Last reviewed 2026-04-20 · How we verify

Spravato (ESKETAMINE)

Spravato works by blocking the action of glutamate, a neurotransmitter involved in mood regulation.

At a glance

Mechanism of action

Esketamine, the S-enantiomer of racemic ketamine, is 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. The major circulating metabolite of esketamine (noresketamine) demonstrated activity at the same receptor with less affinity.

Approved indications

• Depressive disorder

Boxed warnings

• 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 misuse [see Warnings and Precautions (5.4) ] . Because of the risks of serious adverse outcomes resulting from sedation, dissociation, respiratory depression, abuse and misuse, SPRAVATO is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SPRAVATO REMS [see Warnings and Precautions (5.5) ] . Suicidal Thoughts and Behaviors Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. SPRAVATO is not approved for use in pediatric patients [see Warnings and Precautions (5.6) ] .

Common side effects

• Dissociation
• Dizziness
• Nausea
• Sedation
• Vertigo
• Hypoesthesia
• Anxiety
• Lethargy
• Vomiting
• Diarrhea
• Dry mouth
• Constipation

Key clinical trials

• 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 (PHASE3)
• 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 (PHASE3)
• 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 (PHASE3)
• A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression (PHASE3)
• Correlating EEG Dynamics With Consciousness Alteration Under Anesthesia
• A Study of CLE-100 (Oral Esketamine) as an Adjunctive Treatment to Standard Antidepressants for Major Depressive Disorder (PHASE2)
• Phenomenological Explorations of the Esketamine-Induced Transient Dissociative State (NA)
• Intranasal Dexmedetomidine-esketamine Administration and Postoperative Pain in Pediatric Patients (PHASE4)

Patents

Primary sources

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