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SPRAVATO®

(esketamine)

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This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

SPRAVATO® (esketamine)
Medical Information

Concomitant Use of SPRAVATO with Ketamine

Last Updated: 05/28/2026

SUMMARY

  • There are no studies evaluating the efficacy or safety of concurrent treatment with
  • ketamine and SPRAVATO.
  • Esketamine, the S-enantiomer of racemic ketamine, is a nonselective, noncompetitive
  • antagonist of the N-methyl-D-aspartate (NMDA).1-4  However, the precise mechanism
  • of action of esketamine in MDD is unknown. The antidepressant pharmacologic action of esketamine is thought to be similar to ketamine.1,2,4,5 
  • The concomitant use of ketamine and SPRAVATO may increase the risk of additive adverse effects, although this has not been systematically evaluated.
  • The most commonly observed adverse reactions in adult patients treated with SPRAVATO (incidence ≥5% and at least twice that of placebo):
    • Treatment-resistant depression (TRD): dissociation, dizziness, nausea, sedation,
    • vertigo, hypoesthesia, anxiety, lethargy, BP increased, vomiting, feeling drunk, and headache.6-8 
    • Major depressive disorder (MDD) with acute suicidal ideation or behavior: dissociation, dizziness, sedation, BP increased, hypoesthesia, vomiting, euphoric mood, and vertigo.9,10 
  • One case reported the concomitant use of SPRAVATO with sublingual (SL) ketamine in a 63-year-old female patient with multiple psychiatric conditions, including TRD.11 
  • Please contact the manufacturer of ketamine for more information regarding the safety and drug-drug interactions for this product.

Case Report

Gregor et al (2023)11 presented a case report of a 63-year-old female who arrived at the emergency department with catatonia and depressive symptoms. She had a past psychiatric history of bipolar I disorder, schizoaffective disorder, bipolar type, and TRD, with several prior psychiatric hospitalizations. She had not responded to several pharmacological agents, including antipsychotics, mood stabilizers, stimulants, and antidepressants, and multiple rounds of ECT.

During the most recent admission, the patient was started on SL ketamine 50 mg twice a week along with diazepam. Upon symptom improvement, the patient was discharged home on SL ketamine, diazepam, methylphenidate ER, paliperidone, and sertraline. Progressive improvement was observed despite a slight setback when she missed a dose of ketamine. She was later prescribed SPRAVATO twice weekly in place of SL ketamine. After 1.5 months, she was maintained on 84 mg once weekly while also receiving supplemental doses of SL ketamine 150 mg weekly. The patient gradually resumed her baseline activities, remaining clinically stable, with no further acute hospitalizations in the months that followed.

Literature Search

A literature search of MEDLINE®, EMBASE®, BIOSIS Previews®, and DERWENT Drug databases (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 23 March 2026.

 

References

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1 Sanacora G, Zarate CA, Krystal JH, et al. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7(5):426-437.  
2 Duman RS, Aghajanian GK, Sanacora G, et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22(3):238-249.  
3 Kim J, Farchione T, Potter A, et al. Esketamine for treatment-resistant depression - first FDA-approved antidepressant in a new class. N Engl J Med. 2019;381(1):1-4.  
4 Duman RS, Li N, Liu RJ, et al. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 2012;62(1):35-41.  
5 Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23(4):801-811.  
6 Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438.  
7 Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630.  
8 Janik A, Qiu X, Lane R, et al. Efficacy and safety of esketamine nasal spray as monotherapy in adults with treatment-resistant depression: a randomized, double-blind, placebo-controlled study. Poster presented at: American College of Neuropsychopharmacology (ACNP) Annual Congress; December 8–11, 2024; Phoenix, AZ.  
9 Fu DJ, Ionescu DF, Li X, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020;81(3):19m13191.  
10 Ionescu DF, Fu DJ, Qiu X, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021;24(1):22-31.  
11 Gregor EA, Zheng W. Oral and intranasal ketamine use in treatment-resistant catatonia: a clinical case report. Am J Case Rep. 2023;24(suppl 37095688):e939530.