Esketamine Versus Crisis Response Planning Versus Optimized Treatment as Usual for Suicide Prevention: A Pragmatic Controlled Trial in Two Brazilian Cities

1. Background Suicide is a major public health challenge with over 800,000 deaths annually worldwide. Brazil experienced a concerning 57% increase in suicide rates between 2000-2019, highlighting urgent need for effective prevention strategies. This study evaluates two promising interventions: esketamine (rapid-acting pharmacological treatment) and Crisis Response Planning (CRP, evidence-based psychological safety planning approach) in a real-world Brazilian public health setting.
2. Study Design
Pragmatic randomized controlled trial with hybrid implementation-effectiveness design comparing three approaches in emergency departments across two Brazilian cities with combined population of 310,000:
* Group A: Single esketamine infusion (0.5 mg/kg over 40 minutes) + optimized usual treatment (OUT)
* Group B: Crisis Response Planning + OUT
* Group C: OUT alone (enhanced control)
3. Participants
Adults and adolescents (≥14 years) presenting with high suicide risk defined as:
* Recent suicide attempts within 30 days (actual, interrupted, or aborted)
* Severe suicidal ideation (Columbia-Suicide Severity Rating Scale questions 4-5 positive)
* Non-suicidal self-harm requiring emergency medical attention
4. Target enrollment:
272 participants per group (816 total). Key exclusions: esketamine contraindications (cardiovascular disease, aneurysms), psychotic disorders, severe substance use disorders, pregnancy/lactation, inability to consent.
5. Interventions
1. Esketamine Group: IV infusion administered in medical setting with continuous 4-hour monitoring (pulse, blood pressure, ECG, oxygen saturation). Trained medical staff and emergency protocols available.
2. Crisis Response Planning: Collaborative intervention delivered by trained clinical psychologists. 20-45 minute sessions creating personalized, written safety plans identifying warning signs, internal coping strategies, social support contacts, professional resources, and means restriction.
3. Optimized Usual Treatment: Enhanced standard care including guaranteed psychiatric follow-up appointment within one week through municipal mental health services (CAPS - Psychosocial Care Centers).
6. Primary Outcome Repeated suicide-related events over one year including suicide attempts, interrupted attempts, suicide-prevention hospitalizations, deaths by suicide, and non-suicidal self-harm requiring medical attention.
7. Comprehensive Data Collection
1. Biomarkers: 10mL venous blood samples (2 EDTA tubes) collected at baseline by senior clinical nurses. Comprehensive laboratory analysis including complete blood count, metabolic panel, vitamins (B1, B2, B6, B12, B9, D, K), hormones (TSH, T3, T4, testosterone, DHEA, prolactin), inflammatory markers (CRP), brain-derived neurotrophic factor (BDNF), platelet monoamine oxidase (MAO), minerals (iron, ferritin, magnesium, zinc, selenium), and lipid profiles. Samples processed within 24 hours and stored at -80°C for analysis.
2. Clinical Assessments: Comprehensive evaluations at 11 time points (baseline, 24 hours, 7 days, 2 weeks, 4 weeks, 8 weeks, 16 weeks, 24 weeks, 32 weeks, 40 weeks, 1 year) using validated instruments: Columbia-Suicide Severity Rating Scale (C-SSRS), depression scales (PHQ-9, MADRS), anxiety (GAD-7), quality of life (SF-36v2), impulsivity (BIS-11), trauma history (MACE), substance use (ASSIST), sleep quality (PSQI), and additional psychosocial measures.
3. Ecological Momentary Assessment: Real-time data collection via smartphone application for consenting participants. Six daily prompts assessing mood, suicidal thoughts, and emotional states using validated scales. Previous research demonstrates safety and high compliance rates in suicide research populations.
8. Secondary Outcomes
* Time to new suicidal crisis or psychiatric emergency
* Changes in depression and anxiety severity scores
* Quality of life and functional outcome improvements
* Treatment response variability by demographic factors (age, gender, socioeconomic status)
* Comprehensive cost-effectiveness analysis including direct medical costs and indirect productivity losses
* Patient and clinician satisfaction with treatment modalities
* Implementation barriers and facilitators using Consolidated Framework for Implementation Research (CFIR)
* Biomarker predictors of treatment response
9. Clinical Significance This represents the first large-scale, real-world direct comparison of rapid-acting pharmacological (esketamine) versus evidence-based psychological (CRP) interventions for suicide prevention within a public health system. Results will provide crucial evidence for clinical practice guidelines and inform implementation of these interventions in Brazil and similar global contexts. The pragmatic design ensures findings are directly applicable to routine emergency department practice, while comprehensive biomarker analysis may identify biological predictors of treatment response to personalize suicide prevention approaches.

Start Date01 Jan 2026

Sponsor / Collaborator

University of Sao Paulo

NCT07063108

/ Not yet recruitingPhase 4IIT

Efficacy and Safety of S-ketamine Hydrochloride Injection in Elderly Patients Undergoing Elective Non-cardiac Surgery: a Multicenter, Randomized, Placebo Controlled Clinical Trials?ESSENCE?

This national, multi-center, randomized controlled study, through the study of intravenous injection of estaketamine in elderly patients undergoing surgery, is expected to explore whether estaketamine can improve the acute postoperative pain of elderly patients undergoing surgery and reduce the incidence of postoperative depression and delirium.

Start Date01 Dec 2025

Sponsor / Collaborator

Chinese People's Liberation Army General Hospital

ChiCTR2500112064

/ Not yet recruitingNot ApplicableIIT

Effective plasma concentrations of remifentanil, esketamine, or oliceridine for suppressing stress during transperineal prostate biopsy when propofol is continuously infused.

Start Date25 Nov 2025

Sponsor / Collaborator

Changhai Hospital of Shanghai

[+1]

100 Clinical Results associated with Esketamine Hydrochloride

100 Translational Medicine associated with Esketamine Hydrochloride

100 Patents (Medical) associated with Esketamine Hydrochloride

2,338

Literatures (Medical) associated with Esketamine Hydrochloride

01 Jan 2026·JOURNAL OF AFFECTIVE DISORDERS

Real-world clinical data on the long-term effectiveness and safety of generic racemic ketamine treatment

Article

Author: Mitchell, Philip B ; Thornton, Nicollette ; Brettell, Louise ; Samuels, Owen ; Martin, Donel ; Bayes, Adam ; Karunaratne, Natasha ; Moreno, Dalia ; Massaneda-Tuneu, Clara ; Lun, Elizabeth ; Dong, Vanessa ; Ellis, Justine ; Antoniou, Stella ; Flynn, Michaela ; Fowler, Ian ; Barreiros, Ana Rita ; Loo, Colleen K ; Bull, Michael ; Cao, Thanh Vinh ; Glozier, Nicholas

Ketamine is a highly effective treatment for difficult-to-treat or treatment-resistant depression (TRD). The commercially developed intranasal spray containing S-ketamine has demonstrated short and long-term efficacy and safety in phase 3 clinical trials leading to regulatory approval for TRD in many countries. Conversely, generic racemic ketamine is prescribed 'off-label'. There is minimal data on the effectiveness and safety of generic racemic ketamine treatment of >4 weeks duration. The aim of this study was to report the effectiveness and safety of ongoing racemic ketamine treatment for TRD for up to six months in real-world clinical settings. Safety was assessed using a structured monitoring framework (Ketamine Side Effect Tool). Retrospective, deidentified data were collected and analysed from 65 patients with TRD (46.1 ± 14.9 years old; 52.3 % female) who received racemic ketamine treatments over a period of 8 weeks to 6 months. Effectiveness and safety data were summarised using descriptive statistics and frequency distributions. Data suggested effectiveness, with response rates of 35 % at 8 weeks (16/45) and 44.2 % at 6 months (19/43). Suicidality scores improved in 73.3 % of patients at their last available assessment. Similarly, the results indicated that racemic ketamine was well tolerated. Our findings suggest structured safety monitoring facilitated early identification of emerging adverse effects in a few patients, allowing prompt clinical management, with no adverse sequelae. These findings support the effectiveness and safety of long-term racemic ketamine treatment for patients with TRD and highlight the importance of using a structured safety monitoring framework in clinical care.

01 Jan 2026·JOURNAL OF AFFECTIVE DISORDERS

Changes in dynamic and static functional connectivity in amygdala subregions in major depressive disorder treated with esketamine in and sertraline: A pilot study

Article

Author: Deng, Yingke ; Liu, Xiang ; Li, Haijun ; Peng, Dechang ; Wu, Guojiang ; Liu, Yumeng ; Zhou, Xueming ; Li, Lifeng

INTRODUCTION:

Dysfunction in amygdala networks has been implicated in major depressive disorder (MDD). Pharmacological treatments, such as esketamine and sertraline, are believed to exert their antidepressant effects by modulating amygdalar activity. This study aimed to investigate the relationship between changes in dynamic functional connectivity (dFC) within amygdala subregions and treatment outcomes, with a focus on identifying potential neuroimaging markers.

METHODS:

Twenty-eight patients with MDD received six intravenous infusions of esketamine (0.25 mg/kg) combined with 2 weeks of sertraline treatment. Mood and cognitive recovery were assessed using the HAMA, HAMD, BSI, and MoCA. Seed-based dFC analysis of resting-state MRI focused on the dorsal amygdala (DA), medial amygdala (MA), and ventrolateral amygdala (VA).

RESULTS:

All patients demonstrated positive responses to treatment, with significant reductions in HAMA and HAMD scores, as well as improvements in MoCA scores and a decrease in suicidal ideation. Following treatment, static functional connectivity (sFC) was reduced between the right DA and paracentral lobule, the left VA and multiple regions (including the lentiform nucleus, thalamus, medial prefrontal cortex, inferior parietal lobule, precentral gyrus, and superior parietal lobule), and the right VA and middle frontal gyrus. Conversely, dFC was significantly increased between the right DA and cuneus/superior parietal lobule, and between the left VA and superior parietal lobule. A decrease in dFC was also observed between the left MA and superior temporal gyrus. Correlation analysis showed that dFC between the left MA and superior temporal gyrus was positively correlated with HAMA score.

LIMITATION:

The combined use of esketamine and sertraline limits the ability to differentiate their individual effects. A significant proportion of the patients were adolescents, with only a few adults, which may influence the age-related response to treatment. The study utilized the lowest effective dose of esketamine, thereby leaving the dose-response relationships unexamined. The small sample size further restricts the statistical power of the findings, highlighting the need for larger studies to validate these results.

CONCLUSION:

Altered resting-state and dFC in amygdala subregions may play a role in the mechanisms by which the combination of esketamine and sertraline alleviates depressive symptoms, primarily involving the sensorimotor and default mode networks. Together, the sFC and dFC analyses provide an integrated perspective on depression-related connectivity changes and offer potential targets for treatment.

01 Jan 2026·JOURNAL OF AFFECTIVE DISORDERS

Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study

Article

Author: Tarantino, Barbara ; Politi, Pierluigi ; Marcatili, Matteo ; Guffanti, Alessandro ; Motta, Federico Luigi ; Mazzoni, Filippo ; Martiadis, Vassilis ; Cornaggia, Ranieri Domenico ; Clerici, Massimo ; Brondino, Natascia ; Dell'Osso, Bernardo ; Olivola, Miriam ; Prodi, Tiziano ; Martinotti, Giovanni

INTRODUCTION:

Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving mentalization, social cognition and promoting resilience.

OBJECTIVE:

This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on depressive symptoms and explore whether psychological and clinical factors-including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity-could predict treatment response, enabling a more personalized approach to TRD management.

METHODS:

Thirty-six TRD patients treated with esketamine were assessed over a six-month follow-up period using psychometric measures of depression severity, suicidality, mentalization, social cognition, psychache, and cognitive-emotional rigidity.

RESULTS:

A significant association emerged between mentalization deficits and depressive symptoms. Specifically, patients with poor baseline mentalization abilities exhibited higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores both at baseline and throughout follow-up. In contrast, greater cognitive rigidity appeared to have a protective role, potentially mitigating negative thinking and providing emotional stability, which may enhance resilience to stressors.

CONCLUSIONS:

These findings highlight the importance of a personalized treatment approach in TRD. Esketamine may be particularly beneficial in reducing cognitive rigidity, improving mentalization, and breaking the cognitive inflexibility that contributes to sustained negative depressive thinking patterns. Further research is needed to refine patient stratification and optimize treatment strategies for individuals with TRD.

400

News (Medical) associated with Esketamine Hydrochloride

11 Nov 2025

·endpoints.news

Neurocrine reports Phase 2 fail for depression drug it licensed from Takeda

Neurocrine Biosciences said that a candidate for major depressive disorder that it got from Takeda did not succeed in a mid-stage trial. The oral drug, codenamed NBI-1070770, did not meet the primary endpoint. This used the Montgomery-Åsberg Depression Rating Scale (MADRS) to measure improvements in disease severity from baseline to day five. The placebo-controlled Phase 2 “signal-seeking” study recruited 73 adults with MDD who were already taking at least one antidepressant. Neurocrine chief medical officer Sanjay Keswani said in a Monday statement that the company will study the results to plot its next steps, and that “there are aspects of the data that warrant further exploration.” The drug was “generally well-tolerated,” according to the press release ; it did not detail any data. The drug is one of the assets that Neurocrine licensed from the Japanese pharma in 2020 in a deal worth up to $2 billion. Another MDD drug from that pact, called osavampator , entered its Phase 3 program earlier this year. NBI-1070770 is described as a negative allosteric modulator that targets NR2B subunit-containing N-methyl-D-aspartate receptors. In its third-quarter earnings presentation , Neurocrine said the drug is “similar” to Johnson & Johnson’s nasal spray Spravato , but with the potential to have a better safety profile . While the Phase 2 results are “disappointing,” Leerink analysts said in a Monday note that “expectations were minimal” anyway, considering previous NR2B drug failures .

Phase 2Clinical Trial FailurePhase 3

11 Nov 2025

·www.biospace.com

Neurocrine’s Depression Drug Delivers ‘Surprise’ Phase II Miss

iStock, Denis Novikov The mid-stage failure was unexpected to analysts at BMO Capital Markets, who viewed ‘770 as mostly derisked given its similar mechanism of action to Johnson & Johnson’s Spravato. Neurocrine Biosciences’ investigational pill NBI-1070770—or just ‘770—was unable to significantly improve depression severity in a mid-stage study, slowing the momentum the biotech has built in recent weeks. In a brief announcement on Monday, Neurocrine announced that ‘770 “did not meet the primary endpoint” in its Phase II study, which had enrolled 73 patients with major depressive disorder who had shown inadequate response to at least one antidepressant therapy. The study tested three doses of ‘770 for its effect on change in symptom severity from baseline, as measured by the Montgomery-Åsberg Depression Rating Scale. Neurocrine did not provide specific data from the trial, with Chief Medical Officer Sanjay Keswani saying only that the biotech “will continue to analyze” the data “so we can determine appropriate next steps.” Keswani has not laid out a timeline for when Neurocrine expects to announce its plans for ‘770. Writing to investors on Monday, analysts at BMO Capital Markets said the mid-stage fail “comes as a surprise,” given the asset’s mechanism of action. Neurocrine’s ’770 is a negative allosteric modulator of the NMDA receptor and acts via a “similar” pathway to Johnson & Johnson’s FDA-approved Spravato, BMO explained. “While the mechanisms for these agents are not identical,” BMO continued, “going into Ph 2 updates for ‘770 many looked to Spravato as an agent that somewhat derisked the approach Neurocrine proceeded with.” Monday’s outcomes, however, “stand in contrast to [the] path laid forward by Spravato.” “Results today continue to highlight the inherent risk in neuropsychiatric clinical development,” BMO continued, pointing to “higher rates of failure” in this field than in other therapeutic spaces. Neurocrine’s business has built significant momentum in recent weeks. Late last month, the biotech announced $790 million in third-quarter total net product sales, representing a 28% year-on-year growth. Its main franchise, the tardive dyskinesia drug Ingrezza, likewise saw a 12% increase to bring in $687 million in the quarter. Earlier this month, Neurocrine also unveiled an $881.5 million agreement with China’s TransThera Sciences, giving it worldwide rights to the biotech’s NLRP3 inhibitors for “multiple diseases,” likely involving metabolic or inflammatory conditions, though the partners have yet to disclose specific indications. TransThera will retain rights to its portfolio within the Greater China area.

Phase 2License out/inClinical Result

06 Nov 2025

·www.fiercepharma.com

J&J's Caplyta supersizes its reach with FDA nod as add-on treatment for major depressive disorder

A major depressive disorder nod grows Caplyta’s total patient reach to more than 30 million people in the U.S. Johnson & Johnson’s decision to splash out $14.6 billion on its purchase of Intra-Cellular Therapies earlier this year was largely driven by the acquired company's rising antipsychotic star Caplyta and the drug's potential to expand into the massive treatment market for major depressive disorder (MDD).Now, with that coveted approval in hand, the drug is poised to reach many more patients and potentially live up to its blockbuster potential.Already a dominant force in its approved schizophrenia and bipolar depression indications, Caplyta’s FDA label now also includes its use as an adjunctive therapy to antidepressants in U.S. adults with MDD, Johnson & Johnson announced in a Thursday press release.Between the three indications on Caplyta's new label, the biggest by far is MDD, which impacts about 21 million adults each year, according to J&J. Two-thirds of patients with depression fail to achieve remission with first-line treatment, which is where Caplyta will now step in.As an add-on therapy, the drug can help patients “retain the benefit they are receiving from their current antidepressant, while building on it to achieve greater symptom relief,” Intra-Cellular Chief Medical Officer Suresh Durgam, M.D., explained in an emailed statement.In studies, Caplyta paired with an oral antidepressant demonstrated statistically significant and clinically meaningful improvements in depression symptoms compared to an antidepressant plus placebo.In one of two pivotal trials, Study 502, patients who had an inadequate response to ongoing antidepressant therapy experienced a 4.5-point reduction on the Montgomery-Asberg Depression Rating Scale (MADRS) on the Caplyta regimen compared to the placebo group at Week 6. Similar results were observed in Study 501, which saw an average 4.9-point reduction for Caplyta compared to placebo at Week 6 on the same scale.In addition, a six-month open-label extension study showed that 80% of MDD patients who took Caplyta achieved a response and, crucially, 65% reached remission from depression. Caplyta, with $680 million in 2024 sales, has been a commercial and clinical success since its 2019 approval, but MDD represents a much larger market opportunity. At least triple the size of the bipolar space, analysts say, the MDD field is teeming with competition from treatment agents new and old.J&J is anticipating Caplyta will eventually bring in $5 billion in annual sales, CEO Joaquin Duato noted on the company’s recent quarterly earnings call (PDF) with investors. When the company first added the drug to its “industry-leading” neuropsychiatry lineup, the buyout was expected to further solidify sales growth “above analyst expectations now through the remainder of the decade,” J&J said at the time.In recent years, J&J itself has played a key role in moving the MDD market beyond standard selective serotonin reuptake inhibitors with its ketamine-based nasal spray Spravato. Initially approved as a late-line add-on to oral antidepressants, the FDA in January signed off on the N-methyl D-asparate (NMDA) receptor antagonist’s use as a monotherapy for adult patients with MDD who've had an inadequate response to at least two oral antidepressants.At the time of Spravato's first FDA approval in 2019, J&J touted the drug as offering the "first new mechanism of action in decades to treat major depressive disorder." In 2022, Axsome brought its own fast-acting oral NMDA drug to market with Auvelity, while Fabre-Kramer Pharmaceuticals rolled out a first-in-class serotonin-targeting antidepressant called Exxua the following year. AbbVie, too, has an innovative offering on the depression market with Vraylar.Beyond its new approval in depression, Caplyta can be used as a monotherapy or paired with standard lithium or valproate to treat depressive episodes linked to bipolar 1 or bipolar 2 disorder. While the drug already has a wide schizophrenia label, J&J is looking to expand its benefits in the disorder with a potential label expansion that would allow Caplyta to prevent relapses in schizophrenia.

Clinical ResultDrug ApprovalAcquisitionCell Therapy

100 Deals associated with Esketamine Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D10627	Esketamine Hydrochloride	N01AX14 N06AX27	DB11823

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Depressive Disorder	China	Janssen-Cilag International NV	17 Apr 2023
Major depressive disorder, moderate (MDD)	Australia	Janssen-Cilag Pty Ltd.	09 Mar 2021
Depressive Disorder, Major	European Union	Janssen-Cilag International NV	18 Dec 2019
Depressive Disorder, Major	Iceland	Janssen-Cilag International NV	18 Dec 2019
Depressive Disorder, Major	Liechtenstein	Janssen-Cilag International NV	18 Dec 2019
Depressive Disorder, Major	Norway	Janssen-Cilag International NV	18 Dec 2019
Anesthesia	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	18 Nov 2019
Depressive Disorder, Treatment-Resistant	United States	Janssen Pharmaceuticals, Inc.	05 Mar 2019
Pain	Germany	Pfizer Inc.	01 Aug 1997

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Suicidal Ideation	Phase 3	United States	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Bulgaria	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Estonia	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Germany	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Hungary	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Malaysia	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Slovakia	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	South Africa	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Spain	Janssen Research & Development LLC	09 Jun 2017
Suicidal Ideation	Phase 3	Taiwan Province	Janssen Research & Development LLC	09 Jun 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05715671 (Pubmed \| Sleep Med)	Not Applicable	Dyssomnias	150	Esketamine loading dose 0.15 mg/kg plus maintenance dose 0.15 mg·kg^-1·h^-1	xxltrdczjp(sujnbdtwtb) = significantly higher vvroriovzf (ctnqjlsqya ) View more	Positive	01 Dec 2025
				Esketamine loading dose 0.3 mg/kg plus maintenance dose 0.3 mg·kg^-1·h^-1
NCT04829318 (ESCAPE-LTE, CTgov)	Phase 4	Depressive Disorder, Major	183	Esketamine (Esketamine Nasal Spray + Oral Antidepressant (AD))	fyqyjipohx = jkobpyycoy ccotjzpcmu (uykmlxqyvh, csbfmaecvk - knuynazmen) View more	-	18 Sep 2025
				Esketamine (Esketamine + Oral AD)	omwgeljoxo(vgfyenyute) = lyhhhkvimp fsrenqimad (vdmiazppwv, vajlybxxho - bcbrdhntft) View more
Pubmed Manual	Not Applicable	Depressive Disorder	58,483	Esketamine Nasal Spray	rmrufvuocs(fprlwdnxad) = jvyiuotrua tcpksmexmm (kjmpkcsehx ) View more	Positive	10 Sep 2025
NCT04599855 (Pubmed \| JAMA Psychiatry) Manual	Phase 4	Depressive Disorder, Treatment-Resistant	378	esketamine 56 mg	brbexzjreb(ffvwzqkjsv) = nausea (56 participants [24.8%]), dissociation (55 [24.3%]), dizziness (49 [21.7%]), and headache (43 [19.0%]). nttpmhnyxx (kalciughzh )	Positive	02 Jul 2025
				esketamine 84 mg
NCT02782104 (SUSTAIN-3, Pubmed \| Int J Neuropsychopharmacol)	Phase 3	Depressive Disorder, Treatment-Resistant	1,148	Esketamine nasal spray + oral antidepressant	ltojbooocw(ujylwdiver) = n = 3 xrcjiifcmu (petettbhco ) View more	Positive	06 Jun 2025
Pubmed \| JAMA Psychiatry Manual	Not Applicable	Depressive Disorder, Treatment-Resistant	-	EsketamineEsketamine + SNRI	otmgumiyuc(eeimrducon) = lpjcsspqjy qroefvilkr (mgdwelxjcz ) View more	Positive	02 Apr 2025
				EsketamineEsketamine + SSRI	otmgumiyuc(eeimrducon) = bezoylkkrw qroefvilkr (mgdwelxjcz ) View more
NCT03185819 (Pubmed \| J Am Acad Child Adolesc Psychiatry)	Phase 2	Depressive Disorder, Major	147	Esketamine 28 mg	dfftwuujfu(lkvlzewxyb) = incidence ≥20% busgqracuo (dmqrkutqin ) View more	Positive	01 Mar 2025
				Esketamine 56 mg
NCT05464979 (Pubmed \| Sci Rep)	Phase 4	-	80	Esketamine	jfckyhbdpa(eupnhdtxsd) = ecfcwqapob sefvdxuxmh (gcxlysirec, 4.0 - 16.3)	Positive	19 Feb 2025
				Midazolam/sufentanil admixture	jfckyhbdpa(eupnhdtxsd) = jstqviavcb sefvdxuxmh (gcxlysirec, 8.0 - 26.0)
ChiCTR2200065494 (Pubmed \| JAMA Netw Open)	Phase 4	Depression, Postpartum	308	Esketamine	powugfeaab(dbeobrzefy) = oghspoafhf daqvtmrbzq (xcfinsjpbe )	Positive	13 Feb 2025
				Saline	powugfeaab(dbeobrzefy) = lqrwvzqfjn daqvtmrbzq (xcfinsjpbe )
ChiCTR2400087873 (Pubmed \| BMC Anesthesiol)	Not Applicable	Sedation \| Anxiety Disorders	90	Intranasal Dexmedetomidine	mgtmlpnhqm(zndgrwzelz) = bradycardia, hypotension, hypoxia, emergence delirium etc. tierpsersm (mwpzcagjrt )	Positive	11 Feb 2025
				Intranasal Dexmedetomidine-Esketamine

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