Ketamine Therapy for Depression: What to Expect

Considering ketamine therapy for depression? Learn how it works, what a session involves, the risks, and who may benefit from this treatment.

Intrepid Mental Wellness

10/1/20264 min read

If you've tried several antidepressants and still feel stuck, you've probably come across ketamine therapy for depression. It's getting a lot of attention, and for good reason: it works differently from traditional antidepressants and can act quickly for some people. It's also not a cure-all, and it isn't right for everyone. This guide covers what ketamine-based treatment actually involves, who tends to benefit, what the risks are, and what's worth checking first.

Key Takeaways

Ketamine-based treatments target glutamate, a different brain chemical pathway than most antidepressants, and may work within hours to days for some people.
Esketamine (Spravato) is FDA-approved for treatment-resistant depression. IV ketamine is used off-label for depression.
Treatment happens in a monitored setting, and sessions can cause dissociation, dizziness, nausea, and a temporary rise in blood pressure.
Ketamine is generally considered after multiple standard treatments haven't worked, not as a first step.
Before pursuing it, it's worth ruling out fixable contributors like thyroid problems, nutrient deficiencies, sleep issues, and alcohol use.

What is ketamine therapy, and is it approved for depression?

Ketamine has been used as an anesthetic for decades. In mental health care, it is given in carefully controlled doses to treat severe depression. One form, esketamine (brand name Spravato), is a nasal spray the FDA approved in 2019 for treatment-resistant depression, taken alongside an oral antidepressant. Ketamine given by IV infusion is used "off-label" for depression, meaning the FDA hasn't approved that specific use.

Researchers are still actively studying how well these treatments hold up over time. The American Psychiatric Association's October 2025 journal news release, for example, highlights two new papers in The American Journal of Psychiatry: a real-world safety analysis of esketamine nasal spray nearly five years after its first approval, and a review of ketamine's potential neurotoxic effects.

How does ketamine therapy for depression work?

Most antidepressants act on serotonin, norepinephrine, or dopamine. Ketamine works on a different system: it affects glutamate, the brain's main excitatory chemical messenger. Researchers believe this may help brain cells form new connections, which could explain why some people feel relief faster than they would with a standard antidepressant.

The exact mechanism is still being studied, so no one can say precisely why it helps one person and not another. That uncertainty is one reason ketamine is used with careful medical oversight.

Who can ketamine therapy help?

Ketamine is mainly considered for treatment-resistant depression, which the National Institute of Mental Health describes as depression that doesn't improve after trying multiple treatments. In clinical practice, that often means not responding to at least two antidepressants given at an adequate dose for an adequate length of time.

It may also be considered when depression is severe and symptoms are dangerous, such as when someone is having thoughts of suicide. If you are in crisis right now, call or text 988 (the Suicide & Crisis Lifeline) or go to your nearest emergency room.

What should you expect during a ketamine session?

A session takes place in a clinic or medical office, not at home. You'll have your blood pressure checked, receive the medication (by nasal spray or IV, depending on the treatment), and then be monitored while it takes effect and wears off. Esketamine requires at least two hours of observation after each dose, and you can't drive until the next day after a restful night's sleep.

During the session, many people feel detached from their body or surroundings, a sensation called dissociation. It usually fades within an hour or two. Some people find it calm or dreamlike; others find it unsettling. Telling your care team how you feel is part of the process.

Treatment usually follows a schedule: several sessions over a few weeks at first, then less frequent maintenance sessions if it's helping. Exact protocols vary by clinic and by the type of ketamine used.

What are the risks and side effects?

The most common side effects are dissociation, dizziness, nausea, drowsiness, and a short-term rise in blood pressure. These typically resolve the same day. Longer-term safety, especially with repeated use over years, is still being studied.

Ketamine is a controlled substance with misuse potential, which is another reason it is given in supervised settings rather than prescribed for home use. Anyone with a history of substance use should talk this through carefully with their prescriber.

Who may not be a good candidate?

Ketamine may not be a good fit if you have uncontrolled high blood pressure, certain vascular conditions such as an aneurysm, a history of psychosis, or an active substance use disorder. It also isn't recommended during pregnancy. A thorough medical and psychiatric review should happen before the first dose.

Never stop or change your current medications on your own. Some medications interact with ketamine-based treatment, so your prescriber needs the full list.

What should you rule out before trying ketamine?

Before concluding that depression is "treatment-resistant," it's worth asking whether something is getting in the way of treatment working. Low thyroid function, vitamin D, B12, or iron deficiency, poor sleep or sleep apnea, chronic inflammation, hormone shifts, and alcohol use can all keep depression stubborn.

This is where our approach at Intrepid Mental Wellness comes in. Our psychiatric nurse practitioners look for root causes, sometimes using lab work, and combine medication with natural, nutrition-based support. If you've been told your depression is hard to treat, our page on treatment-resistant depression explains how we look deeper, and our overview of holistic depression treatment shows what a whole-person plan can include.

FAQ

Is ketamine therapy for depression FDA-approved? Esketamine (Spravato) is FDA-approved for treatment-resistant depression. IV ketamine is not FDA-approved for depression and is used off-label.

How quickly does ketamine work for depression? Some people notice improvement within hours to a few days, which is faster than most antidepressants. Results vary, and effects can fade, so many people need ongoing maintenance sessions.

Is ketamine a first-line treatment? No. It's typically considered after other treatments, such as multiple antidepressants and therapy, haven't provided enough relief.

Can I drive home after a ketamine session? No. You'll need someone to take you home, and you shouldn't drive until the next day after a restful sleep.

This post is educational and not a substitute for medical advice. Talk with a qualified prescriber about whether any treatment is appropriate for you.

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