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'
βBlossom's Take
Introduction
Albott et al. studied repeated intravenous ketamine for veterans with comorbid chronic PTSD and treatment-resistant depression. The proof-of-concept study was motivated by earlier single-dose ketamine findings in PTSD and TRD, where responses tended to be rapid but short-lived.
Methods
This was an open-label, single-arm study at the Minneapolis VA. Adults with chronic PTSD and treatment-resistant major depression received six 0.5 mg/kg IV ketamine infusions over 12 days. PCL-5 and MADRS were assessed before and 24 hours after each infusion, with weekly follow-up for 8 weeks after the sixth infusion. CAPS-5, remission/response status, relapse, and acute tolerability measures were secondary outcomes.
Results
The N=15 complete-outcome sample showed large reductions from baseline/pretest to 24 hours after the sixth infusion: PCL-5 decreased by 33.27 points (95% CI 23.04 to 43.50, P < .0005), MADRS by 26.60 points (95% CI 22.98 to 30.22, P < .0005), and CAPS-5 by 18.93 points (95% CI 12.62 to 25.24, P < .0005). PTSD remission was 9/15 after the first infusion and 12/15 after the sixth; depression response was 3/15 after the first infusion and 14/15 after the sixth. At 14 days posttreatment, 12/15 remained in PTSD remission, 10/15 retained depression response, and 6/15 were in depression remission.
Discussion
The authors interpret the findings as preliminary evidence that repeated ketamine infusions may produce rapid improvement in both PTSD and depression symptoms in a clinically complex veteran sample. They emphasize the open-label design and small sample as major limitations and call for larger placebo-controlled trials. Safety findings were mainly transient dissociation and acute blood-pressure elevations, without sustained psychotic, manic, or PTSD symptom worsening.
Conclusion
Repeated subanesthetic ketamine infusions were associated with rapid and relatively durable improvement in comorbid PTSD and TRD symptoms in this open-label proof-of-concept study.
Study Details
- Study Typeindividual
- Populationhumans
- Characteristicsopen label
- Journal
- Compound
- Topics
- Author
- APA Citation
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)