Ketamine Therapy: How It Works, What It Treats, and What to Expect

In 2000, a small study at Yale made a quiet but extraordinary observation: patients with severe depression felt significantly better within hours of receiving a low dose of ketamine, a drug that had been used as a surgical anesthetic for decades [1]. That finding upended a core assumption in psychiatry, that antidepressants simply needed weeks to kick in, and opened the door to an entirely new class of treatment.

Today, ketamine therapy is one of the fastest-growing options in mental health care. Hundreds of clinics across the United States offer ketamine infusions for depression, PTSD, chronic pain, and other conditions that haven’t responded to standard treatments. In 2019, the FDA approved a nasal spray form called Spravato (esketamine) specifically for treatment-resistant depression [4]. For people who’ve tried medication after medication without relief, ketamine represents something rare: a treatment that can produce noticeable results within hours or days rather than weeks.

But ketamine therapy also raises real questions. How does it actually work in the brain? Who is it right for? What does a session feel like, and what are the risks? This guide covers all of it, from the science and evidence behind ketamine therapy to the practical details of cost, safety, and finding a qualified provider.

What Is Ketamine?

Ketamine was first synthesized in 1962 and approved by the FDA as an anesthetic in 1970. It quickly became a staple in operating rooms and battlefield medicine because of its unique safety profile: unlike most anesthetics, it doesn’t suppress breathing or blood pressure at standard doses. The World Health Organization lists it as an essential medicine, and it’s still widely used in emergency departments, pediatric surgery, and veterinary medicine around the world.

Ketamine’s story as a mental health treatment began in the late 1990s, when researchers at Yale started exploring its effects on mood. The landmark 2000 study by Berman and colleagues showed that a single sub-anesthetic dose (much lower than what’s used in surgery) produced rapid antidepressant effects in patients with major depression [1]. A larger, more rigorous trial by Zarate and colleagues at the National Institute of Mental Health confirmed these findings in 2006 [2]. Since then, dozens of clinical trials have studied ketamine for depression, PTSD, suicidal ideation, and chronic pain.

It’s important to understand the regulatory picture. The FDA has approved ketamine as an anesthetic, not as an antidepressant. When doctors prescribe ketamine for depression or other psychiatric conditions, they’re using it “off-label,” a legal and common practice in medicine (roughly one in five prescriptions in the U.S. are off-label). The one exception is esketamine (Spravato), a nasal spray derived from ketamine that received FDA approval in 2019 specifically for treatment-resistant depression [4]. This distinction matters for insurance coverage, which we’ll cover later.

Ketamine is also classified as a Schedule III controlled substance in the United States, meaning it has recognized medical uses but also some potential for misuse. This classification places it in the same category as drugs like testosterone and certain sleep medications.

How Ketamine Works in the Brain

Traditional antidepressants like SSRIs (Prozac, Zoloft) and SNRIs (Effexor, Cymbalta) work by increasing serotonin or norepinephrine levels in the brain. They typically take four to six weeks to produce noticeable effects, and for roughly 30% of people with depression, they don’t work well enough even after multiple trials [2]. Ketamine operates through a completely different pathway, and that difference helps explain why it works so much faster.

NMDA Receptor Blockade and the Glutamate Surge

Ketamine’s primary action is blocking NMDA receptors, which are part of the glutamate system, the brain’s main excitatory neurotransmitter network [5]. When ketamine blocks these receptors (particularly on inhibitory interneurons), it triggers a cascade of events that results in a burst of glutamate release. This glutamate surge activates another type of receptor called AMPA receptors, which in turn stimulates a chain of signaling molecules inside neurons [5][8].

BDNF and Synaptogenesis

The downstream result of this glutamate-AMPA cascade is an increase in brain-derived neurotrophic factor (BDNF), a protein that acts like fertilizer for brain cells [5][11]. BDNF promotes the growth of new synaptic connections between neurons, a process called synaptogenesis. In animal studies, a single dose of ketamine can restore synaptic connections in the prefrontal cortex that had been damaged by chronic stress, and these structural changes happen within hours [8][11].

This is why researchers believe ketamine works so quickly compared to SSRIs. Rather than slowly shifting neurotransmitter levels over weeks, ketamine appears to rapidly repair and rebuild the neural circuits involved in mood regulation [8].

The Metabolite Hypothesis (HNK)

A 2016 study published in Nature by Zanos and colleagues added another layer to the story. The researchers found that a ketamine metabolite called hydroxynorketamine (HNK) may be responsible for much of ketamine’s antidepressant effect, and it works through AMPA receptor activation without blocking NMDA receptors at all [6]. If this finding holds up in human trials, it could lead to new drugs that provide ketamine’s benefits without its dissociative side effects. This research is still in early stages, but it has generated significant interest in the field [6].

Why Speed Matters

For someone in a depressive crisis or experiencing suicidal thoughts, the difference between hours and weeks is not academic. Traditional antidepressants leave a dangerous gap during which patients remain at risk. Ketamine’s rapid onset, often within hours of a single infusion, has made it particularly valuable for acute psychiatric emergencies [7][8].

Conditions Treated with Ketamine Therapy

Treatment-Resistant Depression (Strong Evidence)

This is where the evidence for ketamine for depression is strongest. Treatment-resistant depression (TRD) is generally defined as depression that hasn’t responded to at least two adequate trials of different antidepressants. Multiple randomized controlled trials have shown that a single IV ketamine infusion produces rapid antidepressant effects in 50-70% of TRD patients, with effects typically appearing within two to four hours and lasting about one week [2][3].

The largest and most cited trial, led by Murrough and colleagues in 2013, found that ketamine produced a response rate of 64% compared to 28% for an active placebo (midazolam) at 24 hours post-infusion [3]. Repeated infusions (typically six over two to three weeks) appear to produce more sustained results [9].

Suicidal Ideation (Strong Evidence)

One of ketamine’s most striking effects is its rapid reduction of suicidal thoughts, often within hours. A 2018 meta-analysis by Wilkinson and colleagues found that ketamine significantly reduced suicidal ideation within 24 hours of a single dose, regardless of its effects on overall depression scores [7]. This has made ketamine a focus of emergency psychiatry research, though it’s not yet a standard protocol in most emergency departments.

PTSD (Moderate Evidence)

A 2014 randomized controlled trial by Feder and colleagues found that a single IV ketamine infusion significantly reduced PTSD symptoms compared to midazolam in patients with chronic PTSD [10]. Patients receiving ketamine showed rapid improvement in PTSD symptom severity within 24 hours. More research on ketamine for PTSD is underway, including studies on repeated dosing, and the evidence so far is promising but still limited to relatively small trials.

Chronic Pain (Moderate Evidence)

Ketamine has a long history in pain management, and its NMDA-blocking action makes it particularly relevant for certain pain conditions. We cover this in detail in the ketamine for chronic pain section below, but the evidence is moderate for conditions like complex regional pain syndrome (CRPS), neuropathic pain, and fibromyalgia [12].

Anxiety Disorders (Emerging Evidence)

There are fewer studies specifically examining ketamine for anxiety, but several depression trials have noted significant anxiolytic effects as a secondary outcome [13]. Small studies have shown promise for social anxiety disorder and generalized anxiety disorder, but larger, well-designed trials are needed before firm conclusions can be drawn.

OCD (Emerging Evidence)

A handful of small studies have examined ketamine for obsessive-compulsive disorder, with results suggesting rapid but temporary reductions in OCD symptoms [14]. The evidence base is too small to draw strong conclusions, and ketamine is not currently recommended as a standard treatment for OCD.

Substance Use Disorders (Early Evidence)

Early research suggests ketamine may help with alcohol and cocaine dependence, possibly by disrupting the reconsolidation of addiction-related memories and by addressing the depressive symptoms that often drive relapse [15]. These findings are intriguing but preliminary, and this remains an active area of investigation.

Types of Ketamine Therapy

Not all ketamine therapy is the same. The form of delivery affects how quickly it works, how long effects last, the cost, and the level of evidence supporting it. Here’s a comparison of the four main approaches.

IV Ketamine Infusion (Racemic Ketamine)

Ketamine infusion therapy is the most studied form and the one used in the majority of clinical trials. A standard infusion delivers 0.5 mg/kg of racemic ketamine (a mix of two mirror-image molecules, S-ketamine and R-ketamine) over 40 minutes through an IV line.

• Onset: Minutes
• Duration of acute effects: 45-90 minutes
• Typical cost per session: $400-$800
• Evidence level: Strong (dozens of RCTs)
• Insurance coverage: Rarely covered; considered off-label

IV infusion allows precise dose control and produces the most consistent blood levels, which is one reason it’s the preferred method in research settings. A typical course involves six infusions over two to three weeks, followed by maintenance infusions as needed (often monthly) [9].

Intranasal Esketamine (Spravato)

Spravato is the brand name for esketamine, the S-enantiomer (mirror-image version) of ketamine. It’s the only form of ketamine with specific FDA approval for treatment-resistant depression (and, as of 2020, for major depressive disorder with acute suicidal ideation).

• Onset: 15-30 minutes
• Duration of acute effects: 1-2 hours
• Typical cost per session: $600-$900 (before insurance)
• Evidence level: Strong (FDA-approved based on Phase III trials) [4]
• Insurance coverage: Often covered, with prior authorization

Spravato must be administered in a certified healthcare setting under the FDA’s Risk Evaluation and Mitigation Strategy (REMS) program. Patients self-administer the nasal spray under supervision and are monitored for at least two hours. You cannot take it home.

Sublingual/Oral Troches and Tablets

Compounding pharmacies can prepare ketamine as lozenges (troches) or tablets that dissolve under the tongue. These are prescribed off-label by physicians and are the form used by at-home ketamine therapy programs such as Mindbloom and Joyous.

• Onset: 15-30 minutes
• Duration of acute effects: 1-3 hours
• Typical cost per session: $100-$250 (including program fees)
• Evidence level: Limited (few RCTs; mostly case series and clinical experience)
• Insurance coverage: Not covered

Bioavailability is lower and more variable with oral/sublingual administration (roughly 25-30% compared to nearly 100% with IV), so higher doses are needed to achieve therapeutic effects. The trade-off is lower cost and greater convenience. The downside is less medical oversight and less predictable dosing.

Intramuscular (IM) Injection

Some clinics offer ketamine as an intramuscular injection, which provides an intermediate option between IV infusion and oral forms.

• Onset: 3-5 minutes
• Duration of acute effects: 45-90 minutes
• Typical cost per session: $350-$600
• Evidence level: Limited (fewer studies than IV)
• Insurance coverage: Rarely covered

IM ketamine doesn’t require an IV line, which makes it simpler to administer, but it also offers less precise dose control than IV infusion.

What a Ketamine Session Looks Like

If you’re considering ketamine therapy, knowing what to expect can reduce anxiety and help you get the most from treatment. Here’s a typical timeline for an IV infusion, though the process is similar for other forms.

Screening and Assessment

Before your first session, you’ll undergo a thorough evaluation. A qualified provider will review your psychiatric history, current medications, physical health (including blood pressure and heart health), and substance use history. They’ll assess whether ketamine is appropriate for your condition and rule out contraindications such as uncontrolled hypertension, active psychosis, or pregnancy.

Most clinics require you to have tried at least two antidepressants without adequate response before recommending ketamine for depression. Some providers also require a referral from your primary psychiatrist or therapist.

Preparation

On the day of your session, you’ll typically be asked to fast for four to six hours (to reduce nausea), avoid certain medications, and arrange transportation home, as you won’t be able to drive for several hours afterward. Many clinics recommend wearing comfortable clothing and bringing an eye mask or headphones with calming music.

Some clinics that emphasize ketamine-assisted psychotherapy (KAP) will also spend time helping you set an intention for the session and discussing what you hope to explore or process during the experience.

The Infusion Experience

For a standard IV infusion, a nurse or physician places an IV line (usually in your arm) and starts the ketamine drip. The infusion runs for about 40 minutes. Your vital signs (blood pressure, heart rate, oxygen saturation) are monitored throughout.

Within minutes, you’ll likely begin to notice changes. The most common experiences during an infusion include:

• Dissociation: A feeling of being detached from your body or surroundings. This can range from mild (feeling “floaty”) to more intense (feeling like you’re observing yourself from a distance). This is a temporary, expected effect of the drug and not a sign that something is wrong.
• Perceptual changes: Some people notice visual effects (colors appearing more vivid, mild geometric patterns with eyes closed), auditory changes, or an altered sense of time.
• Emotional shifts: You may feel a sense of calm, wonder, or emotional release. Some people cry, laugh, or experience memories surfacing. Others feel relatively little.
• Physical sensations: Mild nausea, dizziness, or a sensation of heaviness or lightness. Some people feel warm.

If you’re wondering whether the experience is similar to recreational use, our article on whether ketamine therapy gets you high explores that distinction in more detail. At therapeutic doses, the experience is typically described as dream-like rather than euphoric.

Post-Session Recovery

The acute effects of ketamine usually wear off within 15 to 30 minutes after the infusion ends. You’ll rest in the clinic for about 30 to 60 minutes while you return to baseline. Most people feel somewhat groggy or “spacey” for a few hours afterward, which is why you need someone to drive you home.

Integration

Many clinics, particularly those offering ketamine-assisted psychotherapy, include an integration session after each infusion. This is a conversation with a therapist about what you experienced during the session and how to apply any insights to your daily life. Even if your clinic doesn’t offer formal integration, many patients find it helpful to journal or discuss their experiences with a therapist between sessions.

Series Structure

A typical course of IV ketamine for depression involves six infusions over two to three weeks [9]. Some patients notice improvement after the first or second infusion, while others don’t respond until later in the series. After the initial series, maintenance infusions (usually monthly or as needed) are often recommended to sustain the benefits, as the effects of a single infusion tend to fade within one to two weeks [9].

For Spravato, the recommended schedule is twice weekly for the first month, weekly for the second month, and then weekly or biweekly for ongoing maintenance [4].

Ketamine vs Esketamine (Spravato)

This comparison matters for practical reasons: it affects what you’ll pay, whether insurance will help, and which clinics you can visit. For a deeper look, see our guide on ketamine nasal spray (Spravato).

Pharmacological Differences

Ketamine is a racemic mixture, meaning it contains equal parts of two enantiomers: S-ketamine and R-ketamine. Spravato contains only S-ketamine (esketamine), which binds to NMDA receptors with roughly three to four times greater affinity than R-ketamine [4][8].

Some researchers have argued that R-ketamine may actually have stronger antidepressant properties with fewer side effects than S-ketamine, based on animal studies [8]. If true, racemic IV ketamine (which contains both) could potentially be more effective than Spravato, though head-to-head trials in humans are still limited.

Insurance and Cost

The biggest practical difference is insurance coverage. Because Spravato has FDA approval for TRD, many insurance plans cover it (with prior authorization). A Spravato session costs $600-$900 before insurance, but many patients pay significantly less with coverage. See our guide on whether ketamine therapy is covered by insurance for details.

IV ketamine is off-label and almost never covered by insurance. You’ll typically pay $400-$800 per infusion out of pocket, with a full course of six infusions running $2,400-$4,800. We break down the full cost picture in our ketamine therapy cost guide.

The REMS Program

Spravato must be administered under the FDA’s Risk Evaluation and Mitigation Strategy (REMS), which means it can only be given at certified healthcare facilities. Patients must be monitored for at least two hours after each dose and cannot take the drug home. This adds logistical burden but also ensures safety monitoring.

IV ketamine has no such formal requirement, though reputable clinics provide similar levels of monitoring.

Which Should You Choose?

If you have insurance that covers Spravato and your primary concern is cost, Spravato may be the more accessible option. If you’re paying out of pocket and want the form with the most research behind it, IV ketamine is well-supported by evidence. Some clinicians prefer IV ketamine because of the ability to precisely control dosing and because the racemic mixture may offer advantages over esketamine alone. Discuss both options with your provider.

Ketamine for Chronic Pain

Ketamine’s role in pain management predates its psychiatric applications. The same NMDA receptor blockade that produces antidepressant effects also interrupts pain signaling pathways, particularly those involved in central sensitization, where the nervous system amplifies pain signals over time [12]. For more details, read our full guide on ketamine for chronic pain.

Complex Regional Pain Syndrome (CRPS)

CRPS is one of the pain conditions with the most evidence supporting ketamine treatment. Multi-day, higher-dose ketamine infusions (often given in hospital settings) have shown meaningful pain reduction in several studies, though the protocols vary widely and the evidence comes primarily from observational studies and small trials [12].

Fibromyalgia

A few small trials have examined IV ketamine for fibromyalgia, with results showing short-term pain reduction in some patients. The evidence is limited but suggests ketamine may be worth considering for patients who haven’t responded to standard fibromyalgia treatments [12].

Neuropathic Pain

Ketamine’s NMDA-blocking action is theoretically well-suited for neuropathic pain, which involves aberrant signaling in damaged nerves. Clinical evidence includes positive results from small trials, but there is no consensus on optimal dosing protocols or patient selection [12].

Migraine

Emerging case reports and small studies suggest ketamine may help with refractory migraine, particularly status migrainosus (migraine lasting more than 72 hours). This application is still in early stages.

Important Caveats

Pain-focused ketamine protocols often involve higher doses and longer infusion durations than psychiatric protocols. These treatments carry greater risks and are typically administered in hospital or specialized pain clinic settings. The evidence base for ketamine in chronic pain, while growing, is not as strong as the evidence for depression.

Risks, Side Effects, and Safety

Ketamine therapy has a well-established safety profile at sub-anesthetic doses when administered in a clinical setting, but it’s not without risks. Being informed about potential side effects will help you make a better decision and prepare for treatment.

Common Side Effects

These occur during or shortly after a session and are typically short-lived:

• Dissociation: The most characteristic effect. It ranges from mild detachment to a more profound altered state. It’s temporary and resolves within an hour of the infusion ending.
• Nausea and vomiting: Occurs in roughly 10-20% of patients. Pre-treatment with ondansetron (Zofran) can help, and fasting before sessions reduces risk.
• Elevated blood pressure: Ketamine causes a transient increase in blood pressure and heart rate. This is usually mild and returns to normal after the session, but it’s the primary reason uncontrolled hypertension is a contraindication [16].
• Dizziness and drowsiness: Common during and for a few hours after treatment.
• Headache: Reported by some patients, usually mild.

Serious Concerns

• Bladder toxicity: Chronic, heavy ketamine use (typically at recreational doses far exceeding therapeutic levels) is associated with ketamine-induced cystitis, a painful condition involving bladder inflammation, reduced capacity, and in severe cases, irreversible damage [16]. At the doses and frequencies used in clinical treatment, bladder problems are rare, but long-term data from maintenance therapy spanning years is still limited. Patients on long-term maintenance should be monitored for urinary symptoms.
• Abuse and dependence potential: As a Schedule III substance, ketamine carries some risk of psychological dependence. This risk is lower in a supervised clinical setting with controlled doses than with unsupervised or recreational use, but it’s not zero. Providers should screen for substance use disorders and monitor patients receiving ongoing treatment [16].
• Cognitive effects: At therapeutic doses, there’s no strong evidence of lasting cognitive impairment, though some patients report transient memory difficulties or brain fog after sessions. Chronic recreational users do show cognitive deficits, but these populations use much higher and more frequent doses [16].

Contraindications

Ketamine therapy is generally not recommended for people with:

• Uncontrolled hypertension
• Active psychosis or a history of psychotic disorders (schizophrenia, schizoaffective disorder)
• Untreated hyperthyroidism
• Pregnancy
• Active substance use disorders involving ketamine or similar drugs
• Certain cardiovascular conditions (discuss with your provider)

Long-Term Safety

One of the most honest things to say about ketamine therapy is that long-term safety data for repeated, low-dose psychiatric use is still limited. Most clinical trials have followed patients for weeks to months, not years. The safety profile of the drug itself is well-characterized from decades of anesthetic use, but the specific pattern of repeated sub-anesthetic dosing over years for depression is a newer phenomenon. This is an area where ongoing research is needed.

Cost of Ketamine Therapy

Cost is one of the biggest barriers to ketamine therapy. Here’s what you can expect to pay in 2026, depending on the form of treatment. For a full breakdown, see our ketamine therapy cost guide.

IV Ketamine Infusion

• Per session: $400-$800
• Initial course (6 infusions): $2,400-$4,800
• Monthly maintenance: $400-$800 per infusion
• First-year estimate: $4,000-$10,000+
• Insurance: Rarely covered (off-label use)

Spravato (Esketamine Nasal Spray)

• Per session (before insurance): $600-$900
• Insurance: Often covered with prior authorization; copays vary widely ($0-$250 per session)
• Janssen CarePath savings program: May reduce costs for commercially insured patients

At-Home Oral/Sublingual Ketamine

• Per month (through telehealth programs): $150-$350 including medication and provider consultations
• Insurance: Not covered
• Initial evaluation: $150-$250

What Affects Your Total Cost

Several factors influence what you’ll actually pay: your geographic location (urban clinics tend to charge more), whether your clinic includes therapy or integration as part of the session, how many maintenance sessions you need, and whether your insurance covers any portion of the treatment.

How to Find a Qualified Provider

Choosing the right provider matters for both safety and outcomes. Here’s what to look for and what to watch out for.

Credentials to Look For

• Medical degree and licensure: Ketamine should be prescribed and supervised by a licensed physician (MD or DO), nurse practitioner, or physician assistant working under physician supervision.
• Relevant training: Look for providers with training in psychiatry, anesthesiology, or pain medicine. Board certification in one of these specialties is a good sign.
• Experience: Ask how many patients they’ve treated with ketamine and how long they’ve been offering it.
• Monitoring protocols: The clinic should monitor vital signs during infusions and have emergency protocols in place.

Red Flags

• Clinics that don’t require a psychiatric evaluation before treatment
• Providers who guarantee results or make claims that sound too good to be true
• No vital sign monitoring during sessions
• Pressure to sign up for expensive packages upfront without a trial session
• Lack of follow-up care or coordination with your existing mental health providers
• Mail-order ketamine programs with minimal medical oversight

Questions to Ask

For related treatment comparisons, see our guide on TMS vs ketamine, and for a broader view of similar approaches, visit our psychedelic therapy overview.

When to See a Doctor

You should talk to a healthcare provider about ketamine therapy if:

• You’ve been diagnosed with depression and haven’t responded adequately to two or more antidepressant medications
• You’re experiencing chronic suicidal thoughts despite ongoing treatment
• You have treatment-resistant PTSD that hasn’t improved with evidence-based therapies like EMDR or prolonged exposure
• You have a chronic pain condition that hasn’t responded to standard treatments
• You’re interested in ketamine but aren’t sure if you’re a good candidate

Start with your psychiatrist or primary care physician. They can help you weigh the evidence, assess whether ketamine is appropriate given your specific situation, and refer you to a qualified provider.

If you’re in a mental health crisis or experiencing active suicidal thoughts, contact the 988 Suicide and Crisis Lifeline (call or text 988) or go to your nearest emergency department. While ketamine shows promise for suicidal ideation, it’s not a substitute for acute crisis care.

The Bottom Line

Ketamine therapy represents a genuine advance in the treatment of depression and several other conditions. The evidence is strongest for treatment-resistant depression, where multiple well-designed trials have shown rapid, meaningful improvement in patients who haven’t responded to conventional antidepressants [2][3]. Its ability to reduce suicidal ideation within hours fills a critical gap that no other available treatment addresses as quickly [7].

That said, ketamine isn’t a miracle cure. Not everyone responds, the effects of individual infusions are temporary (requiring ongoing maintenance), long-term safety data for repeated psychiatric dosing is still accumulating, and the cost can be prohibitive. The unregulated growth of at-home ketamine programs raises legitimate concerns about safety and appropriate medical oversight.

If you’re considering ketamine therapy, approach it with informed optimism. Work with a qualified provider, understand the evidence for your specific condition, and make sure you have a broader treatment plan that includes therapy, lifestyle factors, and ongoing psychiatric care. Ketamine works best not as a standalone fix but as one powerful tool within a larger treatment strategy.

Frequently Asked Questions

Does ketamine therapy actually work, and for what conditions?

The strongest evidence is for treatment-resistant depression, where randomized trials show 50 to 70 percent of patients respond, often within hours. It also rapidly reduces suicidal ideation. Evidence is more moderate for PTSD and chronic pain, and still early for anxiety, OCD, and substance use disorders.

How much does ketamine therapy cost, and does insurance cover it?

IV ketamine runs about $400 to $800 per session, or $2,400 to $4,800 for an initial six-session course, and is almost never covered because it is off-label. Spravato costs about $600 to $900 per session but is often covered with prior authorization, with copays ranging from $0 to $250.

Is ketamine therapy safe, and what are the side effects?

Common side effects include dissociation, nausea or vomiting in 10 to 20 percent of patients, elevated blood pressure, dizziness, and headache. Serious concerns include bladder toxicity from chronic heavy use and abuse or dependence potential. The article notes no strong evidence of lasting cognitive impairment at therapeutic doses.

How long do the effects last, and how many sessions are needed?

A single infusion typically provides relief for about one week. A standard course is six infusions given over two to three weeks, usually followed by monthly maintenance infusions to sustain the benefit. The exact schedule depends on how each person responds to treatment.

Who is a good candidate for ketamine therapy?

Candidates typically include people with treatment-resistant depression who have failed at least two antidepressants, chronic suicidal ideation despite treatment, treatment-resistant PTSD, or chronic pain unresponsive to standard care. Contraindications include uncontrolled hypertension, active psychosis, untreated hyperthyroidism, pregnancy, and active substance use disorders.

What is the difference between IV ketamine and Spravato (esketamine)?

IV ketamine is a racemic mixture of S- and R-ketamine, acts within minutes, lasts 45 to 90 minutes, and is the most studied form. Spravato is a nasal spray containing only the S-enantiomer, is FDA-approved, acts in 15 to 30 minutes, lasts one to two hours, and requires two-hour monitoring at a certified facility.

References

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2. Zarate CA Jr et al. “A randomized trial of an NMDA antagonist in treatment-resistant major depression.” Arch Gen Psychiatry 2006;63(8):856-864. PMID: 16894061
3. Murrough JW et al. “Antidepressant efficacy of ketamine in treatment-resistant major depression.” Am J Psychiatry 2013;170(10):1134-1142. PMID: 23982301
4. Daly EJ et al. “Efficacy and safety of intranasal esketamine in treatment-resistant depression.” JAMA Psychiatry 2018;75(2):139-148. PMID: 29282469
5. Abdallah CG et al. “Ketamine as a promising prototype for rapid-acting antidepressants.” Ann NY Acad Sci 2015;1344(1):66-77. PMID: 25727103
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9. aan het Rot M et al. “Safety and efficacy of repeated-dose IV ketamine for treatment-resistant depression.” Biol Psychiatry 2010;67(2):139-145. PMID: 19897179
10. Feder A et al. “Efficacy of IV ketamine for treatment of chronic PTSD.” JAMA Psychiatry 2014;71(6):681-688. PMID: 24740528
11. Autry AE et al. “NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses.” Nature 2011;475(7354):91-95. PMID: 21677641
12. Cohen SP et al. “Consensus guidelines on the use of intravenous ketamine infusions for chronic pain.” Reg Anesth Pain Med 2018;43(5):521-546. PMID: 29870458
13. Glue P et al. “Ketamine’s dose-related effects on anxiety symptoms in patients with treatment refractory anxiety disorders.” J Psychopharmacol 2017;31(10):1302-1305. PMID: 28441895
14. Rodriguez CI et al. “Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder.” Neuropsychopharmacology 2013;38(12):2475-2483. PMID: 23783065
15. Dakwar E et al. “A single ketamine infusion combined with mindfulness-based behavioral modification to treat cocaine dependence.” Am J Psychiatry 2020;177(2):125-133. PMID: 31230464
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About the medical reviewer

Dr. Bronwyn Holmes, MD, FAARFM is a physician specialising in regenerative medicine, advanced peptide therapeutics, exosome and stem cell biology, hormonal health, and longevity. Last reviewed July 5, 2026.