This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery.

In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk + Dex group (n = 86) and the Dex group a (n = 86). The primary outcome was the incidence of POD within 7 days after surgery and the overall Quality of Recovery−15 (QoR − 15) scores within 3 days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3+, CD4+, and CD8+ were detected from T0 to T5.

Compared with the Dex group, the incidence of POD in the Esk + Dex group was significantly lower at 7 days after surgery (14.6% vs 30.9%; P = 0.013). The QoR − 15 score was significantly increased 3 days after surgery (P < 0.01). Levels of IL-6 and CD8+ were significantly decreased, and IL − 10 levels were significantly increased at T1-T2 (P < 0.05). At T1-T4, NSE levels were significantly decreased, while CD3+ and CD4+/CD8+ values were significantly increased (P < 0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4+ value increased significantly (P < 0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48 hours after surgery (P < 0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened.

Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.

Postpartum depression (PPD), now referred to as perinatal depression, is a prevalent and debilitating mood disorder that reduces health-related quality of life (HRQoL) and psychosocial functioning. Esketamine, which is efficacious in adults with treatment-resistant depression and individuals with depression and suicidality, is also analgesic in pain management during childbirth labour. Herein, we investigate the efficacy of prophylactic esketamine in reducing the incidence of PPD.

We performed a systematic review (i.e., PubMed, Scopus, and Ovid databases; inception to January 22, 2024) of randomized controlled trials that investigated the use of esketamine for PPD. We delimited our search to studies that prespecified the prevention of PPD with esketamine as the primary outcome. A meta-analysis was performed on PPD incidence rates using a random effects model.

Our analysis consisted of seven studies that met our eligibility criteria. We found that esketamine was significantly associated with a decreased incidence of PPD diagnosis within one week of childbirth (OR = 0.30, 95% CI = [0.15, 0.60], p = 0.0047). We also observed that esketamine was significantly associated with a decreased incidence of PPD diagnosis between 4 to 6 weeks post-delivery (OR = 0.33, 95% CI = [0.18, 0.59], p = 0.0034).

Our results indicate that esketamine may have preventive antidepressant effects during the postpartum period. The aforementioned points have both mechanistic and clinically meaningful implications for the treatment of PPD.

Major depressive disorder is present in approximately 7% of the general population. There are some patients that remain treatment-resistant - patients who were treated with two or more different medications and did not demonstrate any improvement in their mental state. These patients can be treated with a new treatment – Esketamine. The recommended Esketamine treatment protocol includes 8-treatment sessions, each session lasts about two hours. In our clinic, we added a therapy group after each treatment. The therapy group is led by two co-therapist and lasts 30 minutes. The patients are invited to share their experiences from the session, their thoughts and emotions.

The study that we will present was conducted in the Esketamine treatment unit at a psychiatric hospital. There were two groups - 1. A group whose treatment included a therapeutic group at the end of each Esketamine treatment (n=30); 2. A group whose treatments did not include a therapeutic group at the end of the Esketamine treatment (n=30).

The current study examines the role of the therapeutic group. It compares between the standard treatment protocol, with and without a therapeutic group. All participants completed three questionnaires, about their emotions, three times during the treatment (before the first session, after 4 sessions and after 8 sessions).

We will present first results as well as vignette to demonstrate.

The expectation is to find a better patient experience and a better insight about the clinical changes following the Esketamine treatment, in the group which participates in the therapy group

No significant relationships.

Patients with major depressive disorder (MDD) with acute suicidal ideation or behavior (MDSI) require immediate intervention. Though oral antidepressants can be effective at reducing depressive symptoms, they can take 4–6 weeks to reach full effect.

This study aimed to identify unmet needs in the treatment of patients with MDSI, specifically exploring the potential clinical benefits of rapid reduction of depressive symptoms.

A Delphi panel consisting of practicing psychiatrists (n=12) from the US, Canada and EU was conducted between December 2020–June 2021. Panelists were screened to ensure they had sufficient experience with managing patients with MDD and MDSI. Panelists completed two survey rounds, and a virtual consensus meeting.

This research confirmed current unmet needs in the treatment of patients with MDSI.

Hopelessness, functional impairment, worsening of MDD symptoms, recurrent hospitalization and higher risk of suicide attempt were considered as key consequences of the slow onset of action of oral antidepressants.

Treatment with rapid acting antidepressant was anticipated by panelists to provide short-term benefit such as rapid reduction of core MDD symptoms which may contribute to shorter hospital stays and improved patient engagement/compliance, allowing for earlier interventions and improved patient outcomes. For long-term benefits, panelists agreed that improved daily functioning and increased trust/confidence in treatment options, constitute key benefits of rapid-acting treatments

There is need for rapid-acting treatments which may help address key unmet needs and provide clinically meaningful benefits driven by the rapid relief of depressive symptoms particularly in patients with MDSI.

SB, ED, KJ, MO’H, QZ, MM, MH, SR, JA and DZ are employees of Janssen and hold stock in Johnson & Johnson Inc. AN is currently employed by Neurocrine Biosciences Inc. RP is an employee of Adelphi Values PROVE hired by Janssen.

The efficacy and of current antidepressants is insufficient. Esketamine, a new antidepressant administered by nasal route, is available since 2019 in the management of resistant characterized depressive episodes.

To evaluate the response profile of patients to Esketamine in our institution specialized in mental health.

We included all patients treated with Esketamine in our institution from November 2019 to September 2021.We collected efficacy and tolerability data using the computerized and paper patient record, prescribing support software, and nursing staff.

Since 2019, we treated 11 patients with Esketamine in combination with an antidepressant as indicated in the MA. Two patients from the 11 were found resistant, three discontinued due to adverse events, four relapsed after an initial clinical response, and two were still ongoing at the end of the study.

Despite an initial and rapid response, our study does not highlight any long-term efficacy of Esketamine in resistant depressive disorder. This highlight the fact that its use in the acute phase of depression or earlier in the management strategy could be a good alternative because of its rapid onset of action. Esketamine was initiated as a last line therapy, which may represent a bias in the evaluation of the molecule, as the later the depression is treated, the lower the response rate. The place of Esketamine in the therapeutic strategy is not yet well determined due to a lack of hindsight, and the question of pharmacological tolerance and dependence on the molecule arises.

No significant relationships.

Esketamine is an S-enantiomer of ketamine approved by the EMA for treatment-resistant depression (TRD). As an NMDA receptor antagonist, its administration results in increase of glutamate release and AMPA receptor activation, supporting both rapid-onset and long-term antidepressant effects. Short-term tolerability seems acceptable but major concerns remain regarding long-term safety, specifically regarding potential neurocognitive toxicity.

To clarify the potential short and long-term cognitive beneficial-effects and side-effects of esketamine.

Research was made using the Medline database, through the Pubmed search engine, using the keywords: “esketamine”, “cognition”. Only randomized-controlled trials were considered.

One study focused on the effects of intranasal esketamine (INE) on cognitive functioning in 24 healthy individuals, who were evaluated pre- and postdose (40 min, 2h, 4h and 6h). The results showed a decline in cognitive performance at 40 min postdose, returning to comparable levels as placebo by 2h postdose. Another study, with a follow-up of 1 year, involving 802 TRD patients, accessed the long-term safety of INE. In patients aged <65 years-old, performance on all cognitive tests remained stable or slightly improved from baseline during long-term treatment. In patients ≥ 65 years-old, the mean performance on all tests improved or remained stable, while the simple and choice reaction time began slowing at week 20.

Esketamine has proven to be a promising new option for the treatment of TRD and available studies have shown promising results regarding patients’ cognitive function. Larger clinical trials are needed to further evaluate its short-term and long-term cognitive effects.

No significant relationships.

Esketamine is a novel antidepressant approved by the FDA in 2019 in the form of an intranasal spray, recommended for Treatment-Resistant Depression (TRD). The intranasal spray system appears to be more manageable than intravenous ketamine infusion. It contains ketamine’s S- isomer which is four-fold more potent for the NMDA receptor.

The aim of this case series is to describe our clinical experience in the use of Esketamine.

6 TRD patients (3 men; 3 women) were recruited in San Raffaele Turro Hospital from March 2021. All patients (2 bipolar and 4 unipolar) were diagnosed with a Major Depressive Episode according to DSM-5 criteria, resistant to at least two antidepressants. Initially, Esketamine was administrated twice weekly for one month; afterward, it was administrated once weekly for a month; finally, it was administrated once weekly or every two weeks for a month. Clinical scales (HAM-D, YMRS, SSI, HAM-A, MADRS, CADSS) were administrated to assess symptoms and sides effects before and after each administration on a weekly basis.

Three patients out of six showed an improvement in depressive symptoms: two patients had remission (final HAM-D score < 8); one patient had a clinical response (final HAM-D score < 50 % respect baseline value). Three patients withdrew the treatment: two for perceived inefficacy, after 16 and 19 administrations, one for personal reasons.

The use of Esketamine in our TRD patients showed good effectiveness and tolerability but randomized controlled clinical trials are needed to confirm our findings.

No significant relationships.

The compassionate use of intranasal esketamine is approved in Spain for treatment-resistant depression (TRD).

The objective of the study is to assess the clinical stability in the medium-term follow-up of patients with TRD after esketamine use.

Descriptive, retrospective and multicenter study carried out in Spain. Patients with TRD who had received esketamine treatment, and for whom there were clinical data of subsequent evolution, were included. The scores on the MADRS and Hamilton scales were changed into scores on the CGI scale according to the studies by Leucht et al. The Student’s t test was performed to assess differences in the CGI.

Eleven patients were included: 72.7% were women and the mean age was 56 (SD: 12.9). The maximum dose of esketamine used was 84mg in 63.7%. The onset of antidepressant action was observed from the 1st dose in 72.6% of the patients. The mean time in treatment was 6.6 months (SD: 2.3) and 90.9% reached remission criteria. After 7.4 months (SD: 3.0) from the end of the treatment, 90.9% remained in remission and without visits to the emergency room or hospitalization for psychiatric reasons. The mean baseline score on the CGI-SI was 5.7 points, at the end of the treatment was 1.2 points and after longitudinal follow-up it was 1. Statistically significant differences were observed (p<0.001) both at the end of the treatment and in the post-esketamine follow-up compared with baseline score.

In our sample, the use of esketamine in TRD shows clinical stability in the medium-term follow-up.

Daniel Hernández has participated in medical meetings and/or received payment for presentations from Otsuka, Lundbeck, Janssen, Angelini, Casen Recordati, and Ferrer.

TRD is a highly disabling condition, often responsible for chronic clinical course, high number of relapses and elevated suicide risk. Intranasal esketamine is currently the only available pharmacological therapy specifically indicated for TRD, as add-on therapy to antidepressant treatment with SSRI or SNRI.

The purpose of the study was to evaluate the safety and efficacy of intranasal esketamine associated with CBT in a complex clinical case of TRD, over a six-month follow-up.

A 67-year-old patient with TRD was selected for treatment with intranasal esketamine+CBT as add-on to antidepressant therapy. Before each treatment session the HAM-D rating scale was administered. The patient underwent weekly CBT sessions throughout the 6 months follow-up. The effect on physical well-being and social functioning was evaluated by means of Short-Form-Health-Survey-36.

After the first two administrations of intranasal esketamine the total score on HAM-D decreased by 10 units (from 26 to 16). After 6 weeks of treatment decreased from 26 to 12 with the disappearance of suicidal ideation present at T0. After 6 months the total HAM-D score decreased from 26 to 8. Treatment was well tolerated, with mild adverse effects, confined to the first two hours post-administration. In particular, mild sedation, dizziness, slight transient blood pressure rise were reported, never required medical intervention and resolved spontaneously during the observation period.

Intranasal esketamine add-on therapy + CBT was an effective and safe treatment allowing to achieve and maintain symptomatic remission in a complex case of TRD, improving quality of life, social functioning, and reducing suicidal ideation over a six-month follow-up.

No significant relationships.

Esketamine nasal spray has been developed to treat adults with treatment resistant depression. On Dec.2019, EMA granted a market access approval in this indication.

ESKALE is a descriptive study of treatment resistant depression patients treated with esketamine in France.

Observational retrospective study. 157 patients are included in 3 cohorts depending on their treatment initiation date. This abstract presents the second interim results of patients treated with esketamine and whom data collection ranges from Oct.2019 and Sept.2021.

66.7% of patients were females. Average age was 49 years old with 26 patients > 65 years old. Duration of the current depressive episode was 26.0 months (mean). 48.8% of patient have > 1 suicide attempt during whole life. At esketamine initiation, 78.2% patients were clinically perceived to have severe depression with a MADRS score of 32.4 (median) and a PHQ9 score of 19.5 (median). For the overall sample, esketamine was prescribed in median as a 3rd line and for 40.5% of patients after neurostimulation. The majority of the patient started esketamine at 28 mg or 56 mg and increased the dose to 84 mg. After 4 months of treatment, clinical benefits are the following: decrease of MADRS total score -16.5 points (median) corresponding to 58% of responders and a PHQ9 total score decrease of -8.6 points (median). No new safety signal detected.

This second interim analysis describes patients’ profiles and clinical evolution over a longer period and a broader population than the first interim analysis. The conditions of use are consistent with the ones approved by health authorities.

I (Marie-Alix Codet) works as a full employee at Janssen Cilag

To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response.

A post hoc analysis of pooled data from ASPIRE I and ASPIRE II evaluated ESK plus SoC vs PBO plus SoC in adults with MDSI without response (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at 24 hours after the first dose or at week 1 after the first two doses (ie, 24-hour and week 1 nonresponders). Response and remission (MADRS score ≤ 12) rates were assessed on day 25.

The analysis included 362 patients (n = 182, ESK plus SoC; n = 180, PBO plus SoC). Among 24-hour nonresponders, more patients receiving ESK plus SoC vs PBO plus SoC achieved response (63.9% vs 48.0%, P = .010) and remission (35.1% vs 24.4%, P = .074) at day 25. Odds of response/remission were higher with ESK plus SoC vs PBO plus SoC (response: 1.89, 95% CI, 1.17-3.05; remission: 1.48, 95% CI, 0.93-2.35). Similar findings were observed among week 1 nonresponders for response (48.4% vs 34.5%, P = .075), remission (25.0% vs 13.1%, P = .060), and odds of response/remission (response: 2.03, 95% CI, 1.22-3.40; remission: 1.63, 95% CI, 1.01-2.62).

Patients with MDSI not responding within the first week of treatment with ESK plus SoC may still benefit from a full 4-week treatment course.

Intravenous infusion of ketamine can produce rapid and large symptom reduction in patients with treatment-resistant depression (TRD) but presents major obstacles to clinical applicability, especially in community settings. Oral esketamine may be a promising addition to our TRD treatment armamentarium.

To explore the safety, tolerability and potential clinical effectiveness of a 3-week treatment with repeated, low-dose oral esketamine.

Seven patients with chronic and severe TRD received 1.25 mg/kg generic oral esketamine daily, over 21 consecutive days. Scores on the Systematic Assessment for Treatment Emergent Events (SAFTEE), Community Assessment of Psychic Experiences (CAPE), Clinician Administered Dissociative States Scale (CADSS) and Hamilton Rating Scale for Depression (HRSD) instruments, as well as blood pressure and heart rate, were repeatedly assessed.

Treatment with oral esketamine was well-tolerated. No serious side-effects occurred, and none of the participants discontinued treatment prematurely. Psychotomimetic effects were the most frequently reported adverse events. Mean HDRS score decreased by 16.5%, from 23.6 to 19.7. Three participants showed reductions in HDRS scores above the minimum clinically important difference (eight-point change), of whom two showed partial response. No participants showed full response or remission.

These results strengthen the idea that oral esketamine is a safe and well-tolerated treatment for patients with chronic and severe TRD, but therapeutic effects were modest. Results were used to design a randomised controlled trial that is currently in progress.

Esketamine nasal spray has been developed for patients with treatment resistant depression.

A cohort Temporary Authorization for Use (ATUc) allowed to collect for a 6-month period the first data in real life

On 02/08/2019 the French National Agency for Medicines and Health Product Safety granted an early access program for Esketamine nasal spray framed by a specific protocol for patients without therapeutic alternatives. Each treatment request was approved based on inclusion and exclusion criteria. Clinical evolution, treatment management and safety were then spontaneously reported by psychiatrists.

From 09/23/2019 to 03/25/2020, 66 patients were treated. The median age was 53 years and 41 (62.1%) were females. At treatment request, 52 patients (79%), presented a severe current depressive episode based on clinical judgment. The median duration of the disease was 12.2 years and the current episode was 2.6 years. Since the beginning of the current depressive episode, all patients (66) were prescribed ≥2 antidepressants (mean 4.2). Esketamine was initiated in a complete hospitalization setting in 27 patients (55.1%) and in day hospitalization in 22 patients (44.9%).Safety profile was consistent with the one described during clinical study. The most frequently adverse events reported (>10%) were dizziness, sedation, sleepiness, anxiety and dissociation. Most of them appeared after treatment administration and were transient.

ATUc ended on 12/18/2019 after Marketing Authorization granted by European Medicines Agency. Data reported by French psychiatrists are the first collected in this specific population and provide descriptive information on patient characteristics, burden of disease; Esketamine management and practical use at hospital level

Data analysis performed by RCTs and poster conception coordinated by Medergy and funded by Janssen

Esketamine had been rised as a potential treatment for Resistant Depression, becoming an alternative for the use of Electroconvulsive Therapy. In Spain since 2020, it has been applied for compassionate use but is not widely used. Although Esketamine is defined safe and effective in preliminary studies, there are common side effects which could reduce it use.

Increasing blood pressure has been found commonly in ederly population treated with Esketamine Nasal. Studies showed as very common side effect (10% or more) increasing systolic and diastolic blood pressure which is higher in elderly people. Our aim is to show that esketamine is well tolerated and safe in ederly people without increasing blood pressure, although is combinate with oral antidepressant therapy.

Presenting female 65-year-old with 4 years of treatment maintaining a moderate-severe symptoms. Althougt numerous pharmacological strategies have been attempted, with optimal time and maximum doses, which have been progressively withdrawing showing lack of efficacy or appearance of adverse effects. Among the drugs used we find; 11 antidepressants, 3 antipsychotics, benzodiazepines and even lithium, without response after 6 weeks of treatment. Futhermore, patient refusal to receive Electro-Convulsive Therapy. Treating with Esketamine nasal and applying the established guidelines.

Assess the response to Esketamine Nasal with Montgomery-Asberg depression scale (MADRS) we found that decrease the initial score in 26 points. Evaluating blood pressure before and after each time with no increased value.

Concluding esketamine is well tolerated and safe in ederly people without increasing blood pressure. These findings and results should be confirmed with futher studies.

The approval of the esketamine nasal spray for treatment-resistant depression in March 2019 by the Food and Drug Administration (FDA), and few months later by the European Medicine Agency, triggered a vivid debate and many concerns, mainly because of the lack of convincing evidence on its efficacy and safety, based on the development programs, approval trials and few post-marketing trials.

We aimed to detect and characterize safety signals for esketamine, by analyzing relevant adverse events (AEs) reports in the FDA Adverse Event Reporting System (FAERS) database (March 2019-March 2020).

We performed disproportionality analysis through the case/non-case approach: reporting odds ratios (ROR) and information components (IC) with 95% confidence intervals (95%CI) were estimated for esketamine-related AEs with at least four counts. We compared serious and non-serious AEs using non-parametrical tests.

The FAERS database registered 962 reports of esketamine-related AEs in one year. Signals (i.e., statistically significant disproportionality) were detected for several AEs, such as dissociation, sedation, feeling drunk, suicidal ideation and completed suicide. Signals for suicidal ideation, but not suicide attempt and completed suicide, remained significant when comparing esketamine to venlafaxine. The comparison of patients with serious vs. non-serious esketamine AEs revealed that females, patients receiving antidepressant polypharmacy, co-medication with antipsychotics, mood stabilizers, benzodiazepines or somatic medications were more likely to suffer from serious AEs.

This real-world pharmacovigilance analysis detected signals of serious unexpected esketamine-related AEs, thus reinforcing current worries regarding esketamine safety/acceptability. Further real-world studies are urgently needed to unravel the safety profile of esketamine.

No significant relationships.