What is ketamine therapy?

Ketamine therapy for depression is an innovative treatment that uses low doses of the medication ketamine to rapidly reduce severe depression symptoms, especially in people who haven’t found relief with standard treatments.

Ketamine was originally developed as a surgical anesthetic in the 1960s, but clinicians later discovered it has potent antidepressant effects when given at sub-anesthetic doses. Unlike typical antidepressant drugs that work on serotonin or other monoamines, ketamine works through a different brain pathway – the glutamate system – and helps stimulate new neural connections in the brain. This unique mechanism often leads to fast-acting relief – many patients notice mood improvements within hours or a day, instead of the weeks that traditional antidepressants can require. At Athena Care in Tennessee, ketamine therapy is provided in a safe, monitored clinical setting by trained professionals, offering new hope to individuals struggling with treatment-resistant depression.

Understanding Ketamine Therapy for Depression

For many people with treatment-resistant depression (TRD) – depression that hasn’t improved after trying multiple antidepressants – ketamine has been called a “game-changer.” Until recently, electroconvulsive therapy (ECT) was one of the only options for such severe cases, despite its risks (ECT involves inducing a brief seizure and can cause memory loss). Now, research shows that ketamine can improve depression as effectively as ECT but with fewer negative side effects, bringing hope to many who felt out of options.

Ketamine’s antidepressant properties were first hinted at in the 1970s, but it wasn’t until the 2000s that clinical studies confirmed a single low dose of ketamine could rapidly reverse depression symptoms in patients who hadn’t responded to other treatments. In fact, a landmark 2000 study showed IV ketamine produced improvements in hours while standard antidepressants took weeks. Building on this finding, in 2019 the FDA approved a form of ketamine (the esketamine nasal spray called Spravato®) specifically for adults with TRD or acute suicidal depression. This history underscores why ketamine therapy is generating so much excitement – it offers a radically different approach for hard-to-treat depression.

How Ketamine Works to Lift Depression

Ketamine works in an entirely different way than typical antidepressants. Instead of primarily targeting serotonin, ketamine acts on glutamate, the brain’s most abundant excitatory neurotransmitter. By blocking a receptor called NMDA, ketamine triggers a surge of glutamate that helps form new synapses (connections) between neurons. This process essentially “rewires” parts of the brain that have been damaged or dormant in depression, making the brain more adaptable and able to forge new pathways.

As Yale researcher Dr. John Krystal explains, “With most medications, like Valium, the effect you get only lasts when it is in your system… When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It’s the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects.” In simpler terms, ketamine acts as a catalyst for the brain’s own ability to heal and change. This may explain why the antidepressant effect of ketamine often persists even after the drug has left the body – it has caused a positive shift in brain circuit functioning rather than just a temporary chemical tweak. Another major difference is speed: ketamine’s impact on mood begins almost immediately, making it especially useful for people in crisis who cannot wait weeks for relief.

How Is Ketamine Therapy Given?

IV Infusions: The most common method of ketamine therapy is via intravenous infusion. In Athena Care’s clinics, patients receive ketamine through a small IV line in the arm over a period of about 40–55 minutes while under medical supervision. Vital signs – blood pressure, oxygen level, pulse – are continuously monitored throughout the session. During the infusion, you might experience a dreamy or dissociative sensation (some describe feeling floaty or detached from reality), which is a known effect of ketamine at these doses. If you feel uncomfortable or nauseous, the medical staff can adjust the drip or give medication (for example, an anti-nausea drug) to help. After the infusion is complete, you’ll relax in the clinic for another 30-45 minutes until the immediate effects wear off. It’s unsafe (and not legal) to drive yourself home after a ketamine treatment, so patients must arrange a ride and avoid driving for the rest of the day. The controlled clinical environment and monitoring ensure that the experience is as safe and comfortable as possible.

Nasal Spray (Esketamine – Spravato®): Athena Care also offers esketamine nasal spray, branded as Spravato®, which is the first FDA-approved ketamine-based treatment for depression. Spravato is an intranasal form of ketamine’s mirror-image molecule. Treatment with Spravato occurs in the clinic as well: you self-administer the nasal spray under a clinician’s direct supervision. Afterward, you remain in a comfortable observation area for at least two hours so staff can monitor for any side effects like blood pressure changes or dissociation. (It’s common for blood pressure to rise briefly after nasal ketamine, so they check it regularly.) Just like IV therapy, you cannot drive until the next day, so a ride home is required. Spravato is typically given twice a week for the first 4 weeks (the induction phase), then once weekly for another month or more (maintenance phase). Notably, FDA guidelines require that Spravato be used in conjunction with an oral antidepressant – it’s meant to augment, not replace, your existing medication. For patients who prefer not to have an IV, the nasal route provides a more patient-friendly option with similar benefits.

Injections and Other Forms: At select Athena Care locations, intramuscular (IM) ketamine injections are available as another mode of delivery. Instead of an IV drip, a single ketamine shot is given into a large muscle (like your thigh or shoulder). The psychedelic/dissociative effects are comparable to IV infusions, and the session timing is similar – about 40 minutes for the acute effects, plus an observation period of around 1–2 hours. Some clinics and physicians also utilize ketamine lozenges (troches) that dissolve in the mouth. Troches can sometimes be used to maintain benefits between infusions or as part of at-home adjunct care, but they are generally less potent than IV or IM routes. Regardless of the form, ketamine therapy must be done under professional oversight. At Athena Care, licensed medical and mental health professionals are present during every ketamine treatment to answer questions, ensure your comfort, and handle any issues that arise. This high level of support and monitoring is a key part of what makes the treatment safe.

The Treatment Process and Timeline

One of the most remarkable aspects of ketamine therapy is how quickly it can work. Many patients experience at least a partial lifting of depression within a day or two of their first ketamine session – sometimes within hours. In one early study, a single IV infusion of ketamine rapidly reversed depressive symptoms in patients who hadn’t responded to other meds. Patients often describe this early relief as a “fog being lifted” or a sudden break in the despair. However, the antidepressant effect from one dose of ketamine isn’t permanent. Typically, the mood boost from an initial ketamine treatment can last anywhere from a few days up to about a week. To prolong and solidify the improvement, ketamine therapy is given as a series of treatments rather than a one-time dose.

At Athena Care, a common protocol for depression is to start with a short induction series of ketamine sessions spread over about 2–3 weeks. For example, you might receive six infusions over two to three weeks (roughly two or three infusions per week) as an initial course. Spacing treatments over a couple of weeks allows the brain to build on the positive changes with each successive dose. Many patients find that their depression symptoms continue to improve or stabilize over the course of the series. Each infusion session lasts about 45 minutes, but you should allow around 1.5 hours per visit including recovery time. After completing the initial series, you and your provider will evaluate how you’re feeling. Because ketamine’s effects can fade with time, booster sessions are commonly used to maintain remission. A booster might be one infusion every month or every few months, depending on your needs. Some individuals require boosters more frequently, while others can go longer between treatments. The goal is to sustain the relief. Research has shown that intermittent, repeated ketamine treatments can extend ketamine’s antidepressant effects and help maintain the benefits over the long term.

Clinical studies to date have reported encouraging success rates with ketamine for depression. In various trials, roughly 50–70% of patients with TRD respond to ketamine therapy – meaning they experience a significant reduction in symptoms. (By comparison, any given antidepressant has about a 50% chance of working for a new patient, and that drops with each additional failed medication trial.) In a recent head-to-head study in patients with non-psychotic TRD, IV ketamine was found to be as effective as ECT – 55% of the ketamine group vs 41% of the ECT group had major improvement, a difference that suggests ketamine is at least on par with the most powerful traditional treatment. Every individual is different, of course, and not everyone will sustain a response to ketamine. Some people are “ketamine responders” and others may not find it helpful. But for those who do respond, the change can be life-changing. Importantly, research indicates that if you’re going to benefit from ketamine, you’ll usually know early in the course (within 1–3 sessions). Additional sessions then serve to maintain and reinforce that benefit rather than create entirely new effects. This is why the protocol involves a few initial treatments close together – to maximize the chance of remission – followed by maintenance as needed.

Safety and Side Effects

Safety Measures: Ketamine’s reputation as a “club drug” in the past might make some people nervous about its safety, but in a controlled medical setting it is very safe. At Athena Care, patient safety is the top priority during ketamine therapy. The dosage of ketamine used for depression is much lower than the doses used in anesthesia, but it can still cause noticeable mind-altering effects, so careful monitoring is essential. All ketamine treatments take place with rigorous medical supervision: a physician or nurse administers the ketamine and watches over you the entire time. Your blood pressure, heart rate, and oxygen levels are tracked throughout the session. The care team ensures you’re physically comfortable (dimming lights, offering a blanket or eye mask, etc., as needed) and emotionally supported. If you do experience a spike in blood pressure or significant nausea, the staff is prepared with medications and interventions to manage those promptly. Because ketamine’s effects can include disorientation, patients remain in the clinic until fully recovered afterward. By the time you leave, you’ll be alert and stable – but should not to drive until the next day. This controlled, professional environment minimizes risks and allows most people to tolerate ketamine therapy very well.

Common Side Effects: Although the ketamine dose for depression is low, you may still experience some side effects during or shortly after treatment. The good news is that these effects are temporary and typically subside by the end of the session or within a couple of hours. The most common side effects of ketamine therapy include:

• Dissociation or “out-of-body” sensation: You might feel strange or disconnected, as if things aren’t fully real (patients have described feeling like time is slowed down or that they’re observing themselves externally). This is an expected effect of ketamine’s action on the brain. It might sound intimidating, but many people find it manageable or even calming. Clinic staff will reassure you during these sensations.
  
• Dizziness or lightheadedness: It’s common to feel a bit dizzy or woozy during the infusion and immediately after. This is why you’ll rest for a while post-infusion.
  
• Drowsiness and fatigue: Ketamine can have a sedating effect. You might feel very relaxed or sleepy during treatment, and some people take a nap afterward.
  
• Nausea: Some patients get an upset stomach or nausea during a session. In anticipation of this, you’ll usually be advised not to eat heavy meals beforehand. If nausea does occur, clinicians can give anti-nausea medicine through the IV, which helps in most cases.
  
• Temporary blood pressure increase: Ketamine can cause blood pressure and heart rate to rise while it’s active. This is usually not dangerous in a healthy individual, and the team will be monitoring your vitals. Once the ketamine wears off, blood pressure returns to normal.
  
• Blurred or double vision: Some people experience vision changes (e.g. things might look fuzzy or you see double briefly). This clears up as the drug exits your system.
  
• Headache: Less commonly, a headache can occur after treatment, but it’s generally mild and responds to a pain reliever if needed.
  

It’s worth emphasizing that these side effects resolve on their own, and many patients find them manageable given the trade-off of depression relief. By the time you’re ready to go home, most side effects have dissipated. Athena Care’s clinicians will discuss all potential effects with you ahead of time, so you feel prepared. They’ll also be right by your side throughout the process, which helps patients feel safe even if they experience weird sensations. In the vast majority of cases, any discomfort is short-lived. In fact, a comprehensive assessment by the National Institute of Mental Health found that while transient feelings like being “spacey” or “loopy” occurred in some patients, none of the side effects lasted more than 4 hours, and there were no drug-related serious adverse events or long-term cognitive problems observed.

Because ketamine has some potential for abuse outside the medical setting, Athena Care and other reputable providers follow strict protocols to prevent misuse. Ketamine therapy is only administered in-clinic, by credentialed professionals – you won’t be taking ketamine at home on your own. (In fact, for Spravato nasal spray, the FDA has a REMS program that limits dispensing to certified clinics and requires observation, precisely to ensure safety and prevent abuse.) Athena Care also screens patients carefully: for example, individuals with a history of psychosis or uncontrolled substance use generally would not be given ketamine, since the drug could worsen those conditions. The controlled clinical approach keeps risks low. Addiction to medically supervised ketamine is exceedingly rare – it’s not like taking home a bottle of habit-forming pills. Patients typically receive only intermittent doses in the clinic, with no access outside. Moreover, studies have found no indication of craving or withdrawal symptoms with the short-term use of ketamine for depression. All of this should reassure you that ketamine therapy, as offered at Athena Care, is a safe and professionally managed procedure. Your care team will talk with you about any concerns and make sure you’re a good candidate before proceeding.

Ketamine Therapy vs. Other Depression Treatments

How does ketamine fit into the landscape of depression treatment? It’s helpful to compare it with a few other options:

• Standard Antidepressants (SSRIs/SNRIs, etc.): Medications like SSRIs (e.g. Prozac, Zoloft) are the first-line treatment for depression. They are effective for many people, but they have limitations. First, they can take several weeks to start working, which is a long time to wait when someone is severely depressed. Second, a significant portion of patients – about 30% or more – don’t get adequate relief from the first antidepressant (or even second or third) that they try. Ketamine differs in that it works on a new pathway (glutamate) and can produce improvement much faster. It’s often considered for those very patients for whom traditional meds have failed. It’s not that ketamine “replaces” SSRIs – indeed, many TRD patients have tried numerous medications – but it offers a new mechanism of action when serotonin-based treatments fall short. Some patients who undergo ketamine therapy will continue on an oral antidepressant as well (these medications can complement each other). Notably, esketamine (Spravato) is always used alongside an oral antidepressant by design.
  
• Therapy and Lifestyle: Psychotherapy (like cognitive-behavioral therapy or counseling) is a cornerstone of depression treatment. Ketamine doesn’t replace therapy – in fact, because ketamine can rapidly alleviate the worst depressive symptoms, it may enable patients to engage more productively in therapy and life changes. At Athena Care, ketamine treatment is often one component of a holistic plan that can include talk therapy, support groups, exercise, and more. Think of ketamine as opening a “window” of relief during which you can make other positive changes. It’s not either/or – many patients do therapy + ketamine together for the best outcome.
  
• Transcranial Magnetic Stimulation (TMS): TMS is a non-invasive treatment Athena Care also provides, which uses magnetic pulses to stimulate brain regions involved in mood. Like ketamine, TMS is typically used for depression that hasn’t responded to medications. TMS has the advantage of not involving any drug or psychedelic experience – there’s no systemic side effect like nausea or dissociation, and you can even drive yourself to and from TMS sessions. However, TMS requires a substantial time commitment: treatments are usually done 5 days a week for about 6 weeks. Each TMS session takes about 20 minutes, and relief gradually accumulates over the course of the treatment series. Many patients do very well with TMS, but if someone needs faster relief or has not responded to TMS either, ketamine is another route. Some people who can’t tolerate medication side effects or who prefer a non-drug approach might opt for TMS before trying ketamine. Others might choose ketamine for its speed. These treatments aren’t mutually exclusive; it’s about finding the right fit for the individual.
  
• Electroconvulsive Therapy (ECT): ECT is one of the most effective treatments known for severe depression and has been used for decades, often in life-threatening depression or when other treatments fail. It does, however, involve general anesthesia and intentionally causing a brief seizure in the brain. ECT can have significant side effects, especially short-term memory loss and confusion, and it carries a certain stigma that makes some patients reluctant to try it. Recent evidence suggests that ketamine infusion therapy can achieve comparable results to ECT for many patients with treatment-resistant depression. In a head-to-head study, ketamine was about equally effective in reducing depression symptoms as ECT, and some findings even showed ketamine outperforming ECT in certain measures. While ECT remains a vital option (particularly for patients with psychotic depression or catatonia, conditions where ECT is uniquely effective), ketamine offers a less invasive alternative for TRD without the cognitive side effects. Patients do not need to be sedated or hospitalized for ketamine – it’s an outpatient procedure – and they typically recover within an hour of each session. This makes ketamine a very attractive option before resorting to ECT in the treatment hierarchy.
  

In summary, ketamine therapy fills an important gap for those who haven’t been helped by more routine treatments. It’s faster-acting than most anything else in psychiatry and works via a novel mechanism. That said, it’s usually considered after trying standard approaches, not before. An ideal treatment plan might be: try therapy and antidepressants first; if those fail, consider adding or switching to something like TMS or ketamine; reserve ECT for cases that resist even these interventions. Athena Care offers all of these modalities – from medication management to TMS, Spravato, and ketamine infusions – so that an individualized plan can be created. Our providers will help weigh the pros and cons of each option. In many cases, ketamine can be the pivotal treatment that finally brings relief, but it’s usually part of a larger strategy that continues to include support from medications or therapy to maintain wellness.

A New Hope: Ketamine Therapy at Athena Care

For people who have felt trapped in depression, ketamine therapy offers a new source of hope and healing. It’s not a magic cure-all or a “happy pill,” but it can work remarkably fast to lift the heaviest of depressive symptoms and create an opportunity for recovery. Patients who have undergone ketamine treatment often describe it as hitting a reset button – the entrenched feelings of despair, numbness, and hopelessness start to loosen their grip. This can be especially life-changing for someone who has tried every antidepressant and therapy without success. In such cases, ketamine’s effects can feel like emerging from a tunnel into daylight. As one Harvard psychiatrist noted about her patients, many have failed so many treatments that “ketamine is sometimes the only option that provides relief”. For those individuals, ketamine truly can be a game-changer.

Athena Care is proud to be among the providers offering this cutting-edge treatment in Tennessee. We have multiple clinics across the state (including Nashville, Knoxville, Murfreesboro, Memphis, and others) staffed by compassionate clinicians who specialize in mental health care. Our ketamine therapy program is conducted by experienced medical professionals in a calm, supportive environment. From the initial consultation through each infusion or Spravato session, your well-being is our top priority. Athena Care also recognizes that accessing innovative treatments can be a financial concern for some, which is why we are in-network with most major insurance plans and have dedicated care coordinators to help patients navigate their insurance coverage for ketamine therapy. We strive to make this therapy as accessible and affordable as possible, coordinating benefits and offering guidance every step of the way.

Depression can make you feel like you’re out of options, but there is hope. Ketamine therapy is opening doors for people who felt stuck in darkness, helping them find relief and reclaim their lives. If you or a loved one is suffering from severe, treatment-resistant depression, Athena Care’s ketamine services in Tennessee provide a safe and supportive path forward. Our team is here to answer your questions, address your concerns, and walk with you on your journey toward better mental health. You don’t have to battle depression alone or stay “stuck” after other treatments falter – ketamine therapy could be the breakthrough that makes the difference, and Athena Care is ready to help you find new light beyond the depression.

Call to Action: If you or someone you love in Tennessee is struggling with treatment-resistant depression, consider exploring ketamine therapy. You can contact Athena Care’s clinics (open Monday–Friday, 7am–6pm) to learn more. Remember, help is available, and you don’t have to face mental health challenges alone.

Dr. Jack L Koch Jr., M.D.

Psychiatrist
Dr. Koch obtained his undergraduate degree at the University of South Alabama, obtained his medical degree at the University of South Alabama College of Medicine, completed his Internship and Residency in General Psychiatry at the Vanderbilt University Medical Center, and completed his Fellowship in Child and Adolescent Psychiatry at the Vanderbilt University Medical Center. During his last year at Vanderbilt University Medical Center, he served as Chief Fellow for the Division of Child and Adolescent Psychiatry.

Learn more about Dr. Koch

Meg Stein, CFP

Editor
Meg is a certified mindfulness instructor and works at Alive and Aware Practice in Durham, NC. She has over ten years of experience as a content creator and marketing consultant, working in mental healthcare and social justice.

Sources:

Athena Care. (n.d.). IV ketamine infusion therapy in Tennessee. https://athenacare.health

Athena Care. (n.d.). Ketamine for depression (IM ketamine therapy). https://athenacare.health

Athena Care. (n.d.). Ketamine: A game‑changing treatment for treatment‑resistant depression [Blog post]. https://athenacare.health

Athena Care. (n.d.). Top signs you should ditch your SSRI [Blog post]. https://athenacare.health

Athena Care. (n.d.). Spravato (esketamine) treatment center in Knoxville, TN. https://athenacare.health

Harvard Gazette. (2024, November 20). Rapid relief for the severely depressed? There’s a catch. https://news.harvard.edu