. doi:10.1038/371702a0.CrossRefGoogle Scholar
Cohen, H, Matar, MA, Buskila, D, Kaplan, Z, Zohar, J. Early post-stressor intervention with high-dose corticosterone attenuates posttraumatic stress response in an animal model of posttraumatic stress disorder. Biol Psychiatry. 2008;64(8):708–717.CrossRefGoogle Scholar
Zohar, J, Yahalom, H, Kozlovsky, N, et al. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies. Eur Neuropsychopharmacol. 2011;21(11):796–809.CrossRefGoogle Scholar
Carmi, L, Fostick, L, Burshtein, S, Cwikel-Hamzany, S, Zohar, J. PTSD treatment in light of DSM-5 and the “golden hours” concept. CNS Spectr. 2016;21(4):279–282.CrossRefGoogle Scholar
Vermetten, E, Zhohar, J, Krugers, HJ. Pharmacotherapy in the aftermath of trauma; opportunities in the “golden hours”. Curr Psychiatry Rep. 2014;16(7):455.CrossRefGoogle Scholar
Pitman, RK, Delahanty, DL. Conceptually driven pharmacologic approaches to acute trauma. CNS Spectr. 2005;10(2):99–106. doi:10.1017/s109285290001943x.CrossRefGoogle Scholar
Zohar, J, Fostick, L, Juven-Wetzler, A, et al. Secondary prevention of chronic PTSD by early and short-term administration of escitalopram: a prospective randomized, placebo-controlled, double-blind trial. J Clin Psychiatry. 2018;79(2):16m10730.CrossRefGoogle Scholar
Schultebraucks, K, Shalev, AY, Michopoulos, V, et al. A validated predictive algorithm of post-traumatic stress course following emergency department admission after a traumatic stressor. Nat Med. 2020;26(7):1084–1088. doi:10.1038/s41591-020-0951-z.CrossRefGoogle Scholar
Blake, DD, Weathers, FW, Nagy, LM, et al. The development of a clinician-administered PTSD scale. J Trauma Stress. 1995;8(1):75–90. doi:10.1007/bf02105408.CrossRefGoogle Scholar
Weathers, FW, Keane, TM, Davidson, JR. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety. 2001;13(3):132–156. doi:10.1002/da.1029.CrossRefGoogle Scholar
Kothgassner, OD, Pellegrini, M, Goreis, A, et al. Hydrocortisone administration for reducing post-traumatic stress symptoms: a systematic review and meta-analysis. Psychoneuroendocrinology. 2021;126:105168.CrossRefGoogle Scholar
Cohen, S, Vainer, E, Matar, MA, et al. Diurnal fluctuations in HPA and neuropeptide Y-ergic systems underlie differences in vulnerability to traumatic stress responses at different zeitgeber times. Neuropsychopharmacology. 2015;40(3):774–790. doi:10.1038/npp.2014.257.CrossRefGoogle Scholar
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