Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression
This is the first open-label study (2018) to assess the effects of repeated ketamine infusions in the treatment of comorbid PTSD and treatment-resistant depression (TRD) (n=15). Participants received six IV ketamine infusions (0.5 mg/kg) on a Monday-Wednesday-Friday schedule over a 12-day period. Ketamine significantly reduced measures of symptoms change for both disorders (MADRS & PTSD Checklist for DSM-V) and the remission rate for PTSD and TRD were 80% and 93.3%, respectively.
Authors
- Paulo Shiroma
Published
Abstract
Objective
The present study examined the efficacy, safety, and durability of repeated ketamine infusions for the treatment of comorbid posttraumatic stress disorder (PTSD) and treatment-resistant depression (TRD) in a sample of veterans.
Methods
Individuals with comorbid DSM-5-defined PTSD and DSM-IV-defined major depressive disorder (N = 15) received 6 intravenous ketamine infusions (0.5 mg/kg) on a Monday-Wednesday-Friday schedule over a 12-day period from May 2015 to June 2016. Data from outcome measures were collected before and 24 hours after each infusion and weekly for 8 weeks following the final infusion.
Results
Continuous measures of symptom change were significant for both disorders and were associated with large effect sizes (mean decrease in PTSD Checklist for DSM-5 score = 33.3 points [95% CI, 23.0-43.5 points], P < .0005, sample size-adjusted Cohen d [d‘ ²] = 2.17; mean decrease in Montgomery-Asberg Depression Rating Scale score = 26.6 points [95% CI, 23.0-30.2 points], P < .0005, d‘ ² = 4.64). The remission rate for PTSD was 80.0%, and the response rate for TRD was 93.3%. Participants in remission from PTSD after the infusion series (n = 12) had a median time to relapse of 41 days. Similarly, participants whose depression symptoms responded to the infusion series (n = 14) had a median time to relapse of 20 days. Repeated ketamine infusions were associated with transient increases in dissociative symptoms. No participant reported worsening of PTSD symptoms over the study duration.
Conclusion
This study, the first open-label study of repeated ketamine infusions in a comorbid population, found rapid and sustained improvement in PTSD and depression symptoms. This report suggests that repeated ketamine treatments are safe and may represent an efficacious treatment for individuals with comorbid PTSD and TRD.
Research Summary of 'Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression'
Introduction
Major depressive disorder is a leading cause of global disability and about one-third of patients fail to remit after multiple standard treatments, a condition termed treatment-resistant depression (TRD). Ketamine has emerged as a rapidly acting, novel treatment for TRD; prior trials have used intravenous racemic ketamine or intranasal S-ketamine (esketamine). Substantive phase III data exist for intranasal esketamine, but randomised controlled trials of repeated racemic ketamine have been few, small and heterogeneous in design. Choice of comparator (saline placebo versus an active psychoactive control such as midazolam) and route of administration (intravenous versus intramuscular, subcutaneous, oral or intranasal) both affect masking and measured effect sizes. Data on cumulative or longer-term safety with repeated dosing are also limited. Loo and colleagues set out to evaluate the efficacy, safety and durability of a 4-week course of repeated subcutaneous racemic ketamine in adults with TRD, using midazolam as an active comparator to improve blinding. The trial aimed to test whether repeated, adequately dosed subcutaneous ketamine would produce higher remission and response rates than midazolam while systematically assessing acute, between-session and short-term cumulative adverse effects.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Author
- APA Citation
Albott, C. S., Lim, K. O., Forbes, M. K., Erbes, C., Tye, S. J., Grabowski, J. G., Thuras, P., Batres-y-Carr, T. M., Wels, J., & Shiroma, P. R. (2018). Efficacy, Safety, and Durability of Repeated Ketamine Infusions for Comorbid Posttraumatic Stress Disorder and Treatment-Resistant Depression. The Journal of Clinical Psychiatry, 79(3). https://doi.org/10.4088/JCP.17m11634
References (5)
Papers cited by this study that are also in Blossom
Bahji, A., Vazquez, G. H., Zarate, C. A. · Journal of Affective Disorders (2021)
Ionescu, D. F., Bentley, K. H., Eikermann, M. et al. · Journal of Affective Disorders (2019)
Singh, J. B., Fedgchin, M., Daly, E. J. et al. · American Journal of Psychiatry (2016)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Short, B., Fong, J., Galvez, V. et al. · Lancet Psychiatry (2017)
Cited By (15)
Papers in Blossom that reference this study
Jones, J. L. · Frontiers in Psychiatry (2023)
Albott, C. S., Lim, K. O., Erbes, C. et al. · Journal of Affective Disorders (2022)
Dutton, M., Can, A. T., Beaudequin, D. et al. · Journal of Affective Disorders (2022)
Abdallah, C. G., Roache, J. D., Gueorguieva, R. et al. · Neuropsychopharmacology (2022)
Asim, M., Wang, B., Hao, B. et al. · Neurochemistry International (2021)
Conley, A. A., Norwood, A. E. Q., Hatvany, T. C. et al. · Psychopharmacology (2021)
Morena, M., Colucci, P., Mancini, G. F. et al. · Neurobiology of Learning and Memory (2021)
Nichols, D. E., Walter, H. · Pharmacopsychiatry (2020)
Varker, T., Watson, L., Gibson, K. et al. · Journal of Psychoactive Drugs (2020)
Shiroma, P. R., Thuras, P., Wels, J. et al. · Translational Psychiatry (2020)
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Sartori, S. B., Singewald, N. · Pharmacology and Therapeutics (2019)
Ross, C., Jain, R., Bonnett, C. J. et al. · American Academy of Clinical Psychiatrists (2019)
O'brien, B., Lijffijt, M., Wells, A. et al. · Pharmaceuticals (2019)
Martial, C., Cassol, H., Charland-Verville, V, Erowid, E. et al. · Consciousness and Cognition (2019)
Abdallah, C. G., Sanacora, G., Duman, R. S. et al. · Chronic Stress (2018)
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