Esketamine 28mg/0.2ml nasal spray unit dose
Requires a prescription from a doctor or prescriber
Strict controls: safe custody, register required
Legal requirements and restrictions
These are medicines with high potential for misuse but with accepted medical uses. Subject to the strictest controls.
Legal requirements
- Must be stored in a locked controlled drugs cabinet
- Pharmacy must keep a controlled drugs register
- Prescriptions valid for 28 days only
- Prescriptions must include specific details (dose, form, strength, total quantity)
- Cannot be emergency supplied by pharmacists
Other medicines in this category
Morphine, Oxycodone, Fentanyl, Methylphenidate (Ritalin), Amphetamines
Safety information for pregnancy and breastfeeding
Pregnancy
Use in pregnancy
This drug may cause fetal harm, based on the findings of animal studies.
Breastfeeding
Esketamine is present in human milk.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
Official documents, adverse reaction reporting, and safety monitoring
Report a side effect
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Official medicine documents
Safety monitoring data
Yellow Card reports
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
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Report a side effect
Submit a Yellow Card report to the MHRA
Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Esketamine
About EudraVigilance
Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
1 branded products available
MHRA licensed products
View all licensed products for Esketamine on the MHRA register
Spravato 28mg/0.2ml nasal spray unit dose
Therapeutically similar medicines
Similarity is based on WHO Anatomical Therapeutic Chemical (ATC) classification and on a factual NHS dm+d therapeutic-grouping code prefix. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
Guidelines from the National Institute for Health and Care Excellence
NICE clinical guidance(3)
Esketamine nasal spray for treatment-resistant depression (TA854)
Esketamine for treating major depressive disorder in adults at imminent risk of suicide (terminated appraisal) (TA899)
Depression in adults: treatment and management (NG222)
Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Pharmacy stock checkers
Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & safety information
Official UK regulator monitoring and safety alerts
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. Shortage and safety information sourced from MHRA drug safety updates (gov.uk, Crown Copyright under OGL v3.0).
Codes for healthcare professionals and prescribing systems
These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF code shown is the factual mapping value distributed by NHS Business Services Authority (NHSBSA) in the dm+d supplementary file under OGL v3.0; it is not affiliated with, nor licensed from, the publishers of the British National Formulary. ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Academic studies and reviews for this medicine's active substance
Showing the 50 most relevant studies.
Reviews & meta-analyses: 49 · Randomised trials: 1 · 2023–2026
Showing the 50 most relevant studies, sorted by most relevant.
K. Fountoulakis, Athanasios Saitis, A. Schatzberg
The American journal of psychiatry, 2025
Ashok Seshadri, Larry J Prokop, Balwinder Singh
Journal of affective disorders, 2024
K.-C. Hung, C.-L. Kao, C. Ho, et al.
British journal of anaesthesia, 2024
A. Kwan, K. Teopiz, Sabrina Wong, et al.
Journal of affective disorders, 2024
Alessandro Rodolico, Pierfelice Cutrufelli, A. Di francesco, et al.
Frontiers in Psychiatry, 2024
Shuying Li, Wenqin Zhou, Ping Li, et al.
Journal of affective disorders, 2024
Juliana Lima Constantino, M. Godschalk, Jens H. van Dalfsen, et al.
Psychiatry research, 2025
M. Cheng, Christine Dri, Hana Ballum, et al.
Journal of affective disorders, 2025
INTRODUCTION The rapid and clinically meaningful antidepressant effects of ketamine and esketamine are well-established in major depressive disorder (MDD) and treatment-resistant depression (TRD) as evidenced by improvement in clinician-and patient-reported depression measures. However, there remains a need to determine how these agents affect patient-reported quality of life (QoL) measures. Herein, we aimed to systematically review extant studies evaluating the effect of ketamine and esketamine on QoL measures. METHODS A literature search was conducted on online databases (PubMed, Scopus, Web of Science, Medline, and clinicaltrials.gov) for articles from inception to September 30th, 2024, reporting on the association between ketamine/esketamine and measures of QoL in persons diagnosed with MDD or TRD. Risk of bias was conducted using ROBINS-1 and the Newcastle-Ottawa Scale. RESULTS 5 studies were identified that investigated the association between ketamine/esketamine and measures of QoL in persons with MDD or TRD. Scales used to measure QoL included the WHOQOL-BREF scale, Assessment of Quality of Life 8D test, and the EuroQol-5 Dimension-5 Layers. Statistically significant findings (p < 0.001) suggest that ketamine and esketamine improve measures of QoL. However, an overall moderate risk of bias was found in the papers included in this analysis. DISCUSSION Extant studies suggest that ketamine and esketamine treatment are associated with improvement in QoL measures in adults with MDD or TRD. Limitations of this study include differences in QoL measures and study lengths between the studies included. Near-term research priorities should endeavour to look at how these two agents can improve specific domains of QoL.
Abstract licence: CC BY
Xinyi Sun, Chengwei Li, Lin Xu, et al.
Frontiers in Pharmacology, 2025
Yazhou Wen, Mingjie Mao, Xian Wang, et al.
Psychiatry research, 2024
Sources: aggregated from Europe PMC (EMBL-EBI), OpenAlex, Crossref, PubMed and other open scholarly databases. Retracted articles are excluded. Study information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
1 found
Half-life
7 to 12 hours
Mechanism
Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-compet…
Food interactions
2 warnings
Human targets
5 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
48%
Half-life
7 to 12 hours
[L12999]
Protein binding
43%
[L12999]
Volume of distribution
709 L
[L12999]
Metabolism
Elimination
1%
Clearance
89 L/h
[L12999]
Elimination…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Esketamine is the s-enantiomer of [Ketamine]. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first time that the FDA has approved esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.[L5593]
Esketamine may prove to be a promising treatment for patients diagnosed with major depressive disorder who have not experienced an improvement in symptoms despite treatment with various medications and therapies. The intranasal route of administration for this drug allows for easy administration and a fast onset of action, which sets it apart from many other antidepressant agents that may take several weeks to take effect.
[L52410]
It is also indicated for the treatment of depressive symptoms in adults with major depressive disorder experiencing acute suicidal ideation or behaviour.
[L12999]
Known interactions with other medications. Always consult a healthcare professional.
Showing 50 of 1441 interactions
Neurotoxicity
In a one-dose neuronal toxicity study with esketamine intranasal administration to adult female rats, no finding of neuronal vacuolation in the brain occurred with doses up to the equivalent of the maximum recommended human dose of 84 mg/day. In a second single dose neurotoxicity study performed with intranasal esketamine administration in adult female rats, no observation of neuronal necrosis up to a dose equivalent to the maximum recommended human dose was made. Neuronal vacuolation was not evaluated in this study.
[L12999]
The relevance of these findings in humans is unknown at this time.
[L12999]
A note on dependence and tolerance
Reports of physical dependence have been made following prolonged use of ketamine. Withdrawal signs and symptoms after abrupt discontinuation or significant dosage reduction of a drug is a common manifestation of drug dependence. There were no withdrawal symptoms observed up to 4 weeks in subjects after stopping esketamine treatment.
Withdrawal symptoms have been observed after the discontinuation of frequently used (more than weekly) high doses of ketamine for a longer duration. These symptoms of withdrawal have a higher chance of occurring if esketamine was similarly abused.
[L12999]
Symptoms of withdrawal reported to be associated with daily intake of high ketamine doses include craving, fatigue, poor appetite, and anxiety. Therefore, monitor esketamine-treated patients for symptoms and signs of physical dependence upon the discontinuation of the drug.
Tolerance has been reported with prolonged use of ketamine. Tolerance is characterized by a decreased response to a drug following repeated doses (i.e., a higher dose of a drug is required to produce the same effect that was previously achieved at a lower dose). Comparable tolerance would be expected to occur with long-term use of esketamine.
[L12999]
Use in pregnancy
This drug may cause fetal harm, based on the findings of animal studies.
Pregnancy planning and prevention in females of reproductive potential should occur before the initiation of esketamine treatment.
[L12999]
There is a pregnancy registry for women who exposed to esketamine during pregnancy. The goal of the registry is to gather data about the health of women and infants exposed to esketamine.
Use in lactation
Esketamine is present in human milk. No safety data on the effects of esketamine on the breastfed infant or on milk production are available.
Studies in young animals report neurotoxicity. Due to the risk of neurotoxicity, advise patients that breastfeeding is not recommended during treatment with this drug.
[L12999]
Esketamine is considered a central nervous system (CNS) depressant agent. It may cause sedation, dizziness, and lethargy, among other symptoms.[L12999] This drug has dissociative and antidepressant properties.[L12999] Acutely, esketamine may impair attention, judgment, thinking, reaction speed, and motor skills. Two placebo-controlled studies were performed to evaluate the effects of ketamine on the ability to drive. The effects of esketamine 84 mg were comparable to placebo at 6 hours and 18 hours post-ingestion.[L12999]
Effects on cardiac electrophysiology
The effect of esketamine (84 mg nasal spray and 0.8 mg/kg esketamine intravenously infused over 40 minutes) on the QTc interval was studied in a randomized, double-blind, placebo-, and positive-controlled (moxifloxacin 400 mg), 4-period, crossover study in 60 healthy volunteers. A marked increase in heart rate (higher than 10 bpm) was measured in subjects receiving intranasal and intravenous esketamine. Summative evidence from both nonclinical and clinical data suggests a lack of clinically relevant QTc prolongation at the normal therapeutic dose of esketamine.[L12999]
Effects on blood pressure
Eskestamine causes increases in systolic and/or diastolic blood pressure at all therapeutic doses. Peak blood pressure elevation after esketamine administration occurs about 40 minutes after administration and lasts approximately 4 hours.[L12999]
Cognitive effects
In a study of healthy volunteers, one dose of this agent caused decline in cognitive performance 40 minutes after administration. Compared to subjects ingesting a placebo, esketamine-treated subjects required a higher level of effort to complete assigned cognitive tests at 40 minutes after administration. Cognitive performance and mental effort were found to be similar between esketamine and placebo at 2 hours after administration.[L12999]
Reports of long-term memory or cognitive impairment have been made following repeated ketamine misuse or abuse. No adverse effects of esketamine nasal spray on cognitive function were seen in a one-year open-label safety study. The long-term cognitive effects of esketamine have not been studied for more than a 1 year period, therefore, the risk of cognitive decline with long-term use is not yet confirmed.[L12999]
How the body processes this drug — absorption, distribution, metabolism, and elimination
Inter-subject variability of esketamine ranges from 27% to 66% for Cmax (maximum concentration) and 18% to 45% for AUC (area under the curve). The intra-subject variability of esketamine is about 15% for Cmax and 10% for AUC.
[L12999]
[L12999]
[L12999]
[L12999]
[L12999]
[L12999]
[L12999]
Elimination of the major esketamine metabolite, noresketamine, from plasma is slower than esketamine. The decrease of noresketamine plasma concentrations occurs in a biphasic fashion, with a more rapid decline for the first 4 hours post-administration, and an average terminal t1/2 of approximately 8 hours.
[L12999]
Proteins and enzymes this drug interacts with in the body
GluN3B subunit also binds D-serine and, in the absence of glycine, activates glycinergic receptor complexes, but with lower efficacy than glycine (By similarity). Each GluN3 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (By similarity)
PMID:24272827 PMID:24863970 PMID:26875626 PMID:26919761 PMID:27839871 PMID:28095420 PMID:28126851 PMID:38538865 PMID:8768735
Participates in synaptic plasticity for learning and memory formation by contributing to the long-term depression (LTD) of hippocampus membrane currents (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) .
PMID:24272827 PMID:24863970 PMID:26875626 PMID:26919761 PMID:27839871 PMID:28095420 PMID:28126851 PMID:38538865 PMID:8768735
NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators .
PMID:26875626 PMID:28095420 PMID:28126851 PMID:38538865 PMID:8768735
In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage.
Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity)
PMID:11152678
During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS.
The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability
PMID:26593721
During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively .
PMID:26593721
Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome PMID:26593721
PMID:15494731 PMID:7574684
Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation .
PMID:15494731
Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades.
Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity.
Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions.
May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia
Enzymes involved in drug metabolism — important for understanding drug interactions
ATC N06AX27
ATC N01AX14
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
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Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Esketamine
Additional database identifiers
Drugs Product Database (DPD)
23459
ChemSpider
158414
PDB
JC9
ZINC
ZINC000035999642
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4584
GenAtlas
GRIN1
GeneCards
GRIN1
GenBank Gene Database
D13515
GenBank Protein Database
219920
Guide to Pharmacology
455
UniProt Accession
NMDZ1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4585
GenAtlas
GRIN2A
GeneCards
GRIN2A
GenBank Gene Database
U09002
GenBank Protein Database
558749
Guide to Pharmacology
456
UniProt Accession
NMDE1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4586
GenAtlas
GRIN2B
GeneCards
GRIN2B
GenBank Gene Database
U90278
GenBank Protein Database
1899202
Guide to Pharmacology
457
UniProt Accession
NMDE2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4587
GenAtlas
GRIN2C
GeneCards
GRIN2C
GenBank Gene Database
L76224
GenBank Protein Database
1196449
Guide to Pharmacology
458
UniProt Accession
NMDE3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4588
GenAtlas
GRIN2D
GeneCards
GRIN2D
GenBank Gene Database
U77783
GenBank Protein Database
2444026
UniProt Accession
NMDE4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:16767
GenAtlas
GRIN3A
GeneCards
GRIN3A
GenBank Gene Database
AJ416950
GenBank Protein Database
20372905
UniProt Accession
NMD3A_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:16768
GenAtlas
GRIN3B
GeneCards
GRIN3B
GenBank Gene Database
AC004528
GenBank Protein Database
3025446
UniProt Accession
NMD3B_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4586
GenAtlas
GRIN2B
GeneCards
GRIN2B
GenBank Gene Database
U90278
GenBank Protein Database
1899202
Guide to Pharmacology
457
UniProt Accession
NMDE2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1033
GenAtlas
BDNF
GeneCards
BDNF
GenBank Gene Database
M37762
UniProt Accession
BDNF_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3214
GeneCards
EEF2
GenBank Gene Database
X51466
GenBank Protein Database
31106
UniProt Accession
EF2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8032
GeneCards
NTRK2
GenBank Gene Database
U12140
GenBank Protein Database
530791
Guide to Pharmacology
1818
UniProt Accession
NTRK2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
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Structured knowledge from the free knowledge base
ATC classifications (Wikidata)
Linked open data from Wikidata (Q2365493), a free and open knowledge base operated by the Wikimedia Foundation. Data is available under the Creative Commons CC0 1.0 Public Domain Dedication. WHO INN from the World Health Organization.