Esketamine in Mental Health: Why It Is Used and What Happens During Treatment
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A patient arrives at a specialist mental health service for a treatment session. Before anything is given, their blood pressure is checked. They use a nasal spray themselves while a healthcare professional supervises them, and afterwards they remain in the clinical area while the team monitors how they are feeling, their level of alertness and their physical observations.
The medicine is esketamine.
If the name sounds familiar, there is a reason. Esketamine is closely related to ketamine, a medicine used in anaesthesia and also known for recreational misuse. But prescribed intranasal esketamine is being used here for a very different purpose, within a controlled treatment pathway for major depressive disorder.
To understand why someone might receive it, it helps to start with a patient whose depression has not responded adequately to treatment.
When depression has not responded to antidepressants
Major depressive disorder can affect mood, motivation, sleep, appetite, concentration, energy and the person's ability to function. Antidepressants are one part of treatment, and many commonly used medicines act predominantly through monoamine neurotransmitter systems such as serotonin and noradrenaline.
Some people continue to have significant symptoms despite receiving appropriate antidepressant treatment. For the licensed treatment-resistant depression indication, Spravato is used in adults with a current moderate-to-severe episode of major depressive disorder who have not responded to at least two different antidepressant treatments during that episode. It is used alongside a selective serotonin reuptake inhibitor (SSRI) or serotonin–noradrenaline reuptake inhibitor (SNRI).
Esketamine is therefore not simply a faster antidepressant offered instead of standard treatment. By the time it is being considered for treatment-resistant depression, the patient has already had a much longer treatment journey.
Why use a medicine related to ketamine?
Ketamine exists as two mirror-image molecular forms, or enantiomers: R-ketamine (arketamine) and S-ketamine (esketamine). Spravato contains esketamine.
Its antidepressant pharmacology differs from that of conventional monoaminergic antidepressants. Esketamine is a non-selective, non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor, one of the receptors involved in glutamate signalling in the brain.
Blocking NMDA receptors changes downstream glutamatergic signalling. The full antidepressant mechanism is not completely resolved, but subsequent changes in signalling are thought to promote synaptic function and plasticity within neural circuits involved in mood, motivation and emotional processing.
That difference in mechanism is clinically interesting because improvement in depressive symptoms can occur relatively quickly in some patients. It should not be interpreted as an instant cure. Response varies, treatment-resistant depression remains a complex illness and ongoing antidepressant and psychiatric care are still required.
What actually happens during an esketamine session?
Spravato is supplied as a single-use nasal-spray device. The patient self-administers the prescribed dose under the direct supervision of a healthcare professional. The treatment session includes both administration and a period of observation afterwards, so this is not a nasal spray the patient takes home to use when their mood deteriorates.
There is preparation before the dose as well. Because nausea and vomiting can occur, current product information advises no food for at least two hours beforehand and no liquids for at least 30 minutes beforehand. If a nasal corticosteroid or nasal decongestant is required on the treatment day, it should not be administered within the hour before esketamine.
Blood pressure is checked before treatment because esketamine can cause a temporary rise in systolic and diastolic pressure. If the baseline blood pressure is elevated, the clinician has to consider whether treatment should proceed. There are also circumstances in which a rise in blood pressure or intracranial pressure would pose a serious risk, making esketamine contraindicated.
After the dose, blood pressure is reassessed at around 40 minutes. That timing is deliberate: the increase in blood pressure typically peaks at approximately 40 minutes and usually lasts around one to two hours. Further measurements are taken when clinically indicated.
The patient stays under professional observation until they are considered clinically stable and ready to leave. There is no single discharge time that applies to everyone. The decision depends on their response to that particular treatment session.
What might the patient experience while you are observing them?
One of the most distinctive effects is dissociation. A patient may describe feeling detached from themselves, their surroundings, their thoughts or their sense of time. Perception can feel altered. Other common effects include dizziness, headache, sleepiness, nausea, vomiting and changes in sensation or taste. Anxiety, vertigo and sedation can also occur.
This is where simply knowing the side-effect list is less useful than watching the patient. Someone who becomes dizzy or sedated may not be safe to stand without assistance. Someone experiencing dissociation may need calm reassurance and an environment that does not add unnecessary stimulation. A patient who becomes unusually drowsy needs assessment rather than the assumption that sleepiness is expected and therefore harmless.
Rare cases of respiratory depression have been reported after esketamine, particularly in post-marketing use. Risk may be greater when central nervous system depressants are also involved or when relevant comorbidities are present. Monitoring after administration therefore includes attention to sedation and respiratory status as well as the patient's psychological experience.
Before leaving, the patient needs to be clinically stable. They should not drive or operate machinery until the following day after a restful sleep.
Why blood pressure deserves particular attention
Esketamine can activate cardiovascular responses that temporarily increase blood pressure. For many patients this rise resolves without intervention, but a substantial increase can occur after any treatment session.
That explains the pattern of assessment rather than leaving blood-pressure measurement as a protocol to memorise: establish where the patient is starting, administer the medicine in a supervised setting, reassess around the expected peak and continue monitoring if the pressure remains elevated or the patient develops concerning symptoms.
Chest pain, shortness of breath, a sudden severe headache, visual disturbance or seizures alongside a significant blood-pressure rise require urgent clinical assessment. Patients with certain aneurysmal vascular disease, a history of intracerebral haemorrhage or a recent cardiovascular event are among those for whom the treatment is contraindicated because an increase in blood pressure could pose serious risk.
What about misuse and dependence?
The relationship with ketamine cannot be ignored, but it needs to be discussed accurately.
Esketamine has recognised potential for abuse and dependence and is a controlled drug. A history of substance use disorder does not automatically define how an individual patient will respond to prescribed treatment, but it does mean the prescriber should consider the person's individual risk and the clinical team should remain alert to signs of misuse or drug-seeking behaviour.
The supervised treatment model is part of that safety framework. The medicine is administered in the healthcare setting rather than supplied for unsupervised use, which limits opportunities for diversion and additional dosing.
It is also useful not to blur prescribed intranasal esketamine with prolonged heavy recreational ketamine use. Ketamine misuse is associated with significant urinary-tract, cognitive and other harms, but that does not mean a patient receiving supervised esketamine should be spoken to as though they are misusing ketamine. Urinary symptoms including frequency, urgency and dysuria have been reported with esketamine and should still be taken seriously and assessed.
Rapid improvement does not remove suicide risk
Spravato also has a UK marketing authorisation, alongside an oral antidepressant, for short-term treatment of certain adults with a moderate-to-severe depressive episode whose symptoms constitute a psychiatric emergency.
There is an important distinction here. Esketamine can reduce depressive symptoms rapidly in some patients, but the product information states that its effectiveness in preventing suicide or reducing suicidal ideation or behaviour has not been demonstrated. An improvement in mood symptoms after a dose therefore does not remove the need for suicide-risk assessment, appropriate observation, safety planning, hospital care where indicated and ongoing treatment.
The medicine sits inside the patient's wider clinical care plan. It does not replace it.
Access is different across the UK
The fact that a medicine has a UK marketing authorisation does not mean it is routinely funded in every NHS service.
In Scotland, the Scottish Medicines Consortium (SMC) has accepted esketamine with an SSRI or SNRI for adults with treatment-resistant major depressive disorder who have not responded to at least two antidepressant treatments in the current moderate-to-severe episode. The recommendation applies within the approved NHSScotland Patient Access Scheme arrangements. Local availability still depends on specialist services and pathways.
The separate licensed indication for acute short-term treatment where depressive symptoms constitute a psychiatric emergency is not recommended for use within NHSScotland because the manufacturer did not make a submission to the SMC for that indication.
In England and Wales, NICE technology appraisal TA854 does not recommend esketamine with an SSRI or SNRI for treatment-resistant depression within its marketing authorisation. NICE reviewed the guidance and decided that the recommendation should remain unchanged.
Northern Ireland has its own medicines commissioning and governance arrangements, so current access should be checked through the relevant Health and Social Care service and local formulary.
What does the student nurse need to notice?
If you encounter esketamine on placement, it is likely to be in a specialist service with its own protocol. Your role is not to memorise a dosing schedule or independently decide whether someone is suitable for treatment. It is to understand what the team is assessing and why.
Before treatment, that may mean understanding the patient's baseline observations and recognising why blood pressure, current physical health, medicines and clinical history are relevant. During and after administration, watch the person rather than only the monitor. Are they alert? Are they becoming heavily sedated? Are they distressed by dissociation? Are they dizzy when they try to mobilise? Is their breathing normal? What has happened to their blood pressure? Do they appear clinically stable?
The patient's mental state remains part of that assessment too. A rapid change in depressive symptoms does not make ongoing risk assessment unnecessary, and someone attending for a specialist biological treatment still needs ordinary therapeutic nursing care: clear explanations, privacy, reassurance, non-judgemental communication and the opportunity to tell you when something does not feel right.
Esketamine is a useful example of why medicines knowledge in mental health nursing extends beyond knowing a drug's indication. The pharmacology explains why the treatment may work differently from conventional antidepressants. The adverse effects explain why it is given under supervision. The patient's history explains why suitability has to be considered individually. And the observation period gives the nurse repeated opportunities to connect those pieces to the person sitting in front of them.
References
Electronic Medicines Compendium. Spravato 28 mg nasal spray: Summary of Product Characteristics.
Scottish Medicines Consortium. Esketamine (Spravato): SMC2258.
Scottish Medicines Consortium. Esketamine (Spravato): SMC2539.
Advisory Council on the Misuse of Drugs. Ketamine: an updated review of use and harms.