Esketamine in Mental Health: The Antidepressant Related to Ketamine

When students first hear about esketamine in mental health care, the reaction is often:

“Wait, isn’t that related to ketamine?”

Yes, it is.

Ketamine is widely known as an anaesthetic and is also associated with recreational misuse, dependence and serious physical harm. Esketamine is closely related to it, but it can also be prescribed as a specialist treatment for certain adults with severe depression.

That does not mean the risks disappear. It means the medicine is supplied, administered and monitored within a tightly controlled clinical setting.

What Is Esketamine?

Ketamine contains two mirror-image forms of the same molecule: arketamine and esketamine.

Esketamine is one of those forms. A nasal-spray preparation marketed as Spravato has a UK marketing authorisation for specific depressive disorders.

This is different from racemic ketamine, which is licensed as an anaesthetic rather than an antidepressant. When standard ketamine is used to treat depression, it is generally being used off-label.

Esketamine and ketamine are both Class B controlled drugs and Schedule 2 controlled drugs in the UK.

Why Is Esketamine Used in Mental Health?

Most traditional antidepressants influence monoamine neurotransmitters such as serotonin and noradrenaline. They can be effective, but their therapeutic effects may take several weeks to develop.

Esketamine acts differently. Its principal action involves the brain’s glutamate system, particularly N-methyl-D-aspartate (NMDA) receptors.

The complete antidepressant mechanism is still being investigated. Researchers believe that downstream changes in glutamate signalling may support synaptic plasticity, the brain’s ability to adapt and form or strengthen connections between neurons.

Some patients experience an improvement in depressive symptoms within hours or days. However, not everyone responds, the improvement may not last and repeated treatment sessions may be needed.

Rapid does not mean permanent, and it certainly does not mean risk-free.

Who Might Receive Esketamine?

Spravato is licensed for adults with treatment-resistant major depressive disorder who have not responded to at least two antidepressant treatments during the current moderate-to-severe depressive episode.

For this indication, it is used with either:

• a selective serotonin reuptake inhibitor
• a serotonin–noradrenaline reuptake inhibitor

These are usually shortened to SSRI and SNRI.

Esketamine also has a separate licensed indication as a short-term treatment, alongside an oral antidepressant, for certain adults whose depressive symptoms constitute a psychiatric emergency.

It is not a first-line antidepressant and is not simply prescribed when someone wants a faster option. A psychiatrist must assess whether it is clinically appropriate.

Is Esketamine Available Through the NHS?

Availability differs across the UK.

Scotland

The Scottish Medicines Consortium accepted esketamine with an SSRI or SNRI for treatment-resistant major depressive disorder under an approved Patient Access Scheme.

This means it may be available through specialist NHS Scotland services. However, acceptance by the Scottish Medicines Consortium does not guarantee that every NHS board has a local esketamine clinic or that every person who meets the licensed criteria will receive it.

The Scottish Medicines Consortium did not recommend its separate psychiatric-emergency indication because the manufacturer did not submit evidence for that appraisal.

England and Wales

NICE does not recommend esketamine with an SSRI or SNRI for treatment-resistant depression within its marketing authorisation.

NICE found important uncertainties relating to the evidence, long-term benefits, treatment pathway and cost effectiveness. The recommendation remained unchanged following review.

This means esketamine is not normally available through the NHS for treatment-resistant depression in England and Wales, although some patients may access treatment privately or through research and highly specialist arrangements.

Northern Ireland

Northern Ireland has separate commissioning and medicines-governance arrangements. Current availability should be checked through the relevant Health and Social Care service.

How Is Esketamine Administered?

Esketamine is supplied as a single-use nasal-spray device.

The patient administers it themselves under the direct supervision of a healthcare professional. It is not taken home and used whenever symptoms worsen.

A treatment session includes the nasal administration followed by a period of clinical observation. Blood pressure is checked before treatment, approximately 40 minutes afterwards and again if clinically required.

The patient remains in the healthcare setting until the team considers them clinically stable and ready to leave. Depending on the service and the person’s response, this may take around two hours or longer.

Patients must not drive or operate machinery until the following day after having a restful sleep.

Why Does Esketamine Require Monitoring?

Esketamine can cause temporary but significant effects, including:

• dissociation or feeling detached from reality
• dizziness or vertigo
• sedation or sleepiness
• nausea or vomiting
• altered perception
• anxiety
• increased blood pressure

Rare cases of respiratory depression have also been reported.

Monitoring allows the clinical team to assess the person’s physical observations, level of alertness, psychological response and readiness to leave safely.

Is There a Risk of Addiction?

Yes. Esketamine has recognised potential for abuse, misuse and dependence.

This does not mean that every patient receiving prescribed esketamine will develop an addiction. It means the risk must be assessed and monitored rather than dismissed.

People with a history of drug misuse or dependence may be at greater risk. Before treatment, the psychiatrist should consider the person’s individual history and vulnerability. During treatment, the team should remain alert to concerns such as drug-seeking behaviour, misuse or attempts to obtain additional doses.

Administering esketamine under direct professional supervision reduces the opportunity for misuse or diversion.

Ketamine dependence, tolerance and withdrawal symptoms have been reported following prolonged misuse. Long-term or heavy ketamine misuse is also associated with bladder and urinary-tract damage, cognitive problems and liver injury.

Urinary symptoms have been reported with esketamine treatment too, so persistent pain, urgency, frequency or blood in the urine should be reported and assessed.

Recognising these risks is not about judging the patient. Controlled-drug safety and compassionate mental-health care should exist together.

Esketamine and Suicidal Thoughts

Esketamine may reduce depressive symptoms rapidly in some patients, including during a psychiatric emergency.

However, an improvement in symptoms is not the same as proof that suicide has been prevented. Patients at risk of suicide still require comprehensive assessment, appropriate observation, safety planning and ongoing psychiatric care.

Esketamine does not replace the rest of the treatment plan.

What About Consent and Detention?

Being detained under mental-health legislation does not automatically prevent someone from receiving esketamine. Detention also does not automatically mean that a person lacks capacity.

Consent, capacity and legal authority must be considered individually under the legislation applying in the relevant UK nation.

Because the nasal spray is self-administered and treatment requires cooperation with monitoring, the person must also be able to participate safely in the session. Complex situations require specialist clinical and legal consideration rather than a blanket rule.

The Student Nurse’s Role

Students are unlikely to administer esketamine independently, but they may observe treatment or help support monitoring within a specialist service.

The nursing role may include:

• confirming that baseline observations have been completed
• supporting a calm and safe environment
• observing for sedation, distress or dissociation
• monitoring physical observations as directed
• reporting significant blood-pressure changes
• assessing falls risk before mobilisation
• documenting the patient’s response
• following controlled-drug procedures

Students should remain within their competence and work under appropriate supervision.

It is also important to use non-judgemental language. A prescribed controlled drug is still a legitimate treatment, while a history of substance misuse is a health concern, not a character flaw.

Bleepbook Memory Line

Esketamine is rapid, supervised and specialist, but not routine, risk-free or right for everyone.

References

Advisory Council on the Misuse of Drugs (2026). Ketamine: an updated review of use and harms. Available at: GOV.UK

Electronic Medicines Compendium (2025). Spravato 28 mg nasal spray: Summary of Product Characteristics. Available at: eMC

National Institute for Health and Care Excellence (2022). Esketamine nasal spray for treatment-resistant depression (TA854). Available at: NICE

National Institute for Health and Care Excellence (2022, surveillance updated 2026). Depression in adults: treatment and management (NG222). Available at: NICE

Scottish Medicines Consortium (2020). Esketamine (Spravato): SMC2258. Available at: Scottish Medicines Consortium

Scottish Medicines Consortium (2022). Esketamine (Spravato): SMC2539. Available at: Scottish Medicines Consortium