Oral ketamine reduces the experience of stress in people with chronic suicidality
This open-label study (n=32) investigated the efficacy of weekly oral ketamine (35-210 mg/70 kg) for reducing stress in adults with chronic suicidality. Results indicate that ketamine produced a robust and clinically significant reduction in self-reported stress, which was sustained in a subgroup of participants during the four-week follow-up.
Authors
- Monique Jones
- Jim Lagopoulos
Published
Abstract
Background
Stress is prevalent in people experiencing suicidality and is a major contributor to the development of mental disorders. Evidence suggests ketamine shows the capacity to reverse stress-induced brain changes. Though stress and ketamine have been explored individually for suicidality, this study is the first to examine ketamine treatment for self-reported stress in adults with chronic suicidality, building on pre-clinical evidence of ketamine's capacity to normalize stress-induced responses and contributing to our understanding of oral ketamine in clinical populations.
Methods
Thirty-two adult participants (22-72 years; 17 female) with chronic suicidality completed 6 weeks of active treatment, receiving low (0.5 mg/kg - 3.0 mg/kg) doses of oral ketamine once per week, with a 4-week follow-up phase, to assess the effect of ketamine on their perceived stress. Stress was measured via self-report utilizing the Depression Anxiety Stress Scale-21(DASS-21) and analysed at pre-treatment (week 0), post-treatment (week 6) and at follow-up (week 10).
Results
Repeated measures ANOVA showed a significant reduction in stress (p<.001) post-treatment and Reliable Change Index calculations confirmed this to be clinically significant. Furthermore, those classified as 'prolonged responders' demonstrated a sustained reduction in stress at follow-up (i.e. after 4 weeks of nil ketamine).
Limitations
Small sample size, open-label design, expectancy, secondary analysis.
Conclusions
Ketamine showed the capacity to produce a robust and sustained improvement in stress symptoms, in people with chronic suicidality. Future larger, controlled studies examining treatment suitability in a range of stress-related disorders are warranted.
Research Summary of 'Oral ketamine reduces the experience of stress in people with chronic suicidality'
Introduction
Suicide is presented as a major public health problem, and the authors situate chronic stress as a key neurobiological risk factor that can produce structural and functional brain changes implicated in suicidal behaviour. They describe how chronic stress is associated with HPA-axis dysregulation, inflammatory changes, altered glutamate signalling, synaptic loss and reductions in NMDA and AMPA receptor expression. Prior research indicates that ketamine, an NMDA receptor antagonist, can reverse some stress-induced brain changes by increasing BDNF, enhancing AMPA function, promoting synaptogenesis and restoring neural connectivity. Clinical trials have demonstrated ketamine's antidepressant and anxiolytic effects, but treatment options specifically targeting suicidality and stress-related pathology remain limited. Dutton and colleagues set out to examine whether a six-week course of subanaesthetic oral ketamine would reduce self-reported stress in adults with chronic suicidality. The study tested the primary hypothesis that weekly oral ketamine over six weeks would produce a significant reduction in the Depression Anxiety Stress Scale (DASS-21) Stress subscale, and additionally assessed concurrent changes in the DASS Depression and Anxiety subscales and the relationship between stress change and suicidality responder status (as defined on the Beck Scale for Suicide Ideation). The trial aimed to extend earlier pilot work on oral ketamine in this population and to explore durability of effects at a four-week no-treatment follow-up.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Dutton, M., Can, A. T., Beaudequin, D., Jensen, E., Jones, M., Gallay, C. C., Schwenn, P. E., Scherman, J. K., Yang, C., Forsyth, G., Lagopoulos, J., & Hermens, D. F. (2022). Oral ketamine reduces the experience of stress in people with chronic suicidality. Journal of Affective Disorders, 300, 410-417. https://doi.org/10.1016/j.jad.2022.01.018
References (7)
Papers cited by this study that are also in Blossom
Abdallah, C. G., Sanacora, G., Duman, R. S. et al. · Chronic Stress (2018)
Albott, C. S., Lim, K. O., Forbes, M. K. et al. · Journal of Clinical Psychiatry (2018)
Can, A. T., Hermens, D. F., Dutton, M. et al. · Translational Psychiatry (2021)
Krystal, J. H., Abdallah, C. G., Averill, L. A. et al. · Current Psychiatry Reports (2017)
Abdallah, C. G., Charney, D. S., Duman, R. S. et al. · Neuron (2019)
Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F. et al. · Journal of Affective Disorders (2014)
Taylor, J. H., Landeros-Weisenberger, A., Coughlin, C. et al. · Neuropsychopharmacology (2017)
Cited By (1)
Papers in Blossom that reference this study
Lagopoulos, J. · International Journal of Neuropsychopharmacology (2023)
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