Ketamine Nasal Spray for Depression: How It Works and How Long It Lasts

Complete Healthcare Team

Most antidepressants take four to seven weeks to make a real difference, which is a long time to wait when you’re struggling. Ketamine nasal spray works on a completely different timeline and a completely different system in the brain, and some people notice a shift within hours or days. That speed is the whole reason it exists, and it’s what makes it an option worth understanding for depression that hasn’t responded to other treatments.

If standard antidepressants haven’t worked for you or someone you care about, this kind of treatment may be worth a conversation. The mental health team at Complete Healthcare helps patients understand options like this one, and this guide explains how ketamine nasal spray works, how the treatment schedule unfolds, and how long its effects actually last.

What Ketamine Nasal Spray Is

The FDA-approved ketamine nasal spray for depression is esketamine, sold under the brand name Spravato. Esketamine is derived from ketamine, a medication used in anesthesia for decades, and it was approved in 2019 for treatment-resistant depression in adults, meaning depression that hasn’t improved after trying other antidepressants. It’s also approved for depressive symptoms in adults with major depressive disorder who have acute suicidal thoughts or behavior.

It’s used together with an oral antidepressant, not as a standalone treatment, and it’s always given in a certified medical setting rather than taken at home.

How Ketamine Nasal Spray Works in the Brain

This is where it genuinely differs from other antidepressants. Standard options like SSRIs and SNRIs work by adjusting serotonin, norepinephrine, or dopamine, the brain’s monoamine neurotransmitters. Esketamine leaves those mostly alone and instead acts on a different system entirely.

Esketamine works on glutamate, the brain’s most abundant neurotransmitter, by blocking a target called the NMDA receptor. Through a chain of downstream effects, this is thought to promote synaptic plasticity, which is the brain’s ability to form and strengthen connections between cells. In depression, those connections are often weakened, and the leading theory is that esketamine helps restore them. That mechanism is why it can act quickly, and why it can help some people for whom serotonin-based medications haven’t.

How Fast It Works and How Long the Effects Last

This is the question most people have, so let’s separate it into the two things “how long does it last” can mean.

How quickly it works. Unlike traditional antidepressants that take weeks, esketamine’s antidepressant effects can begin within hours to a few days for some people. Intranasal esketamine reaches peak levels in the blood within about 20 to 40 minutes, which lines up with when early effects tend to appear.

How long each session’s immediate effects last. The dissociation, drowsiness, and other in-session effects are short-lived. They begin shortly after dosing, and most resolve within about two hours, which is exactly why you’re monitored for that long before going home. For a fuller breakdown of those, see our guide on Spravato side effects.

How long the antidepressant benefit lasts. This is the part that requires honesty. A single treatment doesn’t produce a permanent result. The antidepressant effect is maintained through an ongoing treatment schedule, and for many people the benefit is sustained as long as they continue maintenance dosing at the interval their provider determines. Research on long-term use supports continuing treatment to maintain the response rather than expecting one course to fix things for good.

What the Treatment Schedule Looks Like

Ketamine nasal spray follows a structured schedule with two phases, and knowing it upfront helps set expectations.

Induction phase. For the first four weeks, treatment is given twice a week. Each session involves self-administering the nasal spray in two to three doses spaced five minutes apart, under supervision, followed by the two-hour monitoring period.

Maintenance phase. If treatment is helping, the frequency is gradually reduced. This often means moving to once a week for a period, then to once every two weeks or once a month. The goal is finding the least frequent dosing that keeps the improvement, and that interval is individualized based on how you respond.

Each dose is 56 mg or 84 mg, delivered through single-use devices that contain 28 mg each. The exact dose depends on your situation and how you tolerate it.

Common Questions About Ketamine Nasal Spray

How long does ketamine nasal spray stay in your system?

The drug itself clears quickly. Esketamine reaches peak blood levels within about 40 minutes and is largely out of your system within hours, which is why the in-session effects don’t linger past the monitoring period for most people. The antidepressant benefit, though, can outlast the drug’s presence in your body, because the effect comes from changes in brain signaling rather than the drug staying around. That’s why the treatment works on a schedule rather than requiring the drug to be constantly present.

Is ketamine nasal spray the same as the ketamine used in IV infusions?

Not exactly. Spravato (esketamine) is the only FDA-approved ketamine product for depression, and it’s a specific component of ketamine delivered as a nasal spray under a regulated safety program. IV ketamine infusions and other forms use racemic ketamine off-label, meaning they aren’t FDA-approved specifically for depression and aren’t standardized the same way. They can have similar biological effects, but the oversight and evidence base differ.

How long will I need to keep getting treatments?

There’s no single answer, because it’s individualized. Some people continue maintenance dosing for months, and others longer, with the frequency adjusted to the least often that maintains the benefit. This is a decision made with your provider based on how you respond over time, and it can change as your situation does. We talk through what ongoing treatment realistically looks like so people can plan for it.

Who Ketamine Nasal Spray Is For

It isn’t a first-line treatment, and it isn’t right for everyone. It tends to be considered for:

• Adults with treatment-resistant depression, typically after trying at least two other antidepressants without adequate relief
• Adults with major depressive disorder and acute suicidal thoughts, where the speed of effect matters, alongside standard care
• People who can commit to the schedule, including the in-office monitoring and arranging rides, since you can’t drive afterward

Certain conditions, including some cardiovascular problems and pregnancy, can make it unsafe, which is why a full health review comes first.

Why the Speed Matters More Than People Realize

For someone in the depths of treatment-resistant depression, the weeks that standard antidepressants take to work are not a minor inconvenience. They’re weeks of continued suffering and, for some, continued risk. The rapid onset of ketamine nasal spray is not just a convenience. For people who have waited through failed medication trial after failed medication trial, a treatment that can work in days rather than weeks is a meaningfully different option, which is part of why it’s drawn so much attention.

See If Ketamine Nasal Spray Might Help

If depression hasn’t responded to other treatments and you want to understand whether ketamine nasal spray could be an option, a conversation with a mental health provider is the right starting point. Complete Healthcare offers mental health care with same-day appointments available across our 11 locations in Central Ohio, including Columbus, Pickerington, Newark, Lancaster, Marion, Marysville, and Delaware. Call us at 614-882-4343 or schedule online to talk it through.

If you are having thoughts of harming yourself, help is available right now. Call or text 988 to reach the Suicide and Crisis Lifeline, any time of day.