Esketamine nasal spray, sold as Spravato, is a prescription medicine used for specified adults with depression. It is administered under professional supervision, followed by observation in a clinical setting. It is not a take-home nasal spray for someone to use whenever their mood deteriorates.
Although esketamine is related to ketamine, the two should not be treated as interchangeable. Understanding the exact medicine, authorised indication, evidence and monitoring requirements is essential when considering this treatment.
What is esketamine?
Esketamine is one of the two mirror-image forms present in ketamine. Its activity includes blocking NMDA receptors involved in glutamate signalling. The biological explanation is different from that of many conventional antidepressants, but a different mechanism does not guarantee a better outcome for an individual.
The European Medicines Agency describes Spravato as a supervised treatment for adults with treatment-resistant major depression, in combination with an SSRI or SNRI.
The separate ketamine treatment guide covers other ketamine preparations. Evidence or authorisation for Spravato cannot automatically be transferred to an infusion, lozenge or compounded nasal product.
Who may be eligible?
A specialist should confirm the diagnosis, current episode and previous treatment history. The assessment needs to establish what has been tried, whether it was tolerated and whether the proposed treatment addresses the person’s actual difficulties.
The current Great Britain product information describes use with an SSRI or SNRI after inadequate response to at least two antidepressant treatments during the current moderate-to-severe episode. It also describes a separate, short-term indication within comprehensive care for a psychiatric emergency due to major depression.
These are defined clinical circumstances, not permission to use the medicine for ordinary distress or every diagnosis. The depression treatment guide places specialist interventions within the wider care pathway.
Why information differs between countries
Regulatory indications are not identical everywhere. The current US prescribing information includes treatment-resistant depression in adults as monotherapy or with an oral antidepressant. Its separate indication for depressive symptoms with acute suicidal thoughts or behaviour still requires an oral antidepressant.
That US wording should not be assumed to apply in Europe or the UK. A clinician must confirm the applicable local authorisation and explain any off-label recommendation.
Licensing also differs from public funding or insurance coverage. A medicine can be authorised but not recommended for routine funding by a particular health system.
What happens before the first treatment?
Preparation should include review of physical health, blood pressure, current medicines and relevant psychiatric history. Explain any previous mania, psychosis, substance problems, neurological illness or significant cardiovascular condition.
Discuss pregnancy, breastfeeding or plans for pregnancy with the prescriber. Do not infer reproductive safety from the fact that a medicine is administered in a clinic.
Ask for written instructions about food, drink, nasal medicines and other prescribed treatments before an appointment. Individual instructions matter; do not change medicines independently to fit a general description found online.
The supervised appointment
The patient uses the nasal device under the direct supervision of a healthcare professional. Administration is followed by monitoring, including assessment of blood pressure and the person’s clinical state.
Observation is a central part of treatment, not an optional extra. The team needs to assess alertness, adverse effects and readiness to leave rather than send someone home because the spray itself has been administered.
Plan for the whole visit and the journey afterwards. Ask who will be present, what happens if the experience is distressing and how medical help is provided if an unexpected reaction occurs.
Induction and maintenance treatment
For treatment-resistant depression, the product information distinguishes an initial treatment phase from continued treatment for people who benefit. The frequency is subsequently reviewed according to response and tolerability.
The important decision is not simply whether a person has completed the first appointments. The clinician should assess whether there is meaningful benefit and whether continuing is justified.
Ask when progress will be reviewed, how missed visits are managed and what the plan would be if improvement fades. Treatment schedules should be prescribed by the service, not assembled from online dose tables.
Evidence for reducing depressive symptoms
A 2025 randomised trial examined esketamine without an oral antidepressant in selected adults with treatment-resistant depression. It found greater improvement in depression scores than placebo over four weeks, with common adverse effects including nausea, dissociation and dizziness.
The study supports a treatment effect in the population studied. It does not establish that everyone responds, that a short-term change is permanent or that local prescribing rules should be ignored.
When discussing a trial, consider the comparison treatment, follow-up period and who was excluded. Results from carefully selected adults without psychotic features cannot simply be extended to all people with severe depression.
Comparisons and longer-term evidence
The ESCAPE-TRD analyses compared esketamine with extended-release quetiapine, both alongside an ongoing antidepressant. Outcomes favoured esketamine in that study, but the trial’s design and specific comparator matter when interpreting the result.
A later individual-patient-data reanalysis found a statistically significant but relatively small average benefit in add-on initiation trials and highlighted adverse effects and remaining uncertainties. This analysis helps explain why discussions of the evidence can reach different conclusions about clinical importance.
Neither a favourable trial nor a critical reanalysis predicts your personal outcome. Ask what benefit would be sufficient to justify the treatment burden and how that decision will be revisited.
Side effects and reasons for monitoring
Possible effects include dizziness, nausea, altered taste, sleepiness, dissociation and a rise in blood pressure. Dissociation can feel like being detached from the body or surroundings and may be unsettling.
The US prescribing information carries prominent warnings concerning sedation, dissociation, respiratory depression and misuse. It requires administration through a restricted programme with observation for at least two hours. Local supervision arrangements must meet the requirements where treatment is provided.
Tell staff promptly if you feel unwell or frightened. A powerful subjective experience is not proof that the treatment is more effective, and distress should not be dismissed as something necessary for recovery.
Who needs particular caution?
Some vascular conditions, previous bleeding in the brain and circumstances where increased blood pressure would be dangerous can rule out treatment or require specialist consideration. A full assessment is more useful than a generic checklist on a booking page.
The prescriber also needs to consider other medicines, alcohol and substances that may affect sedation, blood pressure or mental state. Do not conceal non-prescribed use; accurate information supports safer decisions.
Report new urinary symptoms, changes in cognition or a growing preoccupation with obtaining the medicine. Professional supervision reduces some risks but does not make every longer-term concern irrelevant.
Suicidal thoughts and emergency care
The product information explicitly states that effectiveness in preventing suicide or reducing suicidal behaviour has not been demonstrated. Improvement in depressive symptoms after a dose does not remove the need for hospital care when that is clinically indicated.
An emergency indication must not be presented as a promise that the spray prevents suicide. Safety assessment, support and an appropriate setting remain essential.
Someone who cannot stay safe needs urgent local help. Do not wait for a routine enquiry response or travel independently to seek a specialist treatment during an immediate crisis.
Recovery, transport and everyday responsibilities
The patient leaflet explains precautions after treatment. Do not drive or undertake hazardous activities until the next day after restful sleep, and follow any additional restrictions given by the clinical team.
Arrange transport and consider childcare, work and other responsibilities before the appointment. Feeling less depressed does not necessarily mean coordination, attention and judgement have recovered from the medicine’s immediate effects.
A practical support plan should preserve independence while accounting for temporary impairment. Clarify whom to contact if symptoms remain troubling after leaving the clinic.
Costs, access and the wider treatment plan
NICE TA854 did not recommend esketamine for routine NHS use for treatment-resistant depression because of uncertainty about clinical and cost effectiveness. This funding assessment is separate from a medicines licence.
Before starting privately, clarify the total commitment, including assessment, supervised visits, monitoring and ongoing care. Ask what happens if treatment is ineffective or becomes unaffordable.
Medication review, psychological therapy and practical support can remain important. The medicine should not become a substitute for a coherent plan addressing the rest of the person’s needs.
Frequently asked questions about esketamine
Can I use Spravato at home?
Spravato is intended for use under professional supervision in an appropriate clinical setting, followed by observation. It should not be treated like an ordinary nasal medicine to use independently whenever symptoms increase.
Must it always be combined with an antidepressant?
The answer depends on the indication and country. US treatment-resistant-depression authorisation includes monotherapy, while the cited UK and EU indications require combination treatment. Confirm the local prescribing plan with the specialist.
How quickly might it help?
Some trials show an early effect, but response varies and needs review over the prescribed course. A change soon after treatment does not guarantee sustained improvement or remove the need for follow-up.
Does dissociation mean it is working?
No particular subjective experience guarantees benefit. The team should assess depression and functioning after the immediate drug effects have passed, while taking distressing experiences and adverse effects seriously.
Can I drive after the appointment?
Do not drive after treatment. Follow the patient information and the service’s instructions, including waiting until the next day after restful sleep. Arrange suitable transport before attending.
Is esketamine a cure for depression?
No treatment can promise permanent recovery for everyone. Some people benefit, others do not, and ongoing care may be needed. Decisions about continuation should balance improvement, adverse effects and practical burden.
Discussing your options
A clinical assessment can help review persistent depression and compare options. Contact VAYEMA to discuss your treatment history and an appropriate next step.
Sources and further reading
- EMA: Spravato overview
- Spravato: Great Britain product information
- DailyMed: US prescribing information
- Esketamine monotherapy randomised trial
- ESCAPE-TRD sensitivity analyses
- Individual-patient-data reanalysis
- NICE TA854: Evidence and funding assessment
Related conditions and concerns
These links explain the wider care context. They are not a recommendation that this approach is suitable for everyone with the condition. Use the condition treatment guide to understand alternatives and the role of clinical assessment.