Ketamine and Esketamine for Treatment-Resistant Depression

Esketamine (Spravato) is FDA-approved for treatment-resistant depression and is given in a certified clinical setting, not as a do-it-yourself treatment. Ketamine-based therapy works differently from standard antidepressants and can help some people who have not responded to first-line care. Understanding how it works, where it is given, and who qualifies helps you weigh it with your clinician.

This is not an emergency treatment. If you are in crisis or considering self-harm, get help now by contacting local emergency services or a crisis line (in the US call or text 988, or use your local equivalent).

How It Works

Ketamine and its derivative esketamine act mainly on the brain's glutamate system, a different mechanism from SSRIs and SNRIs, which act on serotonin and noradrenaline. This distinct pathway is thought to explain why some people who have not improved on standard antidepressants respond, and why effects can appear relatively quickly compared with the weeks conventional antidepressants take. It is effective for many people with treatment-resistant depression, though results vary and benefits often need maintenance treatment to be sustained.

The Clinic Setting

Esketamine is a nasal spray administered in a certified healthcare setting under a risk-management programme. You self-administer the spray under supervision and are then monitored for a period, commonly around two hours, before going home. Because it can cause temporary dissociation, sedation, or raised blood pressure, you are observed until these effects settle, and you must not drive on treatment days, so plan to have someone take you home. Intravenous ketamine, where used for depression, is given off-label in a supervised medical setting.

Safety and Side Effects

• Temporary dissociation, a feeling of detachment from yourself or surroundings.
• Sedation and dizziness during and after a session.
• Short-term increases in blood pressure.
• Nausea in some people.

These are why treatment is supervised and monitored in a clinic. Your clinician screens your history, including blood pressure, heart or vascular conditions, and any history of substance misuse, before recommending it. There is potential for misuse, which clinical oversight and the certified-setting requirement are designed to manage.

Who Qualifies

Esketamine is approved for adults with treatment-resistant depression, generally meaning depression that has not responded to two or more adequate antidepressant trials, and it is used together with an oral antidepressant. It has also been approved for depressive symptoms in adults with major depressive disorder who have suicidal thoughts or behaviour, used alongside standard care. A clinician determines eligibility based on your history, current treatment, and physical health.

What to Expect Over Time

Treatment usually starts with a more frequent schedule and then, if you respond, moves to less frequent maintenance sessions. Your clinician tracks your symptoms to decide whether to continue. Because the effects on mood may not be permanent, ongoing treatment and a broader plan are typically part of the picture rather than a single course.

How It Fits Your Plan

Ketamine-based therapy is one option among several for treatment-resistant depression, alongside TMS and medication adjustments. It is used as part of a broader plan that usually includes an oral antidepressant and often therapy, not as a standalone or DIY fix. Discuss with your clinician how it compares with other options for your situation, including cost, schedule, and what response would look like.

Ketamine Versus Esketamine

It helps to know the distinction. Esketamine (Spravato) is a specific, FDA-approved nasal-spray medication with a defined approval for treatment-resistant depression and depressive symptoms with suicidal thoughts, delivered under a formal risk-management programme. Intravenous ketamine, by contrast, is an older anaesthetic used off-label for depression in some clinics; it is not FDA-approved for that use, and protocols vary between providers. Both are given under medical supervision, but they differ in regulation, evidence base, and how they are administered, so ask any clinic exactly which they offer and what that means for you.

Questions to Ask a Clinic

Because approaches vary, it is reasonable to ask a clinic detailed questions before starting. Find out who supervises treatment and their qualifications, how you are monitored during and after each session, how they screen for suitability, and how they measure whether it is working. Ask what the full course and any maintenance are likely to cost, whether an oral antidepressant is part of the plan, and how they coordinate with your existing care team. Clear, transparent answers are a good sign; vague promises of a quick cure are not.

Frequently Asked Questions

Is esketamine the same as recreational ketamine?

No. Esketamine is a regulated, FDA-approved medication given under supervision in a certified clinic. Using ketamine outside medical settings is unsafe and not a treatment.

Can I take it at home?

No. Esketamine must be administered in a certified setting with monitoring afterward. It is not a do-it-yourself treatment.

How fast does it work?

Some people notice effects relatively quickly compared with standard antidepressants, but responses vary and maintenance treatment is often needed.

Who should not use it?

Your clinician screens for conditions such as certain blood pressure or vascular problems and reviews your history before recommending it. Eligibility is individual.

Will I need to keep taking my other antidepressant?

Usually yes. Esketamine is approved for use together with an oral antidepressant, and it forms part of a broader plan rather than replacing your other treatment. Your clinician manages the combination.