SPRAVATO (esketamine hydrochloride)
SPRAVATO is indicated for the treatment of Treatment-Resistant Depression; Major Depressive Disorder.
How SPRAVATO Works
Esketamine, the S-enantiomer of racemic ketamine, functions as a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. This target is an ionotropic glutamate receptor, and the drug's primary circulating metabolite, noresketamine, also demonstrates activity at this same receptor. Although the medication binds to and blocks these receptors, the specific biological mechanism by which this action produces an antidepressant effect is currently unknown.
Development Insights
Details
- Status
- Prescription
- First Approved
- 2019-03-05
- Patent Cliff
- 2040
- Revenue
- $520M (Q4-2025)
- Routes
- NASAL
- Dosage Forms
- SPRAY
SPRAVATO Approval History
What SPRAVATO Treats
2 indicationsSPRAVATO is approved for 2 conditions since its original approval in 2019. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Treatment-Resistant Depression
- Major Depressive Disorder
SPRAVATO Boxed Warning
SEDATION; DISSOCIATION; RESPIRATORY DEPRESSION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS WARNING: SEDATION; DISSOCIATION; RESPIRATORY DEPRESSION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Risk for sedation, dissociation, and respiratory depression after administration. Monitor patients for at least two hours after administration. ( 5.1 , 5.2 , 5.3 ) Potential for abuse and misuse. Consider the risks and benefit...
WARNING: SEDATION; DISSOCIATION; RESPIRATORY DEPRESSION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS WARNING: SEDATION; DISSOCIATION; RESPIRATORY DEPRESSION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Risk for sedation, dissociation, and respiratory depression after administration. Monitor patients for at least two hours after administration. ( 5.1 , 5.2 , 5.3 ) Potential for abuse and misuse. Consider the risks and benefits of prescribing SPRAVATO prior to using in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and misuse. ( 5.4 ) SPRAVATO is only available through a restricted program called the SPRAVATO REMS. ( 5.5 ) Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. SPRAVATO is not approved for use in pediatric patients. ( 5.6 ) Sedation Patients are at risk for sedation after administration of SPRAVATO [see Warnings and Precautions (5.1) ]. Dissociation Patients are at risk for dissociative or perceptual changes after administration of SPRAVATO [see Warnings and Precautions (5.2) ]. Respiratory Depression Respiratory depression has been observed in postmarketing experience [see Warnings and Precautions (5.3) ] . Because of the risks of sedation, dissociation, and respiratory depression, patients must be monitored for at least 2 hours at each treatment session, followed by an assessment to determine when the patient is considered clinically stable and ready to leave the healthcare setting [see Warnings and Precautions (5.1 , 5.2 , 5.3) ] . Abuse and Misuse SPRAVATO has the potential to be abused and misused. Consider the risks and benefits of prescribing SPRAVATO prior to use in patients at higher risk of abuse. Monitor patients for signs and symptoms of abuse and
SPRAVATO Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
MoA expansion candidates
Same target(s), different indications — where else is this mechanism being explored?
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
Drugs Similar to SPRAVATO
3 of 20FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.
Clinical Trial Registry
71 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT07227454 AVENUE | 54135419SUI3003 54135419SUI3003, 2024-518615-19-00 | Ph 3 | recruiting | A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder |
| NCT06853041 ESKAPE | 24-PP-09 | Ph 4 | completed | ESKetamine Low-dose vs Ketamine Low-dose for Severe Acute Pain in Emergency Units, Comparison of PsychodyslEptic Effects |
| NCT07179913 esketamine | 2025-185 | Ph 4 | active not recruiting | The Improvement of Low-dose Esketamine on Postoperative Depression in Patients Undergoing Bariatric Surgery With Preoperative Depression |
| NCT07570160 PEDI-NPOBCs | 202512066-2 SWYY2025002065 | Ph 4 | not yet recruiting | Intranasal Dexmedetomidine or Esketamine for Negative Postoperative Behavioral Changes in Children |
| NCT07556172 | IIT-I-2025-061 | Ph 4 | active not recruiting | Clinical Study of Esketamine in Patients With Sepsis Undergoing Invasive Mechanical Ventilation |
| NCT05092152 PROMINE | PROMINE | Ph 2 | completed | Propofol Versus Ketamine for Rapid Sequence Intubation in Critically Ill Patients |
| NCT06062550 | 2023-351 | Ph 4 | active not recruiting | Different Dose Esketamine and Dexmedetomidine Combination for Supplemental Analgesia After Scoliosis Correction Surgery |
| NCT07308756 | 2025-0455 | Ph 4 | recruiting | Impact of Perioperative Dexmedetomidine and Esketamine on Postoperative Quality of Recovery |
| NCT05603104 INTENSIFY | 2022-502185-24-00 (EU CT #) | Ph 3 | recruiting | Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure |
| NCT07317206 | 55068322.2.0000.5440 | Ph 2 | recruiting | Ayahuasca, Esketamine and PTSD |
| NCT07212946 | 32564020000005440 | Ph 2 | completed | Ayahuasca and Esketamine for Major Depression |
| NCT05450432 | 2022P000972 | Ph 4 | recruiting | Long-Term Maintenance With Ketamine and Esketamine for Reduction of Suicide in High-Risk Patients With Depression |
| NCT06853431 | SAHoWMU-CR2025-03-105 | Ph 4 | recruiting | Determination of ED50 and ED95 With Clinical Efficacy of Intranasal Dexmedetomidine Combined With Esketamine for Preoperative Sedation in Pediatric General Anesthesia |
| NCT05973851 INTENSIFY MDD | 2023-506617-21-00 (EU CT#) | Ph 3 | recruiting | The Effect of a Six Week Intensified Pharmacological Treatment for Major Depressive Disorder Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment. |
| NCT04829318 ESCAPE-LTE results posted | CR108992 2020-004291-18, 54135419TRD4010 | Ph 4 | completed | A Long-Term Extension Study for Participants With Treatment-resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment |
| NCT07131033 | CLanXie | Ph 1, Ph 2 | active not recruiting | Esketamine Combined With Magnesium Sulfate for Postoperative Fatigue Syndrome in Patients Undergoing Laparoscopic Cholecystectomy |
| NCT04425473 | Z191100006619067 | Ph 2, Ph 3 | completed | Esketamine and Perioperative Depressive Symptoms |
| NCT06566469 | 2024-405 | Ph 4 | completed | Dexmedetomidine-esketamine Combined Nasal Administration and Emergence Delirium |
| NCT06399185 | 2024-105 | Ph 4 | recruiting | Effect of Dexmedetomidine and Esketamine on Catheter-related Bladder Discomfort |
| NCT05732064 | 2022-761 | Ph 4 | completed | Dexmedetomidine-esketamine Combined Nasal Administration and Perioperative Sleep Quality |
| NCT05950646 | 2023-239 | Ph 4 | recruiting | Mini-dose Dexmedetomidine-Esketamine Infusion and Perioperative Sleep Quality |
| NCT05718544 | 2023-017 | Ph 4 | completed | Mini-dose Esketamine-dexmedetomidine Supplemented Analgesia and Long-term Outcomes |
| NCT06087510 | 2023-351-2 | Ph 4 | recruiting | Different Dose Esketamine and Dexmedetomidine for Supplemental Analgesia and Longterm Outcomes |
| NCT04843982 | YSY202001 | Ph 4 | recruiting | Immunoinflammatory Regulation of Esketamine in Septic Patients |
| NCT07063108 | 2022-698 | Ph 4 | not yet recruiting | Efficacy and Safety of S-ketamine in Elderly Patients Undergoing Non-cardiac Surgery: a RCT（ESSENCE） |
| NCT06958393 | opioid-free anaesthesia | Ph 4 | not yet recruiting | Effect of Opioid-free Anaesthesia on Postoperative Delirium in Elderly Patients Undergoing Gastrointestinal Surgery |
| NCT02417064 TRANSFORM-1 results posted | CR107146 ESKETINTRD3001, 2014-004584-20 | Ph 3 | completed | A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression |
| NCT02418585 TRANSFORM-2 results posted | CR107147 ESKETINTRD3002, 2014-004585-22 | Ph 3 | completed | A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression |
| NCT03185819 results posted | CR108323 2016-004422-42, ESKETINSUI2002 | Ph 2 | completed | Study to Evaluate the Efficacy and Safety of 3 Fixed Doses of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Pediatric Participants Assessed to be at Imminent Risk for Suicide |
| NCT03039192 Aspire I results posted | CR108284 2016-003990-17, 54135419SUI3001 | Ph 3 | completed | 54135419SUI3001: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide |
| NCT03097133 Aspire II results posted | CR108285 2016-003992-23, 54135419SUI3002 | Ph 3 | completed | 54135419SUI3002: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide |
| NCT02133001 results posted | CR103162 ESKETINSUI2001 | Ph 2 | completed | A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide |
| NCT02422186 TRANSFORM-3 results posted | CR107129 ESKETINTRD3005, 2014-004588-19 | Ph 3 | completed | A Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Participants With Treatment-resistant Depression |
| NCT02493868 SUSTAIN-1 results posted | CR107128 ESKETINTRD3003, 2014-004586-24 | Ph 3 | completed | A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression |
| NCT01640080 | CR100843 ESKETIVTRD2001, 2011-005992-17 | Ph 2 | completed | A Study of the Efficacy of Intravenous Esketamine in Adult Patients With Treatment-Resistant Depression |
| NCT02919579 DriveSaFe2 | CR108228 2016-002424-86, 54135419TRD1019 | Ph 1 | completed | A Study to Evaluate the Effects of a Single-Dose and Repeat-Administration of Intranasal Esketamine on On-Road Driving in Participants With Major Depressive Disorder |
| NCT02606084 | CR108058 54135419TRD1014 | Ph 1 | completed | A Study to Assess the Effects of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine |
| NCT02846519 | CR108128 ESKETINTRD1008 | Ph 1 | completed | Pharmacokinetic, Safety, and Tolerability Study of Intranasally Administered Esketamine in Healthy Han Chinese, Korean, Japanese, and Caucasian Participants and the Effects of Rifampin on the Pharmacokinetics of Intranasally Administered Esketamine |
| NCT03298906 | CR108377 54135419TRD1020, 2017-003174-14 | Ph 1 | completed | A Study to Assess the Effect of Ticlopidine on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants |
| NCT05268497 | CR109113 NATRD1001 | Ph 1 | withdrawn | A Study to Assess Feasibility of Using Clinician-directed and Digital Application Supported Cognitive Behavior Therapy (CBT) in Conjunction With Esketamine in Participants With Treatment-resistant Depression |
| NCT06161805 EASYlight | EASYlight-NEK | Ph 3 | recruiting | Esketamine as Treatment for Chronic Pain Due to Endometriosis: a RCT Study |
| NCT06920576 | CLXie | Ph 1, Ph 2 | active not recruiting | Effects of Esketamine Versus Magnesium Sulfate on Emotional State and Postoperative Pain in Patients Undergoing Nasal Endoscopic Surgery |
| NCT06822088 OLV;Esk | (2024)ethical review L No.122 CXPJJH124001-19 | Ph 4 | not yet recruiting | Effects of Esketamine on Oxygenation and Quality of Recovery in Patients Undergoing Thoracoscopic Surgery |
| NCT02568176 | CR108043 ESKETINTRD1010, 2015-002654-13 | Ph 1 | completed | Pharmacokinetic Study of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Participants |
| NCT02611505 | CR108098 ESKETINTRD1011 | Ph 1 | completed | A Study to Assess the Effects of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine |
| NCT02857777 | CR108213 54135419TRD1018 | Ph 1 | completed | Pharmacokinetic, Safety, and Tolerability Study of Intranasally Administered Esketamine in Elderly Japanese, and Healthy Younger Adult Japanese Subjects |
| NCT06051227 FORE-PAIN | FP-2023 2022-500176-63-00, U1111-1287-7486 | Ph 3 | recruiting | Fentanyl or Esketamine for Traumatic PAIN (FORE-PAIN) Trial |
| NCT06744361 KETOHCA | 2024-515987-29-00 2024-515987-29-00 | Ph 2 | recruiting | Ketamine Sedation As Neuroprotective Agent Following Out-of-hospital Cardiac Arrest |
| NCT05698394 | 2022-562 | Ph 4 | active not recruiting | Effect of Low-dose Esketamine on Maternal Depression at 3 Years After Childbirth |
| NCT04548973 | MZK20200831 | Ph 4 | completed | A Multicenter Study of the Efficacy and Safety of Esketamine for Analgesia During Cesarean Section |
Showing 50 of 71 trials
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
SPRAVATO FDA Label Details
Indications & Usage
FDA Label (PDF)SPRAVATO is indicated for the treatment of Treatment-Resistant Depression; Major Depressive Disorder.
WARNING: SEDATION; DISSOCIATION; RESPIRATORY DEPRESSION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS WARNING: SEDATION; DISSOCIATION; RESPIRATORY DEPRESSION; ABUSE AND MISUSE; and SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Risk for sedation...
SPRAVATO Patents & Exclusivity
Patents (7 active)
Exclusivity
Pro Intelligence Preview
Deep insights for SPRAVATO
Revenue Insights
- • Q4-2025: $520M
- • Historical trend analysis
Patent Timeline
- • Cliff: 2040
- • 25 active patents
Trial Analysis
- • 73 total trials
- • Stage: Stable
Competitive Landscape
- • 20 similar drugs
- • Same target/indication analysis
Full approval history • All patents • Revenue trends • Competitor analysis
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.
How We Calculate These Metrics
Trial Activity Stage
Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.
Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.
- Growth: High proportion of early-phase trials (Phase 1/2), active development
- Expansion: Significant Phase 3 activity, approaching or pursuing approvals
- Mature: Substantial Phase 4 post-marketing studies
- Stable: Mixed phase distribution, steady development
- Declining: Low active trial ratio, reduced R&D investment