Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder
This open-label study (n=77) examines the sustained effects of six consecutive ketamine infusions (0.5mg/kg over 40 min) in Chinese patients with major depressive disorder (MDD). Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with MDD.
Authors
- Wei Zheng
- Yanling Zhou
Published
Abstract
Objective
Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder.
Methods
Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday-Wednesday-Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively.
Results
After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, p<0.001), and this decrease was maintained for the duration of the infusion period. The response to ketamine treatment was positively associated with no history of psychiatric hospitalization (odds ratio=3.56, p=0.009). Suicidal ideation rapidly decreased across the entire study sample, even among the nonresponder group. No significant differences were found regarding Brief Psychiatric Rating Scale and Clinician Administered Dissociative States Scale scores from the first infusion at baseline to four hours post-infusion.
Conclusion
Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.
Research Summary of 'Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder'
Introduction
Major depressive disorder (MDD) is a common, chronic and disabling condition for which many patients continue to experience residual symptoms, relapse and treatment resistance despite existing pharmacological and nonpharmacological therapies. Growing interest in glutamatergic mechanisms, particularly dysfunction of the N-methyl-D-aspartate (NMDA) receptor, has led to investigation of NMDA antagonists such as ketamine, which produce rapid but typically transient antidepressant effects when given as a single intravenous (IV) infusion (commonly 0.5 mg/kg over 40 minutes). Previous open-label and small-sample studies of repeated ketamine infusions have reported mixed results and have often enrolled only treatment-resistant samples, been small, or required washout of concomitant medications, limiting generalisability and applicability to real-world clinical settings and to Chinese patients in particular. Zheng and colleagues set out to examine whether a course of six consecutive subanesthetic IV ketamine infusions (0.5 mg/kg over 40 minutes, given Monday–Wednesday–Friday across 12 days) as an augmentation to ongoing antidepressant treatment would increase rates of response and remission compared with the typical single-dose ketamine effect, and to evaluate effects on suicidal ideation, anxiety and safety in Chinese adults with MDD. The investigators hypothesised that repeated infusions would produce higher response and remission rates than a single infusion and sought to describe clinical predictors and tolerability in this population.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- Authors
- APA Citation
Zheng, W., Zhou, Y., Liu, W., Wang, C., Zhan, Y., Li, H., Chen, L., Li, M. D., & Ning, Y. (2019). Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder. Journal of Psychopharmacology, 33(4), 494-501. https://doi.org/10.1177/0269881119827811
References (7)
Papers cited by this study that are also in Blossom
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Wilkinson, S. T., Ballard, E. D., Bloch, M. H. et al. · American Journal of Psychiatry (2017)
Zheng, W., Zhou, Y-L., Liu, W. et al. · Journal of Psychiatric Research (2018)
Cited By (6)
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Hietamies, T. M., Mcinnes, L. A., Klise, A. J. et al. · Journal of Affective Disorders (2023)
Wang, C., Lan, X-F., Zhou, Y. · Frontiers in Neuroscience (2023)
Zheng, W., Gu, L. M., Sun, C. H. et al. · Journal of Affective Disorders (2022)
Cubała, W. J., Szarmach, J., Galuszko-Wegielink, M. et al. · Medicine (2021)
Feeney, A., Hock, R. S., Freeman, M. P. et al. · European Neuropsychopharmacology (2021)
Conley, A. A., Norwood, A. E. Q., Hatvany, T. C. et al. · Psychopharmacology (2021)
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