Esketamine: what it treats, how treatment works, side effects
Last updated September 3, 2026.
Esketamine is an NMDA receptor antagonist - a nasal spray for depression that has not responded to other treatments. You may know it as Spravato. Clinic-only: you give it to yourself in a medical facility, and the two monitored hours after are part of the medicine.
What does it treat?
Treatment-resistant depression in adults - alone or with an oral antidepressant - and depressive symptoms in adults with major depression and suicidal thoughts or actions, alongside an oral antidepressant.
How does treatment work?
Only through the Spravato REMS program - you, your doctor, and your pharmacy all enroll. You use the spray yourself in a medical facility; the care team monitors you before, during, and for at least 2 hours after - sedation, fainting, dizziness, a spinning sensation, feeling disconnected from your body, thoughts, emotions, space and time, and breathing problems are why. Blood pressure gets checked before and after - it can spike for about 4 hours. A caregiver or family member drives you home; no driving, machinery, or anything needing full alertness until the next day, after a real night's sleep. No eating for at least 2 hours before, no liquids for at least 30 minutes before.
Side effects to know
- Common: nausea, vomiting, constipation, diarrhea, dry mouth, headache, feeling drunk, an unusual or metallic taste, and difficulty thinking or remembering.
- Serious - tell your doctor right away: extreme tiredness, dizziness, fainting, shortness of breath, anxiety, feeling disconnected from your body or reality; chest pain, sudden severe headache, vision changes, or seizures - the blood-pressure set. And the antidepressant warning: mental health can change in unexpected ways - new or worsening depression, suicidal thinking, agitation, panic, or frenzied excitement - especially early and after dose changes; family and caregivers watch with you.
Who should not use it?
History of stroke, heart attack, brain injury, or conditions raising brain pressure get weighed carefully; so do heart-valve disease, heart failure, high blood pressure, slow or irregular heartbeat, chest pain, and liver or heart disease. Hallucinations or delusions go on the table. If you are pregnant or planning it, the conversation comes first.
When is it an emergency?
Chest pain, sudden severe headache, vision change, seizure, or trouble breathing after a session is a 911 call. For an overdose, call Poison Control at 1-800-222-1222. If suicidal thoughts arrive or sharpen, call or text 988 - the Suicide and Crisis Lifeline - any hour. Pymander's escalation routing is built and tested specifically for this class of decision; see the safety architecture working paper.
What a Pymander AI doctor consult looks like
Illustrative example, not a real member's messages.
Common questions
Why can't I take it home?
The REMS program: esketamine is available only through a restricted distribution program - you, your doctor, and your pharmacy all enroll - and every dose happens in a medical facility under observation. The reasons are the first two hours: sedation, fainting, dizziness, a spinning sensation, feeling disconnected from your body, thoughts, emotions, space and time, and breathing problems. The monitored window is the medicine's safety container.
Why do I need a driver?
Because the effects outlast the session: no driving, no machinery, nothing needing full alertness until the next day, after a restful night's sleep. The caregiver or family member who drives you is part of the treatment plan, not a courtesy. The good news: the no-drive window is predictable - session day is a rest day by design.
What is the blood-pressure watch?
Esketamine can temporarily raise blood pressure for about 4 hours - so it gets checked before and for at least 2 hours after each session. Chest pain, shortness of breath, sudden severe headache, vision changes, or seizures afterward are the emergency set - 911, not a message. Stroke, heart, and brain-pressure history all shape whether the drug is right before it starts.
What is the disconnected feeling like?
The known dissociation: feeling separated from your body, thoughts, emotions, space, and time - usually strongest in the first hour, fading over the session window. Most people find it strange but tolerable; some find it meaningful; a few find it hard. It is reportable, not alarming - the care team watches for exactly this, and how you ride it shapes dosing.
What is the depression warning about?
The antidepressant-class warning applies: mental health can change in unexpected ways - new or worsening depression, suicidal thinking, agitation, panic, frenzied excitement - especially early and after dose changes, at any adult age. Family and caregivers watch with you and know the call list. If suicidal thoughts arrive or sharpen: call or text 988, the Suicide and Crisis Lifeline, any hour - and tell your doctor the same day.
Why the fasting rules before sessions?
Practical: nausea and vomiting are common - no eating for at least 2 hours before, no liquids for at least 30 minutes before keeps the session comfortable and safe. Small rule, real payoff. The session rhythm - schedule, fast, spray, monitored rest, driver home - becomes routine within a few visits.