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Treatment

Ketamine therapy

also known as esketamine

Medically reviewed by the Shrinkopedia editorial team, led by Shariq Refai, MD, MBA, FAPA.

7 min read · 1,488 words

  • Medically reviewed . Reviewed by a board-certified psychiatrist before publication.
  • Sourced from primary literature . DSM-5-TR, NICE, the American Psychiatric Association, the NIMH, Cochrane, peer-reviewed research.
  • Dated and kept current . Every entry shows when it was published, reviewed, and last updated.
  • Honest about uncertainty . Each entry carries an evidence-strength rating and a "what we know and what we don't" section.
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Quick answer

Ketamine therapy is a newer treatment option, used mainly for depression that hasn't responded to other treatments. At lower doses, ketamine can have rapid antidepressant effects, sometimes within hours to days. It's a genuine and valuable option for people who haven't been helped by other treatments, but it's given in a monitored medical setting and isn't a casual or first-line treatment.

Definition

Ketamine is an anesthetic medication that, at lower doses than those used for anesthesia, has been found to have rapid antidepressant effects. That speed, sometimes within hours to days, is much faster than standard antidepressants, which usually take weeks.

A specific form, esketamine, sold under the brand name Spravato, is a nasal spray that's FDA-approved for treatment-resistant depression and for depressive symptoms with acute suicidal thoughts. Intravenous ketamine is also used for depression, though that use is off-label, meaning it isn't a specifically FDA-approved indication. Ketamine therapy is mainly considered when depression hasn't responded to other treatments.

What it looks like

  • A psychiatrist considers ketamine after other treatments for depression haven't worked.
  • Treatment happens in a clinic, where the person is monitored during and after each dose.
  • During a session, a person may feel dissociated, a sense of detachment from body or surroundings.
  • Blood pressure and other effects are watched, and the person isn't sent home until it's safe.
  • Treatment runs as a course of repeated sessions, with the plan reviewed as it goes.

What people often confuse this with

A first-line antidepressant. Ketamine therapy is mainly for treatment-resistant depression, when other treatments haven't helped. It isn't where treatment usually starts. First-line care for depression generally involves therapy and standard antidepressants such as SSRIs and SNRIs.

A one-time cure. The rapid effect is real and can matter a great deal, but it can also fade. Ketamine therapy isn't a single fix. It usually involves a course of repeated sessions and ongoing planning to maintain any benefit.

Casual or recreational use. Ketamine therapy is a carefully controlled medical treatment given under monitoring. That's a different thing from unsupervised use. Ketamine has potential for misuse, which is part of why medical ketamine therapy is closely regulated.

Reality check

Myth: Ketamine is a miracle cure for depression.

Ketamine therapy is a genuine and valuable option, and the rapid effect can matter a great deal, especially for someone who's been suffering a long time. But it isn't a miracle or a casual treatment. The benefit can fade, it has real effects and risks, and it's used as part of a careful plan, not a one-off.

Myth: It's just like taking another antidepressant pill.

Ketamine therapy is given in a monitored medical setting because it can cause dissociation, increases in blood pressure, and other effects during and after a dose. That monitoring is a core part of the treatment, which makes it quite different from picking up a prescription at a pharmacy.

Myth: The science is fully settled.

The evidence for ketamine and esketamine in treatment-resistant depression is genuinely promising, and esketamine is FDA-approved. But the evidence is still developing, especially on the best long-term approach. That honest mix of promise and open questions is why this entry rates the evidence as mixed.

What research says

Research has found that ketamine, at lower doses, can produce rapid antidepressant effects, and this led to FDA approval of esketamine nasal spray for treatment-resistant depression and for depressive symptoms with acute suicidal thoughts. Intravenous ketamine is also used for depression off-label, supported by a growing body of studies. The rapid onset is one of the most notable features, since standard antidepressants usually take weeks.

The evidence is rated mixed because, while the findings are genuinely promising, important questions remain, particularly about the best long-term approach: how to maintain benefit, how often to treat, and how ketamine therapy fits alongside other treatments over time. It's also given in a monitored setting because of effects like dissociation and raised blood pressure, and ketamine has potential for misuse, which is part of why it's carefully controlled. Decisions about ketamine therapy belong with a psychiatrist.

What we know and what we don't know

What we know

  • Ketamine can have rapid antidepressant effects, and esketamine is FDA-approved for treatment-resistant depression.
  • It's given in a monitored medical setting because of effects like dissociation and raised blood pressure.
  • The benefit can fade, so treatment usually involves repeated sessions and ongoing planning.

What we don't know

  • The best long-term approach, including how often to treat and how to maintain benefit, isn't fully worked out.
  • The long-term safety of repeated, extended use is still being studied.
  • We can't yet reliably predict who will respond well to ketamine therapy.

Questions people ask

Is ketamine therapy the same as esketamine or Spravato?

Related but not identical. Ketamine is the racemic mixture used off-label, often IV. Esketamine (Spravato) is the S-isomer, FDA-approved as a nasal spray for treatment-resistant depression. Both work through NMDA blockade with similar rapid antidepressant effects. Coverage, protocols, and settings differ.

How fast does ketamine work?

Effect often begins within hours after a single dose, peaks in a day or two, and lasts days to weeks. That's very different from standard antidepressants, which take weeks.

Is it addictive?

At therapeutic doses in monitored settings, addiction risk is lower than at recreational doses but not zero. Careful patient selection (avoiding people with substance use histories involving ketamine) and clinic protocols reduce risk.

Does it work for everyone?

No. Around half of people with treatment-resistant depression respond to ketamine or esketamine in trials, with about a third achieving remission at four weeks. Durability varies. Response is not universal and cannot be predicted before trying.

Should I try it before ECT?

For treatment-resistant depression without urgent suicide risk, ketamine or esketamine are often tried before ECT because of the lower procedural burden. For severe depression with active suicide risk, catatonia, or psychotic features, ECT remains first-line.

How it works

What's useful to understand about ketamine therapy:

  • it's an anesthetic medication used at lower doses for its antidepressant effect
  • it can work rapidly, sometimes within hours to days, unlike standard antidepressants
  • esketamine nasal spray is FDA-approved for treatment-resistant depression and for depression with acute suicidal thoughts
  • intravenous ketamine is also used for depression, off-label
  • it's given in a monitored medical setting because of effects during and after a dose
  • the benefit can fade, so treatment usually involves repeated sessions and ongoing planning

Medications in this class

Racemic ketamine (IV)

Receptor mechanism. Non-competitive NMDA glutamate receptor antagonist; downstream AMPA activation and BDNF/mTOR signaling likely mediate rapid antidepressant effect. Also μ-opioid, monoaminergic, and D2 activity contribute.
Typical dosing (off-label for treatment-resistant depression). 0.5 mg/kg IV over 40 minutes; induction 2-3× per week for 2-3 weeks; maintenance individualized (typically every 1-4 weeks).
Safety monitoring. BP and HR every 5-10 min during and after infusion; dissociative symptoms (CADSS); bladder symptoms with long-term/high-frequency exposure; misuse potential; concurrent psychiatric care required.
Sources. APA Consensus Statement on Ketamine (Sanacora et al., 2017; still primary framework); ASKP practice guidance updates through 2025.

Esketamine (Spravato, intranasal)

Receptor mechanism. S-enantiomer of ketamine; higher NMDA affinity than R-ketamine.
Typical dosing (FDA-approved for treatment-resistant depression and MDD with acute suicidal ideation).
  • Induction weeks 1-4: 56 mg (day 1), then 56 or 84 mg twice weekly.
  • Weeks 5-8: 56 or 84 mg weekly.
  • Maintenance week 9+: 56 or 84 mg every 1-2 weeks.
Safety monitoring. REMS program still active, so 2-hour post-dose in-clinic monitoring for sedation and dissociation; BP baseline and 40 min post-dose; can't drive that day; assess suicidality; do not co-administer with sedatives.
Sources. FDA label (Spravato); Spravato REMS program (current as of June 2026).
Shared safety themes.
  • Pregnancy and breastfeeding. Every entry should link to condition-specific perinatal considerations and reference LactMed/NICE/APA perinatal guidance.
  • Drug interactions. SSRIs/SNRIs + MAOIs (14-day washout, 5 weeks for fluoxetine); lithium + NSAIDs/ACEi/thiazides; carbamazepine broad CYP induction; clozapine + fluvoxamine, ciprofloxacin.
  • Discontinuation. Taper SSRIs, SNRIs, benzodiazepines, and antipsychotics gradually. Fastest tapers (paroxetine, venlafaxine, short-acting benzos) carry the most discontinuation symptoms.
  • Metabolic monitoring standard. Per the ADA/APA consensus, still the standard framework in 2026: baseline, 4, 8, 12 weeks, then quarterly: weight/BMI, waist. Baseline, 3 months, then annually: fasting glucose or HbA1c, fasting lipids, BP.
  • QTc considerations. Baseline ECG for citalopram > 20 mg (age > 60), ziprasidone, IV haloperidol, thioridazine, and any combination of QT-prolonging agents.

Sources

  1. U.S. Food and Drug Administration (FDA). Esketamine (Spravato) approval and labeling.
  2. National Institute of Mental Health (NIMH). Research on ketamine and treatment-resistant depression.
  3. American Psychiatric Association (APA). Guidance on ketamine and esketamine in depression.
  4. Clinical trial literature and reviews on ketamine for depression.
  5. FDA prescribing information (label) for each drug, accessed via DailyMed.
  6. APA Practice Guidelines (Schizophrenia 3rd ed.; MDD; Bipolar Disorder; OCD).
  7. NICE Guidelines: NG222 (Depression 2022), CG185 (Bipolar 2014, updated), CG178 (Psychosis and schizophrenia 2014, updated), NG215 (Medicines associated with dependence).
  8. ADA/APA Consensus on Antipsychotic Drugs and Obesity/Diabetes (2004, still foundational; updates via ISBD/EPA metabolic monitoring statements).
  9. Carolan A, et al. Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation. Schizophrenia Bulletin. 2025;51(5):1193-1203.
  10. FDA Drug Safety Communication: Clozapine REMS elimination (February 24, 2025).
  11. AAPP Clozapine in Practice guideline (2025 updates).
  12. International Society for Bipolar Disorders (ISBD) lithium and mood-stabilizer consensus statements.
  13. APA/ASKP Consensus on Ketamine and Esketamine (2017 base; 2023-2025 updates).
  14. Beers Criteria (AGS 2023) and STOPP/START v3 (2023) for prescribing in older adults.
  15. Cochrane systematic reviews for individual class efficacy and safety.

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Ketamine therapy. Shrinkopedia, medically reviewed by Shariq Refai, MD, MBA. https://shrinkopedia.com/treatments/ketamine-therapy/
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Medical disclaimer

Shrinkopedia is for education, not medical advice. It can't tell you whether ketamine therapy is right for you, and it isn't a substitute for care from a licensed clinician. A psychiatrist can assess whether it's an appropriate option and guide the plan.

If you're in crisis or thinking about harming yourself, call or text 988 in the US to reach the Suicide and Crisis Lifeline, or call 911.

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