What is Esketamine Nasal Spray for Depression & Does it Work?
A doctor-administered nasal medication that uses a fast-acting form of ketamine to help treat depression when standard antidepressants haven’t worked — delivered under full clinical supervision.
Book a free initial consult
Pick a time that suits you — no cost, no obligation.
An esketamine nasal spray is an option clinics use for people living with treatment-resistant depression or a depressive episode within major depression. It can support a positive treatment response in people who haven’t improved with at least two different antidepressants — offering a way to treat depression under clinical supervision without relying only on oral medication.
How does a nasal spray for depression work?
Esketamine is delivered directly through the nasal passages so it can act on the brain within a short time. It targets the NMDA receptor — part of the glutamate system that supports mood regulation — creating a rapid shift in glutamate signalling that can produce an antidepressant action much faster than traditional medication.
Intranasal dose
Esketamine is absorbed through the nasal passages and reaches the brain quickly.
NMDA receptor
It acts on the NMDA receptor within the brain’s glutamate system.
Glutamate surge
A rapid shift in glutamate signalling drives a fast antidepressant action.
Mood circuits reset
Underactive mood circuits begin to reset, often within hours to days.
Clinical trials show that intranasal esketamine creates changes in receptor activity that can help adults with treatment-resistant depression who haven’t responded adequately to at least two different antidepressants of adequate dose and duration. The treatment also affects norepinephrine pathways, which can strengthen the overall therapeutic effect.
What are the benefits of a nasal spray for depression?
A nasal spray offers fast-acting therapeutic effects and benefits that other antidepressants can’t. The most profound include:
Rapid relief from symptoms
Improvement can appear within hours, because esketamine works on the glutamate system instead of the slower serotonin pathways most antidepressants use. Antidepressant side effects →
Support for suicidal symptoms
Unlike other options, esketamine helps reduce suicidal thoughts and ideation by targeting receptor activity linked to acute depressive states.
Option for treatment-resistant cases
It helps adults who have responded inadequately to at least two different antidepressants of adequate dose and duration — offering relief where nothing else has.
Lower systemic exposure
Delivered directly through the nasal passages, which may reduce some of the long-term effects seen with certain oral antidepressants.
Backed by long clinical use
Supported by clinical trials and decades of research — ketamine has been used for sedation for a long time, giving a solid base of evidence for its safety and effects.
Does it have any side effects?
Esketamine can cause short-lived changes that usually settle during the treatment session. Because every session is supervised, your care team watches for these from start to finish.
Common, short-lived effects
- Mild dizziness or brief drowsiness
- Short-lived changes in awareness or perception
- A brief, temporary rise in blood pressure
How we keep you safe
- Monitored during and after every session
- Effects typically settle before you leave
- Serious events are rare in supervised care
Who is nasal spray therapy for?
It’s for adults being treated for major depressive disorder who haven’t responded adequately to at least two different antidepressants. It must be administered under clinical supervision and can’t be done at home.
May be suitable if you…
- Are an adult with major depressive disorder
- Have tried 2+ antidepressants without adequate response
- Can attend a clinic for supervised sessions
Not appropriate for…
- Children or teenagers
- At-home or unsupervised use
- Use without a clinician’s assessment
What happens during an appointment?
A nasal spray for depression is always given by a clinician, who manages the full session from start to finish. The medication enters the bloodstream quickly, so you’re closely monitored throughout — which is why it takes place in a clinic rather than at home.
During the session
Each session lasts one to two hours. You’re assessed for short-term effects such as sedation, dissociation or visual distortion while the esketamine acts on the mood-related receptor pathways. Staff stay present throughout to support your comfort and safety.
How long to see results
Some patients feel a shift within forty minutes to one day, as receptor activity resets mood circuits during the early weeks of treatment. Many experience early remission during weeks one to four.
Results from any depression treatment vary between patients, and outcomes are not guaranteed.
How to prepare for a treatment
- Eat a light meal a few hours before you arrive.
- Avoid alcohol or sedating medications on the day of treatment.
- Arrange transport — esketamine may cause temporary dizziness.
- Bring a current medication list so clinicians can check interactions with antidepressant therapies.
How it fits into a treatment plan
Esketamine is used alongside a newly initiated oral antidepressant, so you receive support from two treatment options at the same time. Treatment moves through clear phases as the therapeutic effect builds and stabilises.
Induction
Often twice-weekly sessions for four weeks, establishing a strong early treatment response.
Weekly sessions
Moving to weekly visits for several more weeks as the therapeutic effect stabilises.
Maintenance
Less frequent visits, with clinicians tracking symptoms and long-term effects to guide tapering over time.
Frequently asked questions
No. Esketamine may cause temporary sedation or altered awareness, so clinics require patients to arrange transport. Supervision continues safely after the treatment session.
Treatment follows set phases — an induction period, several weeks of structured dosing, and a maintenance phase based on response. Clinicians review depressive symptoms regularly to decide how long therapy should continue.
Esketamine is a single isomer created for intranasal use and supported by clinical trials, while racemic ketamine contains two isomers and is often given by infusion. Esketamine works through targeted receptor activity and is currently approved for adults with treatment-resistant depression.
It can be used in older adults when clinicians assess medical history and depression severity. Care teams monitor responses closely to guide treatment options safely.
It may cause a brief rise in blood pressure because of how the medication activates receptor pathways. Clinicians check vital signs before and after treatment to support safety and efficacy.
Talk to our TMS team about next-generation treatment
Why not schedule a no-cost, introductory discussion. Tell us a little about your situation and a member of our team will be in touch.
Next-generation treatment
The information provided above is general in nature and not medical advice. Esketamine nasal spray must be administered under clinical supervision. Results from treatment may vary between patients, and outcomes are not guaranteed. Speak with your GP or a member of our team to find out whether this treatment may be right for you.