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

NCT06468436

/ Not yet recruitingNot ApplicableIIT

Effect of Dexmedetomidine-Esketamine Combination for Sedation and Analgesia on Delirium in ICU Patients With Mechanical Ventilation: A Multicenter Randomized Trial

Patients with mechanical ventilation in the intensive care unit (ICU) often develop anxiety and agitation, sleep distuebances, and delirium. Delirium occurrence is associated with worse early and long-term outcomes. Dexmedetomidine and ketamine are recommended for sedation and analgesia in ICU patients, but each may induce side effects. The sedative effects of dexmedetomidine can help mitigate the psychiatric side effects of esketamine. Recent studies showed that dexmedetomidine-esketamine combination improved analgesia and sleep quality without increasing psychiatric side effects. This trial is designed to test the hypothesis that dexmedetomidine-esketamine combination for sedation and analgesia in ICU patients with mechanical ventilation may reduce delirium and improve respiratory recovery.

Start Date01 Nov 2025

Sponsor / Collaborator

Peking University First Hospital

[+2]

100 Clinical Results associated with Esketamine Hydrochloride

100 Translational Medicine associated with Esketamine Hydrochloride

100 Patents (Medical) associated with Esketamine Hydrochloride

2,296

Literatures (Medical) associated with Esketamine Hydrochloride

31 Dec 2025·ANNALS OF MEDICINE

Respiratory depression in women receiving propofol/esketamine versus propofol/fentanyl for abortion surgery or curettage: a randomized clinical trial

Article

Author: Chen, Huihe ; Guan, Xuehai ; Luo, Jiaxin ; Wu, Xiaoshan ; Cao, Huiyu ; Lan, Hongmeng ; Lin, Yuliu ; Zhang, Cuiwen ; Liao, Yeqing ; Huang, Xiaofang

BACKGROUND:

A combination of opioids with propofol is a popular approach to non-intubated general anaesthesia; however, this method usually results in higher incidence of respiratory depression. We compared the incidence of esketamine- and fentanyl-induced respiratory depression in women undergoing abortion surgery or curettage under propofol-based non-intubated general anaesthesia.

METHODS:

This study included 176 women (aged 18-60 years) scheduled for abortion surgery or curettage. Patients were randomized into the fentanyl or esketamine groups. Patients in the fentanyl group received fentanyl (1 µg/kg) combined with propofol intravenously. Patients in the esketamine group received subanaesthetic doses of esketamine (0.15 mg/kg) combined with propofol intravenously. The primary outcome was the incidence of respiratory depression during anaesthesia. Secondary outcomes included respiratory rate, pulse oximetry, blood pressure, heart rate, propofol dose, duration of surgery, duration of anaesthesia, and adverse events.

RESULTS:

The incidence of respiratory depression in the esketamine group was significantly lower than that in the fentanyl group (11% vs. 45%; p < .0001). Propofol administration was lower with esketamine than fentanyl. Respiratory rate, SpO₂ and blood pressure were more stable in the esketamine group than in the fentanyl group. The incidences of hypotension, propofol-induced injection pain and chin lifting in the esketamine group were lower than those in the fentanyl group. The incidence of nightmares was higher in the esketamine than in the fentanyl group.

CONCLUSIONS:

The incidence of respiratory depression was lower with subanaesthetic doses of esketamine than with fentanyl in women undergoing abortion surgery or curettage under propofol-based non-intubated general anaesthesia.KEY MESSAGESOpioids combined with propofol is a popular method for non-intubated general anaesthesia; however, this method usually results in higher incidence of respiratory depression.At subanaesthetic doses, esketamine provides an analgesic effect by antagonizing the N-methyl-d-aspartate receptor.In this trial, the incidence of respiratory depression was lower with subanaesthetic doses of esketamine than with fentanyl in women undergoing abortion surgery or curettage under propofol-based non-intubated general anaesthesia.

31 Dec 2025·ANNALS OF MEDICINE

Opioid-free anaesthesia to reduce postoperative nausea and vomiting after lower extremity wound surgery: a randomised double-blind crossover trial

Article

Author: Liu, Hua-yue ; Ying, Yao-yu ; Qian, Long ; Zhu, Ya-juan ; Ji, Fu-hai ; Liu, Hong ; Peng, Ke

BACKGROUND:

Postoperative nausea and vomiting (PONV) are common complications after surgery. Opioid use is a significant risk factor. We utilised a crossover design to test this hypothesis in the same individuals that opioid-free anaesthesia (OFA) compared with opioid-inclusive anaesthesia reduces PONV.

METHODS:

This randomised double-blind crossover trial included adult patients undergoing two surgical procedures for lower extremity wounds under general anaesthesia. Each patient received both OFA (i.v. lidocaine, esketamine, dexmedetomidine and propofol) and opioid-inclusive anaesthesia (sufentanil and propofol); which came first was determined by randomisation. The primary outcome was the incidence of PONV during the first 48 h postoperatively. Secondary outcomes were the severity of PONV, use of rescue antiemetics, postoperative pain, need for rescue analgesia, adverse events, time to extubation, and length of recovery room stay.

RESULTS:

Sixty-six patients completed this study (mean age 53 years, 36% female). The median washout period was 9 days. Compared with opioid-inclusive anaesthesia, OFA reduced the incidence of PONV 0-48 h postoperatively (5% vs. 23%, odds ratio [OR] = 0.13, 95% CI: 0.03-0.55, p = 0.006), which remained significant in the prespecified adjusted analysis (OR = 0.06, 95% CI: 0.01-0.32, p = 0.001). OFA also led to a reduced severity of PONV, a lower rate of hypotension, and a longer time to extubation. Postoperative pain and other outcomes were similar between the two anaesthetic techniques.

CONCLUSION:

This crossover trial demonstrates that OFA reduced PONV following lower extremity wound surgery, providing compelling evidence for the administration of OFA to enhance perioperative care.

REGISTRATION:

ChiCTR2200061511 (https://www.chictr.org.cn).

31 Dec 2025·ANNALS OF MEDICINE

Effects of esketamine infusion on tourniquet-induced hypertension in patients undergoing below-knee orthopedic surgery: protocol for a randomized controlled trial

Article

Author: Ying, Yao-yu ; Shi, Hai-jing ; Ji, Fu-hai ; Jiang, Kai ; Peng, Ke ; Zhao, Wen-qian ; Zhuang, Min-yuan

INTRODUCTION:

Application of a tourniquet reduces surgical bleeding while causing pain and tourniquet-induced hypertension (TIH). Deeper anesthesia and additional opioids are often insufficient to mitigate TIH but are associated with prolonged recovery and complications. Herein, we describe the protocol for a clinical trial investigating whether intraoperative esketamine infusion would reduce the rate of TIH during below-knee orthopedic surgery.

PATIENTS AND METHODS:

This prospective, randomized, double-blind, controlled trial will include a total of 80 adults scheduled for below-knee orthopedic surgery under general anesthesia. Patients will be randomly assigned in a 1:1 ratio to receive either esketamine infusion at 0.25 mg/kg/h or normal saline infusion after anesthesia induction and during tourniquet inflation. Both groups will receive ultrasound-guided unilateral popliteal sciatic nerve block and adductor canal block with 0.25% ropivacaine. The primary outcome is the occurrence of TIH, defined as an increase in systolic blood pressure >30% of baseline during tourniquet inflation. Secondary outcomes include the incidence of hypotension during surgery; intraoperative hemodynamic changes; intraoperative opioid dose and total amount of esmolol; postoperative nausea and vomiting, dizziness, and mental side effects; postoperative pain at 1, 6, 12, and 48 h after surgery; postoperative analgesic consumption within 48 h after surgery; and length of postoperative hospital stay. Additionally, we will assess patients' quality of recovery at 24 h after surgery.

DISCUSSION:

This trial will determine the effects of esketamine infusion on TIH in patients who undergo below-knee orthopedic surgery under general anesthesia. Our results will offer a new insight into optimizing anesthetic care for surgical patients receiving tourniquet.

TRIAL REGISTRATION:

Chinese Clinical Trial Registry (ChiCTR2400081237).

379

News (Medical) associated with Esketamine Hydrochloride

29 Aug 2025

·www.einpresswire.com

January - March 2021 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS)

Addyi (flibanserin) Drug hypersensitivity The "Contraindications", "Warnings and Precautions", "Adverse Reactions", and "Medication Guide" sections of the labeling were updated in September 2021 to include hypersensitivity reactions. Addyi labeling Glucagon-like peptide-1 (GLP-1) analogues Adlyxin (lixisenatide) Bydureon (exenatide) Bydureon BCise (exenatide) Byetta (exenatide) Ozempic (semaglutide) Rybelsus (semaglutide) Saxenda (liraglutide) Soliqua (insulin glargine and lixisenatide) Trulicity (dulaglutide) Victoza (liraglutide) Xultophy (insulin degludec and liraglutide) Drug-induced liver injury The "Adverse Reactions" section of the liraglutide and dulaglutide labeling was updated in June 2022 to include information about elevations of liver enzymes. Example: Trulicity labeling FDA determined that no action is necessary at the time for lixisenatide, exenatide, and semaglutide based on available information. Alcohol-based hand sanitizers Exposure via inhalation FDA determined that no action is necessary at the time based on available information. A FDA Drug Safety Communication was issued on June 16, 2021. Amlodipine and Levamlodipine Products Azor (amlodipine and olmesartan medoxomil ) Caduet (amlodipine besylate and atorvastatin calcium) Conjupri (levamlodipine maleate) Consensi (amlodipine besylate and celecoxib) Exforge (amlodipine and valsartan) Exforge HCT (amlodipine/valsartan and hydrochlorothiazide) Lotrel (amlodipine besylate and benazepril hydrochloride) Katerzia (amlodipine benzoate) Norvasc (amlodipine besylate) Prestalia (amlodipine besylate and perindopril arginine) Tribenzor (amlodipine besylate/olmesartan medoxomil and hydrochlorothiazide) Twynsta (amlodipine and telmisartan) Non-cardiogenic pulmonary edema FDA determined that no action is necessary at the time based on available information. Avonex (interferon beta-1a) Betaseron (interferon beta-1b) Extavia (interferon beta-1b) Plegridy (pegylated interferon beta-1a) Rebif (interferon beta-1a) Injection site abscess FDA is evaluating the need for regulatory action. Bavencio (avelumab) Imfinzi (durvalumab) Keytruda (pembrolizumab) Libtayo (cemiplimab-rwlc) Opdivo (nivolumab) Tecentriq (atezolizumab) Scleroderma FDA determined that no action is necessary at the time based on available information. Bavencio (avelumab) Imfinzi (durvalumab) Keytruda (pembrolizumab) Libtayo (cemiplimab-rwlc) Opdivo (nivolumab) Tecentriq (atezolizumab) Cholangitis sclerosing The "Adverse Reactions" section of the Keytruda (pembrolizumab) labeling was updated in August 2021 to include sclerosing cholangitis. Example: Keytruda labeling FDA determined that no action is necessary at the time for Bavencio (avelumab), Imfinzi (durvalumab), Libtayo (cemiplimab-rwlc), Opdivo (nivolumab), and Tecentriq (atezolizumab) based on available information. Chloroquine Generic products containing chloroquine Phospholipidosis The “Warnings” section of the labeling was updated in May 2022 to include information about phospholipidosis. Eliquis (apixaban) Pradaxa (dabigatran etexilate mesylate) Savaysa (edoxaban tosylate) Xarelto (ribaroxaban) Generic products containing dabigatran etexilate mesylate Generic products containing ribaroxaban Menorrhagia The “Use in Specific Populations” section was updated April 2021 to add language to describe the risk of clinically significant uterine bleeding in females of reproductive potential. Eliquis label Pradaxa label Savaysa label Xarelto label Depakote (divalproex sodium) Depakote ER (divalproex sodium) Stavzor (valproic acid) Generic products containing divalproex sodium Generic products containing valproic acid Tubulointerstitial nephritis The "Adverse Reactions" section of the labeling was updated in November 2021 to include tubulointerstitial nephritis. Example: Depakote labeling Dupixent (dupilumab) Alopecias FDA is evaluating the need for regulatory action. H.P. Acthar Gel (corticotropin) Anaphylactic and anaphylactoid responses The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in October 2021 to include anaphylaxis. Acthar Gel labeling H.P. Acthar Gel (corticotropin) Cardiac arrhythmias The "Warnings and Precautions" and "Adverse Reactions" sections of the labeling were updated in October 2021 to include atrial fibrillations and palpitations. Acthar Gel labeling Ibrance (palbociclib) Kisqali (ribociclib) Kisqali Femara Co-Pack (letrozole and ribociclib) Verzenio (abemaciclib) Second primary malignancy FDA determined that no action is necessary at the time based on available information. Lynparza (olaparib) Drug-induced liver injury FDA determined that no action is necessary at the time based on available information. Ocrevus (ocrelizumab) Autoimmune colitis The "Warnings and Precautions", "Adverse Reactions", "Patient Counseling Information", and "Medication Guide" sections of the labeling were updated in August 2022 to include colitis. Ocrevus labeling Poteligeo (mogamulizumab-kpkc) Acute kidney injury The "Warnings and Precautions" section of the labeling was updated in March 2022 to include glomerulonephritis. Poteligeo labeling Ravicti (glycerol phenylbutyrate) Product labeling issue regarding stability and instructions for administration The container label, carton label, "Medication Guide", and sections of the Prescribing Information ("Dosage and Administration" and "Patient Counseling Information") were updated in September 2021 to enhance the instructions for administration. Ravicti labeling Spravato (esketamine) Hypertensive crisis FDA determined that no action is necessary at the time based on available information. Tremfya (guselkumab) Device use errors resulting in possible missed or partial doses The Tremfya One Press Instructions for Use (IFU) and carton labeling was updated in June 2023 to mitigate medication errors, such as underdose or no dose delivered. Tremfya labeling Trulance (plecanatide) Drug hypersensitivity The “Adverse Reactions” section of the Trulance labeling was updated April 2021 to include skin itching, hives, and rash. Trulance Label Trulance (plecanatide) Vomiting The “Adverse Reactions” section of the Trulance labeling was updated April 2021 to include vomiting. Trulance Label Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Drug Approval

25 Aug 2025

·firstwordpharma.com

AbbVie strikes $1.2B deal for Gilgamesh's psychedelic depression therapy

Almost a month after rumours surfaced that AbbVie was weighing a $1-billion bid for Gilgamesh Pharmaceuticals, the company announced Monday it will acquire the neuroscience biotech's lead asset — the psychedelic depression candidate bretisilocin (GM-2505) — in a deal worth up to $1.2 billion.Bretisilocin is a serotonin 5-HT2A receptor agonist and 5-HT releaser currently in mid-stage development. Unlike psilocybin or LSD, which can keep patients in a psychoactive state for six to 10 hours, "bretisilocin has been shown to exert a shorter duration of psychoactive experience, while retaining an extended therapeutic benefit," the companies said in a joint release.Topline Phase IIa results suggest the drug may indeed deliver. In patients with moderate-to-severe major depressive disorder, a single 10-mg dose reduced Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline by 21.6 points after two weeks, compared with a 12.1-point reduction in patients given a low-dose active comparator. The antidepressant effect emerged within 24 hours and was durable after just two treatment sessions, Gilgamesh reported in May. Bretisilocin was also generally well tolerated, with no serious adverse events reported.Clinicians see the drug's shorter-acting profile as a potential advantage. "This compound acts in just a couple of hours, so that would position it to really compete well against other psychedelics that are further along but longer-acting," Brian Barnett, clinical director of the psychiatric treatment resistance program at Cleveland Clinic, recently said in an interview with FirstWord. He also suggested bretisilocin could prove to be "a nice alternative" to Johnson & Johnson's Spravato (esketamine), with more durable benefit.Monday's deal includes an upfront payment and development milestones. As part of the transaction, Gilgamesh will also spin out a new entity that will operate under the name Gilgamesh Pharma to hold its employees and remaining programmes, including its oral NMDA receptor antagonist blixeprodil (GM-1020), cardio-safe ibogaine analogue (GM-3009), M1/M4 agonist programme and non-hallucinogenic neuroplastogens, already the centre of an existing $2-billion tie-up with AbbVie (see – Spotlight On: Neuroplastogens hit the mainstream in 2024. What's next for trip-less psychedelics?).

Clinical ResultPhase 2Acquisition

25 Aug 2025

·www.biospace.com

Unswayed by Cerevel Failure, AbbVie Buys Gilgamesh’s Depression Drug for $1.2B

Brain doodle illustration, sketched colored concept about fresh ideas in human mind iStock/ LisaAlisa_ill The deal extends AbbVie’s commitment to the psychedelics space and depression, after emraclidine’s high-pro in schizophrenia last November. Not only is AbbVie jumping back into depression after a stunning failure last year, but the company is doing so with an eye-catching modality: psychedelics. After working closely with Gilgamesh Pharmaceuticals for over a year, AbbVie will buy the neuroscience biotech’s lead depression candidate for $1.2 billion. The deal was announced Monday morning, with AbbVie splitting the cash between an upfront payment and development milestones, which were not disclosed. The transaction will only include Gilgamesh’s lead asset, bretisilocin, which was not involved in the companies’ original May 2024 licensing partnership. The drug is being developed as a fast-acting, two-hour duration treatment option for major depressive disorder (MDD). The remaining assets in Gilagmesh’s stable—including those in the existing AbbVie collaboration—will be spun out into a new company called Gilgamesh Pharma Inc. This new entity will hold all of Gilgamesh’s employees and programs, which include an oral NMDA receptor antagonist called blixeprodil, a cardio-safe ibogaine analog and an M1/M4 agonist program. AbbVie will still have an option to license candidates from the new Gilgamesh entity, according to the terms of the original deal. The deal extends AbbVie’s commitment to the psychedelics space , one of the only Big Pharmas in the game. The other major player is Johnson & Johnson, which owns the esketamine-based Spravato, though the company has told BioSpace it doesn’t consider the depression drug to be a traditional psychedelic. AbbVie was cautious with the deal, reflecting the lower-than-expected valuation for the Gilgamesh asset, BMO Capital Markets said in a note Monday morning. “We believe the lower deal value could reflect conservatism around psychedelic valuations in light of regulatory backdrop for compounds, making today’s deal a well-balanced risk/reward acquisition for the company,” BMO’s Evan David Seigerman and colleagues wrote. Still, the deal reflects a vote of confidence in the psychedelics space. “Historically, large pharma has been less active exploring psychedelic compounds due to potential regulatory concerns surrounding approval, making today’s deal more significant, starting to validate that pharma could see a therapeutic outlet for some of these drugs,” BMO’s note read. And the deal makes sense for AbbVie, the analysts added, noting its existing neuroscience portfolio that features the MDD asset Vraylar. Others in the portfolio include Ubrelvy and Qulipta, which BMO said are under-appreciated compared to AbbVie’s headline-making immunology drugs Skyrizi and Rinvoq. Taking on Gilgamesh’s depression asset means that AbbVie is taking another shot at the condition after the failure of emraclidine . That asset was picked up at the end of 2023 in the nearly $9 billion acquisition of Cerevel Therapeutics but ultimately failed two Phase II trials last November. Meanwhile, a rival asset called Cobenfy from Bristol Myers Squibb’s acquisition of Karuna Therapeutics made its way to the market as the first new schizophrenia treatment in 35 years. In recent months, the drug has struggled to live up to expectations, failing a Phase III test testing it as an add-on treatment to atypical antipsychotics for schizophrenia. AbbVie will now take over development of bretisilocin, a short-acting serotonin (5-HT)2A receptor agonist and 5-HT releaser, which is being tested in a Phase II trial for moderate-to-severe MDD. In Phase IIa data revealed in May, bretisilocin beat a low-dose psychoactive comparator in reducing symptoms of depression. The drug showed a rapid onset within 24 hours, and the results were durable out to day 74 without additional treatment. BMO called the data impressive. At the time, Gerard Sanacora, professor of Psychiatry at Yale University and the director of the Yale Depression Research Program, compared the treatment to J&J’s Spravato, which achieves rapid results in the clinic. “The treatment fits nicely in the two-hour in-clinic framework established by esketamine, but with the potential for significantly fewer annual visits,” Sanacora said in a statement included in Gilgamesh’s May 27 release.

Phase 2AcquisitionPhase 3Clinical ResultLicense out/in

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.

to view more data

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


NCT04599855 (Pubmed \| JAMA Psychiatry) Manual	Phase 4	Depressive Disorder, Treatment-Resistant	378	esketamine 56 mg	uavuijogbp(wgapkcunyu) = nausea (56 participants [24.8%]), dissociation (55 [24.3%]), dizziness (49 [21.7%]), and headache (43 [19.0%]). sixdpuqwot (hbjlwaxagy )	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	yfgvkezxqf(fnlsszbncs) = n = 3 rfjcummnok (rzdpezkkft ) View more	Positive	06 Jun 2025
Pubmed \| JAMA Psychiatry Manual	Not Applicable	Depressive Disorder, Treatment-Resistant	-	EsketamineEsketamine + SNRI	elqwennvkw(qhxnvktgiz) = ockliqwkec xlbmmqyday (pryvkgjiqz ) View more	Positive	02 Apr 2025
				EsketamineEsketamine + SSRI	elqwennvkw(qhxnvktgiz) = mkqclpfngd xlbmmqyday (pryvkgjiqz ) View more
NCT03185819 (Pubmed \| J Am Acad Child Adolesc Psychiatry)	Phase 2	Depressive Disorder, Major	147	Esketamine 28 mg	ofuergmlne(wetbkrdimm) = incidence ≥20% nxixaswmyx (iodttfvmck ) View more	Positive	01 Mar 2025
				Esketamine 56 mg
NCT05464979 (Pubmed \| Sci Rep)	Phase 4	-	80	Esketamine	kvvxcaeeam(bqvwjsrbsv) = svbjxcinvb lxlvsivixl (zgkyoangaq, 4.0 - 16.3)	Positive	19 Feb 2025
				Midazolam/sufentanil admixture	kvvxcaeeam(bqvwjsrbsv) = uazgyyhxxn lxlvsivixl (zgkyoangaq, 8.0 - 26.0)
ChiCTR2200065494 (Pubmed \| JAMA Netw Open)	Phase 4	Depression, Postpartum	308	Esketamine	qewemxlojv(jpccopnbxd) = fbuaftspyq nknmhxbnzc (kybqrrhjlo )	Positive	13 Feb 2025
				Saline	qewemxlojv(jpccopnbxd) = nixwlligtz nknmhxbnzc (kybqrrhjlo )
ChiCTR2400087873 (Pubmed \| BMC Anesthesiol)	Not Applicable	Sedation \| Anxiety Disorders	90	Intranasal Dexmedetomidine	xzkxvfiwrw(qivqgzofga) = bradycardia, hypotension, hypoxia, emergence delirium etc. fxhyfywpze (nkamtbwqct )	Positive	11 Feb 2025
				Intranasal Dexmedetomidine-Esketamine
ChiCTR2300069632 (Pubmed) Manual	Not Applicable	Pain	135	esketamine	tgzwqppiha(cuaofofqcq): P-Value = P<0.05 View more	Positive	20 Jan 2025
				sufentanil
NCT04599855 (FDA_CDER) Manual	Phase 4	Depressive Disorder, Treatment-Resistant	-	SPRAVATO (56 mg)	crrhwufsww(grdqcxegqr) = zxxpqozzci oyfjhrkgbc (adxpbdgawz, 1.2)	Positive	17 Jan 2025
				SPRAVATO (84 mg)	crrhwufsww(grdqcxegqr) = lcrovbxzaz oyfjhrkgbc (adxpbdgawz, 1.2)
NCT03097133 \| NCT03039192 (FDA_CDER) Manual	Phase 3	Depressive Disorder, Major	-	SPRAVATO 84 mgSPRAVATO 84 mg +SOC (NCT03039192)	bnjkdkwupr(lzfurdkobq) = xzfhtyqand jgqbmjnkrf (fogysaveic, 1.04)	Positive	17 Jan 2025
				Placebo nasal spray + SOC (NCT03039192)	bnjkdkwupr(lzfurdkobq) = oicjgpzvvg jgqbmjnkrf (fogysaveic, 1.02)

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