The efficacy and safety of esketamine in the treatment of major depressive disorder with suicidal ideation: study protocol for a randomized controlled trial

Liu, Haiyan; Lan, Xiaofeng; Wang, Chengyu; Zhang, Fan; Fu, Ling; Li, Weicheng; Ye, Yanxiang; Hu, Zhibo; Chao, Ziyuan; Ning, Yuping; Zhou, Yanling

doi:10.1186/s12888-022-04388-y

Cited by 11 publications

(4 citation statements)

References 64 publications

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“…In 2019 the (S)-enantiomer of ketamine (esketamine) was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as an adjunctive treatment for treatment-resistant depression ( Jelen et al, 2021 ). In addition, in 2020, the US Food and Drug Administration approved new supplemental application for (S)-ketamine to treat depressed patients with acute suicidal ideation/behavior to provide fast symptomatic relief ( Liu et al, 2022 ). Thus, (S)-ketamine is the first officially approved and clinically used rapid-acting antidepressant.…”

Section: Introductionmentioning

confidence: 99%

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

Koncz

Papp

Pothorszki

et al. 2023

International Journal of Neuropsychopharmacology

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Background Racemic ketamine consists of two enantiomers, namely (R)ketamine and (S)ketamine, with distinguishable pharmacological properties. Both enantiomers have been reported to show rapid antidepressant effects in rodents. Currently, the (S)enantiomer has been approved for the treatment of major depression, while (R)ketamine failed to show antidepressant effect in recent clinical studies. Major depressive disorder is frequently characterized by disinhibition of rapid eye movement (REM) sleep and disruption of nonREM (NREM) sleep. Racemic ketamine and most conventional antidepressants affect these parameters. However, it remains largely unknown which enantiomer is responsible for these effects. Methods Here, we compared acute effects of the two ketamine enantiomers (15 mg/kg i.p.) on different sleepwake stages in freely moving, EEGequipped rats. We also evaluated the antidepressant-like activity of the enantiomers in a chronic restraint stress model of depression. Results (S)ketamine, but not (R)ketamine increased REM sleep latency and decreased REM sleep time at 2h and 3h, and increased EEG delta power during NREM sleep. In addition, only (S)-ketamine increased wakefulness and decreased NREM sleep in the first 2 hours. In the forced swimming test only (S)-ketamine decreased the immobility time of chronically stressed rats. Conclusion Effects of the two ketamine enantiomers on rat sleepwake architecture and behavior are markedly different when administered in the same dose. (S)ketamine remarkably affects sleepwake cycle and very likely sleeprelated neuroplasticity, which may be relevant for its antidepressant efficacy. Our results regarding (R)-ketamine’s lack of effect on vigilance and behavior are in line with the recent clinical studies.

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Section: Introductionmentioning

confidence: 99%

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

Koncz

Papp

Pothorszki

et al. 2023

International Journal of Neuropsychopharmacology

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“…In this study, the levels of NE and E were signi cantly lower at 24 hours and 1 week after delivery in Group E than in Group C, which also suggested that the maternal stress response was decreased in the tested group. The antidepressant mechanism may be the target of esketamine for monoaminergic nervous system, can affect the brain stem blue spot, and further affect the noradrenergic system, promote the transcription and expression of the gene, increase the synthesis of transporter, resulting in NE migration from plasma membrane to cytoplasm, decrease the concentration of serum NE and E [25]. Additionally, due to the sedative and analgesic effects of esketamine, the Ramsay sedation score was decreased at 5, 10, 20 and 30 minutes after administration of esketamine in this study, which might be one of the reasons for the reduced stress response in the tested group.…”

Section: Discussionmentioning

confidence: 99%

Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial

Ling

Zhu

Yan

et al. 2023

Preprint

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Background：The study was designed to investigate effects of single intravenous injection of esketamine on the incidence of postpartum depression (PPD) after labor analgesia and explore the potential mechanisms. Methods：A total of 120 women who underwent labor analgesia by epidural analgesia pump were enrolled and divided into two groups randomly. Esketamine at a dose of 0.2 mg/kg was intravenously injected after fetal disengagement in the test group and placebo was administered in the control group. The occurrence of PPD and side effects after delivery were recorded. Some indicators related to stress and inflammation were measured before labor analgesia and at 24 hours, 1 week, and 6 weeks after delivery in this study. Data were analyzed by independent t-test, repeated measures analysis of variance and Chi-square test in SPSS software (version 25.0). It was considered statistically significant since a p value less than 0.05. Results：The incidence of PPD was significantly decreased both for one week and six weeks after delivery by using of esketamine (3.4% vs 15.3%, p = 0.004 and 5.2% vs 18.6%, p = 0.006, respectively) . There were also significant differences between the stress and inflammation-related indicators in different time points in this study, while the side effects for 48 hours after delivery were similar between the two groups. Conclusions：Single intravenous injection of esketamine after delivery in participants underwent labor analgesia can decrease the occurrence of postpartum depression for one week and six weeks after delivery, while the side effects were not increased. The antidepressant effects of esketamine may be related to the reduction of stress response and inflammation.

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“…Due to the potential risk of addiction, ketamine has not been approved for use in clinical practice as antidepressant, but in 2019, the US FDA [29] approved esketamine, the s-enantiomer of ketamine, for the treatment of adults with treatmentresistant depression, i.e., patients who have not responded adequately to at least two different trials with antidepressants at adequate dose and duration. This innovative drug provides a rapid response, with reduction of depressive symptoms within 24 h, as opposed to weeks noted with conventional antidepressants [30,31].…”

Section: Key Pointsmentioning

confidence: 99%

New trends in personalized treatment of depression

Sampogna,

Toni,

Catapano

et al. 2023

Current Opinion in Psychiatry

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Purpose of review Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades “a trial and error” approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD. Recent findings In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions. Summary Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.

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The efficacy and safety of esketamine in the treatment of major depressive disorder with suicidal ideation: study protocol for a randomized controlled trial

Cited by 11 publications

References 64 publications

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats

Effect of Single Intravenous Injection of Esketamine on Postpartum Depression after Labor Analgesia and Potential Mechanisms: A Randomized, Double-blinded Controlled Trial

New trends in personalized treatment of depression

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