If you’re considering ketamine therapy for depression, one of the first questions you probably have is how many sessions it takes to see results. The answer depends in part on which treatment option you choose.

At Keta Medical Center, we offer both Spravato and IV ketamine. Spravato is the brand name for esketamine, a nasal spray version of ketamine therapy administered under medical supervision. Most patients complete eight Spravato sessions over four weeks, or six IV ketamine infusions over three weeks, for their induction phase. From there, maintenance sessions continue on a schedule tailored to you.

Below, we break down what a typical course of treatment looks like for our two main options: IV ketamine and Spravato (esketamine nasal spray).

How ketamine treatment plans are structured for depression

Most ketamine protocols follow these phases:

• Induction phase: A concentrated series of sessions delivered close together, designed to build a therapeutic response.
• Optimization phase (Spravato): Once the induction series is complete, Spravato patients move into an optimization phase, with less frequent follow-up sessions.
• Maintenance phase (IV ketamine and Spravato): Both treatment types then continue into a maintenance phase, with follow-up sessions spaced out further to sustain improvement over time.

When people ask how long ketamine lasts, they’re often asking three different questions at once. 

• How long will the infusion session itself take? 
• What will the experience during and after treatment feel like, and for how long? 
• How long might the therapeutic benefits last?

Ketamine is a dissociative anesthetic that has been used in medical settings for decades. In recent years, its application has expanded into the treatment of treatment-resistant depression, post-traumatic stress disorder (PTSD), anxiety, bipolar depression, and other conditions that have not responded adequately to conventional approaches. Understanding the timeline of ketamine therapy, from the first minutes of an infusion to weeks of potential symptom relief, helps patients know what to expect before they begin.

How long does ketamine last?

The answer depends on which aspect of ‘lasting’ you are asking about. Ketamine therapy involves three distinct timelines: the length of the session, the duration of the immediate dissociative effects, and the duration of the therapeutic benefits that follow.

The infusion session

A typical IV ketamine infusion at Keta Medical Center takes approximately 45 minutes. After the infusion ends, patients remain in a private, supervised room for monitoring. Most patients are in the clinic for about 90 minutes, from the start of the infusion until they are ready to leave.

For patients who qualify for Spravato® (an esketamine-based nasal spray), the treatment session follows a different protocol. The dissociative effects of Spravato last approximately 45 minutes. The FDA requires patients to remain in the clinic for 2 hours after administration. Spravato is FDA-approved for treatment-resistant depression and is covered by insurance.

The immediate dissociative experience

During a ketamine infusion, patients experience a temporary dissociative state: a mild sense of altered perception or detachment from their surroundings. This is a known and expected effect of ketamine at therapeutic doses. Our clinical team prepares every patient in advance and provides active support throughout the session.

For most patients, the dissociative effects of Spravato and IV ketamine resolve as the infusion ends or shortly thereafter. Mild grogginess or cognitive haziness may persist for an hour or two after leaving the clinic, which is why patients should arrange transportation and avoid driving after their treatment. Side effects are generally mild and may include temporary dizziness or nausea.

How long ketamine stays in the body

A commonly searched question is how long ketamine remains detectable in the system. IV Ketamine has a half-life of approximately 2 to 3 hours in adults, meaning half of the drug is cleared from the bloodstream in roughly that time. The drug is effectively eliminated from the body within 10 to 15 hours of administration, with trace metabolites potentially persisting slightly longer.

Critically, the clearance of ketamine from the bloodstream is not the same as the end of its therapeutic effects. The antidepressant and mood-stabilizing benefits of ketamine persist well beyond the point at which the drug is no longer detectable: this is one of the most clinically interesting properties of ketamine as a treatment.

How quickly can you see results?

One of ketamine’s most significant clinical distinctions from conventional antidepressants is the speed at which it can produce therapeutic benefit. Traditional antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), typically take 4 to 12 weeks to show a meaningful response, if they work at all. Ketamine works through an entirely different mechanism.

Rather than targeting serotonin or norepinephrine, ketamine acts on the glutamate system: specifically, it blocks NMDA receptors in the brain. This triggers a downstream cascade: the release of brain-derived neurotrophic factor (BDNF), activation of AMPA receptors, and the formation of new synaptic connections, a process called synaptogenesis. These effects are believed to underpin ketamine’s unusually rapid antidepressant action.

Within 24 hours

Clinical research published in peer-reviewed literature, including studies from the National Institutes of Health and landmark trials conducted at Yale University, has consistently shown that ketamine can produce significant reductions in depressive symptoms within hours of a single infusion. In this study, a 71% response rate was observed at 24 hours post-infusion. The peak antidepressant effect is generally observed within 24 to 72 hours.

Spravato (esketamine) has shown similar rapid effects in its own landmark trial: in TRANSFORM-2, patients treated with esketamine showed a statistically significant improvement in depressive symptoms compared to placebo within 24 hours of the first dose, an effect that was largely sustained through the four-week study period.

Duration after a single infusion

For patients who respond to a single ketamine infusion, the therapeutic benefits may last anywhere from several days to approximately two weeks. Research shows most patients experience some symptom return within 7 days, though this varies by individual. This is why treatment follows an induction protocol: a series of infusions over a defined period to build and extend benefits before moving to maintenance. The anti-fatigue, anti-anxiety, and mood-stabilizing effects follow a similar pattern, and integration therapy between sessions is encouraged to help sustain these gains.

Duration with a series of infusions

At Keta Medical Center, ketamine is typically administered as a structured series of infusions rather than a single session. A multi-infusion approach is consistently associated with more durable therapeutic outcomes. Published research on repeated-dose protocols reports that among patients who respond, the median time to symptom return following a completed series can extend to several weeks. In one open-label study involving patients with treatment-resistant major depression, 70.8% of participants met response criteria by the end of a 12-day series of up to 6 infusions, and many responders maintained that benefit for weeks afterward.

Maintenance or booster infusions can help extend the period of relief for patients who respond well to their initial series. The appropriate frequency of maintenance treatment is determined individually by a clinician based on the patient’s response and clinical picture.

What affects how long the results last?

Several factors influence the duration of ketamine’s therapeutic benefits, including:

• The nature and severity of the underlying condition
• Prior treatment history and whether the patient has treatment-resistant depression or another qualifying condition
• Whether ketamine therapy is integrated with adjunct treatments such as psychotherapy
• General health, sleep, lifestyle factors and the patient’s neurobiological response

Long-term efficacy of Spravato

Long-term data support the value of staying on a maintenance schedule. A multi-year study of esketamine (Spravato) followed patients for nearly 5 years and found that improvements achieved during the first 4 weeks of treatment were sustained through the optimization and maintenance phase, with half of participants in remission by the study endpoint. Remission rates rose from 35.6% at the end of induction to 46.1% during ongoing maintenance, reinforcing that consistent, well-managed treatment extends results well beyond what a single session can achieve.

Anxiety disorders are among the most common mental health conditions in the United States, affecting millions of people across every walk of life. For many, standard treatments (therapy, medication, or both) provide meaningful relief. But for a significant number of patients, conventional approaches fall short, leaving them searching for something more effective.

Ketamine, a dissociative anesthetic with a decades-long history in clinical medicine, has emerged as a compelling option for people who haven’t found adequate relief from traditional anxiety treatments. Research into ketamine’s effects on anxiety disorders is growing, and many patients are asking whether it might be right for them. 

Here’s what the clinical evidence tells us.

How ketamine may work for anxiety

Ketamine’s potential effects on anxiety are rooted in its unique mechanism of action. Unlike most psychiatric medications, ketamine works primarily by blocking N-methyl-D-aspartate (NMDA) receptors in the brain and modulating glutamate signaling, a neurotransmitter system central to mood regulation, memory, and learning. Researchers believe this dual effect may help restore synaptic plasticity: the brain’s ability to form new, healthier neural 

connections and break free from entrenched anxiety-driven thought patterns.

Chronic stress and persistent anxiety can dysregulate glutamate balance, impairing the brain’s natural adaptability over time. Clinical evidence suggests ketamine may help counteract this process, promoting neuroplasticity and potentially offering relief where other medications have not. As with all emerging treatments, the full picture of how ketamine works is still being studied, but the early findings are encouraging.

Ketamine vs. conventional anti-anxiety medications

Most first-line anti-anxiety medications, including SSRIs and SNRIs, work by modulating serotonin and related neurotransmitters, and they can take two to six weeks to produce meaningful symptom relief. Ketamine takes a different path, acting directly on the glutamate system and producing effects that may be felt within hours of a single infusion. 

This rapid onset is clinically significant for people living with severe or treatment-resistant anxiety. That said, ketamine is not intended to replace first-line treatments: it is usually considered when conventional approaches have been tried and have not provided sufficient relief or when side effects from other medications have been intolerable.

What the research says about ketamine for anxiety

The evidence base for ketamine’s use in depression is substantial. Research into anxiety disorders is newer but growing steadily, with several studies and systematic reviews now supporting ketamine’s potential as a treatment for multiple anxiety disorders.

Generalized anxiety disorder and social anxiety disorder

In a study examining weekly ketamine treatments in people with generalized anxiety disorder (GAD) and social anxiety disorder, patients reported rapid reductions in anxiety following treatment, with effects lasting up to seven days after a single dose. This study found that single-dose ketamine infusions reduced panic, irritability, and anxiety symptoms in people with GAD and social anxiety disorder, with effects persisting for up to two weeks.

Notably, higher doses were associated with stronger effects, and repeated treatments appeared capable of sustaining relief for months. As with all research in this area, most studies involved relatively small patient populations, and these findings reflect off-label use: factors worth acknowledging alongside the promising results.

Phobias

Research into ketamine for specific phobias has produced early, encouraging results. A 2021 study found that subcutaneous ketamine injections reduced patient-reported ratings of agoraphobia and social phobia, suggesting that ketamine may have a role to play across a broader spectrum of anxiety-related conditions.

Obsessive-compulsive disorder

A 2021 systematic review found that ketamine can rapidly reduce symptoms of obsessive-compulsive disorder (OCD), though these benefits have generally been temporary in duration. Researchers are actively investigating whether combining ketamine with psychotherapy, sometimes called ketamine-assisted psychotherapy (KAP), may produce more durable results for people with treatment-resistant OCD.

“My patient was struggling with severe OCD and treatment-resistant depression, and we had reached a point where various medications hadn’t really brought any relief. After exhausting conventional treatment options, we discussed ketamine as a potential next step, and decided to move forward. The results astounded me – he saw almost immediate, very significant improvement. The patient called me the day after his first appointment, excited to share that his nightly passive ideation was gone. The team at Keta is collaborative – they keep me informed, and the results have been meaningful.”

Treatment-resistant anxiety

Perhaps the most clinically relevant finding for many patients considering ketamine: studies suggest that approximately 50% of people with GAD meet criteria for treatment-resistant anxiety, meaning they do not experience meaningful improvement after an adequate course of anti-anxiety medication. 

For this population, a 2021 review concluded that ketamine may be a safe and effective alternative, particularly when administered as a series of infusions under medical supervision. Ketamine is not a first-line option, but for patients who have already tried conventional treatments without sufficient relief, it represents a clinically meaningful next step worth discussing with a qualified provider.

Research into ketamine for anxiety disorders is still evolving. All of the uses described above are off-label, meaning ketamine is being used in ways not yet formally approved by the FDA for anxiety specifically. Off-label prescribing is a well-established and legally sanctioned practice in medicine, and our clinical team will discuss the evidence, potential benefits, and limitations with you during your consultation.

Who may be a good candidate for ketamine therapy for anxiety?

Ketamine therapy is not appropriate for everyone, and we don’t treat it as a universal solution. At Keta Medical Center, we evaluate each patient individually, taking a thorough history to understand their diagnosis, prior treatments, and overall health before making any recommendations.

The patients who struggle with anxiety and are good candidates for ketamine therapy are those who:

• have not achieved adequate relief from one or more standard anti-anxiety treatments (medication, therapy or both)
• are experiencing anxiety symptoms that significantly impair daily functioning, relationships or quality of life
• are currently under the care of a mental health provider and are looking for adjunctive or alternative clinical support
• are medically eligible after a thorough screening by our clinical team

If you recognize yourself in that description, a conversation with our team is a reasonable next step. An evaluation, not a commitment, is how we begin.

Who should not pursue ketamine therapy?

Ketamine therapy is not for everyone. Our clinical team screens for certain disqualifying factors before any treatment begins, but as a general guide, ketamine therapy may not be appropriate for people with:

• a history of psychosis or a diagnosis of schizophrenia
• an active substance use disorder
• pregnant or trying to conceive

This list is not exhaustive. If you have questions about your eligibility, the best thing to do is schedule a consultation with our team. We’ll review your full medical history and help you understand whether ketamine therapy is a safe and appropriate option for you.

What to expect during a ketamine therapy session at Keta Medical Center

We know that the idea of starting a new treatment can feel daunting, especially for people who have already been through the frustrating cycle of trying approaches that haven’t worked. Our goal is to make the experience as clear, comfortable, and supportive as possible from the first conversation forward.

Ketamine therapy at Keta Medical Center is administered in a private, calm clinical environment, with a physician or qualified clinician present throughout your session. We offer two delivery methods:

• Ketamine infusion (IV ketamine): Delivered intravenously in a controlled clinical setting. A typical session lasts approximately 90 minutes, with effects beginning within minutes of administration. You will rest in a private room while our team monitors you throughout.
• Spravato® (esketamine nasal spray): Spravato is an esketamine-based nasal spray that is FDA-approved for treatment-resistant depression. A typical session lasts approximately two hours, including required monitoring time after administration. It may be considered when anxiety occurs alongside depression, which is common: research shows comorbid anxiety disorder and major depressive disorder occurs in as many as 60% of cases, and among people with either clinically significant depression or anxiety, nearly 50% have comorbid disorders. Spravato® sessions typically last approximately two hours, including monitoring time after administration.

Regardless of which treatment method is right for you, effects begin within minutes and resolve fully within a few hours. You will be monitored after your session before you are cleared to leave, and you will need to arrange a driver for the day of treatment. Please do not drive or operate machinery on the day of your appointment.

Many patients tell us that knowing exactly what to expect before their first session makes a meaningful difference, and we always encourage you to come with questions.

Common experiences and safety considerations

Ketamine therapy involves low, carefully controlled doses administered under direct medical supervision. Most patients tolerate it well. That said, we believe in full transparency about what you may experience.

It’s common to experience some of the following during or after treatment:

• Dissociation: a temporary sense of detachment from your surroundings, which typically resolves as the medication clears. This is normal and is part of what helps patients heal.
• Nausea or mild lightheadedness
• Elevated blood pressure or heart rate
• Temporary visual changes or mild drowsiness

These effects are generally short-lived and resolve within a few hours. Our clinical team monitors patients throughout every session and is trained to respond promptly to any discomfort.

Every patient at Keta Medical Center undergoes a thorough safety screening before treatment begins. We do not administer ketamine therapy without first understanding your full medical history, current medications, and any factors that might affect how you respond to treatment. 

Your safety is the foundation of everything we do.

How to get started with ketamine therapy for anxiety

Taking the first step is often the hardest part. At Keta Medical Center, we’ve designed our intake process to be straightforward and supportive.

Here’s how it works:

• Initial consultation: We review your medical history, current medications, prior treatments, and anxiety symptoms in detail. This is a two-way conversation: you’ll have the opportunity to ask questions and discuss your goals.
• Safety screening: One of our doctors personally evaluates your eligibility for ketamine therapy and speaks with your providers, reviewing any factors that could affect safety or treatment outcomes.
• Personalized treatment plan: If ketamine therapy is appropriate for you, we’ll develop a plan tailored to your specific situation, including the recommended delivery method, frequency, and supporting care.

Keta Medical Center has locations throughout New York and New Jersey. To learn whether ketamine therapy may be appropriate for your anxiety, we invite you to contact us to schedule a consultation.

Book a free consultation

For many people considering ketamine therapy, the most important evidence is not a clinical study or a statistic; it’s hearing from someone who has been where you are. 

At Keta Medical Center, we believe patient voices carry a kind of truth that no medical brochure can replicate. We’ve gathered this collection of testimonials from across our patient community: people living with depression, anxiety, post-traumatic stress disorder, and other conditions, sharing, in their own words, what seeking treatment at our clinic has meant for them.

What follows isn’t a list of reviews. It’s a glimpse into the lives of people who arrived at our doors after exhausting other options, and what changed when they decided to try ketamine therapy.

When nothing else had worked

Research suggests that roughly one-third of people with major depressive disorder do not find adequate relief from standard antidepressants: a group for whom ketamine’s distinct neurobiological pathway may offer a meaningful alternative. For the patients below, ketamine therapy offered something they hadn’t found elsewhere.

“I had tried everything — therapy, medication, hospitalization. Nothing worked. I felt hopeless. But then I found Keta Medical. After just a few treatments, I started to feel like myself again.”

— Sarah S.

“After 58 years of struggling with depression, I finally found relief and hope. The ketamine therapy is given in such a gentle manner that, within a couple of weeks, you feel like you have a brand new start to your life. I highly recommend, as the medical staff is so professional, and it has been one amazing experience.”

— Mark H.

“I have dealt with depression for years and have worked with multiple therapists and psychiatrists, trying numerous medications, but the problem persists. I am still in the induction phase, but the experience has been remarkable and unlike anything I have experienced before. The staff members are exceptional, and I am a physician myself, so I had high expectations. I urge you to seriously consider treatment at Keta Medical because there is a way forward here.”

— James E.

“I pretty much was raised thinking that everything that was wrong with me was my fault. If I just tried harder, I would get better. The idea that there might be something physically off — it never came up. It was always my guilt, my problem. I think ketamine has really freed me from that.

My mind is always running, and it’s running really hard. I’ve got a lot of worries, and they creep up, and they stay. Ketamine has helped alleviate that and helped me limit the negative self-talk — tell it to go take a hike, which I wasn’t really able to do before.

On my third session, I was walking along the street, and I was whistling. I wasn’t going anywhere particularly marvelous. I was noticing the trees. And I thought: oh, holy crap. I think I’m happy. I didn’t have to feel bad about it. I didn’t have to have a purpose for it. I was just happy. And I don’t think I’ve felt that since I was a little kid.”

— Richard S.

“Literally without any doubt. The clinic saved my life. This is real.”

— Raymond M.

“They saved my life. Wonderful facility. Beautiful souls.”

— Seth M.

Real changes patients notice

Beyond the initial sense of relief, patients often describe concrete, day-to-day shifts in how they feel and function. Ketamine is thought to work in part by acting on NMDA receptors in the brain, promoting neuroplasticity: the brain’s ability to form new connections. Research indicates this mechanism may help explain improvements in energy, cognition, and emotional regulation that some patients report, often beginning within hours or days of treatment.

“The ketamine treatments have definitely helped me more than anything else has in the past. Hands down, this has been the most effective way to address my depression and anxiety — getting to the root causes and understanding how to overcome it. I have noticed so much improvement, and it’s sustainable. I know that all my insight and progress will help me for the rest of my life — not just this moment in time.”

— A.G.

“My depression had started to impact my quality of life, and ketamine is helping me with energy levels; lethargy has diminished, and I am able to think more clearly. Less brain fog. Anyone severely depressed might want to consider ketamine treatments.”

— Irene S.

“I’m not worrying as much. My anxiety has lessened.”

— Mark D.

“As someone who went in for severe anxiety, I found myself much more mellow and able to use rational thought in daily situations more often. I look forward to more sessions and how my anxiety will continue to improve.”

— Zoe S.

Reconnecting with life and self

For some patients, the most meaningful change isn’t symptom relief: it’s a restored sense of self. Ketamine-assisted psychotherapy (KAP), in particular, may support lasting shifts in how people relate to difficult emotions and past experiences.

“I have a condition called myalgic encephalomyelitis. When I tell you I had seen hundreds of doctors and specialists, that’s not an exaggeration. None of them had ever mentioned ketamine as an option. When you’ve gone for years without real hope, putting hope on the horizon is — I can’t even explain how important that is.

The first couple of sessions, my head was full of negative thoughts. Loud. And then at the third session, it was like a little tiny blip, just for a couple of seconds, and then it was gone. Those thoughts that used to plague me every day, all day, are just gone. That has been such a relief.

The absence of negativity: that is by far the biggest difference in your daily experience, not having that hanging over your head all day. It’s not some artificial sense of positivity, like rainbows and smurfs. It’s just the relief of not having to fend off those negative thoughts.

I have things on my calendar now. Music lessons. Things to look forward to. I would never have done that before. You’ve already tried everything else. Believe that you’re investing in yourself and make that investment, because it’s worth it. You’re worth it.”

— Andrew E.

“I am finally healing after many years of a deep, dark depression.”

— Lynn D.

“I have major depression and it’s hard to treat. I felt haunted all the time, and I couldn’t work myself up to get out of the slumps. I’ve been on medication since my 40s — I’m now 71, and my mood would stay pretty negative. The self-talk was always very negative: you’re doing it wrong, why are you bothering?

After one of my sessions, I actually thought: I can make it better. That would never have occurred to me, ever. Nor would I have said it out loud. And then I just felt like I could, and it was okay.

One of my early sessions, my intention going in was: what about love? I saw my grandmother, and how she loved me when I was a baby, without judgment, without criticism. She just loved me. It was such a wonderful thing to remember and feel. I try to keep it in mind, because that’s what I felt I didn’t have, and I did.

I recommend it to all the people that I know who have mood problems. I just think it can help you in ways you don’t even think about. I never thought I’d come out of here saying, “I can make it better.” This is a place where you can actually say, “I’m really nervous about this.” You tell them that and they’re interested in your misgivings as well as your expectations.”

— Ellen W.

Chronic fatigue affects millions of people living with serious medical conditions. For many of them, unfortunately, effective treatments remain frustratingly out of reach. But a dissociative anesthetic, already used in clinical settings to treat depression, is now showing early promise as a fast-acting intervention for chronic fatigue. 

This article explains the current evidence, how ketamine may reduce chronic fatigue, and what patients should know before speaking with their doctors.

What is chronic fatigue? 

Chronic fatigue is not the same as feeling tired. It’s a persistent, overwhelming exhaustion that isn’t relieved by rest and significantly disrupts daily life, affecting one’s ability to work, exercise, complete basic tasks, and even maintain relationships. 

It’s most commonly associated with conditions such as cancer survivorship, fibromyalgia, lupus, chronic fatigue syndrome (CFS/ME), and post-viral illness. The scale of the problem is significant: In the U.S., alone, the CDC estimates that 3.3 million adults live with chronic fatigue syndrome.

Despite how debilitating chronic fatigue can be, treatment options are limited. While structured exercise is the most consistently evidence-based recommendation, starting and maintaining such a program is a challenge for people with chronic fatigue. Effective pharmacological options for chronic fatigue have historically been scarce, which is why emerging research into new treatment pathways is generating interest. 

What is ketamine? 

Ketamine is a dissociative anesthetic that has been used safely in medical settings for decades, first as a surgical anesthetic, and later for a wider range of applications in emergency and critical care medicine. Recently, ketamine has gained clinical attention as a rapid-acting treatment for treatment-resistant depression and acute suicidal ideation, both conditions that have historically been difficult to treat quickly with conventional medications. 

Ketamine works differently from traditional antidepressants. Rather than targeting serotonin, it affects glutamate, one of the brain’s key chemical messengers. By acting on specific glutamate receptors, ketamine sets off a chain reaction that encourages brain cells to build and strengthen connections with each other. This may help the brain adapt more quickly and could explain ketamine’s rapid antidepressant effects.

Spravato®, an esketamine-based nasal spray, has been FDA-approved for treatment-resistant depression and is available here at Keta Medical Center. Ketamine infusions (administered intravenously) remain an off-label treatment for depression and are not yet approved for chronic fatigue.

What does the research say about ketamine for chronic fatigue? 

Research into ketamine as a chronic fatigue treatment is still in its early stages, but the preliminary findings are meaningful enough to warrant attention. 

The first significant signal came from a 2016 clinical study led by researchers at the National Institutes of Health (NIH). 36 patients with treatment-resistant bipolar depression were enrolled in the trial and given either a single low-dose ketamine infusion (0.5 mg/kg IV over 40 minutes) or a placebo saline solution. 

Ketamine significantly reduced fatigue scores compared to the placebo, with effects beginning within 40 minutes of the infusion and peaking around day two. Notably, 65% of patients on ketamine experienced a greater-than-50% reduction in fatigue at some point during the trial, compared to just 10% on the placebo. The anti-fatigue effect persisted even after statistically controlling for ketamine’s antidepressant action, suggesting that fatigue and depression, while often co-occurring, may involve distinct biological pathways.

A decade later, a 2026 clinical trial led by researchers at the NIH and Rutgers University extended this investigation to people living with chronic fatigue tied to a range of conditions, including cancer survivorship, fibromyalgia, chronic fatigue syndrome and lupus. In this randomized, double-blind crossover trial, 10 participants received either a single low-dose ketamine infusion or midazolam, a sedative used as an active comparison treatment.

Three days after infusion, fatigue scores in the ketamine arm fell by 21%, crossing the 20% threshold the trial had set in advance as its primary measure of efficacy. The largest drop came at 24 hours, when fatigue scores fell by nearly 39%. Midazolam also reduced fatigue, but it was the ketamine arm alone that met the predefined 20% threshold. The difference between the two drugs was not statistically significant, which limits how strongly the results can be interpreted. The trial was also substantially underpowered. It was designed to enroll 59 participants but reached only 10 because of disruptions, and a larger follow-up trial involving breast cancer survivors is planned.

Despite the small sample sizes, there is a compelling biological rationale underlying both studies. Earlier research from the same NIH team connected fatigue to a glutamate receptor called mGluR5, finding that its signaling in immune cells helped predict which patients would develop fatigue after cancer treatment. Because ketamine acts directly on glutamate receptors, it offers a biologically plausible mechanism for addressing fatigue, one that is fundamentally different from the serotonin and norepinephrine-targeting pathways of most existing treatments.

This evidence is preliminary. No large-scale trials in a fatigue-specific population have been completed yet. While early evidence suggests ketamine may be an option for some patients, it’s not an established or approved fatigue treatment.

How might ketamine help with fatigue? 

To understand why ketamine might reduce fatigue, it helps to understand what it does in the brain. 

Ketamine primarily works by blocking NMDA receptors, a subtype of glutamate receptor involved in regulating neural signaling, inflammation, and synaptic plasticity. By temporarily blocking these receptors, ketamine may reduce neuroinflammation and interrupt the dysfunctional signaling patterns that researchers believe contribute to chronic fatigue. 

This blockade also triggers downstream effects. It releases BDNF (brain-derived neurotrophic factor), a protein that supports neural health. It also activates AMPA receptors in a process that promotes synaptogenesis, the formation of new synaptic connections. These effects are thought to underpin ketamine’s rapid antidepressant action and may similarly explain its impact on fatigue-related neural pathways. 

Dr. Leorey Saligan, the lead researcher on both the 2016 and 2026 studies and a faculty member at Rutgers School of Nursing, has proposed a bridge hypothesis: Ketamine may not be a long-term, standalone solution for chronic fatigue but rather a short-term, biological reset. The idea is that a single ketamine infusion could provide enough of an energy window for patients to engage with exercise, physical therapy, or other fatigue-reduction strategies proven to produce lasting benefit but difficult to initiate when fatigue is severe. If proven in larger trials, this could position ketamine as a catalyst for broader rehabilitation efforts rather than as an isolated treatment. 

Who might be a candidate for ketamine therapy for fatigue? 

Ketamine has not been specifically approved by the FDA for the treatment of chronic fatigue syndrome. However, physicians often use approved medications in areas where promising research and clinical experience suggest potential benefit. Early studies of ketamine in patients with chronic fatigue offer clues about who may respond best to treatment.

The 2026 Rutgers/NIH trial selected people living with persistent fatigue linked to cancer survivorship, fibromyalgia, CFS/ME, and lupus, particularly those who had not found meaningful relief from standard treatments. People also suffering from treatment-resistant depression may also be relevant candidates for ketamine therapy, given the overlap in the biological mechanisms that ketamine targets. Researchers hypothesize that people whose fatigue has a neuroinflammatory or glutamatergic component may be the most likely to respond to ketamine therapy. 

Ketamine is not appropriate for everyone. It is generally not recommended for people with: certain cardiovascular conditions, a history of psychosis, active substance abuse disorder, or other contraindications that a physician would assess individually. A thorough clinical evaluation is necessary before any treatment decision. 

If you are living with chronic fatigue and have not found relief from conventional approaches, speaking with a Keta Medical Center clinician can help you understand whether ketamine may be appropriate as part of your care plan.