CLINICAL TRIALS PROFILE FOR ESKETAMINE HYDROCHLORIDE

505(b)(2) Clinical Trials for esketamine hydrochloride

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Formulation	NCT06853041 ↗	ESKetamine Low-dose vs Ketamine Low-dose for Severe Acute Pain in Emergency Units, Comparison of PsychodyslEptic Effects	RECRUITING	Centre Hospitalier Universitaire de Nice	PHASE4	2025-05-06	Almost 30% of painful patients in emergency departments (ED) describe their pain as severe (i.e. a Verbal Numerical Rating Score VNRS 6 on a scale ranging from 0 to 10). The management of such severe pain needs to be rapid and safe, and for this purpose intravenous (IV) morphine titration is still the gold-standard. However, morphine titration takes up considerable caregiver time, as patients need to be monitored and treated progressively with small quantities of morphine every 5 minutes until analgesia. This is sometimes difficult to reconcile with a saturating flow of patients, and overcrowding in ED is proven to significantly delay time-to-analgesia, and even lead to deleterious under-treatment. Finally, the opioid crisis is a major concern, explaining why strategies are being advocated to develop other ways of managing severe acute pain in the ED and to limit the use of opioids. Recent studies show that ketamine administered in small IV doses ("low-dose" ketamine LDK: 0.2 to 0.3 mg/kg) possesses potent analgesic activity as well as interesting anti-hyperalgesic and anti-allodynic properties. Compared with morphine, LDK does not induce respiratory depression, but can sometimes induce disturbing psychodysleptic effects. These may include a sensation of unreality, fatigue, anxiety, dizziness or hallucinations. According to studies, 30-80% of LDK-treated patients experience psychodysleptic effects. However, two recent studies suggest that slow IV injections of LDK (over 10 minutes) may improve patient tolerance, although these slow infusions do not totally reduce this discomfort. Pharmacologically, ketamine is a racemic mixture of 2 isomers: esketamine S(+), which is dextrorotatory, and arketamine R(-), which is levorotatory. In recent years, a new formulation containing only esketamine has been made available to hospitals in some northern European countries, and more recently in France. Esketamine appears to have twice the analgesic efficacy of racemic ketamine, and studies on healthy volunteers or in peri-operative settings suggest that it is also better tolerated psychologically than ketamine. For the moment, however, scientific data are lacking, and no comparative trial has yet been conducted in the ED setting. The investigators plan to conduct in their ED a prospective, single-center, randomized, double-blind study aiming to compare the tolerance and efficacy of esketamine versus racemic LDK in patients presenting with severe acute pain (VNRS 6/10).

All Clinical Trials for esketamine hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00847418 ↗	Pharmacokinetics and Pharmacodynamics of Nasally Applied Esketamine	Completed	University Hospital, Basel, Switzerland	Phase 1	2009-02-01	The purpose of this study is the determination of blood concentration and the effectiveness of esketamine after nasal application.
NCT01640080 ↗	A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression	Completed	Janssen Research & Development, LLC	Phase 2	2012-06-27	The purpose of this study is to assess the efficacy of esketamine compared with placebo in improving symptoms of depression in patients with treatment resistant depression.
NCT01780259 ↗	A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants	Completed	Janssen Research & Development, LLC	Phase 1	2012-12-01	The primary purpose of the study is to evaluate the pharmacokinetics (what the body does to the medication) of intranasally (through the nose) administered esketamine in healthy participants.
NCT01980303 ↗	A Study to Assess the Pharmacokinetics of Intranasally Administered Esketamine in Healthy Japanese and Caucasian Volunteers	Completed	Janssen Research & Development, LLC	Phase 1	2013-11-01	The purpose of this Phase 1 study is to characterize the pharmacokinetic profile (what the body does to the medication) of esketamine when given by the intranasal route (through the nose) to healthy adult Japanese and Caucasian participants.

Clinical Trial Conditions for esketamine hydrochloride

Condition Name

Condition Name for esketamine hydrochloride
Intervention	Trials
Esketamine	38
Dexmedetomidine	19
Healthy	15
Major Depressive Disorder	12

Condition MeSH

Condition MeSH for esketamine hydrochloride
Intervention	Trials
Depression	53
Depressive Disorder	44
Depressive Disorder, Major	24
Depressive Disorder, Treatment-Resistant	23

Clinical Trial Locations for esketamine hydrochloride

Trials by Country

Trials by Country for esketamine hydrochloride
Location	Trials
United States	283
China	119
Belgium	20
Canada	15
Poland	14

Trials by US State

Trials by US State for esketamine hydrochloride
Location	Trials
California	17
Texas	16
Georgia	16
Maryland	15
Ohio	14

Clinical Trial Progress for esketamine hydrochloride

Clinical Trial Phase

Clinical Trial Phase for esketamine hydrochloride
Clinical Trial Phase	Trials
PHASE4	23
PHASE3	3
PHASE2	3

Clinical Trial Status

Clinical Trial Status for esketamine hydrochloride
Clinical Trial Phase	Trials
Recruiting	70
Completed	58
Not yet recruiting	49

Clinical Trial Sponsors for esketamine hydrochloride

Sponsor Name

Sponsor Name for esketamine hydrochloride
Sponsor	Trials
Janssen Research & Development, LLC	34
Beijing Tiantan Hospital	18
Peking University First Hospital	17

Sponsor Type

Sponsor Type for esketamine hydrochloride
Sponsor	Trials
Other	231
Industry	48
UNKNOWN	9

Clinical Trials Update, Market Analysis, and Projection for ESKETAMINE HYDROCHLORIDE

Last updated: October 28, 2025

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Introduction

Esketamine Hydrochloride, a derivative of ketamine, has garnered significant attention in psychiatric therapeutics, particularly for treatment-resistant depression (TRD) and major depressive disorder with suicidal ideation. Its unique mechanism offers an innovative approach to mental health treatment, disrupting traditional monoaminergic pathways. This article provides a comprehensive update on clinical trials, analyzes current market dynamics, and offers a forward-looking projection for Esketamine Hydrochloride.

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Clinical Trials Update

Regulatory Approvals and Clinical Development

Esketamine received FDA accelerated approval in 2019 as a nasal spray (Spravato) for treatment-resistant depression, marking a breakthrough as the first novel drug approved for this indication in decades. This approval was based on pivotal Phase III trials demonstrating rapid antidepressant effects when administered alongside oral antidepressants.

Post-approval, ongoing trials aim to explore broader applications and optimize dosing strategies:

• Phase IV Studies: Focus on real-world effectiveness, safety profiles, and long-term outcomes. Data is being collected from diverse populations, including elderly patients and those with comorbidities. Preliminary results confirm sustained efficacy with acceptable safety, though concerns regarding dissociative effects persist.

• Expanded Indications: Trials are evaluating Esketamine's efficacy in various conditions, including bipolar depression, postpartum depression, and agitation in schizophrenia. For instance, a notable Phase II trial (NCT04085406) is assessing efficacy in postpartum depression, with promising early data indicating rapid symptom reduction.

• Ongoing Investigations: The ASCEND trial (NCT04654349), a large-scale Phase III trial designed to solidify Esketamine's role in TRD, is nearing completion. This trial aims to compare Esketamine plus standard care versus standard care alone, emphasizing safety and durability of response.

Safety and Efficacy Trends

Clinical data underscore Esketamine's rapid-onset antidepressant effect, often within hours to days, contrasted with traditional antidepressants requiring weeks. However, adverse events such as transient dissociation, elevated blood pressure, and potential abuse liability remain concern points. Current trials are evaluating mitigation strategies to balance efficacy and safety.

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Market Analysis

Market Overview and Key Players

The global depressive disorders therapeutics market is projected to reach USD 18.3 billion by 2027, with a compound annual growth rate (CAGR) of approximately 4.5%. Esketamine's entry has catalyzed growth within the mental health treatment segment, driven by robust unmet needs.

Leading Market Participants:

• Johnson & Johnson: Developed and commercialized Spravato, holding significant market share post-approval.
• Other Biotech Firms: Competing pipeline drugs like SAGE-217 (Zuranolone) and brexanolone (for postpartum depression) are emerging alternatives, emphasizing a diversified therapeutic landscape.

Market Drivers

• Unmet Medical Need: TRD affects ~30% of depressed patients, lacking sufficient treatment options.

• Rapid Response Demand: Preference for fast-acting therapeutics among clinicians and patients.

• Regulatory Endorsement: FDA approval, along with approvals in Europe (EMA) and Japan, accelerates market penetration.

• Innovative Administration: Intranasal delivery enhances patient compliance compared to intravenous or oral routes.

Market Challenges

• Safety Concerns: Potential for misuse and dissociative adverse effects limit widespread acceptance.
• Cost and Reimbursement: High treatment costs (~$590–$885 per dose) create barriers, though insurance coverage has improved.
• Long-term Data Gaps: Limited long-term efficacy and safety data hinder broader clinical adoption.

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Market Projection and Future Outlook

Growth Trajectory

Anticipated CAGR for Esketamine's market segment is approximately 11–13% over the next five years, driven by expanding indications, increasing awareness, and evolving clinical practices.

Key Growth Opportunities

• Expanded Indications: Efficacy in bipolar depression, postpartum depression, and acute agitation will diversify revenue streams.
• Global Expansion: Entry into emerging markets with rising mental health awareness and increasing healthcare infrastructure.
• Formulation Innovations: Development of oral formulations or combination therapies to enhance convenience and compliance.

Potential Market Risks

• Regulatory Caution: Future approvals may be restricted due to safety and abuse potential concerns.
• Competitive Dynamics: Emergence of novel rapid-acting antidepressants, such as S-adenosylmethionine (SAMe) derivatives or neurosteroids, could erode market share.
• Pricing Pressure: Payer resistance to high costs may limit adoption in cost-sensitive regions.

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Regulatory and Commercial Outlook

Evolving regulatory landscapes are crucial. The US FDA’s REMS program underscores ongoing safety monitoring. European agencies have approved Spravato under similar risk management systems. As real-world data accumulates, additional indications may pave the way for further approvals, expanding market potential.

Johnson & Johnson, leveraging its established infrastructure, is poised to maintain dominant market status, though competition continues to intensify. Strategic collaborations and pipeline diversification will be critical to sustain growth.

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Key Takeaways

• Clinically, Esketamine Hydrochloride remains a cornerstone for treatment-resistant depression, with ongoing trials expanding its therapeutic scope.
• Market-wise, it operates in a high-growth segment, bolstered by regulatory backing and unmet medical needs but faces challenges related to safety and costs.
• Future projections indicate steady growth driven by new indications, formulation advances, and global expansion.
• Risks include regulatory constraints, competition, safety concerns, and reimbursement issues.
• Investors and clinicians should monitor clinical trial outcomes, safety profiles, and evolving regulations to navigate this dynamic landscape effectively.

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FAQs

1. What are the primary approved uses of Esketamine Hydrochloride?
   Approved primarily for treatment-resistant depression in adults, administered as a nasal spray alongside oral antidepressants. It is also authorized under REMS programs to ensure safe use.

2. Are there ongoing studies exploring other conditions?
   Yes. Currently, trials are investigating Esketamine for postpartum depression, bipolar depression, and agitation associated with schizophrenia.

3. What safety concerns are associated with Esketamine?
   Potential side effects include dissociation, increased blood pressure, dizziness, and abuse potential. Long-term safety data is still emerging.

4. How does Esketamine compare to traditional antidepressants?
   It offers a rapid onset of therapeutic effects, often within hours, whereas traditional antidepressants typically require weeks. However, safety and dependence risks limit its use to specific settings.

5. What is the outlook for Esketamine’s market growth?
   The market is projected to grow at a CAGR of approximately 11–13% over the next five years, driven by expanding indications and global adoption.

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Sources

[1] U.S. Food and Drug Administration. (2019). FDA approves esketamine nasal spray for treatment-resistant depression.
[2] MarketWatch. (2022). Global depression therapeutics market to reach USD 18.3 billion by 2027.
[3] ClinicalTrials.gov. (2023). Ongoing clinical trials involving Esketamine Hydrochloride.
[4] Johnson & Johnson. (2022). Spravato product information and market strategy.
[5] European Medicines Agency. (2021). Approval and guidelines for Spravato in Europe.

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Note: This report synthesizes the latest available data up to early 2023. Future developments may influence clinical and market dynamics.