Audrey Evers

All Publications

• A randomized pilot study of the prophylactic effect of ketamine on laboratory-induced stress in healthy adults NEUROBIOLOGY OF STRESS Costi, S., Evers, A., Jha, M. K., Klein, M., Overbey, J. R., Goosens, K. A., Burgess, J., Alvarez, K., Feder, A., Charney, D. S., Murrough, J. W. 2023; 22: 100505

  Abstract

  Stress exposure is a key risk factor for the development of major depressive disorder and posttraumatic stress disorder. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced disorders. The administration of ketamine one week prior to an acute stressor prevents the development of stress-induced depressive-like behavior in rodents. This study aimed to test if the prophylactic effect of ketamine against stress also applies to humans.We conducted a double-blind, placebo-controlled study wherein 24 healthy subjects (n = 11 males) were randomized to receive either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) intravenously one week prior to an acute stress [Trier Social Stress Test (TSST)]. The primary endpoint was the anxious-composed subscale of the Profile of Mood States Bipolar Scale (POMS-Bi) administered immediately after the TSST. Salivary and plasma cortisol and salivary alpha amylase were also measured at 15-min intervals for 60 min following the stressor, as proxies of hypothalamic pituitary adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axis activity, respectively.Compared to the midazolam group (n = 12), the ketamine group (n = 12) showed a moderate to large (Cohen's d = 0.7) reduction in levels of anxiety immediately following stress, although this was not significant (p = 0.06). There was no effect of group on change in salivary cortisol or salivary alpha amylase following stress. We conducted a secondary analysis excluding one participant who did not show an expected correlation between plasma and salivary cortisol (n = 23, ketamine n = 11). In this subgroup, we observed a significant reduction in the level of salivary alpha amylase in the ketamine group compared to midazolam (Cohen's d = 0.7, p = 0.03). No formal adjustment for multiple testing was made as this is a pilot study and all secondary analyses are considered hypothesis-generating.Ketamine was associated with a numeric reduction in TSST-induced anxiety, equivalent to a medium-to-large effect size. However, this did not reach statistical significance . In a subset of subjects, ketamine appeared to blunt SAM reactivity following an acute stressor. Future studies with larger sample size are required to further investigate the pro-resilient effect of ketamine.

  View details for DOI 10.1016/j.ynstr.2022.100505

  View details for Web of Science ID 000920570500001

  View details for PubMedID 36620306

  View details for PubMedCentralID PMC9813787

• Ketamine as a prophylactic resilience-enhancing agent FRONTIERS IN PSYCHIATRY Evers, A. G., Murrough, J. W., Charney, D. S., Costi, S. 2022; 13: 833259

  Abstract

  Stress exposure is one of the greatest risk factors for psychiatric illnesses, including major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). Enhancing stress resilience could potentially protect against the development of stress-induced psychiatric disorders, yet no resilience-enhancing pharmaceuticals have been developed to date. This review serves to consider the existing evidence for a potential pro-resilience effect of ketamine in rodents as well as the preliminary evidence of ketamine as a prophylactic treatment for postpartum depression (PPD) in humans. Several animal studies have demonstrated that ketamine administered 1 week prior to a stressor (e.g., chronic social defeat and learned helplessness) may protect against depressive-like behavior. A similar protective effect has been demonstrated against PTSD-like behavior following Contextual Fear Conditioning (CFC). Recent work has sought to explore if the administration of ketamine prevented the development of postpartum depression (PPD) in humans. Researchers administered ketamine immediately following caesarian-section and found a significantly reduced prevalence of PPD in the ketamine-treated groups compared to the control groups. Utilizing ketamine as a resilience-enhancing treatment may have unique applications, including leading to a deeper understanding of the neurobiological mechanism underlying resilience. Future trials aiming to translate and replicate these findings with humans are warranted.

  View details for DOI 10.3389/fpsyt.2022.833259

  View details for Web of Science ID 000838967800001

  View details for PubMedID 35966469

  View details for PubMedCentralID PMC9365980

• Antidepressant effect of prolonged twice-weekly intranasal esketamine treatments after nonresponse to electroconvulsive therapy in a patient with treatment-resistant depression ANNALS OF CLINICAL PSYCHIATRY Evers, A., Klein, M., Aloysi, A., Murrough, J., Jha, M. K. 2022; 34 (1): 61-64

  View details for DOI 10.12788/acp.0055

  View details for Web of Science ID 000834882100012

  View details for PubMedID 35166666

• The Adaptation and Evaluation of a Pilot Mindfulness Intervention Promoting Mental Health in Student Athletes JOURNAL OF CLINICAL SPORT PSYCHOLOGY Evers, A. G., Somogie, J. A., Wong, I. L., Allen, J. D., Cuevas, A. G. 2021; 15 (3): 206-226

  View details for DOI 10.1123/jcsp.2019-0083

  View details for Web of Science ID 000719457400003