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Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study.

ABSTRACT: Objective:The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known. Methods:Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday-Wednesday-Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational period. The assessment of neurocognitive function was conducted using the MATRICS Consensus Cognitive Battery at baseline, 13 and 26 days. Tasks were designed to test speed of processing, working memory, visual learning and verbal learning. Results:A significant improvement was found only in scores of speed of processing (F = 9.9, p = 0.001) after a 2-week observational period, which was accounted for by the improvement of depression symptoms. There were no significant changes over time in terms of working memory, visual learning and verbal learning. Pearson correlation analysis showed that the improvement of depression symptoms through six ketamine infusions was greater among TRBD patients with lower working memory at baseline (r = 0.54, p = 0.03). In multiple regression analysis, the significant correlation was still maintained (beta = 0.67, t = 2.2, p = 0.04). Conclusion:This preliminary study indicated that six ketamine infusions were not harmful but were slightly beneficial for speed of processing in TRBD. However, this change was mainly accounted for the improvement of depression symptoms over time. Lower baseline working memory appears to be associated with greater antidepressant response after completion of six ketamine infusions in patients with TRBD.

SUBMITTER: Zheng W

PROVIDER: S-EPMC7646297 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study.

Zheng Wei W Zhou Yan-Ling YL Wang Cheng-Yu CY Lan Xiao-Feng XF Zhang Bin B Yang Ming-Zhe MZ Nie Sha S Ning Yu-Ping YP

PeerJ 20201103

<h4>Objective</h4>The N-methyl-D-aspartate subtype glutamate receptor antagonist ketamine has rapid antidepressant and antisuicidal effects in treating treatment-resistant bipolar depression (TRBD). The neurocognitive effects of repeated ketamine infusions in TRBD are not known.<h4>Methods</h4>Six intravenous infusions of ketamine (0.5 mg/kg over 40 min) were administered on a Monday-Wednesday-Friday schedule during a 12-day period on 16 patients with TRBD followed by a 2-week observational peri ...[more]

PMID: 33194410

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Project description:BACKGROUND:Multiple lines of evidence support a role for the glutamatergic system in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, rapidly improves depressive symptoms in individuals with treatment-resistant depression. The neural mechanisms underlying this effect remain unknown. METHODS:In this preliminary study, 20 unmedicated participants with treatment-resistant MDD underwent positron emission tomography to measure regional cerebral glucose metabolism at baseline and following ketamine infusion (single dose of .5mg/kg intravenous over 40minutes). Metabolic data were compared between conditions using a combination of region-of-interest and voxelwise analyses, and differences were correlated with the associated antidepressant response. RESULTS:Whole-brain metabolism did not change significantly following ketamine. Regional metabolism decreased significantly under ketamine in the habenula, insula, and ventrolateral and dorsolateral prefrontal cortices of the right hemisphere. Metabolism increased postketamine in bilateral occipital, right sensorimotor, left parahippocampal, and left inferior parietal cortices. Improvement in depression ratings correlated directly with change in metabolism in right superior and middle temporal gyri. Conversely, clinical improvement correlated inversely with metabolic changes in right parahippocampal gyrus and temporoparietal cortex. CONCLUSIONS:Although preliminary, these results indicate that treatment-resistant MDD subjects showed decreased metabolism in the right habenula and the extended medial and orbital prefrontal networks in association with rapid antidepressant response to ketamine. Conversely, metabolism increased in sensory association cortices, conceivably related to the illusory phenomena sometimes experienced with ketamine. Further studies are needed to elucidate how these functional anatomical changes relate to the molecular mechanisms underlying ketamine's rapid antidepressant effects.

Dataset Information

Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study.

Publications

Neurocognitive effects of six ketamine infusions and the association with antidepressant effects in treatment-resistant bipolar depression: a preliminary study.

Similar Datasets

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