The potential pro-cognitive effects with intravenous subanesthetic ketamine in adults with treatment-resistant major depressive or bipolar disorders and suicidality

Zhou, Yanling; Wang, Chengyu; Lan, Xiaofeng; Zheng, Wei; Li, Hanqiu; Chao, Ziyuan; Wu, Kai; McIntyre, Roger S.; Ning, Yuping

doi:10.1016/j.jpsychires.2021.10.037

Cited by 13 publications

(6 citation statements)

References 51 publications

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“…Furthermore, McIntyre et al showed a significant reduction in depressive symptomatology after four ketamine infusions in TRD individuals (defined as an insufficient response to two drugs), either unipolar or bipolar, who were measured with a decrease in Quick Inventory for Depression Symptomatology-Self Report-16 (QUIDS-SR16; [ 98 ]), Generalized Anxiety Disorder-7 Scale (GAD-7), and SDS [ 68 , 69 ]. Moreover, a positive effect on anhedonia [ 75 ]; anxiety, overall psychosocial function, and suicidal ideation [ 68 ]; cognitive domains such as processing speed and verbal learning [ 77 ] as well as a moderating effect of total functional disability; and the subdomains social life and family life/home responsibilities [ 69 ] were found. No serious side effects and no exclusions because of side effects were observed, but the following symptoms were found during and after treatment: dizziness, drowsiness, confusion, depersonalization, derealization, blurred vision, double vision, nausea, and headache [ 68 ].…”

Section: Resultsmentioning

confidence: 99%

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

et al. 2023

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The persistence of depressive morbidity is frequent in bipolar disorder, and the pharmacological management of this symptomatology often lacks effectiveness. This systematic review aimed to summarize the results of the naturalistic observational studies on the pharmacological treatment of bipolar depression published through April 2022. The certainty of evidence was evaluated according to the GRADE approach. In sum, 16 studies on anticonvulsants, 20 on atypical antipsychotics, 2 on lithium, 28 on antidepressants, and 9 on other compounds were found. Lamotrigine, quetiapine, aripiprazole, and ketamine were the most investigated compounds. Overall, the results support the recommendations regarding the effectiveness of lamotrigine and quetiapine. In contrast to the current recommendations, aripiprazole was shown to be effective and generally well tolerated. Additionally, SSRIs were shown to be effective, but, since they were associated with a possibly higher switch risk, they should be used as an adjunctive therapy to mood stabilizers. Lithium was only studied in two trials but was shown to be effective, although the serum concentrations levels were not associated with clinical response. Finally, ketamine showed divergent response rates with a low certainty of evidence and, so far, unclear long-term effects. Heterogeneity in diagnosis, sample sizes, study designs, reporting of bias, and side effects limited the possibility of a head-to-head comparison.

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Section: Resultsmentioning

confidence: 99%

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

et al. 2023

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“…2 The intravenous administration seems to bring a rapid amelioration (ie, within 24 hours after infusion) of specific cognitive symptoms, with beneficial effects enduring for the following week 2 that are potentially independent from mood improvement in adults with TRD and suicidality. 19 Interestingly, a recent review reported that clinical trials on therapeutic esketamine found that cognition generally remains stable or improves over time. 20 Thus, it could be argued that there is a different effect on cognition depending on the dosage 6 and the time of assessment, with an acute impact and selective dysfunctions immediately after administration, but with no relevant impairment if considering the global effect of the compounds.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, some evidence points toward favorable effects of ketamine on certain cognitive domains in adults with MDD or bipolar depression, 3 and to comparable procognitive properties and safety profile of both drugs when given intravenously in patients with TRD 2 . The intravenous administration seems to bring a rapid amelioration (ie, within 24 hours after infusion) of specific cognitive symptoms, with beneficial effects enduring for the following week 2 that are potentially independent from mood improvement in adults with TRD and suicidality 19 . Interestingly, a recent review reported that clinical trials on therapeutic esketamine found that cognition generally remains stable or improves over time 20 …”

Section: Discussionmentioning

confidence: 99%

Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series

Pepe

Bartolucci

Marcelli

et al. 2023

Journal of Psychiatric Practice

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Background: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine. Methods: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI). Findings: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores. Conclusions: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted.

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“…Furthermore, ketamine metabolites (rac)-dehydronorketamine and (2S,6S)-hydroxynorketamine decrease intracellular D-serine concentrations in a concentration dependent manner in PC-12 cells ( Singh et al, 2016 ). Previous study has found potential pro-cognitive effects with intravenous subanesthetic ketamine in BD patients ( Zhou et al, 2021 ). Based on these findings, we suggest that gut microbiota may influence synaptic D-serine availability and thus modulate cognitive function in BD patients.…”

Section: The Role Of Gastrointestinal Hormones and Neurotransmitters ...mentioning

confidence: 94%

Gut Microbial Dysbiosis and Cognitive Impairment in Bipolar Disorder: Current Evidence

et al. 2022

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Recent studies have reported that the gut microbiota influences mood and cognitive function through the gut-brain axis, which is involved in the pathophysiology of neurocognitive and mental disorders, including Parkinson’s disease, Alzheimer’s disease, and schizophrenia. These disorders have similar pathophysiology to that of cognitive dysfunction in bipolar disorder (BD), including neuroinflammation and dysregulation of various neurotransmitters (i.e., serotonin and dopamine). There is also emerging evidence of alterations in the gut microbial composition of patients with BD, suggesting that gut microbial dysbiosis contributes to disease progression and cognitive impairment in BD. Therefore, microbiota-centered treatment might be an effective adjuvant therapy for BD-related cognitive impairment. Given that studies focusing on connections between the gut microbiota and BD-related cognitive impairment are lagging behind those on other neurocognitive disorders, this review sought to explore the potential mechanisms of how gut microbial dysbiosis affects cognitive function in BD and identify potential microbiota-centered treatment.

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The potential pro-cognitive effects with intravenous subanesthetic ketamine in adults with treatment-resistant major depressive or bipolar disorders and suicidality

Cited by 13 publications

References 51 publications

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

Pharmacological Treatment of Bipolar Depression: A Review of Observational Studies

Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series

Gut Microbial Dysbiosis and Cognitive Impairment in Bipolar Disorder: Current Evidence

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