Ketamine for Depression

What is ketamine?

Ketamine is a dissociative anesthetic that has been used in medical settings since 1970 — originally for surgical anesthesia and emergency pain control. In the past two decades, researchers found that at much lower doses than used for anesthesia, ketamine can have rapid antidepressant effects.

That's what's meant when people say "ketamine for depression." We're not putting patients under for surgery. We're giving a carefully measured, monitored, sub-anesthetic dose that acts on the brain differently from standard antidepressant medications.

How does it work?

Most antidepressant medications (SSRIs, SNRIs, etc.) work on the brain's serotonin, norepinephrine, or dopamine systems. Ketamine works very differently. It acts on a receptor system called NMDA (N-methyl-D-aspartate) and another called AMPA, both of which are part of the brain's glutamate signaling system — a different neurotransmitter pathway entirely.

Without going into heavy neuroscience, what's thought to happen is something like this: ketamine briefly changes the way certain neurons communicate, which triggers a cascade of downstream effects — including the release of growth factors (like BDNF) and increased formation of new synaptic connections between brain cells. This is sometimes described as increased neuroplasticity, and it's thought to be the underlying reason for the antidepressant effect.

The important takeaway for patients: ketamine works through a completely different mechanism than standard antidepressants, which is part of why it can help people who haven't responded to other medications.

Is ketamine right for me?

Ketamine is most commonly considered for:

• Treatment-resistant depression — major depression that hasn't responded adequately to two or more antidepressant trials
• Severe depression with suicidality — where rapid effect is clinically valuable
• Bipolar depression (in carefully selected cases)
• PTSD (mixed evidence: small positive studies and one larger negative study; see below)

When ketamine isn't the right fit

Some patients shouldn't get ketamine because of medical or psychiatric factors. Key ones include:

These aren't always absolute — some can be worked around with careful screening and planning. The point of a thorough psychiatric and medical evaluation before starting is to figure out whether ketamine makes sense for you specifically.

How well does it work?

The honest answer: ketamine helps many people with hard-to-treat depression, it does not help everyone, and the benefit is usually temporary unless treatment continues. The numbers below come from the published clinical trials; the full list of sources is at the bottom of this page. “Response” means depression scores fell by at least half. “Remission” means few or no remaining symptoms.

IV ketamine, in more detail

In the first well-controlled study (18 patients at the National Institute of Mental Health, 2006), 71% of the 17 who received ketamine responded and 29% were in remission the day after one infusion, but only 35% still met response criteria a week later. In a 73-patient study (2013) designed with an active placebo, 64% responded at 24 hours compared with 28% of those given midazolam, a sedative chosen so that patients could not easily tell which drug they received.

Repeating infusions extends the benefit. In a 2019 study, 59% of patients responded after six infusions over two weeks, and those who responded held their improvement through four weekly maintenance infusions. But not every study of repeated dosing has been positive: a 2020 trial found six infusions were not significantly better than one at its main endpoint, and a small 2019 trial in people with long-standing suicidal thoughts found six infusions no better than placebo.

Dose matters. In a 174-patient Australian and New Zealand trial of ketamine injections under the skin, a fixed 0.5 mg/kg dose was no better than a sedative placebo (midazolam), while a dose adjusted upward for non-responders produced remission in 19.6% versus 2.0%. Four weeks after the last dose, most of that difference had faded.

Spravato (esketamine nasal spray)

In the main 4-week study that led to FDA approval, people taking esketamine plus a newly started antidepressant improved by about 20 points on a 60-point depression scale; people taking a placebo spray plus the same kind of antidepressant improved by about 16 points. The 4-point difference was statistically significant but modest, and most of it appeared in the first 24 hours. Two of the three short-term approval studies (one using fixed doses, one in adults 65 and older) did not meet their main goal.

A 2025 study of esketamine used on its own (378 patients) was positive: about 6–7 people needed to be treated for one additional person to respond, and about 7–12 for one additional remission (the lower-dose remission estimate was not statistically significant). That study's data and design have since been publicly questioned by independent researchers. An independent re-analysis of the patient-level data from the company's trials found that, across the five short-term trials of esketamine plus an antidepressant, the average extra benefit was about 3 points on the 60-point scale, which the authors called “statistically significant but small.”

Continuing esketamine matters. Among people who got well and kept taking it, 27% relapsed during follow-up, compared with 45% of those switched to a placebo spray. Against a common alternative, the antipsychotic quetiapine, esketamine produced remission at 8 weeks in 27% of patients versus 18% in a trial where patients knew which treatment they were getting.

Compared with ECT

Two large randomized studies compared IV ketamine with electroconvulsive therapy. In a U.S. study of 403 mostly outpatient adults with treatment-resistant depression without psychosis (ELEKT-D, 2023), 55% responded to ketamine and 41% to ECT; ketamine was judged “non-inferior,” and ECT caused a temporary drop in memory recall that ketamine did not. Two caveats: patients and clinicians knew which treatment was given, and the ECT arm’s remission rate (22%) was unusually low, which ECT researchers attribute to the type of ECT used and a cap of nine sessions. In a Swedish study of 186 hospitalized, more severely ill patients (KetECT, 2022), 63% reached remission with ECT versus 46% with ketamine, so ECT was better; about two-thirds of those who remitted relapsed within a year after either treatment.

Suicidal thoughts

A pooled analysis of 10 trials found that a single ketamine infusion reduced suicidal thinking within a day and for up to a week. In a French hospital study of 156 suicidal patients, two infusions a day apart brought full remission of suicidal ideas by day 3 in 63% versus 32% on placebo. That benefit was concentrated in people with bipolar disorder; in those with major depressive disorder the difference was not statistically significant, and by six weeks the two groups overall were no longer significantly different. In the esketamine studies of patients with suicidal thinking, depression scores improved faster than with placebo, but the clinician's rating of suicidality did not differ. The FDA label states plainly that esketamine has not been shown to prevent suicide or reduce suicidal thoughts or behavior. If you are in crisis, ketamine is not a substitute for emergency care.

Real-world results

Trial results are usually better than everyday results. Pooling 79 real-world studies of ketamine for treatment-resistant depression (2,665 patients), 45% responded and 30% remitted, with wide variation. At one academic clinic, only 18% of outpatients (15 of 82 with rating-scale data) responded on a self-rating scale after the induction series, and about half stopped during or right after it. In a French esketamine cohort, 40% of patients still on treatment had responded at one month and 20% had remitted, and 80% had stopped within a year.

What a treatment is like

The details depend on which form of ketamine you're receiving (IV, nasal spray, oral). For an IV ketamine infusion — the most common form — here's roughly what to expect:

1. Arrival and setup (10–15 minutes): You'll settle into a comfortable reclining chair. A nurse or technician will check your vital signs and place an IV line. You'll be connected to monitors: a blood pressure cuff, a pulse oximeter (measures heart rate and oxygen), and often an EKG (measures heart activity).
2. Infusion (40–60 minutes): The ketamine is delivered slowly through your IV. Most patients feel the effects begin within a few minutes. The dose is carefully measured to your body weight.
3. Recovery (30–60 minutes): After the infusion ends, the effects wear off over about 30–60 minutes. You'll remain monitored until you're fully clear-headed and able to safely leave. You cannot drive afterward and will need someone to pick you up.

What the experience feels like

Because ketamine is a dissociative anesthetic, most patients have some kind of altered-state experience during the infusion. This varies enormously from person to person:

• Some feel very heavy, grounded in their body; others feel like they're floating or flying
• Some feel euphoric; some feel anxious or scared; some feel nothing at all notable
• Some people hallucinate mildly; others don't
• Strange thoughts, feelings, memories, or emotional material may surface during the session — sometimes pleasant, sometimes difficult

The different forms of ketamine

Ketamine can be delivered in several ways, each with its own tradeoffs:

IV ketamine (intravenous)

The most studied form. Delivered through an IV over 40–60 minutes, 100% of the dose reaches your bloodstream, dosed by body weight. Typically given in a clinic under direct physician supervision. Often not covered by insurance; check with your insurer.

Spravato (esketamine nasal spray)

The only ketamine-based medicine that is FDA-approved for depression: approved in 2019 for treatment-resistant depression together with an oral antidepressant, in 2020 for depression with acute suicidal thoughts or behavior (with an oral antidepressant), and in January 2025 for use on its own for treatment-resistant depression. It can only be given in a certified clinic under a federal safety program; you stay for at least 2 hours of monitoring after each dose and cannot drive until the next day. The usual schedule is twice a week for 4 weeks, then weekly, then weekly or every other week. About 48% of the dose is absorbed through the nose. Often covered by insurance, but coverage varies; check with your insurer.

Oral ketamine

Lozenges or tablets made by compounding pharmacies, sometimes prescribed for home use through telehealth companies. Cheaper and more convenient, but only about 17–30% of the dose is absorbed, and the controlled evidence is small (a handful of trials, with mixed results). In October 2023 the FDA warned that ketamine is not approved for any psychiatric condition and that taking compounded ketamine at home without a provider monitoring for sedation, dissociation and blood-pressure changes “may put patients at risk for serious adverse events.” Requires careful prescribing because of the potential for misuse.

Intramuscular (IM) ketamine

Delivered as an injection into muscle. Less common in clinical practice, but an option in some settings. About 93% of the dose is absorbed, but there is less precise control than with an IV, and the research is limited to small studies. Injections under the skin (subcutaneous) were used in a large Australian trial and are practical in some clinics.

Preparing for treatment

The day of your infusion

• Nothing to eat or drink for 8 hours before (though some clinics allow clear liquids up to 3 hours before — follow your specific provider's instructions)
• Arrange a ride home. You cannot drive yourself after the infusion
• Bring comfortable clothes. You'll be reclining for an hour or more
• Bring headphones and music if your clinic allows it — music can shape the experience significantly
• Avoid heavy caffeine or stimulants beforehand

Medications that can interfere

Certain medications can reduce ketamine's effectiveness. Talk to your prescriber before your first infusion about whether you need to adjust any of these:

• Benzodiazepines (Valium, Klonopin, Ativan, Xanax) — some studies suggest they can blunt the antidepressant effect; they also add to sedation on treatment days
• Lamotrigine (Lamictal) — some studies suggest it may blunt the effect; the evidence is mixed
• Naltrexone — in one small study, taking naltrexone first largely blocked ketamine's antidepressant effect

Other medicines matter for safety rather than effectiveness: sedatives, opioids and alcohol add to sedation, and stimulants (such as amphetamines or methylphenidate) and MAOI antidepressants can add to the blood-pressure rise, so tell us about everything you take. Do not stop any medication without talking to your prescriber first.

Mindset and setting (the psychology of preparation)

There's a concept borrowed from the psychedelic literature called "set and setting" — the idea that your mental state going in (set) and your physical surroundings (setting) shape the experience you have. Ketamine isn't the same as a classical psychedelic, but the principle applies.

Setting includes the room, the lighting, the chair, what you're wearing, whether you have music, the people around you. Most of this is handled by the clinic, but you can influence pieces of it.

Mindset is more about what you bring: your expectations, intentions, self-awareness, and attitude. Thinking about questions like how do I interface with discomfort? How do I self-soothe? What do I do if difficult feelings come up? beforehand tends to make the experience itself go more smoothly.

Side effects and safety

In a medical setting with proper monitoring, serious problems with ketamine are uncommon: in the pooled esketamine trials, serious adverse events were no more frequent than with placebo, although in one real-world esketamine cohort 17% of patients had a serious adverse event over a year and 15% stopped because of side effects. That said, every effective treatment has side effects, and ketamine has some specific ones worth knowing. The most detailed safety data come from the esketamine (Spravato) trials and its FDA label, which carries a boxed warning for sedation, dissociation, slowed breathing, abuse and misuse, and suicidal thoughts in young adults.

Common side effects (during and shortly after treatment)

• Feeling intoxicated or "out of body" (dissociation; in the esketamine trials 61–84% of patients had dissociative or perceptual changes on a clinician-rated scale)
• Elevated blood pressure and heart rate
• Anxiety, especially during the infusion
• Blurred vision, dizziness
• Nausea
• Headache

Dissociation and sedation usually fade within one to two hours; the blood-pressure rise after esketamine peaks at about 40 minutes and can last about 4 hours, which is why monitoring and the no-driving rule are not optional. In the esketamine trials, about half to 60% of patients were noticeably sedated on a monitoring scale, and 3–19% had a blood-pressure rise of at least 40 points (top number) or 25 points (bottom number) at some point during the first four weeks, compared with 1–4% on placebo. Loss of consciousness was rare (about 3–4 in 1,000). This is why monitoring is not optional.

Less common but important risks

Will it keep working?

This is one of the most important things to understand about ketamine: it is not a one-and-done cure. After a single infusion, most people's benefit fades within one to two weeks; in one series, only 35% still met response criteria at one week, and in a larger group only about 1 in 8 did at two weeks. After a course of six infusions in an early study, 8 of 9 responders relapsed an average of 19 days later. To get sustained relief, ketamine is usually given as a course:

• Initial series: Typically 6 treatments over 2–3 weeks (usually 2–3 per week). For Spravato, twice a week for 4 weeks.
• Taper: After the initial series, treatments are spaced out gradually — weekly, then every 2 weeks, then less often as tolerated
• Maintenance: Some patients continue every 2–4 weeks for an extended period; others are able to stop after a successful initial course. In one study, patients who responded held their gains through weekly maintenance infusions. Among people who got well on esketamine, continuing it roughly halved the chance of relapse compared with stopping.

Can therapy replace ongoing ketamine? Not yet proven. One small study that added cognitive behavioral therapy after a ketamine course found a trend toward longer-lasting benefit on some measures but not on its main measure, and its authors called for larger trials. A brief computer-based training program after a single infusion kept depression scores lower for 30 days in a 154-person study. Ketamine still works best as part of an overall plan that includes therapy, medication review, exercise, sleep, and social support.

Common questions

How does ketamine compare to ECT?

ECT remains the most effective treatment we have for the most severe depression, including depression with psychosis or in people who cannot eat or drink. In a large U.S. trial of outpatients without psychosis, ketamine was at least as effective as ECT over three weeks (55% vs 41% responded) and did not cause the temporary memory-recall drop seen with ECT. In a Swedish trial of hospitalized, more severely ill patients, ECT produced more remissions (63% vs 46%). Ketamine avoids general anesthesia and has shorter sessions, but causes dissociation and blood-pressure rises and usually needs ongoing treatment. The best choice depends on severity, urgency, prior treatments, and personal factors. Neither is universally better.

Is ketamine the same as a "ketamine clinic" or street ketamine?

"Ketamine clinics" vary in quality and clinical rigor. Some are excellent, closely integrated with psychiatric care. Others provide infusions without adequate screening, monitoring, or follow-up. The quality of the program matters. Street ketamine is different — uncontrolled dose, often contaminated, no medical supervision, and with much higher risks.

Will I be myself during the treatment?

You'll be awake and aware, but the experience feels altered. You can usually speak, respond to staff, and signal if something is wrong. The goal is for you to stay awake and able to respond; loss of consciousness is rare (about 3–4 per 1,000 esketamine doses in the trials), which is one reason you are monitored. The dissociation itself is expected, not a sign of something going wrong.

How will I know if it's working?

Most patients who respond notice meaningful improvement within the first one to three treatments, sometimes within hours of the first infusion; in one study the typical responder needed three infusions. We track symptoms with standardized rating scales at every visit. If after the initial series there is no meaningful benefit, we stop and re-evaluate rather than continuing indefinitely.

Can ketamine treat things other than depression?

The strongest evidence is in depression. For bipolar depression, two small studies found rapid benefit from a single infusion given with lithium or valproate, lasting a few days; a Cochrane review rated this evidence low certainty. For PTSD, a 30-person study of six infusions was positive, but a larger 158-person study in veterans found no benefit on PTSD symptoms. Use for these conditions is off-label and should be approached with realistic expectations.

Helpful resources

Where these numbers come from

Every figure on this page was checked against the original publication or FDA document in September 2026. The clinician version of this page has the full reference list.

1. Zarate CA Jr, et al. A randomized trial of an NMDA antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006. PubMed
2. Murrough JW, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013. PubMed
3. Pennybaker SJ, et al. Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion. J Affect Disord 2017. PubMed
4. aan het Rot M, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry 2010. PubMed
5. Phillips JL, et al. Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: a randomized controlled trial. Am J Psychiatry 2019. PubMed
6. Shiroma PR, et al. Repeated vs single subanesthetic ketamine for treatment-resistant depression. Transl Psychiatry 2020. PubMed
7. Ionescu DF, et al. Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation. J Affect Disord 2019. PubMed
8. Loo C, et al. Repeated subcutaneous ketamine injections for treatment-resistant depression (KADS). Br J Psychiatry 2023. PubMed
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39. U.S. FDA. Compounding risk alert on compounded ketamine products for psychiatric disorders, October 10, 2023. Archived copy (linked from the FDA Compounding Risk Alerts index).

Get in touch

If ketamine might be a fit for you, or if you're considering treatment and want to talk through your options, our program provides consultations and ketamine treatment, and will tell you honestly if another treatment is a better fit.