Esketamine

Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N -methyl- D -aspartate (NMDA) receptor, an ionotropic glutamate receptor. The mechanism by which esketamine exerts its antidepressant effect is unknown.

• SPRAVATO is indicated for the treatment of: Treatment-resistant depression (TRD) in adults as monotherapy or in conjunction with an oral antidepressant Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant SPRAVATO is a non-competitive N -methyl D -aspartate (NMDA) receptor antagonist indicated for the treatment of: Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant. ( 1 ) Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant.ICD-10: F32.9

• SPRAVATO is contraindicated in patients with: Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation [see Warnings and Precautions (5.7) ] History of intracerebral hemorrhage [see Warnings and Precautions (5.7) ] Hypersensitivity to esketamine, ketamine, or any of the excipients. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.contraindicated

Administer SPRAVATO intranasally under the supervision of a healthcare provider. ( 2.1 ) Assess blood pressure prior to and after administration. ( 2.1 ) TRD: Evidence of therapeutic benefit should be evaluated at the end of the 4-week induction phase to determine need for continued treatment. ( 2.2 ) Depressive symptoms in MDD with acute suicidal ideation or behavior : Evidence of therapeutic benefit should be evaluated after 4 weeks to determine need for continued treatment. Treatment beyond 4 weeks has not been systematically evaluated. ( 2.3 ) See Full Prescribing Information for recommended dosage. ( 2.2 , 2.3 ) See Full Prescribing Information for important administration instructions. ( 2.4 ) 2.1 Important Considerations Prior to Initiating and During Therapy SPRAVATO must be administered under the direct supervision of a healthcare provider. A treatment session consists of nasal administration of SPRAVATO and post-administration observation under supervision. Respiratory Status Assessment During Treatment Monitor patients for changes in respiratory status for at least 2 hours (including pulse oximetry) at each treatment session [see Warnings and Precautions (5.3) ] . Blood Pressure Assessment Before and After Treatment Assess blood pressure prior to dosing with SPRAVATO [see Warnings and Precautions (5.7) ] . If baseline blood pressure is elevated (e.g., >140 mmHg systolic, >90 mmHg diastolic), consider the risks of short term increases in blood pressure and benefit of SPRAVATO treatment [see Warnings and Precautions (5.7) ].

Increases in Blood Pressure: Patients with cardiovascular and cerebrovascular conditions and risk factors may be at an increased risk of associated adverse effects. ( 5.7 ) Cognitive Impairment: SPRAVATO may impair attention, judgment, thinking, reaction speed and motor skills. ( 5.8 ) Impaired Ability to Drive and Operate Machinery: Do not drive or operate machinery until the next day after a restful sleep. ( 5.9 ) Embryo-fetal Toxicity: May cause fetal harm. Consider pregnancy planning and prevention in females of reproductive potential. ( 5.11 , 8.1 , 8.3 ) 5.1 Sedation SPRAVATO may cause sedation or loss of consciousness. In some cases, patients may display diminished or less apparent breathing. In clinical trials, 48% to 61% of SPRAVATO-treated patients developed sedation based on the Modified Observer's Assessment of Alertness/Sedation scale (MOAA/S) [see Adverse Reactions (6.1) ] , and 0.3% to 0.4% of SPRAVATO-treated patients experienced loss of consciousness (MOAA/S score of 0). Because of the possibility of delayed or prolonged sedation, patients must be monitored by a healthcare provider 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 Dosage and Administration (2.5) ] . Closely monitor for sedation with concomitant use of SPRAVATO with CNS depressants [see Drug Interactions (7.1) ] . SPRAVATO is available only through a restricted program under a REMS [see Warnings and Precautions (5.5) ] .

The following adverse reactions are discussed in more detail in other sections of the labeling: Sedation [see Warnings and Precautions (5.1) ] Dissociation [see Warnings and Precautions (5.2) ] Respiratory Depression [see Warnings and Precautions (5.3) ] Increase in Blood Pressure [see Warnings and Precautions (5.7) ] Cognitive Impairment [see Warnings and Precautions (5.8) ] Impaired Ability to Drive and Operate Machinery [see Warnings and Precautions (5.9) ] Ulcerative or Interstitial Cystitis [see Warnings and Precautions (5.10) ] Embryo-fetal Toxicity [see Warnings and Precautions (5.11) ] The most commonly observed adverse reactions (incidence ≥5% and at least twice that of placebo): TRD: dissociation, dizziness, nausea, sedation, vertigo, hypoesthesia, anxiety, lethargy, blood pressure increased, vomiting, feeling drunk, and headache. ( 6 ) Treatment of depressive symptoms in adults with MDD with acute suicidal ideation or behavior: dissociation, dizziness, sedation, blood pressure increased, hypoesthesia, vomiting, euphoric mood, and vertigo. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Lactation: Breastfeeding not recommended. ( 8.2 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including SPRAVATO, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ . Risk Summary SPRAVATO is not recommended during pregnancy. There are insufficient data on SPRAVATO use in pregnant women to draw conclusions about any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on published findings from pregnant animals treated with ketamine, the racemic mixture of arketamine and esketamine, SPRAVATO may cause fetal harm when administered to pregnant women (see Data ) . Advise pregnant women of the potential risk to an infant exposed to SPRAVATO in utero . There are risks to the mother associated with untreated depression in pregnancy (see Clinical Considerations ). If a woman becomes pregnant while being treated with SPRAVATO, treatment with esketamine should be discontinued and the patient should be counseled about the potential risk to the fetus.

Metabolism

Esketamine exposure increases with dose from 28 mg to 84 mg. The increase in C max and AUC values was less than dose-proportional between 28 mg and 56 mg or 84 mg, but it was nearly dose proportional between 56 mg and 84 mg.

Management of Overdosage There is no specific antidote for esketamine overdose. In the case of overdose, the possibility of multiple drug involvement should be considered. Contact a Certified Poison Control Center for the most up to date information on the management of overdosage (1-800-222-1222 or www.poison.org).

• Mar 5, 2019NDANDA211243Janssen Pharms

1. 1Dissociation3,58821%
2. 2Sedation2,62016%
3. 3Suicidal Ideation1,2857.6%
4. 4Drug Ineffective1,0546.3%
5. 5Nausea9115.4%
6. 6Depression8405.0%
7. 7Hypertension7724.6%
8. 8Product Dose Omission Issue7554.5%
9. 9Hospitalisation7474.4%
10. 10Anxiety7074.2%
11. 11Vomiting6864.1%
12. 12Dizziness6203.7%
13. 13Blood Pressure Increased5363.2%
14. 14Feeling Abnormal4782.8%
15. 15Off Label Use3922.3%

The 10 most recently updated of 344 ClinicalTrials.gov registrations naming Esketamine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• The Effects of Different Anesthetics on the Brain's Neural Networks
  Not yet recruiting · Phase 4 · Interventional · 120 enrolled · Fudan University
  NCT07644663updated 2026-06-12
• The Effect of Esketamine on Cough Reflex During Tracheal Extubation in Patients Undergoing Non-inflatable Transoral Endoscopic Thyroid Surgery
  Not yet recruiting · Interventional · 186 enrolled · The Second Hospital of Anhui Medical University
  NCT07641673updated 2026-06-11
• Intranasal Esketamine-dexmedetomidine Combination and Postpartum Depression
  Not yet recruiting · Phase 4 · Interventional · 164 enrolled · Peking University First Hospital
  NCT07639099updated 2026-06-10
• Efficacy and Safety of Esketamine Combined With Dexmedetomidine in Non-Invasive ICU Patients With Hyperactive Delirium (ESSENTIAL Trial): Protocol of a Randomized Controlled Trial
  Not yet recruiting · Phase 4 · Interventional · 388 enrolled · The First Affiliated Hospital with Nanjing Medical University
  NCT07377981updated 2026-06-10
• A Study to Evaluate the Efficacy and Safety of Esketamine for Reduction of Symptoms of Major Depressive Disorder
  Recruiting · Phase 3 · Interventional · 258 enrolled · Janssen Research & Development, LLC
  NCT07227454updated 2026-06-05
• A Study of Esketamine Nasal Spray in Korean Participants With Treatment-resistant Depression
  Recruiting · Phase 4 · Interventional · 47 enrolled · Janssen Korea, Ltd., Korea
  NCT07053345updated 2026-06-05
• The Effect of Esketamine on Cough Reflex During Tracheal Extubation in Patients Undergoing Open Thyroid Surgery
  Not yet recruiting · Interventional · 136 enrolled · The Second Hospital of Anhui Medical University
  NCT07625826updated 2026-06-04
• Opioid-Free Anesthesia and Pain Study in Cardiac Surgery Patients
  Not yet recruiting · Interventional · 400 enrolled · Clinical Centre of Serbia
  NCT07618130updated 2026-06-01
• Intranasal Dexmedetomidine-esketamine on Sleep and Cognition in Older Adults With Mild-to-moderate Cognitive Impairment
  Not yet recruiting · Phase 4 · Interventional · 60 enrolled · Peking University First Hospital
  NCT07610343updated 2026-06-01
• Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression
  Recruiting · Phase 4 · Interventional · 162 enrolled · The George Institute
  NCT06278779updated 2026-05-29

Frequently asked questions

How does Esketamine work?

Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N -methyl- D -aspartate (NMDA) receptor, an ionotropic glutamate receptor. The mechanism by which esketamine exerts its antidepressant effect is unknown.

What is Esketamine used for?

According to FDA labeling, Esketamine carries indications including: SPRAVATO is indicated for the treatment of: Treatment-resistant depression (TRD) in adults as monotherapy or in conjunction with an oral antidepressant Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant SPRAVATO is a non-competitive N -methyl D -aspartate (NMDA) receptor antagonist indicated for the treatment of: Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant. ( 1 ) Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Esketamine?

Esketamine is classified as Other antidepressants, Other general anesthetics, Noncompetitive NMDA Receptor Antagonists, Central Nervous System Depression, Decreased Central Nervous System Organized Electrical Activity.

What are the brand names for Esketamine?

Esketamine is marketed under brand names including Spravato.

What are the contraindications for Esketamine?

Esketamine labeling lists contraindications including: SPRAVATO is contraindicated in patients with: Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation [see Warnings and Precautions (5.7) ] History of intracerebral hemorrhage [see Warnings and Precautions (5.7) ] Hypersensitivity to esketamine, ketamine, or any of the excipients. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.. Always consult the full prescribing information and a clinician.