Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder

Davis, Margaret T.; DellaGiogia, Nicole; Maruff, Paul; Pietrzak, Robert H.; Esterlis, Irina

doi:10.1038/s41398-021-01327-5

Cited by 25 publications

(15 citation statements)

References 78 publications

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“…It is also relevant that ketamine, attracting attention as a rapidly acting antidepressant, may act primarily on the TRN ( Dawson et al, 2011 ; Pratt et al, 2017 ). Indeed, the cognitive impairment also observed with ketamine administration ( Davis et al, 2021 ) is also likely to involve an action on the TRN. It would be of interest to directly manipulate MT2 receptors in components of the TRN–MD–PFC/OFC network in order to determine their involvement in the aforementioned behaviours.…”

Section: Discussionmentioning

confidence: 99%

Mice lacking melatonin MT2 receptors exhibit attentional deficits, anxiety and enhanced social interaction

et al. 2021

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Background: Aside from regulating circadian rhythms, melatonin also affects cognitive processes, such as alertness, and modulates the brain circuitry underlying psychiatric diseases, such as depression, schizophrenia and bipolar disorder, via mechanisms that are not fully clear. In particular, while melatonin MT1 receptors are thought primarily to mediate the circadian effects of the hormone, the contribution of the MT2 receptor to melatonin actions remains enigmatic. Aims: To characterise the contribution of MT2 receptors to melatonin’s effects on cognition and anxiety/sociability. Methods: Mice with a genetic deletion of the MT2 receptor, encoded by the Mtnr1b gene, were compared with wild-type littermates for performance in a translational touchscreen version of the continuous performance task (CPT) to assess attentional processes and then monitored over 3 days in an ethological home-cage surveillance system. Results: Mtnr1b knockout (KO) mice were able to perform at relatively normal levels in the CPT. However, they showed consistent evidence of more liberal/risky responding strategies relative to control mice, with increases in hit rates and false alarm rates, which were maintained even when the cognitive demands of the task were increased. Assessment in the home-cage monitoring system revealed that female Mtnr1b KO mice have increased anxiety levels, whereas male Mtnr1b KO mice show increased sociability. Conclusions: The results confirm that the MT2 receptor plays a role in cognition and also modulates anxiety and social interactions. These data provide new insights into the functions of endogenous melatonin and will inform future drug development strategies focussed on the MT2 receptor.

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Section: Discussionmentioning

confidence: 99%

Mice lacking melatonin MT2 receptors exhibit attentional deficits, anxiety and enhanced social interaction

et al. 2021

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“…On the contrary, a study by Murrough et al involved the use of a randomized controlled trial to access the neurocognitive effects after infusion of 0.5 mg/kg ketamine amongst 65 depressed patients, and found a significant decrease in their condition with no cognitive impairment [ 47 ]. Likewise, a study by Davis et al, accessed the acute cognitive effects of ketamine with a single intravenous infusion and found no association with cognitive impairment or working memory performance [ 48 ]. Multiple studies show that minimal usage of ketamine at a controlled rate in accordance with the person’s tolerability induces no cognitive impairment [ 49 ].…”

Section: Recent Clinical Findingsmentioning

confidence: 99%

The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease

Shehata

Masood

Nemr

et al. 2022

Neurology International

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Depression is a leading cause of disability globally, with a prevalence of 3.8% among the whole population, 5% of the adult population, and 5.7% of the elderly population over 60 years of age. There is evidence that depression is linked to certain neurodegenerative diseases, one being Alzheimer’s disease (AD). The efficacy of conventional antidepressants to treat depression in AD is conflicting, especially regarding selective serotonin reuptake inhibitors (SSRIs). A recent systemic review and meta-analysis of 25 randomized controlled trials including fourteen antidepressant medications showed no high efficacy in treating AD patients’ symptoms. However, ketamine, a nonselective N-methyl-D-aspartate (NMDA) receptor antagonist, can mediate a wide range of pharmacological effects, including neuroprotection, anti-inflammatory and anticancer properties, multimodal analgesia, and treatment of depression, suicidal attempts, and status epilepticus. Esketamine, which is ketamine formulated as a nasal spray, was approved by the Federal Drug Administration (FDA) in March 2019 as an adjuvant drug to treat treatment-resistant depression. NMDA receptor antagonists treat AD through offsetting AD-related pathological stimulation of subtypes of glutamate receptors in the central nervous system. Recent clinical findings suggest that ketamine may provide neuroprotection and reduce neuropsychiatric symptoms associated with AD. In the present investigation, we evaluate the potential role of ketamine and its postulated mechanism in AD management.

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“…Hesitancy surrounding the use of ketamine in treatment primarily involves the potential for adverse effects. However, studies suggest these effects, if present at all, are typically mild and resolve relatively quickly [ 51 - 53 ]. On the evaluation of cognitive decline two hours post ketamine infusion, results demonstrated: decreased attention, executive function, and verbal memory, but sparing of working memory and a complete return to baseline performance within 24 hours [ 53 ].…”

Section: Reviewmentioning

confidence: 99%

“…However, studies suggest these effects, if present at all, are typically mild and resolve relatively quickly [ 51 - 53 ]. On the evaluation of cognitive decline two hours post ketamine infusion, results demonstrated: decreased attention, executive function, and verbal memory, but sparing of working memory and a complete return to baseline performance within 24 hours [ 53 ]. While short-term dissociative effects were reported in some participants immediately post administration, these effects may be more likely to occur with repeated infusions [ 50 - 52 ].…”

Section: Reviewmentioning

confidence: 99%

The Therapeutic Effects of Ketamine in Mental Health Disorders: A Narrative Review

Ramos¹,

Thornburg²,

Long³

et al. 2022

Cureus

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Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is commonly used as an anesthetic and analgesic but has recently shown promising research in treating certain psychiatric conditions such as depression, post-traumatic stress disorder (PTSD), suicidal ideation, and substance use disorder. Due to its euphoric, dissociative, and hallucinogenic properties, ketamine has been abused as a recreational drug, which has led to rigid regulation of medication. The COVID-19 pandemic has been an unprecedented challenge for the American population which was reflected in increased reports of problems regarding their mental health. Mood disorders have dramatically increased in the past two years. Approximately one in ten people stated that they had started or increased substance use because of the COVID-19 pandemic. Furthermore, rates of suicidal ideation have significantly increased when compared to pre-pandemic levels, with more than twice the number of adults surveyed in 2018 indicating suicidal thoughts “within the last 30 days” at the time they were surveyed. Moreover, many responders indicated they had symptoms of PTSD. The PubMed database was searched using the keyword “ketamine,” in conjunction with “depression,” “suicidal ideation,” “substance use disorder,” and “post-traumatic stress disorder.” The inclusion criteria encompassed articles from 2017 to 2022 published in the English language that addressed the relationship between ketamine and mental health disorders. With this sharp increase in the prevalence of psychiatric disorders and an increased public interest in mental health combined with the promise of the therapeutic value of ketamine for certain mental health conditions, including suicidal ideation, this narrative review sought to identify recently published studies that describe the therapeutic uses of ketamine for mental health. Results of this review indicate that ketamine’s therapeutic effects offer a potential alternative treatment for depression, suicidal ideation, substance use disorders, and PTSD.

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Acute cognitive effects of single-dose intravenous ketamine in major depressive and posttraumatic stress disorder

Cited by 25 publications

References 78 publications

Mice lacking melatonin MT2 receptors exhibit attentional deficits, anxiety and enhanced social interaction

Mice lacking melatonin MT2 receptors exhibit attentional deficits, anxiety and enhanced social interaction

The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease

The Therapeutic Effects of Ketamine in Mental Health Disorders: A Narrative Review

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